Cushing's & Cancer

Expanding treatment options for Cushing's disease

2012-01-26T16:09:00.001-05:00

Contact: Karen Honey
press_releases@the-jci.org
734-546-5242
Journal of Clinical Investigation

Expanding treatment options for Cushing disease

Cushing disease is a hormone disorder that causes a diverse array of symptoms, including fat accumulation, high blood pressure, osteoporosis, muscle wasting, and ultimately death. It is caused by a tumor in the anterior pituitary gland that results in the secretion of excess amounts of adrenocorticotropic hormone (ACTH). Treatment options are essentially limited to surgical resection.

However, tumors commonly recur, meaning that new treatment options are needed. A team of researchers, led by Shlomo Melmed, at Cedars-Sinai Medical Center, Los Angeles, has now identified a potential new therapeutic target -- the protein EGFR, which is the target of a drug used to treat some patients with non–small cell lung cancer (gefitinib).

As discussed by Melmed and colleagues in their paper, as well as Frederic Wondisford, at Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, the data generated in human, canine, and mouse models provide strong support to investigate the clinical effects of gefitinib in patients with Cushing disease.

TITLE: EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas

AUTHOR CONTACT:

Shlomo Melmed

Cedars-Sinai Medical Center, Los Angeles, California, USA.

Phone: 310-423-4691; Fax: 310-423-0119; E-mail: Melmed@csmc.edu.

ACCOMPANYING COMMENTARY TITLE: A new medical therapy for Cushing disease?

AUTHOR CONTACT:

Fredric E. Wondisford

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Phone: 410-502-5761; Fax 410-502-5779; E-mail: fwondisford@jhmi.edu.

Signifor: Novartis Drugs Backed by CHMP

2012-01-26T14:40:00.001-05:00

By: Zacks Equity Research

Novartis (NVS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) rendered positive opinion for two of its drugs.

First, the CHMP gave a positive opinion to update the label of its marketed drug Gleevec for extended use of adjuvant treatment for three years in patients with KIT (CD117)-positive gastrointestinal stromal tumors (GIST) versus the standard one-year treatment currently approved.

Secondly, the CHMP issued a positive opinion on Novartis’ pipeline candidate Signifor (SOM230) for the treatment of Cushing's disease, for which no medicines are currently available in the European Union (EU).

The positive opinion on Gleevec was based on data from a large phase III trial (n=400) which demonstrated that Gleevec led to significant improvement in both recurrence-free survival and overall survival after three years of adjuvant treatment in patients with KIT (CD117)-positive GIST versus the standard one-year treatment currently approved.

This is the first-ever study demonstrating the survival benefits of longer-term treatment with Gleevec. Novartis is also seeking approval for a Gleevec label update in the US and has been granted priority review by the US Food & Drug Administration (FDA). Besides GIST, Gleevec is currently marketed for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+CML).

The Signifor positive opinion was based on data from a phase III trial in which the candidate demonstrated significant efficacy in reducing the level of urinary free cortisol (UFC). In the US, Novartis filed a new drug application (NDA) in June 2011 for Cushing's disease which was subsequently withdrawn due to some problem in the chemistry, manufacturing and controls (CMC) section.

The NDA will be resubmitted following discussion with the FDA. Other than Cushing's disease, Signifor is also being studied for the treatment of acromegaly and carcinoid syndrome in phase III trials.

Earlier this month, Novartis also announced that its drug Lucentis has been approved in China for the treatment of wet age-related macular degeneration (wet AMD). Lucentis is currently marketed for wet AMD as well as visual impairment due to diabetic macular edema (DME) and macular edema following retinal vein occlusion (RVO) in many countries including the US and EU. Novartis’ diabetes drug, Galvus, was also launched in China recently as an add-on to metformin, the standard of care.

Our Recommendation

Currently, we have a Neutral recommendation on Novartis. The company carries a Zacks #3 Rank (Hold rating) in the short run. Though pleased with Novartis’ wide range of products and its efforts to diversify further, as is evident by the acquisition of eye-care company Alcon, we prefer to remain on the sidelines in the long term due to the imminent patent cliff faced by the company.

Read the full analyst report on NVS

From http://www.zacks.com/stock/news/68482/Novartis+Drugs+Backed+by+CHMP

Dr. Theodore Friedman's Interviews

2012-01-26T13:00:00.001-05:00

Theodore C. Friedman, M.D., Ph.D. has opened a private practice, specializing in treating patients with adrenal, pituitary, thyroid and fatigue disorders. Dr. Friedman has privileges at Cedars-Sinai Medical Center and Martin Luther King Medical Center. His practice includes detecting and treating hormone imbalances, including hormone replacement therapy. Dr. Friedman is also an expert in diagnosing and treating pituitary disorders, including Cushings disease and syndrome.

Dr. Friedman's career reflects his ongoing quest to better understand and treat endocrine problems. With both medical and research doctoral degrees, he has conducted studies and cared for patients at some of the country's most prestigious institutions, including the University of Michigan, the National Institutes of Health, Cedars-Sinai Medical Center, and UCLA's Charles Drew University of Medicine and Science.

Read Dr. Friedman's First Guest Chat, November 11, 2003.
Read Dr. Friedman's Second Guest Chat, March 2, 2004.

Listen to Dr. Friedman First Live Voice Interview, January 29, 2009.
Listen to Dr. Friedman Second Live Voice Interview, March 12, 2009.
Listen to Dr. Friedman Third Live Voice Interview, February 13, 2011.

From http://www.cushie.info/index.php?option=com_content&view=article&id=1146:dr-theodore-friedman-interviews&catid=10:media&Itemid=18

Have You Been Diagnosed With Cushing's? Earn $125 or $250

2012-01-25T09:13:00.001-05:00

We invite you to help us create better information, tools, and resources

for people with Cushing’s Syndrome

How: Share your opinions and give input in a one-on-one confidential interview. Your opinions will remain confidential. The overall results will help others with Cushing’s Syndrome.

When: Market research interviews can be conducted by phone or in-person, in a location near you. The interview will last approximately 45 minutes.

If you are interested in a phone interview or in-person interview, please contact Clair Carmichael Johnstone (see details below). More information (including cities and locations for in-person interviews) will be provided on the phone.

Am I Eligible? If you’ve been diagnosed with Cushing’s Syndrome and still experience symptoms of Cushing’s you are eligible to participate. Cushing’s Syndrome includes: Cushing’s Disease, ectopic Cushing’s and adrenal Cushing’s. Patients should have been diagnosed within the last 10 years.

At this time, patients who are in remission, were diagnosed more than 10 years ago, or have had a bilateral adrenalectomy are not eligible for research.

Details: Participants eligible for market research will be asked to participate in the 45-minute interview. Patients participate also receive an honorarium (payment) for your time. Those who participate in an in-person interview will be compensated $250 and those who choose a phone interview will receive $125 for their time.

Why? Corcept Therapeutics is interested in hearing from people who suffer from Cushing’s Syndrome in order to improve treatment and information available. This can lead to improved education and resources for those with Cushing’s and physicians treating Cushing’s.

How do I find out more?

If you have questions or would like to participate, please contact Clair Carmichael Johnstone at:

Toll-free number: (800) 856-6706, or

E-mail: cushing@compasshc.com

Please provide your name, phone number, and the best times to reach you so we can follow up promptly.

Novartis drug Signifor® recommended by CHMP for EU approval to treat patients with Cushing's disease

2012-01-20T14:51:00.001-05:00

Basel, Switzerland, Jan 20, 2012 (Thomson Reuters ONE via COMTEX) -- Novartis International AG / Novartis drug Signifor® recommended by CHMP for EU approval to treat patients with Cushing's disease . Processed and transmitted by Thomson Reuters ONE. The issuer is solely responsible for the content of this announcement.

- If approved, Signifor (SOM230, pasireotide) would be the first approved medication targeting Cushing's disease[1]

- In clinical trials, pasireotide suppresses overproduction of cortisol caused by an underlying pituitary tumor, a critical factor in controlling the disease[2],[3],[4]

- A debilitating endocrine disorder, Cushing's disease most commonly affects women from 20 to 50 years old[2],[5]

Basel, January 20, 2012 - The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Signifor® (SOM230, pasireotide) for the treatment of Cushing's disease. There are currently no approved medicines in the European Union (EU) targeting Cushing's disease, a debilitating endocrine disorder caused by excess cortisol in the body due to the presence of a non-cancerous pituitary tumor[1],[2].

"We are pleased with the decision by the CHMP in support of pasireotide in the European Union," said Herve Hoppenot, President, Novartis Oncology. "We are now one step closer to being able to offer patients in Europe the first approved medical treatment for Cushing's disease."

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. Pasireotide has orphan drug designation for Cushing's disease, a condition which affects no more than five in 10,000 people in the EU, the threshold for orphan designation[6].

The CHMP positive opinion is based on data from the Phase III PASPORT-CUSHINGS (PASireotide clinical trial PORTfolio - CUSHING'S disease) trial, the largest randomized study to evaluate a medical therapy in patients with Cushing's disease[4].

In the study, patients were randomized to receive pasireotide subcutaneous (sc) injection in doses of 900ug and 600ug twice daily. For the 900ug group, the study met the primary endpoint of normalizing urinary-free cortisol (UFC) levels, the key measure of biochemical control of the disease[4].

Urinary-free cortisol levels were normalized in 26.3% and 14.6% of patients randomized to receive pasireotide 900ug and 600ug twice daily, respectively, at six months of treatment. After 12 months of treatment, results confirmed the durability of the effect. On average, as UFC levels were reduced, clinical manifestations of Cushing's disease improved including reduction of blood pressure, total cholesterol, weight and body mass index[4].

The most frequently reported adverse events (AE) (>10%) by investigators for pasireotide were diarrhea, nausea, hyperglycemia, cholelithiasis, abdominal pain, diabetes mellitus, injection site reactions, fatigue and increased glycosylated hemoglobin (HbA1c), with most events being Grade 1-2. The tolerability profile of pasireotide was similar to that of other somatostatin analogs with the exception of the greater degree of hyperglycemia[4].

About Cushing's disease

Cushing's syndrome is an endocrine disorder caused by excessive cortisol, a vital hormone that regulates metabolism, maintains cardiovascular function and helps the body respond to stress[2]. Cushing's disease is a form of Cushing's syndrome, in which excess cortisol production is triggered by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma[1]. The first-line and most common treatment approach for Cushing's disease is surgical removal of the tumor[2].

Cushing's disease is a rare but serious disease that affects approximately one to two patients per million per year[7]. It most commonly affects women from 20 to 50 years old[2],[5]. Cushing's disease may present with weight gain, central obesity, moon face, severe fatigue and weakness, striae (purple stretch marks), buffalo hump, depression and anxiety[1],[5].

About pasireotide

Pasireotide, an investigational multireceptor targeting somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3 and 5)[1].

For the treatment of Cushing's disease, pasireotide has been studied as a twice-daily subcutaneous (sc) injection and is currently being evaluated as a long-acting release (LAR), once-monthly intramuscular (IM) injection as part of a global Phase III program. Pasireotide LAR is also being studied in three large-scale, global Phase III clinical trial programs: two in patients with acromegaly and one in patients with metastatic carcinoid tumors whose disease-related symptoms are inadequately controlled by somatostatin analogs.

Information about Novartis clinical trials for pasireotide can be obtained by healthcare professionals at www.pasporttrials.com .

Important Safety Information about pasireotide

Pasireotide is contraindicated in patients with hypersensitivity to pasireotide or to any of the excipients and in patients with severe liver impairment. Hyperglycemia is commonly reported as an adverse event and elevated glucose was the most frequently reported Grade 3 laboratory abnormality (23.2% of patients) in the Phase III study in Cushing's disease patients. Glycemic status should be assessed prior to starting treatment with pasireotide. Patients need to be monitored for hyperglycemia; if hyperglycemia develops, the initiation or adjustment of antidiabetic treatment is recommended.

Mild transient elevations in AST (aminotransferases) are commonly observed in patients treated with pasireotide. Rare cases of concurrent elevations in ALT (alanine aminotransferase) greater than 3 times the upper limit of normal (ULN) and bilirubin greater than 2 times ULN have also been observed. Patients need to be monitored closely for liver function for the first 3 months and thereafter as clinically indicated. Therapy should be discontinued if the patient develops jaundice, other clinical signs of significant liver dysfunctions, sustained AST or ALT increase 5 times ULN or greater, or if ALT or AST increase 3 times ULN with concurrent bilirubin elevation greater than 2 times ULN.

Patients with cardiac disease and/or risk factors for bradycardia need to be closely monitored. Caution is to be exercised in patients who have or may develop QT prolongation. Hypokalemia or hypomagnesemia must be corrected prior to initiating therapy and monitored thereafter.

Treatment with pasireotide leads to rapid suppression of ACTH (adrenocorticotropic hormone) secretion in Cushing's disease patients. Patients need to be monitored for signs and symptoms of hypocortisolism. Temporary exogenous steroid (glucocorticoid) replacement therapy and/or dose reduction or interruption of pasireotide therapy may be necessary.

Pasireotide should not be used during pregnancy unless clearly necessary. Breast feeding should be discontinued during treatment with pasireotide.

Pasireotide may affect the way other medicines work, and other medicines can affect how pasireotide works. Caution is to be exercised with the concomitant use of drugs with low therapeutic index mainly metabolized by CYP3A4, bromocriptine, cyclosporine, anti-arrhythmic medicines or drugs that may lead to QT prolongation.

The foregoing release contains forward-looking statements that can be identified by terminology such as "would," "will," "being evaluated," "being studied," or similar expressions, or by express or implied discussions regarding potential marketing approvals for pasireotide or regarding potential future revenues from pasireotide. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with pasireotide to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that pasireotide will be approved for sale in any market. Nor can there be any guarantee that pasireotide will achieve any particular levels of revenue in the future. In particular, management's expectations regarding pasireotide could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 121,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com .

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis .

References

[1] Pedroncelli A.M. Medical Treatment of Cushing's Disease: Somatostatin Analogues and Pasireotide. Neuroendocrinology. 2010;92 (suppl 1): 120-124.

[2] National Endocrine and Metabolic Diseases Information Service. National Institutes of Health. Cushing's Syndrome. Available at http://www.endocrine.niddk.nih.gov/pubs/cushings/Cushings_Syndrome_FS.pdf . Accessed December 2011.

[3] Boscaro M., et al. Treatment of Pituitary-Dependent Cushing's Disease with the Multireceptor Ligand Somatostatin Analog Pasireotide (SOM230): A Multicenter, Phase II Trial. J Clin Endocrinol Metab. 2009; 94(1):115-122.

[4] Colao, A. Pasireotide (SOM230) provides clinical benefit in patients with Cushing's disease: results from a large, 12-month, randomized-dose, double-blind, Phase III study. Abstract# OC1.7. European Neuroendocrine Association (ENEA) 14th Congress.

[5] Newell-Price J, et al., The Diagnosis and Differential Diagnosis of Cushing's Syndrome and Pseudo-Cushing's States. Endocrine Reviews. 19(5): 647-672. Available at http://edrv.endojournals.org/content/19/5/647.full.pdf +html Published 1998. Accessed December 2011.

[6] European Medicines Agency. Committee for Orphan Medicinal Products. Public Summary of Positive Opinion for Orphan Designation of Pasireotide for the treatment of Cushing's Disease. Available at http://www.emea.europa.eu/docs/en_GB/document_library/Orphan_designation/2009... . Accessed December 2011.

[7] Lindholm S., et al. Incidence and Late Prognosis of Cushing's Syndrome: A Population-Based Study. J Clin Endocrinol Metab. 2001; 86 (1): 117-123.

# # #

Novartis Media Relations

From http://www.marketwatch.com/story/novartis-drug-signifor-recommended-
by-chmp-for-eu-approval-to-treat-patients-with-cushings-disease-2012-01-20

Pregnancy-induced Cushing’s Syndrome: A Case Report

2012-01-19T06:43:00.001-05:00

Cushing’s syndrome(CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause.The other causes include tumors in hypothalamus and pituitary. Ectopic ACTH secretion has been reported to cause CS.

There is a very rare condition. Cushing’s syndrome develops in pregnancy and resolving after delivery. The mechanisms underlying these conditions are poorly understood.

There are non-significant differences in the clinical features of pregnant and non-pregnant women with CS.The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, The normal gestational changes in the HPA axis alter these parameters and complicate the screening process for CS.

Comparing with non-pregnant women with CS, the treatment is different in Cushing’s syndrome during pregnancy.

We described here the case of a 25-year-old woman with CS during her forth [sic] pregnancy. Hypertension, diabetes, hypopotassaemia, purple striae and acne are present. Cushing’s syndrome in the patient resolved within four weeks of artificial termination. Eight months after artificial termination, the patient became pregnant again and rapidly developed Cushing’s syndrome with typical clinical symptoms and signs and laboratory results.

Title: Pregnancy-induced Cushing’s Syndrome: A Case Report

Category: Tumor Biology

Filename: Pregnancy-induced Cushing’s Syndrome: A Case Report.pdf

Pages: 101

Price: US$48.00

Buy this pater at http://www.tumorres.com/tumor-biology/25201.htm

First potential Prader-Willi treatment among EMA’s orphan recommendations

2012-01-19T06:33:00.001-05:00

Ferring’s carbetocin, potentially the first treatment for Prader-Willi syndrome, is among 16 new medicines recommended to receive orphan drug designation in Europe.

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) said work on carbetocin’s use to treat the rare genetic disorder should be granted development incentives.

Prader-Willi syndrome, which is estimated to affect less than 1 in 5,000 people in the EU, causes a variety of symptoms, including a constant desire to eat food, leading to obesity, impaired function of the gonads, learning difficulties and behavioural problems.

Patients with the disease often have a significantly reduced life span and require lifelong care.

Carbetocin’s recommendation was supported by the European Organisation for Rare Diseases (Eurordis), a European alliance of patient organisations and individuals involved in the promotion of research for rare diseases and development of orphan drugs.

Other treatments to be recommended by the COMP for orphan drug designation, which is granted to products for life-threatening or very serious conditions that affect no more than 5 in 10,000 people in the EU, included Nexus Oncology’s diamidophosphate.

The drug, which is being investigated as a treatment for soft tissue sarcoma, was joined on the list by TMC Pharma Service’s chlormethine for treatment of cutaneous T-cell lymphoma and Laboratoire HRA Pharma’s ketoconazole for treatment of Cushing's syndrome.

Therapies for neglected tropical diseases also featured in the COMP’s recommendations, with Dafra Pharma’s oleylphosphocholine intended to treat leishmaniasis – a disease caused by sand fly parasites that is estimated to cause as many as 50,000 deaths per year.

The EMA said that orphan medicine incentives can be also used to support the development of treatments for similar neglected diseases, which would not be developed under normal market conditions.

All the COMP’s recommendations are now with the European Commission, which will make the final decision on each drug.

The full list of EMA orphan drug recommendations

From http://www.pmlive.com/pharma_news/potential_first_prader-willi_treatment_ema_orphan_recommendation_357835

Treatment Options in Cushing’s Disease

2012-01-19T06:20:00.001-05:00

Download PDF

Authors: Ahmed Rizk, Juergen Honegger, Monika Milian and Tsambika Psaras

Publication Date: 11 Jan 2012

Journal: Clinical Medicine Insights: Oncology

Citation: Clinical Medicine Insights: Oncology 2012:6 75-84

doi: 10.4137/CMO.S6198

Abstract

Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol.

The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy.

Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed.

Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome.

Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated.

Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect.

The aim of this review is to analyze and present current treatment options in Cushing’s disease.

From http://www.la-press.com/treatment-options-in-cushings-disease-article-a2985

Healthy New Year Video Challenge

2012-01-19T05:52:00.001-05:00

$5,000 in prizes!

Let’s get the new year off to a healthy start! The Office of the National Coordinator for Health Information Technology (ONC) Healthy New Year Video Challenge (#HealthIT4U2012) invites you to create a short, compelling video (up to 2 minutes in length) sharing one New Year’s resolution for improving your health or the health of a loved one, and how you will use technology to achieve your resolution.

We encourage you to create videos that are creative, inspiring and instructive — share a resolution that others can relate to, and demonstrate how technology will make it easier to achieve. Your resolution can be anything health related, such as quitting smoking or drinking, eating healthier, losing weight, reducing stress, or managing a chronic condition. Videos must show how you will use information technology to achieve your resolution and how you plan to maintain it. Entries could include the following kinds of resolutions (these are just examples — be creative and craft your own resolution!):

I will set up an online personal health record for myself (or another family member) so I can have all of my health information conveniently stored in one place.
I will ask my doctor for a copy of my own health records — electronically if available — and help him or her to identify any important information that may be missing or need to be corrected.
I will find an online community that helps me figure out the best ways to manage my health condition (depression, cancer, diabetes, etc.)
I will use an electronic pedometer to help me track my physical activity and will try to take 10,000 steps per day.
I will find an app on my smartphone to help me track my food intake so I can lose 10 pounds by my high school reunion.
I will sign up for a text reminder program on my cell phone to help me stop smoking or remind me to take my medications on time.

The goal of the challenge is to make 2012 a healthier year by motivating and inspiring others to use health information technology to be more engaged in improving health and increasing adoption of consumer health technology.

Note: To participate, you must be a citizen or permanent resident of the United States. Team members must be at least 18, but your video can include minors under 18 as long as a parent or legal guardian signs their consent forms. For details on eligibility, review the Official Rules.

More at http://healthynewyea...v/details/about

GH replacement therapy associated with development of diabetes

2012-01-19T05:39:00.001-05:00

Posted on EndocrineToday.com

Luger A. Diabetes Care. 2012;35:57-62.

The incidence of diabetes was increased in patients with growth hormone deficiency who were on growth hormone replacement therapy, according to researchers in Europe.

The researchers selected patients from KIMS — Pfizer International Metabolic Database. Patients were selected if they had severe adult-onset GH deficiency that was confirmed with a GH stimulatory test and naive to GH treatment. Patients with a history of Cushing’s disease or acromegaly or with diabetes at baseline were excluded.

The study included data from 5,143 patients. Plasma glucose, HbA1c values, lipid and insulin-like growth factor I concentrations and serum IGF-I measurements were obtained.

Five hundred twenty-three patients developed diabetes after a median of 1.7 years. Patients who developed diabetes were older, had higher BMI, waist circumference, waist-to-hip ratio and triglyceride concentrations. They also had higher systolic and diastolic blood pressure and lower HDL cholesterol.

The incidence of diabetes was 2.6/100 patient-years, decreasing from 4.1/100 patient-years during the first year of GH replacement therapy to 1/100 patient-years after more than 8 years of treatment. The overall observed cases/expected cases ratio was 6, decreasing from 10.8 in the first year of treatment to 1.9 after 8 or more years of treatment.

Sex, BMI, attained age during follow-up, years between pituitary diagnosis and GH treatment start and years since first treatment were significantly associated with diabetes occurrence. There was no significant association with GH dose. In patients who did not develop diabetes, plasma glucose concentrations increased from 84.4 mg/dL to 89.5 mg/dL, and HbA1c levels increased from 4.74% to 5.09% after 6 years of treatment.

“Despite widely demonstrated benefits of growth hormone replacement treatment in adult growth hormone deficiency, a marked increase in the risk of developing diabetes must be considered,” the researchers wrote. “All patients, but particularly those with an adverse risk profile, should be carefully followed regarding parameters of glucose metabolism.”

From http://www.endocrinetoday.com/view.aspx?rid=91303

(Adrenal Cushing's) Tumour behind 7-yr-old's weight gain, moustache

2012-01-10T14:21:00.001-05:00

By: Priyanka Vora Date: 2012-01-03 Place: Mumbai

Tanzania resident Mohammad Abdulrazaq Jussa recuperating after city doctors removed 7-cm tumour from his adrenaline [sic] gland, which was responsible for his 12-kg weight gain, growth of facial hair

Painful and embarrassing stories about one's childhood years, when inexplicable physical changes take place, are not uncommon. But for Mohammad Abdulrazaq Jussa, a resident of Tanzania, it wasn't just ordinarily painful. The seven-year-old was harbouring a tumour in his adrenaline [sic] gland, causing him to suddenly gain 12 kg in a year, and develop a pencil moustache, much to the amusement of his classmates.

Growing pains: Mohammad at age six weighed 25 kg but suddenly his
weight shot up to 37 kg without any explanation. Doctors are now hoping
that after the removal of the tumour, the physical changes will regress.

The tumour was discovered last year when the boy suddenly started becoming fatter and started growing facial hair. "We had to start buying bigger clothes for him. Initially, my son was thin and active but suddenly, he began growing at a considerable pace.

"He would keep complaining to me about stomach pains but I thought it was just an excuse to miss school and the taunts he received from his friends. Now I regret not paying heed to his cries for help," said Bilkis, Mohammad's mother.

When the weight gain did not stop and he had put on about 12 kg, Mohammad's family sensed something was amiss and took him to doctors in Tanzania.

"The doctors we consulted at first told us that we should restrict his diet but when we told them that there was no change in his diet, doctors started investigating further. We even went to Jerusalem where physicians finally diagnosed that he had a tumour in his adrenaline gland. Seeking treatment for our son, we finally reached Mumbai," added Bilkis.

What doctors found

After the family finally reached city shores a week back, doctors at Saifee Hospital started treatment.

According to Mohammad's doctors, a tumour had grown inside his left adrenaline gland, causing the excess release of hormones resulting in weight gain. Doctors say that Mohammad is suffering from Cushing's syndrome

Under the knife

On Thursday, Mohammad underwent a laparoscopic surgery to remove the tumour, which was seven-cm long and weighed approximately 450 g.

"Mohammad's case was a challenging surgery as he is just seven and at the same time the tumour was as big as his kidney. As we did the surgery laparoscopically, there was no blood loss, giving us excellent post-operative results," said Dr Anup Ramani, uro-oncological surgeon at Saifee Hospital.

'Hoping for normalcy'

Now recuperating at the hospital, Mohammad and his family hope the boy starts looking his age again. Commenting on the changes, Bilkis said, "He was really active before but once he started putting on weight, he started becoming introverted and his studies were also affected. I now pray that everything returns to normal."

When asked about the pace of growth, Dr Ramani said most physical changes would regress in a year's time. "We have put him on a dose of steroids to compensate for the growth spurts he has experienced and hope that all the changes regress."

Cushing's syndrome

Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumours that produce cortisol. Cushing's disease refers to one specific cause of the syndrome: a tumour in the pituitary gland that elevates cortisol.

From http://www.mid-day.com/news/2012/jan/030112-Tumour-behind-7-yr-olds-weight-gain-moustache.htm

What is the best long-term management strategy for patients with primary adrenal insufficiency?

2012-01-04T20:15:00.001-05:00

Authors: Quinkler, Marcus¹; Hahner, Stefanie²

Source: Clinical Endocrinology, Volume 76, Number 1, 1 January 2012 , pp. 21-25(5)

Publisher: Wiley-Blackwell

Abstract Summary

Primary adrenal insufficiency is treated with glucocorticoid and mineralocorticoid replacement therapy. Recent data revealed that health-related quality of life in adrenal insufficiency is impaired in many patients and that patients with adrenal insufficiency are also threatened by an increased mortality and morbidity. This may be caused by inadequate glucocortiocid therapy and adrenal crisis. Therefore, the optimization of hormone replacement therapy remains one of the most challenging tasks in endocrinology because it is largely based on clinical grounds because of the lack of objective assessment tools.

This article provides answers to the important daily clinical questions, such as correct dose finding, dose adaptation in special situations, e g, pregnancy, improvement of quality of life and measures for protection from adrenal crisis. Other important aspects discussed are side effects of glucocortiocid replacement therapy and interactions with other drugs.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2265.2011.04103.x

Affiliations: 1: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin 2: Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wuerzburg, Germany

Publication date: 2012-01-01

From http://www.ingentaconnect.com/content/bsc/cend/2012/00000076/00000001/art00005

Synchronous bilateral adrenalectomy by midline incision: A reliable method for treatment of hypercortisolism

2012-01-04T19:59:00.001-05:00

Sayyed Abbas Tabatabaee, Sayyed Mozaffar Hashemi, Mohamadreza Fazel Najafabadi, Amirhossein Davarpanah Jazi

Abstract

Cushing syndrome is one of the diseases associated with adrenals secreting too much cortisol. The syndrome was first described by Harvey Cushing in 1932.¹ It can be caused either by a tumor originating from the corticotroph cells located in pituitary glands, called corticotroph adenoma, or primary adrenal hyperplasia. It can be also the consequence of some other rare conditions such as ectopic corticotropin-releasing hormone (CRH) causing increased adrenocorticotropic (ACTH) secretion and macronodular adrenal hyperplasia (a primary pigmented nodular adrenal disease).^2,3 To manage the situation, previous articles demonstrated some strategies including two main groups of surgical treatments and non-surgical procedures.
Surgical interventions are very important to completely cure this condition. Pituitary surgery, referred to as transsphenoidal operation, is the treatment of choice for patients with secondary disease.² However, in some situations, e.g. in patients with recurrent or persistent Cushing syndrome and those not responding to medical therapies after the surgery, the effectiveness of pituitary surgery is under question. Such patients are the best candidates for bilateral adrenalectomy. Some previous articles outlined this method.⁴ Laparoscopy is one of the methods recently used for adrenalectomy. During the surgery, some complications may occur which deteriorates patient's condition with noticeable rates of 9.5 to 12%. These complications are bleeding, organ damages, pain and deep vein thrombosis.^7,8
Although in recent years the experts have achieved great improvements in management and treatment of the patients suffering from Cushing syndrome, some controversies still exist. In this manuscript, we explained a new method to accomplish a reliable bilateral adrenalectomy to manage the disease and cure the condition completely.
After opening the abdomen, left adrenal gland is determined and adjacent vessels are ligated. Then, the enlarged adrenal gland would be entirely removed. However, adrenalectomy at the right side is not as simple as the left side. Renal vein detachment from the inferior vena cava can be a serious complication of right adrenalectomy if it is performed without enough exposure and experience. Massive bleeding in such clinical setting may significantly compromise patient's outcome. To avoid this complication during the procedure we can perform a new method explained below.
Access to the right gland cannot be obtained by conventional retraction of the liver and it is necessary to mobilize the right hepatic lobe by fully incising the falciform ligament, the right triangular ligament, and rotating the right lobe medially. In this procedure, the bare area of the liver is dissected from the diaphragm. Care must be taken to avoid twisting and occluding the vena cava during this maneuver. After medial rotation of the liver in the proper position, the right adrenal and inferior vena cava can be directly visualized. This excellent exposure makes adrenalectomy very simple and minimizes the risk for renal vein detachment as a significant complication.
This method was conducted on 6 cases admitted due to Cushing syndrome in Alzahra Hospital, Isfahan, Iran. While no major complications were observed, favorable outcomes were found in the 6-month follow-up period.
Based on our experience, bilateral adrenalectomy via a midline incision is a promising and acceptable technique for patients with Cushing syndrome. However, due to excess adipose tissue and lack of enough exposure, adrenalectomy by lumbotomy in such patients has prominent limitations. Therefore, midline incision provides feasible exposure for direct visualization of both adrenals.

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This work is licensed under a Creative Commons Attribution 3.0 Unported License.

A New Link in the Stress Response Could Mean Better Treatment Soon

2012-01-02T19:07:00.001-05:00

Hoping to pave the way for improved treatment options, researchers have found that they can significantly reduce our response to stress.

A team at Tufts University appears to have found an important step in the body's stress reaction, and blocking this step from occurring can significantly reduce the response. The finding may pave the way for improved treatments for depression and anxiety.

The stress cascade is governed by the brain's hypothalamus, which communicates with the pituitary and adrenal glands, which in turn secrete stress hormones like cortisol. Disruptions in this pathway are also connected with problems like postpartum depression, obesity, Cushing's syndrome (hypercortisolism), premenstrual syndrome (PMS), epilepsy, and osteoporosis, according to the study's press release.

Using mice as their subjects, the researchers set out to fill in some of the blanks in the cascade of events that leads to the secretion of the stress hormone coriticosterone (the mouse equivalent to our cortisol). They used brain samples from mice, and tracked the activity of the brain cells that release corticotrophin-releasing hormone (CRH), which ultimately stimulates the secretion of stress hormones.

They discovered that specific "neurosteroids" are needed to bind to receptors on the CRH neurons to activate them, serving as an important early step in the stress response. The team reasoned that disrupting the synthesis of the neurosteroids should significantly reduce the stress response by stopping it almost before it begins.

This is just what they found. When they blocked the neurosteroids' synthesis in live mice, their coriticosterone levels were reduced after stressful situations compared to normal mice. Additionally, if neurosteroid synthesis was halted, the mice did not show anxiety-like behaviors after they had been stressed.

One of the authors, Jamie Maguire, said that the data "suggest that these receptors may be novel targets for control of the stress-control pathway. Our next work will focus on modulating these receptors to treat disorders associated with stress, including epilepsy and depression-like behaviors."

The study is published in The Journal of Neuroscience.

From http://www.theatlantic.com/health/archive/2012/01/a-new-link-in-the-stress-response-could-mean-better-treatment-soon/250570/

Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis.

2012-01-02T18:57:00.001-05:00

Michael A Flierl, Daniel Rittirsch, Sebastian Weckbach, Markus Huber-Lang, Kyros Ipaktchi, Peter A Ward and Philip F Stahel

Annals of Intensive Care 2011, 1:53 doi:10.1186/2110-5820-1-53

Published: 30 December 2011

Background

Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.

Methods

Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared to healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-) and magnesium (Mg2+).

Results

ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. While plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.

Conclusion

CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone and aldosterone levels. In addition, electrolyte levels showed significant disturbances following CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

From http://www.annalsofintensivecare.com/content/1/1/53/abstract

We have been Nominated for a Health Activist Hero 2011!

2012-01-02T18:36:00.001-05:00

We were nominated for a wego Health Activist Hero 2011 award!

Our Health Activist Awards program will award Health Activists for their outstanding achievements in online health leadership and advocacy in 2011.

Health Activist Hero 2011

Who has changed your life? There are some people who can truly change your entire outlook on life just with their story, their dedication, their words, and their encouragement. Who is your Health Activist Hero? Who would you like to thank and why? For so many Health Activists, impacting the life of just one reader is worth more than 1,000s of page views. This award is an emotional one but will yield some incredible stories.

Do you know a Health Activist who has changed your life, your condition, or your Health Activism? Thank them by recognizing them as a Health Activist Hero!

Vote for us here: http://info.wegohealth.com/hero-2011

Our nominating post:

Award: Health Activist Hero (http://info.wegohealth.com/hero-2011)

Link: https://www.facebook.com/mary.oconnor

Reason: If it wasn't for MaryO's hard work in creating an online community I don't know if I'd have made it through all these years. She's a behind the scenes kind of person, she doesn't ask for much and often winds up on the periphery but despite her own health challenges she gives and gives and gives and has helped thousands of people.

Red alert: Hypertension on the prowl

2012-01-01T16:15:00.001-05:00

The family of Mr. Adulphus Opara of Umunokwu in Okwuato, Aboh Mbaise Local Government Area of Imo State was shocked to its nerves as the man slumped from the chair on which he was sitting and cuddling his little daughter who was just less than five months. Scampering and running up and down, all efforts by family members to revive their breadwinner were too little and too late as he died that sunny Saturday afternoon. It was later revealed by doctors at a private hospital that Adolphus died of hypertension attack.

The case of Adolphus is just one out of the numerous complaints of the havocs wreaked by untreated or unchecked hypertension. Medical experts say it has sent so many victims to their untimely grave.

Dr. Francis Duru, a physician and senior lecturer in Human Anatomy, College of Medicine, University of Lagos Teaching Hospital (LUTH), Idi Araba, described hypertension as a silent killer and the major cause of most sudden deaths in Nigeria. He said high blood pressure is when one’s BP is consistently above 140/90 mmHg.

According to him, “Normal blood pressure is when your blood pressure is measured at 120/80 mmHg most of the time. If your blood pressure is consistently above 140/90, then the person has hypertension or is hypertensive. Untreated hypertension can lead to many health complications and the worst of all is sudden death.”

MedicinePlus, a medical publication, defines hypertension or high blood pressure as a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump blood around the body. Blood pressure involves two measurements, systolic and diastolic. Normal blood pressure is 120/80 mm/Hg.

The first figure is the systolic blood pressure, the pressure there is in the arteries when your heart is contracting. The second, or lower figure, is the diastolic blood pressure, which is the pressure in your arteries between heartbeats. High blood pressure is anything above 140/90 mm/Hg. Hypertension is the opposite of hypotension. Hypertension is classified as either primary (essential) hypertension or secondary hypertension; about 90–95% of cases are categorised as “primary hypertension,” which means high blood pressure with no obvious medical cause.

The remaining 5–10% of cases (secondary hypertension) are caused by other conditions that affect the kidneys, arteries, heart or endocrine system. MedicinePlus added: “Persistent hypertension is one of the risk factors for stroke, myocardial infarction, heart failure and arterial aneurysm, and is a leading cause of chronic kidney failure. Moderate elevation of arterial blood pressure leads to shortened life expectancy. Dietary and lifestyle changes can improve blood pressure control and decrease the risk of associated health complications, although drug treatment may prove necessary in patients for whom lifestyle changes prove ineffective or insufficient.”

The American Heart Association, in one of its recent reports, made it known that the World Health Organisation (WHO) attributes hypertension, or high blood pressure, as the leading cause of cardiovascular mortality. The World Hypertension League (WHL), an umbrella organisation of 85 national hypertension societies and leagues, recognised that more than 50% of the hypertensive population worldwide are unaware of their condition. To address this problem, the WHL initiated a global awareness campaign on hypertension in 2005 and dedicated May 17 of each year as World Hypertension Day (WHD). Over the past three years, more national societies have been engaging in WHD and have been innovative in their activities to get the message to the public. In 2007, there was record participation from 47 member countries of the WHL. During the week of WHD, all these countries – in partnership with their local governments, professional societies, nongovernmental organisations and private industries – promoted hypertension awareness among the public through several media and public rallies.

Causes and risk factors

Although Duru noted that there were several causes of hypertension, he still insisted that there were instances when it had no direct link or cause. He said: “Medically, we have causes, incidences and risk factors that are associated with hypertension. I am talking about factors that can cause or lead to hypertension. In this case we have issues like the level of water or salt in a person’s body; ability or inability of some organs like the kidneys or blood vessels to function at optimum levels; life history, that is, does hypertension run in your family? lifestyle, that is, the type of food you eat; lack of exercises and always being in a noisy place or being in a state of anxiety all the time. Let me also quickly add that excessive smoking and over-indulgence in alcohol can lead to hypertension.”

He added: ‘“You can easily become hypertensive when you reach the stage of adult age because one’s blood vessels are stiffer as one reaches old age. This leads to HBP. I can also tell you that high blood pressure increases your chances of having a stroke, heart attack, heart failure, kidney disease, and early death. I must also state it here that there are some conditions of health one will find oneself and one will surely expect to be hypertensive. For instance, some pregnant women are usually hypertensive especially from the sixth month until they put to birth. Diabetic patients are sometimes hypertensive although there is no causal relationship between hypertension and diabetes.

People who are obsessed are at risk of suffering from hypertension just as chronic kidney diseases and poor conditions or disorders of the adrenal glands can as well lead to hypertension.” The LUTH medical expert revealed that wrong or too much application of some drugs could also lead to hypertension. “Wrong application or continuous administration of some medications such as birth control pills, diet control pills, cold medications, etc are other ways by which hypertension can hit at a person”, he warned. Meanwhile, Duru noted that there were some instances when hypertension had no cause or trace and it is described as essential hypertension.

Symptoms

Most medical experts agree that hypertension, in most cases, has no external symptoms. To this effect, Duru said: “You can now see why we call hypertension a silent killer. It is a silent killer because it gives no sign, no symptom and no warning before it strikes. I must comment here that most Nigerians are suffering from hypertension without knowing it. This is why we also recommend that people should go for BP check regularly to confirm their status. Based on these facts, so many Nigerians develop sicknesses like heart diseases, kidney failures and other complications without any prior knowledge that all their problems started from untreated or unchecked hypertension.

It is also important to note that a hypertensive patient can live his normal life if he abides by medical advice and that means taking his drugs.” ADAM Medical Encyclopedia listed certain conditions as symptoms of hypertension. According to its report, “If you have a severe headache, nausea or vomiting, bad headache, confusion, changes in your vision, or nosebleeds you may have a severe and dangerous form of high blood pressure called malignant hypertension.” The publication recommended that there should be several checks before it could be ascertained that one has hypertension. It noted that: “Your health care provider will check your blood pressure several times before diagnosing you with high blood pressure. It is normal for your blood pressure to be different depending on the time of day. Blood pressure readings taken at home may be a better measure of your current blood pressure than those taken at your doctor’s office.”

Among the tests to be taken to confirm whether or not one has hypertension, according to Duru, are physical examinations to look for bad conditions of the heart or diseases severely affecting it, poor state or damage of the eyes, as well as other bad physical changes in your body. In this case, tests that enable doctors to handle the situation well include: cholesterol level; level of heart disease like echocardiogram or electrocardiogram; level of metabolic panel/ urinalysis or ultrasound of the kidney and this is when the case has become a chronic one.

Types

A widely posted medical material stated: “A blood pressure is usually classified based on the systolic and diastolic blood pressures. Systolic blood pressure is the blood pressure in vessels during a heartbeat. Diastolic blood pressure is the pressure between heartbeats. A systolic or the diastolic blood pressure measurement higher than the accepted normal values for the age of the individual is classified as pre hypertension or hypertension. Hypertension has several sub-classifications, including hypertension stage I, hypertension stage II, and isolated systolic hypertension. Isolated systolic hypertension refers to elevated systolic pressure with normal diastolic pressure and is common in the elderly.

These classifications are made after averaging a patient’s resting blood pressure readings taken on two or more office visits. Individuals older than 50 years are classified as having hypertension if their blood pressure is consistently at least 140 mmHg systolic or 90 mmHg diastolic. Hypertension is also classified as resistant if medications do not reduce blood pressure to normal levels.”

Accelerated hypertension – this is associated with headache, drowsiness, confusion, vision disorders, nausea, and vomiting. These symptoms are collectively called hypertensive encephalopathy. Hypertensive encephalopathy is caused by severe small blood vessel congestion and brain swelling, which is reversible if blood pressure is lowered.

Secondary hypertension– some additional signs and symptoms suggest that the hypertension is caused by disorders in hormone regulation. Hypertension combined with obesity distributed on the trunk of the body, accumulated fat on the back of the neck (“buffalo hump”), wide purple marks on the abdomen (abdominal striae), or the recent onset of diabetes suggests that an individual has a hormone disorder known as Cushing’s syndrome. Hypertension caused by other hormone disorders such as hyperthyroidism, hypothyroidism, or growth hormone excess will be accompanied by additional symptoms specific to these disorders. For example, hyperthyroidism can cause weight loss, tremors, heart rate abnormalities, reddening of the palms, and increased sweating.

In pregnancy–Hypertension in pregnant women is one symptom of pre-eclampsia. Pre-eclampsia can progress to a life-threatening condition called eclampsia, which is the development of protein in the urine, generalised swelling, and severe seizures. Other symptoms indicating that brain function is becoming impaired may precede these seizures such as nausea, vomiting, headaches, and vision loss.

In children –Some signs and symptoms are especially important in newborns and infants such as failure to thrive, seizures, irritability, lack of energy, and difficulty breathing. In children, hypertension can cause headache, fatigue, blurred vision, nosebleeds, and facial paralysis. Even with the above clinical symptoms, the true incidence of paediatric hypertension is not known. In adults, hypertension has been defined due to the adverse effects caused by hypertension. However, in children, similar studies have not been performed thoroughly to link any adverse effects with the increase in blood pressure. Therefore, the prevalence of paediatric hypertension remains unknown due to the lack of scientific knowledge.

Essential hypertension– this is the most prevalent hypertension type, affecting 90–95% of hypertensive patients. Although no direct cause has been identified, there are many factors such as sedentary lifestyle smoking, stress, visceral obesity, potassium deficiency (hypokalemia), obesity (more than 85% of cases occur in those with a body mass index greater than, salt (sodium) sensitivity, alcohol intake, and vitamin D deficiency that increase the risk of developing hypertension. Risk also increases with aging, some inherited genetic mutations, and having a family history of hypertension. An elevated level of rennin, a hormone secreted by the kidney, is another risk factor, as is sympathetic nervous system over activity.

Secondary hypertension–By definition, this results from an identifiable cause. This type is important to recognise since it’s treated differently to essential hypertension, by treating the underlying cause of the elevated blood pressure. Hypertension results in the compromise or imbalance of the path physiological mechanisms, such as the hormone-regulating endocrine system, that regulates blood plasma volume and heart function.

Treatment

According to an ADAM Medical Encyclopedia research work, “The goal of treatment is to reduce blood pressure so that you have a lower risk of complications. You and your health care provider should set a blood pressure goal for you. If you have pre-hypertension, your health care provider will recommend lifestyle changes to bring your blood pressure down to a normal range. Medicines are rarely used for pre-hypertension. You can do many things to help control your blood pressure, including: Eat a heart-healthy diet, including potassium and fibre, and drink plenty of water.

Exercise regularly — at least 30 minutes of aerobic exercise a day. If you smoke, quit – find a programme that will help you stop. Limit how much alcohol you drink — one drink a day for women, two a day for men. Limit the amount of sodium (salt) you eat — aim for less than 1,500 mg per day Reduce stress — try to avoid things that cause you stress. You can also try meditation or yoga. Stay at a healthy body weight — find a weight-loss program to help you, if you need it.

There are many different medicines that can be used to treat high blood pressure but must be prescribed by well-qualified physician. Often, a single blood pressure drug may not be enough to control your blood pressure, and you may need to take two or more drugs. It is very important that you take the medications prescribed to you. If you have side effects, your health care provider can substitute a different medication. Most of the time, high blood pressure can be controlled with medicine and lifestyle changes.

Effects

It has been gathered through various medical work that a patient is at risk and may likely suffer from complications when BP is not treated or controlled. The ADAM Medical publication warned that the following poor conditions of health might result as an evidence of poor treatment: Bleeding from the aorta, the large blood vessel that supplies blood to the abdomen, pelvis, and legs. Chronic kidney disease, heart attack and heart failure, poor blood supply to the legs, stroke and problems with the vision.

Here Duru was of the view that most of the sudden death now recorded in Nigeria was as a result of untreated hypertension. ‘ I have explained earlier that most Nigerians are hypertensive without knowing it. In other words, they carry on their daily activities or life style without undergoing the tests and living the medically prescribed way a hypertension victim suppose to observe’. ‘ The effect’, he explained, ‘is that the patient might likely be attacked or hit by stroke, kidney failure or heart attack which leads to instant death. You know I described it as a silent killer and this is exactly what I mean.

So many Nigerians have been killed by heart failure resulting from hypertension. In some instances the person slumps at home, on the road, in the office or anywhere as the case might be. At some other time, the victim goes to bed and does not wake up. When we experience such situations, some us, in the usual Nigerian way, blame it on the wicked landlord, the envious next door neighbour or a witch or wizard in the village.’

Prevention

Doctors have unanimously agreed that hypertension has no permanent cure. At best, it can be managed or controlled. Duru explains further. He said: ‘first, for now, there is no permanent cure for hypertension, medically speaking. As a Christian, I believe in miracles but in medical terms, it is yet to be proved that hypertension has any known permanent cure. If you a victim, it means that you have to be on drugs all the days of your life. And such a patient must be ready to go for BP check regularly. He has to abstain from certain behaviour like too much salt in-take, smoking, taking more than two bottles of beer daily and he must watch his weight and do regular exercises.

I am aware the trado-medicine people usually come up with so many claims but they are also not bold enough to submit their claims to empirical proves or thorough laboratory tests.’ A medical sponsored by the American National Heart, Lung and Blood Institute reported that the prevention depends on so many factors: It wrote thus: ‘ The degree to which hypertension can be prevented depends on a number of features including current blood pressure level, sodium/potassium balance, detection and omission of environmental toxins, changes in end/target organs (retina, kidney, heart, among others), risk factors for cardiovascular diseases and the age at diagnosis of pre hypertension or at risk for hypertension.

A prolonged assessment that involves repeated blood pressure measurements provides the most accurate blood pressure level assessment. Following this, lifestyle changes are recommended to lower blood pressure, before the initiation of prescription drug therapy. According to the British Hypertension Society, the process of managing pre hypertension includes lifestyle changes such as the following: Weight reduction and regular aerobic exercise (e.g., walking): Regular exercise improves blood flow and helps to reduce the resting heart rate and blood pressure. Reduce sodium (salt) in the body by disuse of condiment sodium and the adoption of a high potassium diet, which rids the renal system of excess sodium.

Many people use potassium chloride salt substitute to reduce their salt intake.’ In 2003 the American Heart Association recommended the following drugs for the treatment of hypertension: Potassium - is essential for the proper functioning of the heart, kidneys, muscles, nerves, and digestive system. Usually the food you eat supplies all of the potassium you need.

Bosentan - is used to treat Pulmonary Arterial Hypertension (PAH, high blood pressure in the vessels that carry blood to the lungs). Bosentan may improve the ability to exercise and slow the worsening of symptoms in patients with PAH. Tadalafil (Cialis) is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Tadalafil (Adcirca) is used to improve the ability to exercise in people with pulmonary arterial hypertension (PAH; high blood pressure in the vessels carrying blood to the lungs, causing shortness of breath, dizziness, and tiredness.

From http://www.sunnewsonline.com/webpages/features/icon/2012/jan/01/icon-01-10-2012-003.html

Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature

2011-12-31T09:52:00.001-05:00

PITUITARY

DOI: 10.1007/s11102-011-0368-2

Mustafa Berker, Derya Burcu Hazer, Taşkın Yücel, Alper Gürlek,Ayşenur Cila, Mustafa Aldur and Metin Önerci

Abstract

Endoscopic transsphenoidal surgery is emerging as a minimally invasive and maximally effective procedure for pituitary adenomas. In this report we analyzed the complications in 624 procedures of endonasal transsphenoidal endoscopic surgery in the treatment of 570 patients with pituitary adenomas. The leading author (MB) operated pituitary adenomas via pure endoscopic endonasal transsphenoidal surgery between January 2006 and August 2011 at the Hacettepe University, Department of Neurosurgery in Ankara. Complications were assessed in 624 surgical procedures under five groups; rhinological, CSF leaks, infection, vascular and endocrinologic complications. We observed a total of 76 complications (12.1%). Rhinological complications occurred in 8 patients (1.3%): 4 epistaxis (0.6%) and 4 hyposmia (0.6%). Postoperative CSF leaks occurred in 8 patients (1.3%), and infectious complications occurred in 8 patients: 3 cases of sphenoidal sinusitis (0.4%), 5 cases of meningitis (0.8%). Only 1 case of internal carotid aneurysm rupture during the opening of sellar floor (0.16%) was observed. Endocrinologic complications occurred in 51 (8.1%) patients: Anterior pituitary deficiency in 12 (1.9%), transient diabetes insipidus (DI) in 29 (4.6%), permanent DI in 3 (0.4%) and inappropriate antidiuretic hormone secretion syndrome occurred in 7 (1.1%). There was no mortality directly related to the surgical procedure. The complication rates observed in our study suggests that the endoscopic pituitary surgery is at least as safe as microscopic transphenoidal surgery. These rates were obtained with due experience and well-coordinated teamwork. To further improve these rates, new technological developments will be helpful.

Keywords Pituitary – Adenoma – Endonasal endoscopic surgery – Complication

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From http://www.springerlink.com/content/y17223k8481p64r0/

FDA Will Not Require a Risk Evaluation and Mitigation Strategy in Connection With Corcept's Proposed Distribution of Korlym(TM) for Cushing's Syndrome

2011-12-31T09:32:00.001-05:00

MENLO PARK, CA, Dec 15, 2011 (MARKETWIRE via COMTEX) -- Corcept Therapeutics Incorporated CORT -0.02% , a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders, today announced that it has been advised by the U.S. Food and Drug Administration (FDA) that no Risk Evaluation and Mitigation Strategy (commonly known as a "REMS" program) will be required in connection with Corcept's proposed distribution of its lead product candidate, mifepristone, to which Corcept has given the brand name Korlym. The FDA is currently reviewing Corcept's New Drug Application (NDA) for Korlym, a glucocorticoid receptor type II (GR-II) antagonist that blocks the cortisol receptor, for the treatment of the clinical and metabolic effects of hypercortisolism in patients with endogenous Cushing's Syndrome. The FDA's decision with respect to REMS does not alter the Prescription Drug User Fee Act (PDUFA) date for completion of FDA review, which remains February 17, 2012.

About Cushing's Syndrome

Endogenous Cushing's Syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing's Syndrome is an orphan indication which most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients in the United States. An estimated 20,000 patients in the United States have Cushing's Syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing's Syndrome can affect every organ system in the body and can be lethal if not treated effectively.

About Korlym

Corcept's first-generation compound, Korlym, also known as mifepristone, directly blocks the cortisol (GR-II) receptor and the progesterone (PR) receptor. Intellectual property protection is in place to protect important methods of use for Korlym. Corcept retains worldwide rights to its intellectual property related to Korlym.

About Corcept Therapeutics Incorporated

Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. The company has completed its Phase 3 study of Korlym for the treatment of Cushing's Syndrome, and has an ongoing Phase 3 study of Korlym for the treatment of the psychotic features of psychotic depression. Corcept also has a developed a portfolio of new selective GR-II antagonists that block the effects of cortisol but not progesterone and has an extensive intellectual property portfolio covering the use of GR-II antagonists in the treatment of a wide variety of psychiatric and metabolic disorders, including the prevention of weight gain caused by the use of antipsychotic medication, as well as composition of matter patents for our selective GR-II antagonists.

Statements made in this news release, other than statements of historical fact, are forward-looking statements, including, for example, statements relating to the potential benefit of Korlym for patients diagnosed with Cushing's Syndrome, the timing of completion and potential outcome of the FDA's review of our NDA filing, Corcept's clinical development and research programs, the timing of introduction of Korlym and future product candidates and the ability to create value from Korlym or other future product candidates. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances with respect to the timing of completion and outcome of the FDA's review of our NDA filing, the cost, rate of spending, completion or success of clinical trials; or that Corcept will pursue further activities with respect to the development of Korlym or any of its other selective GR-II antagonists. These and other risk factors are set forth in the Company's SEC filings, all of which are available from our website ( www.corcept.com ) or from the SEC's website ( www.sec.gov ). We disclaim any intention or duty to update any forward-looking statement made in this news release.

INVESTOR CONTACT:

Charles Robb

Chief Financial Officer

Corcept Therapeutics

650-688-8783

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FDA Rare Disease Patient Advocacy Day

2011-12-31T08:44:00.001-05:00

On March 01, 2012, the Food and Drug Administration (FDA) will celebrate the fifth annual Rare Disease Day by hosting a "FDA Rare Disease Patient Advocacy Day" to engage and educate the rare disease community on regulatory processes related to rare diseases.

This meeting is intended to enhance the awareness of the rare disease community as to FDA’s roles and responsibilities in the development of products (drugs, biological products and devices) for the diagnosis, prevention, and/or treatment of rare diseases or conditions.

This educational meeting will consist of live and interactive simultaneous webcast of presentations provided by FDA experts from various Centers and Offices, as well as from outside experts. The interactive meeting will include two general panel discussion sessions, as well as afternoon breakout sessions for more in-depth information on the roles of FDA. In addition, on-site attendees will have an opportunity during lunch to engage with FDA and outside experts in a small group setting.

Registration:

While attendance is free, registration is required to attend the event.

Register for FDA Rare Disease Patient Advocacy Day

If you need sign language interpretation during this meeting, please contact Megan McNamee at mmcnamee@icfi.com by February 15, 2012.

Location and Directions:

White Oak Campus
10903 New Hampshire Ave
Silver Spring, MD, 20993

Location, directions, and other information about White Oak

Date:

March 01, 2012

Agenda:

Event agenda is in preparation and will be posted prior to the meeting

Webcast:

To connect to the live webcast of the meeting please follow the Connect Pro instructions.

Sponsors:

The FDA Rare Disease Patient Advocacy Day is supported by the Food and Drug Administration (FDA), the National Institutes of Health (NIH), the National Organization for Rare Disorders (NORD), and the Genetic Alliance.

The FDA encourages all attendees to also plan on attending the National Institutes of Health (NIH) Rare Disease Day day-long celebration on February 29, 2012.

Rare Disease Day at NIH

2011-12-31T07:29:00.001-05:00

Rare Disease Day at NIH (RDD@NIH)

On February 29, 2012, the National Institutes of Health (NIH) will celebrate the fifth annual Rare Disease Day with a day-long celebration and recognition of the various rare diseases research activities supported by the NIH Office of Rare Diseases Research, the NIH Clinical Center, other NIH Institutes and Centers; the Food and Drug Administration’s Office of Orphan Product Development; the National Organization for Rare Disorders; and the Genetic Alliance. Rare Disease Day at NIH (RDD@NIH) will be held in the Clinical Center’s Masur Auditorium (Building 10) from 8:30 a.m. to 5:00 p.m. Attendance is free and open to the public.

In addition to the various scheduled talks, we expect to have posters and exhibits from many groups relevant to the rare diseases research community. In association with the Global Genes Project, we again encourage all attendees to wear their favorite pair of jeans.

While attendance is free, we would like to know how many people are planning to attend to prepare accordingly. If you would like to display a poster or exhibit, please include that information on your registration form. You can contact Dr. David J. Eckstein at eckstein@od.nih.gov for more information.

The NIH Office of Rare Diseases Research encourages all attendees to also plan on attending the Food and Drug Administration’s Rare Disease Day activities on March 1, 2012.

Visit the NIH Visitors and Security website for the latest instructions and updates. Please allow 30 minutes to move through security.

Sign language interpreters will be provided. Individuals with disabilities who need reasonable accommodation to participate in this event should contact Kimberly Potter at kpotter@icfi.com or 301-251-4962.

About Rare Disease Day

Rare Disease Day was established to raise awareness with the public about rare diseases, the challenges encountered by those affected, the importance of research to develop diagnostics and treatments, and the impact of these diseases on patients' lives. The focus of Rare Disease Day 2010 was 'Patients and Researchers, Partners for Life!' and is aligned with ORDR's philosophy that researchers need to work closely with patients and patient advocacy groups to maximize chances for success. This philosophy has been put into practice in our very successful Rare Diseases Clinical Research Network.

There are about 7000 rare diseases identified in the United States. About 80 percent of rare diseases are genetic in origin and it is estimated that about half of all rare diseases affect children. Rare diseases can be chronic, progressive, debilitating, disabling, severe and life-threatening. Information is often scarce and research is usually insufficient. People affected face challenges such as delays in obtaining a diagnosis, misdiagnosis, psychological burden and lack of support services for the patient and family. The goals remain for rare disease patients to obtain the highest attainable standard of health and to be provided the resources required to overcome common obstacles in their lives.

By highlighting these issues, the NIH Office of Rare Diseases Research hopes to

Raise awareness of rare diseases
Strengthen the voice of patients and patient advocacy groups
Give hope and information to patients
Bring stakeholders closer together
Coordinate policy actions within the United States and with other countries
Inspire continued growth of the awareness of rare diseases
Emphasize rare disease research and the search for new therapeutics
Get equality in access to care and treatment

The first Rare Disease Day sponsored by EURORDIS was held in Europe on February 29, 2008. February 29th was chosen since it is a rare day and it is symbolic of rare diseases. 2009 was the first time that Rare Disease Day was observed in the U.S. In addition to 17 European countries participating in Rare Disease Day 2009, the United States was joined by Argentina, Australia, Canada, China, Colombia, and Taiwan in celebrating the first global Rare Disease Day. The National Organization for Rare Disorders serves as the coordinator of this activity in the United States.

The Global Genes Project

A video developed by a rare disease parent advocate circulated on YouTube as part of World Rare Disease Day 2009, making a connection between jeans and genes. This video inspired a group of individuals and rare disease organizations to take this connection to the next level by creating the Global Genes Project, a grassroots effort to use jeans to raise awareness for rare genetic disorders.

This group has grown and continues to add individuals and organizations that want to be involved. The hope is that the rare disease community as a whole will view this initiative as an opportunity to build unity around this important cause. The goal is to create a platform for collaboration, while building awareness about the prevalence of rare diseases, educating the public about genes and the impact they play in rare diseases, and engaging support from the general public.

There are numerous organizations that are working to help some of the individual diseases. They are funding much needed research, helping drive policy and develop educational programs, all in an effort to bring hope to this underserved community. The Global Genes Project encourages those who are concerned and compelled to join the cause to help both individual rare disease organizations, children and their families affected, as well as the community as a whole.

More information: http://rarediseases.info.nih.gov/RareDiseaseDay.aspx

Subclinical Cushings syndrome: definition and management

2011-12-22T22:16:00.001-05:00

Subclinical Cushing's syndrome is an ill-defined endocrine disorder that may be observed in patients bearing an incidentally found adrenal adenoma. The concept of subclinical Cushing's syndrome stands on the presence of ACTH-independent cortisol secretion by an adrenal adenoma, that is not fully restrained by pituitary feed-back. A hypercortisolemic state of usually minimal intensity may ensue and eventually cause harm to the patients in terms of metabolic and vascular diseases, and bone fractures.

However, the natural history of subclinical Cushing's syndrome remains largely unknown. The present review illustrates the currently used methods to ascertain the presence of subclinical Cushing's syndrome and the surrounding controversy. The management of subclinical Cushing's syndrome, that remains a highly debated issue, is also addressed and discussed.

Most of the recommendations made in this chapter reflects the view and the clinical experience of the Authors and are not based on solid evidence.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2265.2011.04253.x

Affiliations: 1: Internal Medicine I, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy

Buy the article at http://www.ingentaconnect.com/content/bsc/cend/2012/00000076/00000001/art00003

Investigational drugs may expand medical treatment of Cushing’s syndrome

2011-12-22T20:26:00.001-05:00

Endocrinologists face many challenges when treating patients with Cushing’s syndrome. Diagnosis can be difficult because many of the disease’s characteristics, such as obesity, depression and hypertension, are also common in the general population.

Treating the disease presents hurdles as well. With its potential for total cure, transsphenoidal surgery remains the first-line treatment. However, the problems of achieving permanent remission in all cases demonstrate the need for medical therapies for this condition.

Currently, endocrinologists use several medical therapies to treat hypercortisolism, although none have FDA approval for that particular indication. Two new investigational drugs — mifepristone (Korlym, Corcept Therapeutics) and pasireotide (SOM230, Novartis) — have the potential to meet those unmet needs, according to experts interviewed by Endocrine Today.

“Recently completed research studies, which involved innovative medical therapeutic strategies that target the corticotroph adenoma itself or block the effects of cortisol in the periphery, should bring new treatment options in the future,” Maria Fleseriu, MD, associate professor, director of the Northwest Pituitary Center at Oregon Health & Science University, said in an interview.

Manufacturers of both new medications have submitted new drug applications to the FDA. Corcept expects to hear from the FDA on Feb. 17, according to a spokesperson for the company.

Mifepristone has a unique mode of action in that it blocks the cortisol receptor, Robert L. Roe, MD, president of Corcept Therapeutics, said in an interview.

“With that receptor blocked, many of the problems associated with Cushing’s syndrome can be greatly improved, including: obesity, diabetes, insulin resistance, high blood pressure, quality of life and depression,” Roe said.

The SEISMIC trial, a 24-week, multicenter, open-label study, included 50 patients with persistent or recurring Cushing’s disease, metastatic adrenal cortical carcinoma or ectopic adrenocorticotropic hormone (ACTH) syndrome that was not amenable to surgery, according to Fleseriu, who was an investigator on the study. There were two primary endpoints: blood sugar improvement in patients with glucose intolerance and an improvement in BP in patients with a diagnosis of hypertension but without abnormal blood sugar levels. The key secondary endpoint looked for global clinical improvement as determined by a three-member independent data review board.

Results from the phase 3 study showed that, overall, mifepristone yielded significant clinical and metabolic improvement in patients with refractory Cushing’s syndrome, Fleseriu said. Of the glucose-intolerant patients, 60% responded, and BP improved in 38% of patients. The global clinical endpoint was positive in 87% of patients, Roe said.

Maria Fleseriu

“In addition, out of 34 patients who completed the main study, 30 elected to continue in the long-term extension study,” Fleseriu said.

She said mifepristone “offers a new approach for the treatment of Cushing’s syndrome that [has] failed other therapies. Keeping in mind that biochemical parameters will not be available for monitoring these patients, close clinical observation is recommended.”

Yet, there are aspects of mifepristone that are still unknown.

“There will be a learning curve with this drug on how to dose it and use it properly to get a good response,” said James Findling, MD, professor of medicine, Endocrinology Center and Clinics, Medical College of Wisconsin, Milwaukee, who was the principal investigator of the study.

James Findling

Also on the horizon is the investigational agent pasireotide, a multiligand somatostatin analogue with a high affinity for the somatostatin receptor type 5, which is often expressed by corticotroph adenomas in Cushing’s disease. Pasireotide blocks the secretions from ACTH-secreting pituitary tumors.

“Pasireotide works by attacking the pituitary tumor to reduce the ACTH level,” according to Laurence Katznelson, MD, professor of medicine and neurosurgery at Stanford University and medical director of the pituitary program at Stanford Hospital and Clinics. “Possibly, this drug could prevent tumor growth or lead to tumor shrinkage, although we await data to support that.”

Results of the multicenter, phase 3 PASPORT-CUSHINGS trial, presented at the Endocrine Society’s 93rd Annual Meeting & Expo in June, included 162 patients with persistent/recurrent or newly diagnosed Cushing’s disease who were ineligible for surgery. Researchers randomly assigned participants to receive twice-daily subcutaneous pasireotide injections of 600 mcg or 900 mcg. The primary endpoint was urinary-free cortisol levels at 6 months without dose up-titration.

Of the patients in the 900-mcg dose group, 26.3% had normal urinary-free cortisol levels at 6 months; at 12 months, 25% maintained normal levels. The median reduction from baseline in urine-free cortisol after 6 months of treatment was 47.9% for both dose groups.

The researchers noted significant clinical benefit in most patients, including lower BP and total cholesterol, as well as weight loss, Fleseriu said.

“It is noteworthy that while urinary-free cortisol normalization was seen in just a subset of patients, the rate of normalization was higher in patients with lower baseline urinary-free cortisol, making it, in my opinion, an attractive treatment for patients with mild elevations in urinary-free cortisol,” Fleseriu, who was also an investigator for this trial, told Endocrine Today.

Pasireotide was well tolerated in the studies, she added.

“Adverse events were comparable to the other somatostatin analogues, with the exception of a much higher incidence of hyperglycemia,” Fleseriu said. “Patients treated with this drug will require strict monitoring and prompt treatment of hyperglycemia.” The reasons for hyperglycemia are related to inhibition of insulin release from the pancreas by this multiligand somatostatin analogue. The type 5 receptor is abundant on pancreatic insulin secreting cells of the pancreas.

Timely diagnosis, treatment critical

Cushing’s syndrome is the result of chronic exposure to high levels of cortisol. Cortisol, typically released in stressful situations, controls how the body uses carbohydrates, fats and proteins. In addition, it helps decrease the immune system’s response to inflammation.

Untreated, Cushing’s syndrome can have serious consequences, including significant mortality and morbidity. Timely diagnosis and appropriate treatment are critical for this rare disorder, according to Fleseriu, who is also associate professor of medicine/endocrinology and neurological surgery at Oregon Health & Science University.

The endocrinologist uses the following tests to diagnose the disorder: 24-hour urinary-free cortisol levels; late-night salivary cortisol measurements; and low-dose dexamethasone suppression test.

After making the diagnosis of hypercortisolism, the next step is to determine the cause of excess cortisol secretion. There are several tests available for this purpose: corticotropin-releasing hormone (CRH) simulation test; direct radiologic visualization of the pituitary and adrenal glands; and inferior petrosal sinus sampling for ACTH.

The most common cause is long-term synthetic steroid use to treat inflammatory illnesses such as asthma or rheumatoid arthritis, according to Katznelson. In these cases, gradually reduction of the glucocorticoid will reverse the disorder.

Another cause is an ACTH-secreting pituitary adenoma. The excess stimulates the adrenals to produce and secrete excess cortisol release, Katznelson said. This is also known as Cushing’s disease.

Pituitary adenomas are responsible for 70% of Cushing’s syndrome cases, according to information from the National Institute of Diabetes and Digestive and Kidney Diseases.

Surgery is first-line treatment

John Carmichael

First-line therapy for Cushing’s disease is transsphenoidal adenomectomy, in which the surgeon approaches the pituitary through the nose and, using either a microscope or endoscope by trained neurosurgeons, according to John Carmichael, MD, assistant professor of medicine, The Pituitary Center, Cedars-Sinai Medical Center, Los Angeles.

The procedure boasts an excellent cure rate.

“In good hands, with a small tumor, you can get cure rates of about 85%,” Carmichael said. “It depends on a number of factors: the skill of the surgeon, the size of the tumor and the level of invasiveness.”

If surgery is curative, the patient will require cortisol replacement.

“Once you remove the tumor, the normal tissue has been suppressed by the activity of the tumor for so long that it takes a long time for patients to recover and start making cortisol on their own,” Carmichael said. “It can take as long as 6 to 12 months for patients to completely recover their normal cortisol secretion once they’ve been cured.”

David M. Cook

However, the surgery is associated with risks, including bleeding and infection, although they are “pretty rare,” according to Carmichael. One of the most common risks is a pituitary injury that can cause diabetes insipidus, which is almost always transient. Other postoperative problems include possible cerebrospinal fluid leaks and the possibility of recurrence, said David M. Cook, MD, an endocrinologist in the department of medicine, Oregon Health & Sciences University.

Sometimes the tumor is hard to find during the first surgery, Katznelson said.

“The problem is, in 40% to 50% of patients who have Cushing’s disease, the tumor is very small, if not almost invisible, on the MRI scan,” he said. As a result, the surgeon may remove normal gland or possibly the entire pituitary, resulting in hypopituitarism. The patient would require hormone replacement and would still have Cushing’s syndrome.

Radiation is a possible treatment for these cases.

“The role of radiation is in the patient who has already had surgery for Cushing’s syndrome. The tumor is visible but cannot be completely removed. Radiation is most useful when there is a target to irradiate,” Katznelson said, adding that even in these cases, radiation cannot promise 100% efficacy.

Unfortunately, radiation takes a significant amount of time to work.

“People are a little reluctant to use radiation because it takes years to help,” Cook said. “It is not curative and patients can relapse from radiation also; it is not foolproof.”

Ectopic ACTH syndrome

Sometimes, tumors located outside the pituitary can produce ACTH, resulting in the ectopic ACTH syndrome. The tumors are usually malignant. In more than half of the cases, the tumors are found in the lungs, according to information from the NIDDK.

“You would need surgery in that location to get rid of the tumor,” Carmichael said.

If an adrenal tumor is stimulating an overabundance of cortisol, the definitive cure is adrenalectomy.

“If we do adrenalectomy, all of the [symptoms of] Cushing’s syndrome go away, but the primary pituitary tumor, which may have been microscopic, can start to become more aggressive and grow and become more difficult to treat in the long run,” Katznelson said. “That is Nelson’s syndrome.”

The adrenal insufficiency that follows adrenalectomy is serious, Cook said.

“It is dangerous to not have your adrenals; it is the most dangerous disease that endocrinologists treat,” he said. “A number of sudden deaths have been reported in patients without adrenals.”

Katznelson also said that managing these patients can be challenging.

“Management of primary adrenal insufficiency is sometimes difficult, because not only does the patient lack cortisol, but will also lack aldosterone, which is important for maintaining electrolytes and volume status,” he said. “Patients often find it quite challenging to manage primary adrenal insufficiency.”

Medical therapies for Cushing’s syndrome

Besides surgery and radiation, endocrinologists can use several medical therapies to treat Cushing’s syndrome; however, to date, none has obtained FDA approval to treat the disorder.

The medical treatment used most often in the United States is ketoconazole, an antifungal agent that blocks the enzymes in the adrenal glands that produce steroids, Findling told Endocrine Today.

Ketoconazole, administered two to three times daily, is generally successful.

“It is an effective therapy,” Findling said. “Probably 50% to 70% of patients will have a response.”

However, this drug is not the optimal choice for long-term use.

“Ketoconazole has been associated with some toxicity; liver function abnormalities can occur and, in fact, liver failure can occur,” he said.

Another medical treatment option is mitotane (Lysodren, Bristol-Myers Squibb), which blocks adrenal steroid enzymes, Findling said. This toxic agent takes considerable time to work; in fact, it may require roughly 3 or 4 months for cortisol levels to normalize. It is used rarely in the United States.

“Mitotane has a limited future as a therapy for Cushing’s syndrome, except for in patients who have adrenal cancer, at least in the US,” Findling said.

Metyrapone (Metopirone, Novartis), another agent, effectively blocks adrenal steroid enzymes; however, it is not commercially available in the United States, Findling said.

Etomidate is an anesthetic agent that also inhibits adrenal steroidogenesis and is employed successfully in patients with very severe hypercortisolism who are not ready for surgery.

“If etomidate were available in a pill, it would be an excellent medical treatment for Cushing’s syndrome,” Findling said. “With subhypnotic doses, etomidate lowers the cortisol level smoothly down into the normal range. … It is well tolerated, but has to be given as a continuous IV infusion, so it is not practical.”

All of these medications have severe adverse effect profiles, according to Carmichael.

No replacement for surgery … yet

Although mifepristone and pasireotide show some promise as treatments for Cushing’s syndrome, it is not time to put the scalpels in storage, the experts said.

“Neither of these drugs, at least for the foreseeable future, will replace surgical treatment of Cushing’s syndrome,” Findling said. “Like most disorders, if you have a surgical procedure that will resolve the endocrinopathy and restore normal hormonal function, it is usually the treatment of choice.”

However, these medications are a welcome addition to the armamentarium, Carmichael said.

“It remains to be seen exactly what their place will be and how they will be best used. But, certainly, in cases where surgery is not an option or where you need to control the disease in someone who has very severe disease, they would have a role,” he said. Currently, Carmichael sees medical therapy as an adjuvant treatment, which would follow surgery if it was not curative. Also, endocrinologists may use them in place of surgery if surgery was not an option.

“There is a lot more room for work,” Carmichael said. “The ideal paradigm of having a medication that is safe and controls the disease and in a sense would replace surgery would be an ideal goal, but we are certainly not there yet.”– by Colleen Owens

For more information:

Colao A. OR09-6. Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston.

Fleseriu M. [OR09-5] Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with refractory Cushing syndrome: results from the Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome (SEISMIC). Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston.

Gross BA. Neurosurg Focus. 2007;23:E10.

National Institute of Neurological Disorders and Stroke. NINDS Cushing’s syndrome information page. Available at: www.ninds.nih.gov/disorders/cushings/cushings.htm.

National Endocrine and Metabolic Diseases Information Service. Cushing’s syndrome. Available at: www.endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#causes.

Disclosures: Dr. Fleseriu is principal investigator in multiple Cushing’s trials and past consultant for Novartis; she is also the principal investigator on Corcept Cushing’s trials. Dr. Findling is a paid consultant for Corcept Therapeutics. The other doctors in this article did not report any relevant financial disclosures.

Which is the most reliable screening method for Cushing’s syndrome?

Tests are equally accurate, but have limitations

The diagnosis of Cushing’s syndrome is problematic. It is one of the most difficult endocrine diseases to diagnose. Diagnosis includes assessing the symptoms and signs of Cushing’s syndrome because the symptoms and signs overlap with common disorders, including obesity, depression and polycystic ovary syndrome. Many patients consult websites in an attempt to find an explanation for their weight gain, fatigue, depression and other symptoms. They ask frequently after a Web search if their symptoms could be Cushing’s syndrome.

Screening tests for Cushing’s syndrome include three different tests: an 11 p.m. or midnight salivary cortisol level; a 24-hour urine free cortisol level; and an 8 a.m. cortisol level after ingestion of 1 mg of dexamethasone at midnight the previous night. How reliable are these tests? They are equally accurate — approximately 90% to 92% reliable, which is actually good for screening tests.

However, all three tests have limitations. Results of the nighttime salivary cortisol test are affected by laboratory accuracy (not all laboratories are equally reliable) and sleep patterns. In severe depression cases, the results may be falsely elevated. The 24-hour urine free cortisol test is an indicator of overall cortisol production. The most accurate method of measurement — tandem mass spectrometry with concomitant measurement of urine volume and urine creatinine — provides a good measure. It may take several 24-hour urine collections to confirm hypercortisolism. The 1-mg overnight dexamethasone suppression test is reliable, but with several caveats. The test is standardized according to administering dexamethasone at midnight and measurement of serum cortisol promptly at 8 a.m. the following day. However, while the patient may have gone to the lab at 8 a.m., the blood sample may have been obtained later, which invalidates the test. Additionally, if the patient is taking medications that alter dexamethasone metabolism, the results may not be valid. The endocrinologist must measure a serum dexamethasone level to confirm the validity of the test.

The diagnosis of Cushing’s syndrome is dependent upon confirming consistent overproduction of cortisol. The diagnosis may require repeated testing and this should be done in any patient in which there is a suspicion of Cushing’s syndrome.

Mary Lee Vance, MD, is professor of medicine and neurosurgery at University of Virginia Health System, Charlottesville, Va.

Disclosure: Dr. Vance reports no relevant financial disclosures.

Late-night salivary cortisol is best initial test

Ty Carroll

No test is perfect for all patients. In addition, it is important to remember that some patients will require multiple, different tests to confirm or exclude Cushing’s syndrome. However, that being said, late-night salivary cortisol is the best initial screening for most patients with suspected Cushing’s syndrome.

Late-night salivary cortisol is the most specific test for Cushing’s syndrome. The sensitivity and specificity are very good. Multiple studies have examined late night salivary cortisol testing, and the majority of those studies show sensitivity of more than 95% and a specificity in the range of 90% to 100%. That is comparable to — or better than — other methods to diagnose Cushing’s syndrome.

Also important to note: It is easy for patients to perform late-night salivary testing. Patients are able to do the collection at home and mail in the completed samples to a reference lab, whereas urinary free cortisol and dexamethasone suppression testing can be difficult for some patients to complete. In addition, for the most part, late-night salivary cortisol is not affected by other medications that patients take, unlike dexamethasone suppression testing, which can be affected by several medications that patients often take to treat other conditions.

Ty Carroll, MD, is assistant professor of medicine at Endocrinology Center and Clinics, Menomonee Falls, Wisc.

Disclosure: Dr. Carroll is an investigator in Corcept’s clinical trials of mifepristone.

From http://www.endocrinetoday.com/view.aspx?rid=90578

A Pill That Stops Stress In Your Brain Before You Feel It

2011-12-16T11:02:00.001-05:00

Stress makes many of us miserable — but it can also kill you. Besides just causing horrible anxiety and depression, the physiological basis for stress has also been linked to diseases as varied as obesity, postpartum depression, Cushing's syndrome, epilepsy, and osteoporosis. But what if we could just turn your brain's stress response off?

Now, researchers from Tufts claim to have pinpointed the way that stress hormones hit specific receptors in your brain — and they've even been able to block them. This could lead to the next great psychopharmaceutical breakthrough.

The Tufts researchers discovered that stress pathways are activated by neurosteroids acting on corticotrophin-releasing hormone neurons in what's known as the Hypothalamus-Pituitary-Adrenal axis. By blocking the synthesis of the neurosteroids, they stopped the elevation of corticosterone, and prevented anxiety in mice.

"We have identified a novel mechanism regulating the body's response to stress by determining that neurosteroids are required to mount the physiological response to stress. Moreover, we were able to completely block the physiological response to stress as well as prevent stress-induced anxiety," said author Jamie Maguire, PhD.

Now the team is focusing on modulating the neuroreceptors to treat some of the diseases that accompany stress — be they depression, anxiety, or epilepsy.

From http://io9.com/5867762/a-pill-that-stops-stress-in-your-brain-before-you-feel-it

P36 - Severe Osteoporosis in Cushing’s Syndrome

2011-12-14T22:06:00.001-05:00

Clin Cases Miner Bone Metab. 2010 Sep-Dec; 7(3): 240.

PMCID: PMC3213844

M.C. Caffetti

Specialist Rehabilitation Unit, Hospital of Voghera, Voghera, Italy

Abstract

Cushing’s syndrome is characterised by a series of clinical manifestations due to hypersecretion of cortisol. These include: arterial hypertension, diabetes mellitus (DM), asthenia, amenorrhea, osteoporosis and pathological fractures. We describe the case of a 70-year-old woman with Cushing’s syndrome with right adrenal adenoma, vertebral compression fractures (VCFs) and severe secondary osteoporosis. This patient had been diagnosed with Cushing’s syndrome in May 2008, three years after the onset of arterial hypertension and type II DM, treated with insulin; in July 2008, she underwent right adrenalectomy and replacement therapy with cortisone acetate, 37.5 mg/day, in association with a multiple drug regimen for hypertension and DM; she also had an at least 10-year history of dorso-lumbar pain with multiple disc protrusions. As part of a series of investigations for Cushing’s syndrome the patient underwent femoral bone mineral densitometry, recording a T-score <−3, radiographic examination of the dorso-lumbar spine, which revealed collapse of the superior endplate of D7 and a wedge fracture of D8. At the endocrinology centre of reference for Cushing’s syndrome, she began treatment with alendronate 70 mg/day without undergoing blood chemistry tests of bone metabolism and without calcium and vitamin D supplementation. At the end of August 2009, she experienced worsening spinal pain due to a new severe fracture of D9, which was confirmed on MRI as a recent fracture. At the end of December 2009 she received kyphoplasty of D9, antiresorptive therapy and a CAMP-C35 brace.

In January 2010 she was admitted to the specialist rehabilitation unit for functional recovery, in view of her comorbidities, and bone disease investigation, with collection of history relating to osteoporosis risk factors. First- and second-level blood chemistry analyses revealed the presence of iron-deficiency anaemia, mild chronic renal insufficiency, and secondary hyerparathyroidism (PTH 101ng/ml); spinal radiography revealed severe VCFs of D7, D8 and D9, treated with kyphoplasty; the patient was also assessed using the VAS for pain, the FIM to evaluate independence in activities of daily living, and the SF-36 to investigate quality of life. The alendronate treatment was suspended and the patient was given cholecalciferol 300,000 IU, administered as an oral bolus, followed by a maintenance dose of 800 IU/day. When PTH values had returned to normal, she began treatment with teriparatide 20 mcg/day s.c. (therapeutic plan in compliance with Note 79 issued by the AIFA - Italian Drug Agency).

In conclusion, this case underlines the importance of a correct diagnostic and therapeutic approach in patients with severe osteoporosis. Over time, we will evaluate the efficacy of the treatment in preventing new fractures and the whether the use of a bone anabolic agent might be the correct choice also in order to control pain and improve quality of life. There are no reports in the literature of patients with Cushing’s syndrome treated with teriparatide.

Do patients with Type 2 Diabetes Mellitus have an increased prevalence of Cushing's Syndrome?

2011-12-14T08:35:00.001-05:00

Therese Krarup, Thure Krarup, Claus Hagen

Keywords: Type 2 diabetes; Cushing's syndrome; hypercortisolism

Abstract

Many clinical features are common for patients with Type 2 Diabetes Mellitus (T2DM) and Cushing's Syndrome (CS) such as central obesity, hypertension and dyslipidaemia. Patients with CS often have T2DM. Since T2DM is much more frequent than CS it is possible that some patients with T2DM have increased production of cortisol and thus represent patients with CS.

The aim of this review is to evaluate the prevalence of CS in patients with T2DM.

A search was performed in Pubmed and Medline. We found 7 prospective studies, 2 case control studies and 2 cross sectional studies.

The difficulties in diagnosing subclinical Cushing's Syndrome is discussed.

The most frequent tests for diagnosing CS, late night salivary cortisol, 1 mg dexamethasone suppression test, and urinary free cortisol are discussed and put in relation to the results of the literature found.

The observed prevalence of CS in patients with T2DM varies widely between the different studies, ranging from 0% - 9,4%. This may be due to patient selection, differences in test methodology, including choice of test, cut off values and different cortisol assays. The true prevalence of CS in T2DM has not been determined. We need more studies investigating the prevalences of CS in T2DM patients. There is a need for developing more specific tests for diagnosing CS in patients with only slightly elevated cortisol secretion and subclinical CS.

We suggest that examination for hypercortisolism should only be performed in T2DM patients with a cushingoid appearance and hypertension or truncal obesity or dyslipidaemia. Copyright © 2011 John Wiley & Sons, Ltd.

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From http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2262/abstract;
jsessionid=BFC6D112B014B14DF8973B1EF380E381.d03t01

Cushing’s Syndrome Clinical Analysis of 77 Cases

2011-12-10T14:16:00.001-05:00

OBJECTIVE To analyze the cause of Cushing’s syndrome classification, the major clinical manifestations and laboratory features of frequency of occurrence, and the efficiency of various diagnostic methods to evaluate the clinical doctors to improve diagnosis and treatment of disease, improve patient prognosis.

METHODS from 2004 to 2009 in our hospital by clinical or pathological diagnosis of Cushing’s syndrome in patients with clinical data, of which 57 cases of females, 20 males. For the 77 cases of clinical manifestations, laboratory examination, imaging studies, clinical diagnostic tests, pathological characteristics and with the results of literature analysis and summary of them were analyzed retrospectively.

RESULTS 1. From 2004 to 2009 were diagnosed 77 cases of Cushing’s syndrome, of which 20 males, female 57 cases, male: female = 2:2.85, adrenal adenoma 80% of female patients of childbearing age women.

2. In Cushing’s disease causes the most common (35 cases), followed by adrenal cortical adenoma (30 cases, the left side of 21 cases), there is a growing trend in the latter. Cushing’s disease course and age of onset of adrenal adenomas were higher than those, the difference was statistically significant (P <0.05), the shortest duration of adrenal carcinoma.

3. Clinical performance, the performance of the diversity of its starter, Hypertension and central obesity were the most frequently occur in 75%, and 79.22% suffering from hypertension, Hypertension 1 11.48%, Hypertension 2 62.30%, Hypertension 3 grade 26.23%, and the incidence of abnormal glucose metabolism and hyperlipidemia, respectively 41% and 68%, of which the proportion of diabetes by 30%, 65% of patients had hypokalemia, mostly mild to moderate, adrenal cortex carcinoma 100% of patients with a low potassium, and is of moderate to severe hypokalemia. Cushing’s disease and adrenal adenoma in serum potassium, blood pressure and gender showed no significant difference.

4. In the diagnosis of Cushing’s syndrome test, blood cortisol circadian rhythm disappeared (98.65%), elevated midnight serum cortisol (98.55%), 4Pm serum cortisol increased (97.14%), low-dose dexamethasone suppression test (94.59%), 24hUFC increased (91.22%), morning serum cortisol increased (71.62%). Low-dose dexamethasone suppression of serum cortisol in the morning the next day the basis of 8:00 of serum cortisol of 50% and 275,200,138,50 nmol/Lthe sensitivity of the cut-off point were 94.6%, 95.9%, 97.3% , 97.3% and 100%.

5. Patients with Cushing’s syndrome in the differential diagnosis, 80% of Cushing’s patients can be high-dose dexamethasone suppression, while more than 95% of patients with adrenal cortical adenoma can not be high-dose dexamethasone suppression. Cushing’s patients compared with blood cortisol and ACTH levels were significantly higher in patients with adrenal tumors, while the latter’s rhythmic performance is worse, the differences were statistically significant (P<0.05). Both urinary free cortisol showed no significant difference.6. imaging examination, pituitary MRI can detect 88% of Cushing’s disease there is pituitary adenoma, while the adrenal CT 100% can find out the adrenal tumors, adrenal CT of adrenal tumors and hyperplasia pathology consistent rate of 97.5%.

CONCLUSION 1. The present study in Cushing’s disease and adrenal cortical adenoma is still the most common cause of this group a high proportion of cases of adrenal adenoma, left more common. Cushing’s syndrome more common in women of childbearing age women, more common adrenal adenoma, Hypertension is the most common symptoms, mostly moderate to severe hypertension, diabetes, low potassium, high incidence of dyslipidemia.

2. Diagnostic tests in the CS, the morning cortisol increase the sensitivity of the worst, and serum cortisol circadian rhythm disappeared, midnight serum cortisol increased, 4PM cortisol rise, low-dose dexamethasone suppression test, 24hUFC elevated. There was no significant difference。

3. Patients with Cushing’s disease course, age of onset, blood cortisol and ACTH levels were higher than the adrenal adenoma, the latter comparison rhythm of blood cortisol rhythm performance is worse. The serum potassium, blood pressure and no significant difference in gender.

4. High-dose dexamethasone suppression test is to identify Cushing’s disease and adrenal cortical adenoma of the most appropriate method, CT of the adrenal lesion positive rate and help confirm the diagnosis and localization, B super-positive rate was significantly lower than CT, head MRI in Cushing’s disease positive rate.

From http://www.tumorres.com/tumor-metastasis/15968.htm

Book: Harvey Cushing: A Life In Surgery

2011-12-09T15:29:00.001-05:00

Harvey Cushing: A Life In Surgery

Review by Dr. Alfredo Quiñones-Hinojosa. Dr. Alfredo Quiñones-Hinojosa (also known as "Dr. Q") is the Associate Professor of Neurosurgery, Neuroscience, Oncology and Cellular and Molecular Medicine, and the Director of the Brain Tumor Stem Cell Laboratory at Johns Hopkins University School of Medicine.

Michael Bliss, Paperback, 591 pages

Here is the first biography to appear in fifty years of Harvey Cushing, a giant of American medicine and without doubt the greatest figure in the history of brain surgery.

Drawing on new collections of intimate personal and family papers, diaries and patient records, Michael Bliss captures Cushing's professional and his personal life in remarkable detail. Bliss paints an engaging portrait of a man of ambition, boundless, driving energy, a fanatical work ethic, a penchant for self-promotion and ruthlessness, more than a touch of egotism and meanness, and an enormous appetite for life. Equally important, Bliss traces the rise of American surgery as seen through the eyes of one of its pioneers. The book describes how Cushing, working in the early years of the 20th century, developed remarkable new techniques that let surgeons open the skull, expose the brain, and attack tumors--all with a much higher rate of success than previously known. Indeed, Cushing made the miraculous in surgery an everyday event, as he and his team compiled an astonishing record of treating more than two thousand tumors.

This is the definitive Cushing biography, an epic narrative of high surgical adventure, capturing the highs and lows of an extraordinary life.

Review below by Dr. Alfredo Quiñones-Hinojosa. Dr. Alfredo Quiñones-Hinojosa (also known as "Dr. Q") is the Associate Professor of Neurosurgery, Neuroscience, Oncology and Cellular and Molecular Medicine, and the Director of the Brain Tumor Stem Cell Laboratory at Johns Hopkins University School of Medicine.

Without the influence of Cajal and Halsted, the career of Harvey Cushing, born in 1869, might not have been possible. And without Cushing, many careers, including my own, would not exist. In this marvelous biography, Michael Bliss examines both the icon and the person. A genius with relentless ambition, Cushing was a mentor and tormentor, a perfectionist who often forgot the line between confidence and arrogance, yet ultimately he was a healer who once said that brain surgery amounts to "20 percent science, 75 percent artistry and 5 percent community benefit." Bliss vividly details Cushing's obsession with improving all aspects of surgical care, as well as clinical diagnostic methods. Cushing's life is like a great ghost story — it will haunt you long after it's over.

Adrenal glands: The reserve tank for stress?

2011-12-09T14:14:00.001-05:00

Have you ever noticed that when you are "stressed" you can feel either emotionally/physically depleted or energized? When our body is under stress the brain responds by producing epheniphrine (aka adrenaline), sending signals to our adrenal glands, increasing the rate at which our heart beats while releasing oxygen to our muscles. The long term response to this process produces cortisol (aka the stress hormone) facilitating the release of energy throughout our body. However, when our body isn't properly balanced these hormones can wreak havoc on our wellness possibly resulting in one of three conditions: Cushing's syndrome, Cushing's disease or Addison's disease.

The actual Adrenal glands sit physically atop both kidneys, taking on a triangular shape and a roundish rectangular type shape. These glands are responsible for our sex hormones and cortisol, helping us respond to stress amongst other functions. When our body is under stress, physically and/or nutritionally, it responds one of two ways: Produces too much or too little of the cortisol hormone. Our Adrenal glands also contribute to regulating our blood sugar, blood pressure, salt and water.

Adrenal disorders can cause our body to make too much or not enough of these hormones, bringing about adrenal gland related syndromes and disease. Cushing's syndrome results from our body making too much versus Addison's disease produces too little.

Cushing's syndrome vs Cushing's disease

Glucocorticoids (naturally produced in our body or received through medicine) are groups of corticosteroids (cortisol or dexamethasone) involved in metabolizing our carbohydrates and proteins. When taken synthetically (i.e. treatment of allergies, skin problems, and respiratory problems) or over-produced naturally, the side effects can result in "Cushing's syndrome".

Cushing's syndrome can occur one of two ways: Endogenous or Exogenous. Endogenous is caused by the body (usually through tumors). Exogenous is caused by medication. In both cases, the body produces too much cortisol.

Symptoms: Severe fatigue/muscle weakness, high blood sugar and high blood pressure, upper body obesity, thin arms/legs, bruising easily.

Treatment: The cure and treatment for Cushing's Syndrome and disease can come through medicine, surgery, or by lowering the dosage of your current synthetic hormone treatment and can likely be cured.

Cushing's disease is the most common form of endogenous Cushing's syndrome and is likely treatable. Caused by a tumor in the pituitary gland secreting too much Adrenocorticotropic hormone (ACTH), this type of tumor does not spread and can be removed through surgery.

Nutrition: See a nutritionist or dietician for your condition. Mostly, avoid excess sodium. High blood sugar (hyperglycemia) and high blood pressure can easily occur with this condition. Bone loss density is common with this condition, so be extra aware of your calcium (800 – 1200 mg per day, based upon age) and Vitamin D intake (5mcg from age 0-50, increasing up to 10 mcg 50-71, and 15 mcg after 71). Eating healthy, balanced and whole food (versus processed) is extremely important. (Resource: http://www.aboutcushings.com/understanding-cushings-disease/causes-and-differences.jsp)

Addison's disease Opposite from Cushing's syndrome, Addison's disease doesn't make “enough” of the sex hormones and cortisol. The result of this disease causes our immune system to attack our tissue, damaging our adrenal glands.

Symptoms: Weight loss, muscle weakness, increasingly worse fatigue, low blood pressure and patchy or dark skin.

Treatment: If left untreated, the condition can be fatal. Lifetime hormone treatment is usually required. Addison disease patients should always carry medical/emergency ID on them, listing their medication, dosage and disease

Lab tests can confirm that you have Addison's disease. If you don't treat it, it can be fatal. Very likely, you will need to take hormone pills for the rest of your life. If you have Addison's disease, you should carry an emergency ID. It should say that you have the disease, list your medicines and say how much you need in an emergency.

(Ref: http://www.nlm.nih.gov/medlineplus/cushingssyndrome.html, NIH: National Institute of Neurological Disorders and Stroke)

If all of this sounds a little overwhelming there is hope. Learning how to balance our stress-filled lives is extremely important to our overall health. Healthy nutrition always contributes benefits to our overall wellness. We can overwhelm our endocrine system by simply not eating nutritionally. Understanding that “Food is a drug” is vitally important to how we help our body naturally heal itself. The above conditions are the result of our body not handling the stress we are putting it through, causing our body to producing too much or too little of the sex hormones and cortisol.

Unless we first address what we can do naturally through nutrition, the medicine we consume will only do so much in helping our body heal completely. You simply cannot continue doing the same thing over and over again, expecting the medicine to do all the work. Some diseases are brought upon us through our environment (emotionally as well as physically) as well as our diet/nutrition. Reviewing our entire wellness is always wisdom whenever we're diagnosed with anything.

Certainly listen to your doctor and their advice. But also ask your doctor to refer you to a nutritionist or clinical/registered dietician for a complete evaluation that includes a review of your nutritional diet/wellness. Too often we reach for a pill or a procedure to “fix” our health problems, ignoring what we should be doing on our own to help our body heal. Medical intervention is "sometimes" the result of providing our body with what it cannot produce on its own. Nutrition should always be the “natural” medicine we take, as well as what we might need through prescribed medication.

Quick Tips for Wellness: Living “well” requires living nutritionally balanced.

Adapted From http://hamptonroads.com/2011/12/adrenal-glands-reserve-tank-stress

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2011-12-08T11:49:00.001-05:00

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Overt immune dysfunction after Cushing's syndrome remission: a consecutive case series and review of the literature

2011-12-06T15:19:00.001-05:00

J Clin Endocrinol Metab. 2011 Oct;96(10):E1670-4. Epub 2011 Aug 3.

Overt immune dysfunction after Cushing's syndrome remission: a consecutive case series and review of the literature.

da Mota F, Murray C, Ezzat S.

Source

Department of Medicine, University Health Network, Toronto, Ontario, Canada M5G 2M9.

Abstract

CONTEXT:

Autoimmune diseases frequently improve during active Cushing's syndrome. Several studies have reported new onset or exacerbation of these conditions upon cortisol normalization.

OBJECTIVE:

Our objective was to investigate the incidence and clinical characteristics of patients with autoimmune or allergic diseases after Cushing's syndrome remission.

METHODS:

Consecutive cases of confirmed Cushing's syndrome were characterized. A review of the literature was conducted to identify previous descriptions of immune dysfunction upon remission and evidence of the hypothalamic-pituitary-adrenal axis influence on the immune system.

RESULTS:

Among 66 patients who achieved Cushing's syndrome remission, the incidence of immune dysfunction was 16.7%, where eight cases (72.7%) were noted for the first time and three (27.3%) were exacerbated. All had an ACTH-dependent cause. Glucocorticoids reduce proinflammatory cytokines and interact with other transcription factors affecting T cell and mast cell survival.

CONCLUSION:

Hypercortisolism induces a state of immunosuppression. After Cushing's syndrome remission, rebound immunity frequently results in overt conditions extending beyond thyroid dysfunction.

from http://www.ncbi.nlm.nih.gov/pubmed/21816785

Video - Cushing's Disease Misdiagnosis (Sharmyn)

2011-12-06T14:30:00.001-05:00

Misdiagnosed for seven years, Sharmyn takes control of her own health, finds the answers she's been searching for and a doctor that can help. Dr. Daniel Kelly, the Director of Saint John's Brain Tumor Center in Santa Monica, CA, successfully removes her tumor and gives her back her life.

View Sharm's video here: http://www.aol.com/video/cushings-disease-misdiagnosis/517219481

Pennsylvania Cushing's disease victim in need of goodwill

2011-12-05T13:27:00.001-05:00

By Chad Smith

Pocono Record Writer

December 05, 2011

Eric Allman is having car troubles. Actually, his problems are more extensive than car troubles. But he's having car troubles.

Allman's home in Emerald Lakes is being foreclosed on, and he must move with his family to a subsidized apartment complex in Stroudsburg. While this alone may be difficult, Allman also has Cushing's disease, a hormonal disorder that causes excessive weight gain and a host of other problems.

The disease has prevented him from holding a job in recent years.

"The bank wants me to pay $50,000 to stay in my house," Allman said. "I can't even pay $5."

Which is why it came as such a crushing blow recently when he found out he'd have to pay $3,500 to get his broken-down Subaru station wagon fixed. The car is one of his only lifelines to the world.

It's the thing that gets him to his doctor appointments every month. Without it, he says, he's stranded, and that puts him in serious jeopardy.

Allman said if someone could help him pay for the station wagon's repairs or help him find some solution, he'd be grateful.

"It's just been so hard," said Allman, 49, who relies primarily on a motorized wheelchair to travel small distances.

In order to move all of his and his family's belongings into their new apartment, Allman rented a van. Allman's wife is also ill, and his son takes care of him full time.

Allman thought the van was a good stopgap measure, but it wasn't, because he fell twice while exiting the vehicle. Both times, an ambulance and the fire department were called to help him.

Allman's station wagon, however, which is sitting in the shop, was specially outfitted to allow him easy access into it and out of it.

"The mechanics say they'll give me a good deal to fix it. But like I said, I just don't have any money for this."

Allman's plight really began around 2005, when he was diagnosed with Cushing's disease.

People with Cushing's disease produce too much cortisol, a naturally occurring hormone that controls the body's use of carbohydrates, fats and proteins. This hyper-production of cortisol leads to weight gain. But it also weakens bones and muscles. So as a person with the disease gains weight, his or her body becomes less able to support it.

Allman, who used to work as an armed security guard, said his weight shot up nearly 225 pounds since he got the disease. He now weighs 400 pounds.

"Sometimes it feels like I'm just existing. My bones are turning to powder," he said.

Allman said he has some lights in his life, like his family and some hobbies. But without his station wagon, he can't go to his three doctor appointments each month — which means he can't get his prescriptions.

In addition, Allman said he was crushed when he recently had to give up his 10 cats to a local animal rescue, Animals Can't Talk, because the Westgate Apartments only allows two pets per household.

"That was terrible. But I would do anything to be able to be mobile again," Allman said. "We just need a little help."

Allman can be reached at 570-856-0948.

From http://www.poconorecord.com/apps/pbcs.dll/article?AID=/20111205/NEWS/112050318/-1/NEWSMAP

The Message Boards will be Down

2011-11-30T23:55:00.001-05:00

The boards will be down for a few days for an upgrade and move to a new server.

For more information, please see this post.

After the upgrade, there will be a learning curve for everyone, so please be patient!

The Availability Of An Investigational Drug For Severe Cushing’s Syndrome On a Compassionate Use Basis

2011-11-30T22:25:00.001-05:00

From Dr. Theodore Friedman: Cushings-Help.com Announces: The Availability Of An Investigational Drug For Severe Cushing’s Syndrome On a Compassionate Use Basis

November, 2011

We would like to make patients aware that mifepristone, an investigational drug that blocks the action of cortisol and is being developed by Corcept Therapeutics Incorporated, is now available on a compassionate use basis for eligible patients in the United States with Cushing’s syndrome who have no other treatment options.

Under this compassionate use program, the FDA allows seriously ill patients who lack satisfactory alternative treatment options to use an investigational new drug that is still under development. Corcept has completed a Phase III trial investigating the safety and efficacy of mifepristone in patients with endogenous Cushing’s syndrome. The information from that study has been submitted to the FDA for review of safety and efficacy.. For information on the trial results see http://www.corcept.com/cushings_clinical_trials. The company has submitted a New Drug Application (NDA) seeking approval for this drug.

Patients interested in using mifepristone should consult with their endocrinologist. Their endocrinologist, in turn, should contact Corcept for information about the compassionate use program. Please note that Corcept will provide information solely to physicians.

Toll Free: 1-877-367-6550

Website: www.corcept.com/cushings_expanded_access

E-mail: EAP@Corcept.com

Corcept Therapeutics: Clinical Development and Trials

www.corcept.com

DH investigating suspected case of Cushing's syndrome with history of taking medicines prescribed by Chan Kwok-wing

2011-11-30T14:03:00.001-05:00

Hong Kong (HKSAR) - The Department of Health (DH) is today (November 30) investigating a suspected case of Cushing's syndrome involving an eight-year-old girl who patronised Mr Chan Kwok-wing of PCRC Chinese Medicine Clinic in Mongkok for management of allergic conditions.

The case was reported to the DH by the Hospital Authority. The girl, who had history of eczema and allergic rhinitis, consulted Chan for around two months since mid-September 2011 and was supplied with some pills, including pills in orange and black colour respectively, and green capsules and green tablets.

"The girl has stopped taking the pills after noting DH's announcement on November 28 of a previous incident related to Chan involving a seven-year-old patient who developed features compatible with steroid overdose after taking pills supplied by Chan," a spokesman said. However, her mother started to notice that the girl had some features of obesity and moon face.

The girl was admitted to the Prince of Wales Hospital today where the girl was found to have moon face, truncal obesity and recent weight gain.

Her clinical diagnosis was iatrogenic Cushing's syndrome. Cushing's syndrome can be caused by steroid overdose. The patient is now in stable condition.

The spokesman added, "Investigation of the present case, including testing of the pills for adulteration of western medicines, is in progress,"

The spokesman again appealed to members of the public, who patronised Chan for management of allergy and was supplied with a type of green and another type of orange oral tablets, to consult healthcare professionals for advice as soon as possible.

"Chan is suspected of practising Chinese medicines without licence as there is no record to show that he is either a registered medical practitioner or a pharmacist.

DH is assisting with Police investigation," the spokesman said.

Source: HKSAR Government

Endocrine disorders & female infertility

2011-11-30T13:48:00.001-05:00

David Unuane, MD (Doctor), Department of Endocrinology, Universitair Ziekenhuis Brussel, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium, Herman Tournaye, MD, PhD (Professor, Doctor), Brigitte Velkeniers, MD, PhD (Professor, Doctor), Kris Poppe, MD, PhD (Professor, Doctor)

Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established.

Acromegaly and Cushing’s disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed.

We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

Keywords: female infertility, pituitary, adrenal, ovarian, thyroid

From http://www.bprcem.com/article/PIIS1521690X1100087X/abstract?rss=yes

More Treatments for Cushing’s Disease

2011-11-23T01:15:00.001-05:00

(Ivanhoe Newswire) – Cushing’s disease is a hormone disorder that causes many symptoms, such as high blood pressure, fat accumulation, osteoporosis and ultimately ending in death. It is caused by a tumor in the anterior pituitary gland that secretes excess amounts of adrenocorticotrophic hormone (ACTH). The only treatment is removal of the tumor, however, researchers have found a new treatment for these reoccurring tumors.

Researchers, led by Shlomo Melmed, at Cedars-Sinai Medical Center, Los Angeles, have now identified a potential new therapeutic target -- the protein EGFR, which is the target of a drug used to treat some patients with non–small cell lung cancer (gefitinib). As discussed by Melmed and colleagues in their paper, as well as Frederic Wondisford, at Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, the data generated in human, canine, and mouse models provide strong support to investigate the clinical effects of gefitinib in patients with Cushing disease.

SOURCE: Journal of Clinical Investigation, published online November 21, 2011

From http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=28468

Full Endoscopic Transsphenoidal Surgery for Pituitary Adenoma-emphasized on Surgical Skill of Otolaryngologist

2011-11-18T14:14:00.001-05:00

INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY

DOI: 10.1007/s12070-011-0317-4

Yun-ping Fan, Ming-hui Lv, Shao-yan Feng, Xiang Fan, Hai-yu Hong,Wei-ping Wen and Hua-bin Li

Abstract

The purpose is to summarize the experience in full endoscopic transsphenoidal resection of pituitary adenoma in 28 patients by rhinologist, and introduce the surgical skill of otolaryngologist, especially skills and cautions when operating inside nose. We removed pituitary adenoma in 28 patients via entirely endoscopic transsphenoidal approach with the help of special-designed instruments; we performed the procedure bloodlessly within limited time. The skill emphasized bilateral nostrils and four hands technique which was as delicate as possible not to scratch nasal mucosa or injure nasal frame. The special instruments included curette with suction, monopolar electrotome and bipolar coagulation forceps with suction, powered surgical equipments (Diamond Bur, Irrigation Tubing for Blades and Burs for nasal endoscopic surgery). Among 28 patients, there were 16 total resections, 8 subtotal resections, 3 partial resections, and 1 only biopsy due to excessive bleeding and hard nature. Of 19 patients with preoperative visual impairment, 12 patients had postoperative improvement in visual acuity and visual field. All the procedures were finished within 60 to 90 min. Complications seldom occurred except transient diabetes insipidus, especially no nasal-related signs or complications but 1 had epistaxis. The full endoscopic transsphenoidal surgery is a promising approach for pituitary adenoma resection. Multidisciplinary collaboration will lead to optimal cure for the patients. New technique and special-designed instruments can facilitate greatly this procedure.

Keywords Nasal endoscopy – Pituitary adenoma – Complication – Surgical skill

Fulltext Preview

From http://www.springerlink.com/content/wr21116515633t38/

Not the Usual Suspects: Animal Study Finds Surprising Clues to Obesity-Induced Infertility

2011-11-18T11:37:00.001-05:00

Source: Johns Hopkins Medicine

FOR IMMEDIATE RELEASE

Newswise — Infertility is common among obese women, but the reasons remain poorly understood and few treatments exist. Now a team of Johns Hopkins Children's Center scientists, conducting experiments in mice, has uncovered what they consider surprising evidence that insulin resistance, long considered a prime suspect, has little to do with infertility in women with type-2 diabetes, polycystic ovary syndrome (PCOS) and metabolic syndrome, all obesity-related conditions in which the body becomes desensitized to insulin and loses the ability to regulate blood sugar.

In a report, published online Nov.10 in the journal Diabetes, the Johns Hopkins scientists say the real culprit appears to be insulin sensitivity in the ovaries and the pituitary.

The Johns Hopkins team said its findings show that these organs escape insulin resistance and, awash with high levels of circulating insulin common in obesity, develop abnormal cell signaling that disrupts ovulation and eventually leads to infertility.

"Our findings suggest that the focus should shift from treating insulin resistance in peripheral tissue to taming insulin sensitivity in the pituitary and ovaries," says lead investigator Sheng Wu, Ph.D., of the Johns Hopkins Children's Center. Scientists traditionally have treated obesity-induced infertility by lowering blood insulin to counter the effects of insulin resistance.

A 2010 study by the same team discovered that the pituitary gland, insensitive to insulin in lean mice, became sensitive to elevated levels of insulin seen in human and rodent obesity. By knocking out the insulin receptors in the pituitary glands of obese mice, the researchers were able to partially restore fertility, thus proving that abnormal insulin signaling in the pituitary was only part of the story.

"In the original study, disrupting insulin signaling in the pituitary restored 50 percent of fertility in obese mice, but the search was on for the accomplice," says senior investigator Andrew Wolfe, Ph.D., an endocrinologist at the Johns Hopkins Children's Center. "Our new findings point to the ovaries."

In the pituitary, faulty insulin signaling stimulates increased secretion of luteinizing hormone, the researchers say. In the ovary, it puts testosterone production into overdrive. Both disrupt ovulation, the researchers explain.

In the latest study, lean mice and mice made obese on a three-month high-fat diet received injections of progressively higher doses of insulin to mimic the effects of high circulating insulin seen in obesity, diabetes and PCOS. In lean mice, the ovaries and pituitaries were insensitive to the hormone at low-dose injections, and responded only when injected with higher doses of insulin. The "trigger" doses corresponded to insulin levels typically seen in obesity. Obese mice with naturally elevated insulin levels exhibited high levels of insulin signaling in their pituitary and ovarian cells. When injected with insulin, the livers and muscles of obese mice showed greatly reduced response to insulin -- or insulin resistance. Their ovaries and pituitary glands, however, responded to insulin injections, confirming that in obese mice, these reproductive organs escape the insulin resistance seen in other organs.

To determine insulin sensitivity, the researchers focused on two signaling proteins, IRS-1 and IRS-2, regulators of cell-insulin communication involved in the development of insulin resistance in liver and muscle tissue. The scientists hypothesized that in the pituitary and ovaries, these messenger proteins would remain dormant under normal insulin levels, but would get activated once exposed to high levels of insulin. Indeed, the researchers found, the pituitary glands of obese mice showed higher IRS-2 signaling activity compared with lean mice, while the ovaries of obese mice had higher signaling activity in both IRS-1 and IRS-2 proteins, compared with lean mice.

In a follow-up study now under way, the Hopkins team is trying to determine whether knocking out the insulin receptors in both the ovaries and the pituitary would fully restore fertility in obese mice with high insulin levels.

Other co-investigators on the study included Sara Divall, M.D., and Fred Wondisford, M.D., both of the Johns Hopkins Children's Center.

The research was funded by the Endocrine Fellow Foundation, by The Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, and by the Baltimore Diabetes Research and Training Center, which is supported by the National Institute for Diabetes and Digestive and Kidney Diseases.

Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, treating more than 90,000 children each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation.
Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, please visitwww.hopkinschildrens.org

From http://www.newswise.com/articles/not-the-usual-suspects-animal-study-finds-su.../articles/list&category=medicine&page=1&search%5Bstatus%5D=3&search%5Bsort%5D=date+desc&search%5Bsection%5D=10&search%5Bhas_multimedia%5D=

(Addison's Disease) Coma man defies odds to write book

2011-11-12T09:20:00.001-05:00

By Lisa Smyth

A Northern Ireland man has defied medical predictions and overcome the effects of a rare condition that left him in a coma for three months.

Jonathan Fisher is a survivor of an Addisonian crisis which affected him so badly doctors feared he would never recover.

His mother ignored medical advice to switch off his life-support system as doctors believed he was brain dead.

However, convinced he could recover after noticing that he was reacting to her with the occasional slight movement of his little finger she refused to give up on her son.

Now — against all the odds — he has made a remarkable recovery and has regained many of the skills lost as a result of his condition.

Addison’s disease is a rare disorder of the adrenal glands. It affects the production of two hormones — cortisol and aldosterone — which help to regulate blood pressure.

If left untreated, the amount of steroid hormones in the body will gradually fall and the symptoms of Addison’s disease will get progressively worse.

Eventually, this will cause an adrenal crisis — when the symptoms become very severe and blood pressure drops to a dangerously low level. An adrenal crisis can be fatal if it is not treated immediately.

Jonathan can now get around Lisburn in his electric wheelchair and has even managed to complete his first book, August Always — a triumph as he has considerable speech impairment and great difficulty using his hands to operate a keyboard.

The process has been long and laborious but Jonathan said he was determined to share his experience with others.

“There are moments in life that define us, like birth and death,” he said.

“Along the journey there will be crises of passion, of love, of faith and desire, but none so devastating as an Addisonian crisis. I am Jonathan Fisher, a survivor.

“August Always is my memoir. I believe in the incredible. I dream of a better future.”

Background

Addison’s disease is a rare disorder of the adrenal glands which are located on top of the kidneys. The condition affects the production of two hormones. Cortisol, which helps to regulate blood pressure, maintaining blood glucose and heart function. And aldosterone which also helps regulate blood pressure. Addison’s sufferers must get treatment if their blood pressure falls as it can be fatal.

From http://www.belfasttelegraph.co.uk/news/health/coma-man-defies-odds-to-write-book-16076458.html

Patients Diagnosed With Severe Adult GH Deficiency Using The Insulin Tolerance Test, Arginine Or Glucagon Stimulation Tests Share Similar Clinical Features

2011-11-10T14:36:00.001-05:00

PDF (277.1 KB)

Authors

Andy Toogood, MD, FRCP¹, Georg Brabant, MD, PhD FRCP², Dominique Maiter, MD, PhD³, Björn Jonsson, PhD⁴, Ulla Feldt-Rasmussen, MD, PhD⁵, Maria Koltowska-Haggstrom, PhD⁶, Ase Krogh Rasmussen, MD, PhD⁵, Michael Buchfelder, MD⁷, Bernhard Saller, MD, PhD⁸, Beverly M K Biller, MD⁹

¹Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, United Kingdom
² Experimental and Clinical Endocrinology, MedizinischeKlinik I, RatzeburgerAllee 160, D-23538, Lübeck, Germany
³Department. of Endocrinology, CliniquesUniversitaires Saint-Luc, Avenue Hippocrate, 54.74, 1200 Brussels
⁴Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
⁵Department of Medical Endocrinology, Rigshospitalet, Copenhagen, 2100, Denmark
⁶KIMS Pfizer Endocrine Care, Specialty Business Unit, Pfizer Health AB, Sollentuna, 190 91, Sweden
⁷Department of Neurosurgery, University of Erlangen Nuernberg, Erlangen, 91045, Germany
⁸ Pfizer Endocrine Care Europe, Tadworth, United Kingdom
⁹Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States

Abstract

Objective: To determine whether the ITT, arginine (AST) and glucagon stimulation tests (GST) identify patients who have similar features of GH deficiency using a diagnostic threshold of 3 μg/l.

Patients and Methods: 5453 tests were available from 4,867 patients registered in the KIMS database (49.9% females, ITT = 3111, AST = 1390, GST = 952). Comparisons were made for GH peak, BMI, lipids, waist circumference, waist:hip ratio and quality of life (QoL-AGHDA questionnaire).

Results. There were significant (p<0.0001) intra-individual correlations between the GH peaks for the ITT vs AST (r = 0.655), ITT vs GST (r = 0.445) and AST vs GST (r = 0.632). GH peaks in response to all tests were negatively correlated to the number of additional pituitary hormone deficiencies, and positively correlated to IGF-I SDS. BMI had a negative influence on all three tests.

Comparing GHD patients according to the diagnostic test used, most clinical variables did not differ between the groups. The only exceptions showing any difference were BMI being slightly higher in the AST and GST groups, triglyceride levels increased in the GST group, and IGF-I SDS was lower in the ITT and AST than in the GST group. Waist circumference was larger and quality of life was worse in the GST group than in the other groups.

Conclusions. This study demonstrates that the ITT, AST and GST produce similar GH peaks, are influenced by similar clinical factors and identify patients with similar features of GH deficiency at a diagnostic threshold of 3 μg/L.

Keywords

Growth hormone deficiency, ITT, stimulation tests, glucagon, arginine, clonidine, IGF-I

Show References

From http://aace.metapress.com/content/h4228513un4m6370/

ACTH-secreting pituitary adenomas: size does not correlate with hormonal activity

2011-11-10T14:22:00.001-05:00

Nestoras Mathioudakis, Courtney Pendleton, Alfredo Quinones-Hinojosa, Gary S. Wand and Roberto Salvatori

Abstract

ACTH-secreting pituitary adenomas (Cushing’s disease, CD) are the most frequent cause of Cushing’s syndrome. To test whether the size of ACTH-secreting adenomas correlates with the degree of biochemical and clinical features of hypercortisolism, we retrospectively reviewed all newly diagnosed CD patients seen at our institution by two neuro-endocrinologists over a 10-year time period. We documented the number of clinical manifestations and baseline hormonal measurements.

There were 37 microadenomas (μAs) and 16 macroadenomas (MAs). We sought to characterize the relationship between tumor size (μA vs. MA) and number of signs and symptoms of hypercortisolism and biochemical assessment of hypercortisolemia. There were no significant differences in mean age, BMI, or prevalence of hypertension and type 2 diabetes between the μA and MA groups. However, the MAs had fewer clinical manifestations of hypercortisolism (29.4% vs. 36.1%, P = 0.02) compared to μAs.

There was a higher prevalence of easy bruisability and proximal muscle weakness in the μAs, but otherwise the prevalence of signs and symptoms were similar between groups. The MAs had a lower random serum cortisol (18.2 ± 2.4 vs. 25.9 ± 1.8 mcg/dl, P = 0.018), lower cortisol:ACTH ratio (0.25 ± 0.03 vs. 0.42 ± 0.05, P < 0.048), and lower cortisol:tumor diameter ratio (14.1 ± 2.2 vs. 56.8 ± 7.2, P < 0.0001) than the μAs.

We conclude that tumor size does not directly correlate with the extent of hormonal activity in ACTH-secreting adenomas. Biochemical activity and clinical manifestations may be mild even in larger tumors, and therefore a high index of suspicion may be necessary to recognize hypercortisolism in pituitary MAs.

Keywords Pituitary adenoma – Cushing – ACTH – Symptoms

Fulltext Preview

From http://www.springerlink.com/content/m624211x08224761/

Diabetes in Cushing syndrome: basic and clinical aspects

2011-11-10T14:11:00.001-05:00

Diabetes mellitus is a frequent complication of Cushing syndrome (CS) which is caused by chronic exposure to glucocorticoid excess, either endogenous or exogenous, and that is characterized by several clinical symptoms such as central obesity, purple striae, proximal muscle weakness, acne, hirsutism and neuropsychological disturbances.

Diabetes occurs as a consequence of an insulin-resistant state together with impaired insulin secretion which are induced by glucocorticoid excess. The management of patients with CS and diabetes mellitus includes the treatment of hyperglycemia and, when possible, the correction of glucocorticoid excess.

This review focuses on the disorders of glucose metabolism in patients exposed to glucocorticoid excess, addressing both the pathophysiological aspects and the clinical and therapeutic implications.

Read the entire article at http://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(11)00138-X

November Cushing's News

2011-11-10T14:00:00.001-05:00

Something new of interest to Cushies most every day. Please note that there is a current backlog of about three weeks for submitted bios to be added to the website.

November 10, 2011:

Three New Helpful Doctors added: Dr. Gordon Wotton (Atlanta, Georgia)
Dr. Amel Arnaout (Ottowa, Ontario, Canada)
Dr. Emilie Collins (Kent, Michigan) http://cushie.info
Korlym: Corcept Therapeutics Announces Third Quarter Results and Corporate and Development Update http://cushie.info
Google+ page for Cushings http://cushie.info
Patients Diagnosed With Severe Adult GH Deficiency Using The Insulin Tolerance Test, Arginine Or Glucagon Stimulation Tests Share Similar Clinical Features http://cushie.info
ACTH-secreting pituitary adenomas: size does not correlate with hormonal activity http://cushie.info
Diabetes in Cushing syndrome: basic and clinical aspects http://cushie.info
DuoCort Pharma's Orphan Drug Plenadren® Granted European Marketing Authorization for Adrenal Insufficiency http://cushie.info
Endoscopic bilateral adrenalectomy in patients with ectopic Cushing's syndrome http://cushie.info
Pituitary glands grown from mouse embryonic stem cells http://www.guardian.co.uk
Hot Topics: Cushings Disease and Acromegaly https://www.aace.com
Cushing's and Cancer Blog (Updated 11/10/11) http://www.cushingshelp.blogspot.com
Cushing's Help on Posterous Blog (Updated 11/10/11) http://cushings.posterous.com
The CushieWiki updated 11/10/2011. http://www.CushieWiki.com
Addison's Help Blog (Updated 11/10/11) http://www.addisonshelp.blogspot.com
Addison's and Cushing's Help and Support RSS Feed. Last updated 11/10/11. http://www.cushingsonline.com

November 5, 2011:

What Is the Best Approach for the Evaluation and Management of Endocrine Incidentalomas? http://cushie.info
Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of giant pituitary adenomas http://www.cushie.info
Where Does My Donation Go? Spreadsheet Updated 11/3/11 https://docs.google.com/a/cushings-help.org
Comment has been added: Discussion/debate topics http://cushie.info
The Cushing's Daily http://www.cushie.info
Addison's and Cushing's Help and Support RSS Feed. Last updated 11/5/11. http://www.cushingsonline.com
Our Locations (Updated 11/5/11) http://cushie.info
Lou, undiagnosed bio http://www.cushie.info
Caryn, undiagnosed bio http://www.cushie.info
Mallissa F, undiagnosed bio http://www.cushie.info

November 2, 2011:

The CushieWiki updated 11/2/2011. http://www.CushieWiki.com
New Comment added: Gail M W, undiagnosed bio http://cushie.info
Clinical trial: Effects of Hormone Stimulation on Brain Scans for Cushing's Disease http://cushings.posterous.com
New FAQ Question added http://www.cushie.info
Tweeting about Cushing's? Use this hashtag: #cushings
Where Does My Donation Go? Spreadsheet https://docs.google.com/a/cushings-help.org
Help Cushing's Help at No Cost to You http://www.cushie.info
Comment has been added: Discussion/debate topics http://cushie.info
Updated Upcoming Meetings (Updated 11/2/11) http://www.cushie.info
Cushing's and Cancer Blog (Updated 10/27/11) http://www.cushingshelp.blogspot.com
Cushing's Help on Posterous Blog (Updated 10/27/11) http://cushings.posterous.com
The Cushing's Daily http://www.cushie.info
Cushing's Podcasts on Posterous Blog (Updated 10/20/11) http://cushingspodcasts.posterous.com
A New FAQ (Frequently Asked Questions) is being added. 109 questions answered so far. Last updated 10/28/11. http://cushie.info
Addison's and Cushing's Help and Support RSS Feed. Last updated 11/2/11. http://www.cushingsonline.com
New Male Only bio. http://cushie.info
Our Locations (Updated 11/2/11) http://cushie.info
Updated: Gail M W, pituitary bio http://www.cushie.info
Kim, pituitary bio http://www.cushie.info
Crystal's son, undiagnosed bio http://www.cushie.info
Maureen, adrenal bio http://www.cushie.info
Lou, undiagnosed bio http://www.cushie.info
Carmen, undiagnosed bio http://www.cushie.info
Maureen, adrenal bio http://www.cushie.info

DuoCort Pharma's Orphan Drug Plenadren® Granted European Marketing Authorization for Adrenal Insufficiency

2011-11-10T13:58:00.001-05:00

HELSINGBORG, Sweden and EXTON, Pa., Nov. 7, 2011 /PRNewswire/ -- The Swedish specialty pharma company, DuoCort Pharma, announced today that the European Commission has granted a European Marketing Authorisation for Plenadren®(hydrocortisone, modified release tablet), an orphan drug for treatment of adrenal insufficiency in adults, bringing these patients their first pharmaceutical innovation in over 50 years.

Developed by DuoCort Pharma, Plenadren® is a dual release hydrocortisone replacement therapy designed to better mimic the normal physiological cortisol profile in order to improve outcomes for patients suffering from adrenal insufficiency. Plenadren® is given as an oral tablet once daily. It has an outer layer releasing hydrocortisone immediately and an inner core releasing the rest of the drug more slowly during the day.

Although glucocorticoid hormone replacement therapy for adrenal insufficiency has been available for decades, studies have recorded complications and comorbidities including premature death, impaired quality of life, increased risk of cardiovascular diseases, and decreased bone mineral density in treated patients, most likely because it is difficult to match the natural secretion pattern of cortisol.

Maria Forss, CEO of DuoCort Pharma, said: "The marketing authorization for Plenadren® in Europe is an important step towards addressing the unmet needs of these patients."

The approval of Plenadren® follows the positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) in July 2011. Plenadren® is now approved for marketing in all countries of the European Union (EU) as well as in the European Economic Area (EEA), namely Iceland, Norway and Lichtenstein.

Professor Gudmundur Johannsson of the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden, and Chief Medical Officer of DuoCort Pharma, said: "Plenadren® offers a welcome new treatment option to help patients suffering from adrenal insufficiency. Plenadren® can improve therapy for many of the almost 200,000 patients in Europe who suffer from this disease and who need life-long cortisol replacement therapy for their survival."

On October 26, 2011, ViroPharma Incorporated (NASDAQ: VPHM) signed a definitive agreement to acquire DuoCort Pharma AB. The companies expect to complete the acquisition in November 2011. On closing, ViroPharma will pay an upfront closing cost of 220 million Swedish kroner (SEK) or $33 million in US dollars (USD). Additionally, there are contingent milestone payments of up to 860 million SEK or $130 million USD associated with manufacturing, sales thresholds and territory expansion.

About Adrenal insufficiency

Adrenal insufficiency (cortisol deficiency) is a rare, life-threatening disease that affects patients in their active years. To survive, patients suffering from this disease need lifelong replacement therapy with hydrocortisone. Treatment of adrenal insufficiency involves replacing, or substituting, the hormones that the patient's own adrenal glands are not producing. Cortisol is replaced using hydrocortisone, the synthetic form of cortisol.

About Plenadren® (hydrocortisone, modified release tablet)

Plenadren is the first true innovation in over 50 years in the treatment of adrenal insufficiency.

Hypersensitivity to the active substance of Plenadren or to any of the excipients may occur. During acute adrenal insufficiency, parenteral administration of hydrocortisone in high doses, together with physiological sodium chloride solution for injection, must be given. Use of Plenadren with potent CYP 3A4 inducers and inhibitors may merit an adjustment of hydrocortisone dosage. High (supra-physiological) dosages of cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. Long-term treatment with higher than physiological hydrocortisone doses can lead to clinical features resembling Cushing's syndrome with increased adiposity, abdominal obesity, hypertension and diabetes, and thus result in an increased risk of cardiovascular morbidity and mortality. All glucocorticoids increase calcium excretion and reduce the bone remodeling rate. Patients with adrenal insufficiency on long term glucocorticoid replacement therapy have been found to have reduced bone mineral density. Psychiatric adverse events may occur with systemic glucocorticoids.

The most common adverse reactions observed in clinical studies have been fatigue, gastroenteritis, upper respiratory tract infection, sedation, vertigo and dry eyes.

About ViroPharma Incorporated

ViroPharma Incorporated is an international biopharmaceutical company committed to developing and commercializing novel solutions for physician specialists to address unmet medical needs of patients living with diseases that have few if any clinical therapeutic options, including C1 esterase inhibitor deficiency, treatment of seizures in children and adolescents, and C. difficile infection (CDI). Our goal is to provide rewarding careers to employees, to create new standards of care in the way serious diseases are treated, and to build international partnerships with the patients, advocates, and health care professionals we serve. ViroPharma's commercial products address diseases including hereditary angioedema (HAE), seizures in children and adolescents, and CDI; for full U.S. prescribing information on our products, please download the package inserts athttp://www.viropharma.com/Products.aspx; the prescribing information for other countries can be found atwww.viropharma.com.

ViroPharma routinely posts information, including press releases, which may be important to investors in the investor relations and media sections of our company's web site, www.viropharma.com. The company encourages investors to consult these sections for more information on ViroPharma and our business.

About DuoCort Pharma

DuoCort Pharma is a drug development company focused on improving glucocorticoid therapy. The company has its origins among researchers at the Sahlgrenska Academy at Gothenburg University and at Uppsala University in Sweden. DuoCort Pharma has developed Plenadren®, an improved glucocorticoid replacement therapy for patients with adrenal insufficiency, which is a rare disease. DuoCort Pharma has orphan drug designations in EU, Switzerland and the USA for Plenadren®. Plenadren® is a once daily, dual-release hydrocortisone oral tablet. It has an outer layer that releases the drug immediately and an inner core that releases the drug over the day. The tablets come in both 5 mg and 20 mg strengths. For more information please visit www.duocort.com.

DuoCort Pharma is a project company of the life science incubator PULS. For more information visit www.pulsinvest.se.

Disclosure Notice

Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. Forward-looking statements provide our current expectations or forecasts of future events, including statements about the benefits of the business combination transaction involving ViroPharma and DuoCort Pharma, including, among others, future financial and operating results, enhanced revenues, ViroPharma's plans, objectives, expectations and intentions and other statements that are not historical facts. The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the ability to achieve the other conditions to closing on the proposed schedule; the risk that the business will not be integrated successfully; the risk that revenues following the acquisition will be lower than expected, including the successful commercialization of Plenadren; potential for disruption from the transaction making it more difficult to maintain relationships with manufacturers, employees or other suppliers; competition and its effect on pricing, spending, third-party relationships and revenues; our ability to achieve favorable pricing for Plenadren from European regulatory authorities; the risk that the safety and/or efficacy results of existing clinical trials for Plenadren will not be consistent with the results of additional clinical studies, including the required registry study, or with commercial usage; market acceptance of Plenadren; and our inability to maintain the orphan drug status associated with Plenadren. These factors, and other factors, including, but not limited to those described in our annual report on Form 10-K for the year ended December 31, 2010 and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release are made as of the date hereof and may become outdated over time. ViroPharma does not assume any responsibility for updating any forward-looking statements. These forward looking statements should not be relied upon as representing our assessments as of any date subsequent to the date of this press release.

SOURCE DuoCort Pharma

From http://www.prnewswire.com/news-releases/duocort-pharmas-orphan-drug-plenadren-granted-european-marketing-authorization-for-adrenal-insufficiency-133348658.html

Endoscopic bilateral adrenalectomy (BLA) in patients with ectopic Cushing's syndrome

2011-11-10T13:42:00.001-05:00

Alberda WJ, van Eijck CH, Feelders RA, Kazemier G, de Herder WW, Burger JW; Surgical Endoscopy (Nov 2011)

BACKGROUND: Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing's syndrome (ECS) for whom surgical treatment of the responsible nonpituitary tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS.

METHODS: From 1990 to present, 38 patients were diagnosed and treated for ECS in the Erasmus University Medical Center, a tertiary referral center. Twenty-four patients were treated with BLA (21 endoscopic, 3 open), 9 patients were treated medically, and 5 patients could be cured by complete resection of the adrenocorticotropic hormone (ACTH)-producing tumor. The medical records were retrospectively reviewed and entered into a database. For evaluation of the efficacy of BLA, preoperative biochemical and physical symptoms were assessed and compared with postoperative data.

RESULTS: Endoscopic BLA was successfully completed in 20 of the 21 patients; one required conversion to open BLA. Intraoperative complications occurred in two (10%) patients, and postoperative complications occurred in three (14%) patients. Median hospitalization was 9 (2-95) days, and median operating time was 246 (205-347) min. Hypercortisolism was resolved in all patients. Improvements of hypertension, body weight, Cushingoid appearance, impaired muscle strength, and ankle edema were achieved in 87, 90, 65, 61, and 78% of the patients, respectively. Resolution of diabetes, hypokalemia, and metabolic alkalosis was achieved in 33, 89, and 80%, respectively.

CONCLUSION: Endoscopic BLA is a safe and effective treatment for patients with ectopic Cushing's syndrome.

From http://www.docguide.com/endoscopic-bilateral-adrenalectomy-patients-ectopic-cushings-syndrome?tsid=5

Corlux: Corcept Therapeutics Announces Third Quarter Results and Corporate and Development Update

2011-11-10T11:26:00.001-05:00

MENLO PARK, CA, Nov 07, 2011 (MARKETWIRE via COMTEX) -- Corcept Therapeutics IncorporatedCORT -1.58% , a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders, today reported financial results for the quarter ended September 30, 2011, and updated its corporate progress.

"Following the acceptance by the U.S. Food and Drug Administration (FDA) of our New Drug Application (NDA) for the use of our lead product candidate, Korlym(TM), in Cushing's Syndrome," said Joseph Belanoff, M.D., Chief Executive Officer of Corcept, "we continue to focus our efforts on building our commercial capabilities to support the launch of Korlym, if Korlym is approved by the FDA, in order to allow us to provide an important treatment option to patients suffering from Cushing's Syndrome."

Corporate and Development Highlights

--  Received notification in October 2011 that the FDA had accepted our proposed brand name, Korlym (formerly referred to as CORLUX(R)), for our lead product candidate in the treatment of endogenous Cushing's Syndrome.   --  Advanced our commercial launch preparations related to Korlym for the treatment of Cushing's Syndrome, including developing our internal infrastructure and engaging third-party vendors to provide market analytics and to support distribution and other logistical needs in the event Korlym is approved by the FDA.   --  Received notification in October 2011 that the European Commission had granted Korlym Orphan Designation for the treatment of endogenous Cushing's Syndrome (hypercortisolism) in the European Union (EU). Benefits of Orphan Drug Designation in the EU are similar to those in the U.S., but include ten years of marketing exclusivity in all 27 member states, free scientific advice during drug development, access to a centralized review process and a reduction or complete waiver of fees levied by the European Medicines Agency.   --  Enrolled additional patients in our double-blind placebo controlled Phase 3 trial of Korlym for the treatment of the psychotic features of psychotic depression.   --  Continued the clinical portion of our Phase 1b/2a multi-dose safety and proof of concept studies of CORT 108297, one of our selective GR-II antagonists.   --  Identified additional compounds from among our proprietary series of selective GR-II antagonists to advance toward an Investigational New Drug submission.

Third Quarter Financial Results

For the third quarter of 2011, Corcept reported a net loss of $6.4 million, or $0.08 per share, compared to a net loss of $7.1 million, or $0.10 per share, for the third quarter of 2010.

In the third quarter of 2011, research and development expenses decreased to $3.2 million from $5.2 million in the third quarter of 2010. This decrease in research and development expenses was due primarily to decreases in clinical trial costs related to drug-drug interaction and other NDA-supportive studies with Korlym, which were substantially completed in late 2010, and decreases in the clinical trial costs related to the Phase 1b/2a studies with CORT 108297. These decreases were partially offset by increased costs associated with the prosecution of our NDA for Korlym for the treatment of Cushing's Syndrome. General and administrative expenses increased to $3.2 million for the third quarter of 2011 from $1.9 million for the same period in 2010 due primarily to additional expenditures on commercialization activities for the potential launch of Korlym for Cushing's Syndrome.

Our cash balance as of September 30, 2011 was $45.9 million, up from $24.6 million at December 31, 2010. "We anticipate that our current cash balance is sufficient to fund the company through the end of 2012," said Charles Robb, the company's Chief Financial Officer.

Anticipated Activities for the Remainder of 2011

We continue to concentrate our efforts on advancing Korlym toward approval and commercialization for the treatment of Cushing's Syndrome. We also continue our efforts to be prepared to respond in a timely fashion to any questions posed by the FDA during the course of their review of our NDA.

"We are focused intently on developing the commercial and logistical capabilities we will need to make Korlym available to patients suffering from Cushing's Syndrome, should the FDA approve our drug for this indication," added Dr. Belanoff. "Korlym is the first step in unlocking the value of our scientific platform. The regulation of cortisol is a critical biological function; its dysregulation is equally critical in many important disease states. Our own research and research from increasing numbers of academic investigators point to the potential importance of cortisol antagonism in a wide variety of diseases. We believe our expanding library of selective cortisol antagonists may help address these unmet medical needs."

About Cushing's Syndrome

About Psychotic Depression

Psychotic depression is a serious psychiatric disorder that affects approximately three million people annually in the United States. It is more prevalent than either schizophrenia or bipolar I disorder. The disorder is characterized by severe depression accompanied by delusions, hallucinations or both. People with psychotic depression are approximately 70 times more likely to commit suicide than the general population and often require lengthy and expensive hospital stays. There is no FDA-approved treatment for psychotic depression.

About Weight Gain Caused by Antipsychotic Medications

The group of medications known as second-generation antipsychotics, including olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) and clozapine (Clozaril), are widely used to treat schizophrenia and bipolar disorder. All medications in this group are associated with treatment emergent weight gain of varying degrees and also carry warning labels relating to treatment emergent hyperglycemia and diabetes mellitus. There is no FDA-approved treatment for the weight gain associated with the use of antipsychotic medications.

About Korlym

About CORT 108297

CORT 108297 is a potent, selective antagonist of the cortisol (GR-II) receptor that we have discovered and for which Corcept owns worldwide intellectual property rights. In in vitro binding affinity and functional assays this compound has no affinity for the progesterone (PR), estrogen (ER), androgen (AR) or mineralocorticoid (GR-I) receptors.

About Corcept Therapeutics Incorporated

Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. The company has completed its Phase 3 study of Korlym for the treatment of Cushing's Syndrome, and has an ongoing Phase 3 study of Korlym for the treatment of the psychotic features of psychotic depression. Corcept also has a Phase 2 program for CORT 108297, a selective GR-II antagonist that blocks the effects of cortisol but not progesterone. Corcept has developed an extensive intellectual property portfolio that covers the use of GR-II antagonists in the treatment of a wide variety of psychiatric and metabolic disorders, including the prevention of weight gain caused by the use of antipsychotic medication, as well as composition of matter patents for our selective GR-II antagonists.

Statements made in this news release, other than statements of historical fact, are forward-looking statements, including, for example, statements relating to the potential benefit of Korlym for patients diagnosed with Cushing's Syndrome, Corcept's clinical development and research programs, the outcome of the FDA's review of our NDA filing, our estimates for our capital requirements and needs for additional financing, the introduction of Korlym and future product candidates, including CORT 108297, the ability to create value from Korlym or other future product candidates or our scientific platform and our commercialization plans. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances with respect to the cost, rate of spending, completion or success of clinical trials; financial projections may not be accurate; there can be no assurances that Corcept will pursue further activities with respect to the development of Korlym, CORT 108297, or any of its other selective GR-II antagonists. These and other risk factors are set forth in the Company's SEC filings, all of which are available from our website ( www.corcept.com ) or from the SEC's website ( www.sec.gov ). We disclaim any intention or duty to update any forward-looking statement made in this news release.

CORCEPT THERAPEUTICS INCORPORATED CONDENSED BALANCE SHEETS (in thousands)  September 30,  December 31, 2011           2010 -------------- -------------- (Unaudited)      (Note) ASSETS: Current assets: Cash and cash equivalents                    $       45,909 $       24,578 Other current assets                                    427            418 -------------- -------------- Total current assets                               46,336         24,996  Other assets                                               43            108 -------------- -------------- Total assets                               $       46,379 $       25,104 ============== ==============  LIABILITIES AND STOCKHOLDERS' EQUITY: Current liabilities: Accounts payable                             $        1,066 $          817 Other current liabilities                             1,647          3,043 -------------- -------------- Total current liabilities                           2,713          3,860  Total stockholders' equity                             43,666         21,244 -------------- --------------  Total liabilities and stockholders' equity $       46,379 $       25,104 ============== ==============  Note: Derived from audited financial statements at that date.  CORCEPT THERAPEUTICS INCORPORATED CONDENSED STATEMENTS OF OPERATIONS (in thousands, except per share amounts)  (Unaudited)  For the Three Months Ended   For the Nine Months Ended September 30,               September 30, --------------------------  -------------------------- 2011          2010          2011          2010 ------------  ------------  ------------  ------------  Operating expenses: Research and development*      $      3,228  $      5,224  $     14,355  $     14,286 General and administrative*          3,209         1,881         8,049         5,327 ------------  ------------  ------------  ------------ Total operating expenses               6,437         7,105        22,404        19,613 ------------  ------------  ------------  ------------  Loss from operations       (6,437)       (7,105)      (22,404)      (19,613)  Interest and other income, net                    3             4             3           758 Other expense                  (1)           (3)          (17)          (18) ------------  ------------  ------------  ------------ Net loss         $     (6,435) $     (7,104) $    (22,418) $    (18,873) ============  ============  ============  ============   Basic and diluted net loss per share  $      (0.08) $      (0.10) $      (0.27) $      (0.28) ============  ============  ============  ============ Shares used in computing basic and diluted net loss per share                 84,188        72,045        83,000        66,982 ============  ============  ============  ============  *Includes non-cash stock-based compensation of the following: Research and development     $        110  $         45  $        432  $        170 General and administrative           844           500         1,971         1,361 ------------  ------------  ------------  ------------ Total non-cash stock-based compensation  $        954  $        545  $      2,403  $      1,531 ============  ============  ============  ============

CONTACT: Charles Robb Chief Financial Officer Corcept Therapeutics 650-688-8783 Email Contact  www.corcept.com

SOURCE: Corcept Therapeutics

http://www2.marketwire.com/mw/emailprcntct?id=150008C85C40D638      http://www.corcept.com/

Today in Medical History

2011-11-08T01:04:00.001-05:00

Among the important early researchers in X-rays were Professor Ivan Pulyui, Sir William Crookes, Johann Wilhelm Hittorf, Eugen Goldstein, Heinrich Hertz, Philipp Lenard, Hermann von Helmholtz, Nikola Tesla, Thomas Edison, Charles Glover Barkla, Max von Laue, and Wilhelm Conrad Röntgen.

Wilhelm Röntgen
On November 8, 1895, Wilhelm Conrad Röntgen, a German physics professor, began observing and further documenting X-rays while experimenting with Lenard and Crookes tubes. Röntgen, on December 28, 1895, wrote a preliminary report "On a new kind of ray: A preliminary communication". He submitted it to the Würzburg's Physical-Medical Society journal.^[13] This was the first formal and public recognition of the categorization of X-rays. Röntgen referred to the radiation as "X", to indicate that it was an unknown type of radiation. The name stuck, although (over Röntgen's great objections), many of his colleagues suggested calling them Röntgen rays. They are still referred to as such in many languages, including German. Röntgen received the first Nobel Prize in Physics for his discovery.

There are conflicting accounts of his discovery because Röntgen had his lab notes burned after his death, but this is a likely reconstruction by his biographers.^[14] Röntgen was investigating cathode rays with a fluorescent screen painted with barium platinocyanide and a Crookes tube which he had wrapped in black cardboard so the visible light from the tube wouldn't interfere. He noticed a faint green glow from the screen, about 1 meter away. The invisible rays coming from the tube to make the screen glow were passing through the cardboard. He found they could also pass through books and papers on his desk. Röntgen threw himself into investigating these unknown rays systematically. Two months after his initial discovery, he published his paper.

Röntgen discovered its medical use when he saw a picture of his wife's hand on a photographic plate formed due to X-rays. His wife's hand's photograph was the first ever photograph of a human body part using X-rays.

Johann Hittorf
Physicist Johann Hittorf (1824 – 1914) observed tubes with energy rays extending from a negative electrode. These rays produced a fluorescence when they hit the glass walls of the tubes. In 1876 the effect was named "cathode rays" by Eugen Goldstein, and today are known to be streams of electrons. Later, English physicist William Crookes investigated the effects of electric currents in gases at low pressure, and constructed what is called the Crookes tube. It is a glass cylinder mostly (but not completely) evacuated, containing electrodes for discharges of a high voltage electric current. He found, when he placed unexposed photographic plates near the tube, that some of them were flawed by shadows, though he did not investigate this effect. Crookes also noted that his cathode rays caused the glass walls of his tube to glow a dull blue colour. Crookes failed to realise that it wasn't actually the cathode rays that caused the blue glow, but the low-level X-rays produced when the cathode rays struck the glass.

Ivan Pulyui
In 1877 Ukranian-born Pulyui, a lecturer in experimental physics at the University of Vienna, constructed various designs of vacuum discharge tube to investigate their properties.^[15] He continued his investigations when appointed professor at the Prague Polytechnic and in 1886 he found that that sealed photographic plates became dark when exposed to the emanations from the tubes. Early in 1896, just a few weeks after Röntgen published his first X-ray photograph, Pulyui published high-quality x-ray images in journals in Paris and London.^[15] Although Pulyui had studied with Röntgen at the University of Strasbourg in the years 1873-75, his biographer Gaida (1997) asserts that his subsequent research was conducted independently.^[15]

The first medical X-ray made in the United States was obtained using a discharge tube of Pulyui's design. In January 1896, on reading of Röntgen's discovery, Frank Austin of Dartmouth College tested all of the discharge tubes in the physics laboratory and found that only the Pulyui tube produced X-rays. This was a result of Pulyui's inclusion of an oblique "target" of mica, used for holding samples of fluorescent material, within the tube. On 3 February 1896 Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Edwin had treated some weeks earlier for a fracture, to the x-rays and collected the resulting image of the broken bone on gelatin photographic plates obtained from Howard Langill, a local photographer also interested in Röntgen's work.^[16]

Nikola Tesla
In April 1887, Nikola Tesla began to investigate X-rays using high voltages and tubes of his own design, as well as Crookes tubes. From his technical publications, it is indicated that he invented and developed a special single-electrode X-ray tube ^[17] ^[18], which differed from other X-ray tubes in having no target electrode. The principle behind Tesla's device is called the Bremsstrahlung process, in which a high-energy secondary X-ray emission is produced when charged particles (such as electrons) pass through matter. By 1892, Tesla performed several such experiments, but he did not categorize the emissions as what were later called X-rays. Tesla generalized the phenomenon as radiant energy of "invisible" kinds.^[19] ^[20] Tesla stated the facts of his methods concerning various experiments in his 1897 X-ray lecture ^[21] before the New York Academy of Sciences. Also in this lecture, Tesla stated the method of construction and safe operation of X-ray equipment. His X-ray experimentation by vacuum high field emissions also led him to alert the scientific community to the biological hazards associated with X-ray exposure.^[22]

Fernando Sanford
X-rays were first generated and detected by Fernando Sanford (1854-1948), the foundation Professor of Physics at Stanford University, in 1891. From 1886 to 1888 he had studied in the Hermann Helmholtz laboratory in Berlin, where he became familiar with the cathode rays generated in vacuum tubes when a voltage was applied across separate electrodes, as previously studied by Heinrich Hertz and Philipp Lenard. His letter of January 6, 1893 (describing his discovery as "electric photography") to The Physical Review was duly published and an article entitled Without Lens or Light, Photographs Taken With Plate and Object in Darkness appeared in the San Francisco Examiner.^[23]

Heinrich Hertz
In 1892, Heinrich Hertz began experimenting and demonstrated that cathode rays could penetrate very thin metal foil (such as aluminium). Philipp Lenard, a student of Heinrich Hertz, further researched this effect. He developed a version of the Crookes tube and studied the penetration by X-rays of various materials. Philipp Lenard, though, did not realize that he was producing X-rays. Hermann von Helmholtz formulated mathematical equations for X-rays. He postulated a dispersion theory before Röntgen made his discovery and announcement. It was formed on the basis of the electromagnetic theory of light (Wiedmann's Annalen, Vol. XLVIII). However, he did not work with actual X-rays.

Thomas Edison
Diagram of a water cooled X-ray tube. (simplified/outdated) In 1895, Thomas Edison investigated materials' ability to fluoresce when exposed to X-rays, and found that calcium tungstate was the most effective substance. Around March 1896, the fluoroscope he developed became the standard for medical X-ray examinations. Nevertheless, Edison dropped X-ray research around 1903 after the death of Clarence Madison Dally, one of his glassblowers. Dally had a habit of testing X-ray tubes on his hands, and acquired a cancer in them so tenacious that both arms were amputated in a futile attempt to save his life. "At the 1901 Pan-American Exposition in Buffalo, New York, an assassin shot President William McKinley twice at close range with a .32 caliber revolver." The first bullet was removed but the second remained lodged somewhere in his stomach. McKinley survived for some time and requested that Thomas Edison "rush an X-ray machine to Buffalo to find the stray bullet. It arrived but wasn't used . . . McKinley died of septic shock due to bacterial infection."^[24]

The 20th century and beyond
Before the 20th century until the 1920s, X-rays were generated in cold cathode tubes, called Crookes tubes. These tubes had to contain a small quantity of gas (invariably air) as a current will not flow in such a tube if they are fully evacuated. One of the problems with early X-ray tubes is that the generated X-rays caused the glass to absorb the gas and consequently the efficiency quickly falls off. Larger and more frequently used tubes were provided with devices for restoring the air, known as 'softeners'. This often took the form of small side tube which contained a small piece of mica – a substance that traps comparatively large quantities of air within its structure. A small electrical heater heats the mica and causes it to release a small amount of air restoring the tube's efficiency. However the mica itself has a limited life and the restore process was consequently difficult to control.

In 1904, John Ambrose Fleming invented the thermionic diode valve (vacuum tube). This used a heated cathode which permitted current to flow in a vacuum. This idea was quickly applied x-ray tubes, and heated cathode x-ray tubes, called Coolidge tubes, replaced the troublesome cold cathode tubes by about 1920.

Two years later, physicist Charles Barkla discovered that X-rays could be scattered by gases, and that each element had a characteristic X-ray. He won the 1917 Nobel Prize in Physics for this discovery. Max von Laue, Paul Knipping and Walter Friedrich observed for the first time the diffraction of X-rays by crystals in 1912. This discovery, along with the early works of Paul Peter Ewald, William Henry Bragg and William Lawrence Bragg gave birth to the field of X-ray crystallography. The Coolidge tube was invented the following year by William D. Coolidge which permitted continuous production of X-rays; this type of tube is still in use today.

ROSAT image of X-ray fluorescence of, and occultation of the X-ray background by, the Moon. The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis [1].

The X-ray microscope was invented in the 1950s.

The Chandra X-ray Observatory, launched on July 23, 1999, has been allowing the exploration of the very violent processes in the universe which produce X-rays. Unlike visible light, which is a relatively stable view of the universe, the X-ray universe is unstable, it features stars being torn apart by black holes, galactic collisions, and novas, neutron stars that build up layers of plasma that then explode into space.

An X-ray laser device was proposed as part of the Reagan Administration's Strategic Defense Initiative in the 1980s, but the first and only test of the device (a sort of laser "blaster", or death ray, powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was de-funded (though was later revived by the second Bush Administration as National Missile Defense using different technologies).