US FDA approves Novartis' Signifor for first medication to treat Cushing's disease

Basel

Monday, December 17, 2012, 16:00 Hrs  [IST]

 

The US Food and Drug Administration (FDA) has approved Novartis' Signifor (pasireotide) injection for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative. 

 

Signifor is the first medicine to be approved in the US that addresses the underlying mechanism of Cushing's disease, a serious, debilitating endocrine disorder caused by the presence of a non-cancerous pituitary tumour which ultimately leads to excess cortisol in the body.

 

This approval follows a unanimous recommendation from the FDA Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) in support of the use of Signifor.

 

"The FDA approval of Signifor for Cushing's disease brings a novel pituitary-directed therapy to patients with limited treatment options," said Hervé Hoppenot, president, Novartis Oncology. "Today's milestone reinforces Novartis' commitment to addressing unmet needs and advancing treatments for rare pituitary-related disorders."

 

Cushing's disease most commonly affects adults as young as 20 to 50 years and affects women three times more often than men. It may present with weight gain, central obesity, a round, red full face, severe fatigue and weakness, striae (purple stretch marks), high blood pressure, depression and anxiety. Cushing's disease can cause severe illness and death with mortality up to four times higher than in the healthy population.

 

The approval is based on data from PASPORT-CUSHINGS (PASireotide clinical trial PORTfolio - CUSHING'S disease), the largest randomized Phase III study to evaluate a medical therapy in patients with Cushing's disease. Results from the PASPORT-CUSHINGS study found that a decrease in mean urinary-free cortisol (UFC), the key measure of biochemical control of the disease, was sustained during the treatment period in most patients with a subset of patients reaching normal levels. The study also showed that certain clinical manifestations of Cushing's disease tended to improve.

 

"Patients with Cushing's disease may suffer from debilitating manifestations, and there are many serious health complications associated with the disease," said Mary Andrews, CEO and Co-Founder of the US non-profit, The MAGIC Foundation. "The FDA approval of Signifor offers the option of a medical therapy that may help certain patients with Cushing's disease."

 

In April 2012, the European Commission approved Signiforfor the treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed. Other worldwide regulatory filings for pasireotide for this use are also underway.

Signifor (pasireotide) is approved in the US for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative, and in the European Union for the treatment of adult patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.

 

For the treatment of Cushing's disease, Signifor 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 in Cushing's disease and acromegaly. Signifor is a multireceptor targeting somatostatin analog that binds with high affinity to four of the five somatostatin receptor subtypes (sst 1, 2, 3 and 5).

 

From http://pharmabiz.com/NewsDetails.aspx?aid=72752&sid=2

RARE Video Project

Global Genes | RARE Project would like your voice to be heard!

Share your home videos!

We are currently looking for your home videos that illustrate what life is like for rare disease patients and caregivers on this complex and often emotional journey.  This could be an assortment of moments that you’ve captured on your phone, a camera, or a digital recording device.  We want the key moments, the most beautiful, personal moments that represent not only the diseases, but you and your child(ren) as well.

A few examples of what we are looking for in these clips:

Births	In Pain	Overcoming
Birthdays	Sadness	Happiness
Hospital Visits	Loss	Laughter
Medicines	Struggle	Important Events
At Play	Tears	Family

Be creative, think outside the box.   Look for clips that are shot well, with nice light.  Give us variety!  Old footage, new footage, maybe even something your child has shot.  We want personal, private moments.  That is what will send the strongest message.

What are we going to do with this?

We are working with an award-winning filmmaking team to select submissions that will be compiled together to create a visual storyline of the years of your ongoing journey.  This is your chance to share the moments that you see and experience with a global audience.

This is your moment to be heard.

More information at http://globalgenes.org/rare-video-submission-form/

Cushing Syndrome Overview

Cushing’s syndrome (pronounced KOOSH-ingz SIN-drohm) is a condition that occurs when a person’s body tissues are exposed over time to too much of the hormone cortisol (pronouncedKAWR-tuh-sawl). The syndrome can be caused by taking certain medicines or, less commonly, it can be caused by noncancerous or cancerous tumors. Cushing’s syndrome includes a range of symptoms, but they can be treated and, in most cases, the syndrome can be cured. The NICHD is one of the many federal agencies that support and conduct research on the causes of Cushing’s syndrome, detection of its symptoms as soon as possible, and development of improved treatments.

For more information about this topic, select the Condition Information, Research Information, Clinical Trials, or Resources and Publications link in the menu on the left.

Fast Facts

Common Name

• Cushing's syndrome

Scientific Name

• Hyperadrenocorticism (pronounced HAHY-per-uh-dree-noh-KAWR-ti-siz-uhm)
• Hypercortisolism (pronounced HAHY-per-KAWR-ti-sol-iz-uhm)

Causes

The most common cause of Cushing’s syndrome is taking medication that contains the hormone cortisol. This leaves the body with more cortisol than it would normally contain from the natural production of cortisol.¹ Less commonly, a cancerous or noncancerous tumor in the body can cause too much cortisol production.²

Number of People Affected

Among 1 million people, two or three will develop endogenous (non-medicine-related) Cushing’s syndrome each year in the United States.³ Women are three times more likely than men to have the condition.⁴

Common Symptoms

The symptoms of Cushing’s syndrome vary, especially in mild cases, but patients may have some or most of the following¹:

• Upper-body obesity, with thin arms and legs
• A round, red face
• Skin problems, such as acne, reddish-blue streaks, or easy bruising
• Muscle and bone weakness, including backache
• Fat that collects between the shoulders
• Poor growth in children⁵

Common Treatments

In most cases Cushing’s syndrome can be cured. The treatment depends on what is causing the excess cortisol in the body.^6,7

Cushing’s syndrome can be treated by the following:

• Medication. If medication is to blame, a health care provider can reduce the dose or change the type of drug.
• Overproduction. If the body is making too much cortisol because of a tumor, treatments may include oral medication, surgery, radiation, or a combination of these approaches.

 

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1. Stewart P. M., & Krone, N. P. (2011). The adrenal cortex. In Kronenberg, H. M., Shlomo, M., Polonsky, K. S., & Larsen, P. R. (Eds.). Williams textbook of endocrinology (12th ed.) (chap. 15). Philadelphia, PA: Saunders Elsevier. [top]
2. Nieman, L. K., & Ilias, I. (2005) Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340-1346. PMID 16378774. [top]
3. Lindholm, J., Juul, S., Jørgensen, J. O. L, Astrup, J., Bjerre, P., Feldt-Rasmussen, U., et al. (2001). Incidence and late prognosis of Cushing’s syndrome: A population-based study. Journal of Clinical Endocrinology and Metabolism, 86(1), 117-123. PMID 11231987. [top]
4. Steffensen, C., Bak, A. M., Rubeck, K. Z., & Jørgensen, J. O. (2010). Epidemiology of Cushing’s syndrome. Neuroendocrinology, 92(Suppl 1), 1-5. PMID 20829610. [top]
5. Batista, D. L., Riar, J., Keil, M., & Stratakis, C.A. (2007). Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics, 120(3), e575-e586. [top]
6. Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., et al. (2008). The diagnosis of Cushing’s syndrome: An Endocrine Society clinical practice guideline. Retrieved April 8, 2012, fromhttp://www.endo-society.org/guidelines/final/upload/Cushings_Guideline.pdf (PDF - 510 KB). [top]
7. Boscaro, M., & Arnaldi, G. (2009). Approach to the patient with possible Cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism, 94(9), 3121. [top]

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Last Updated Date: 11/30/2012
Last Reviewed Date: 11/30/2012

From https://www.nichd.nih.gov/health/topics/cushing/Pages/default.aspx

Mifepristone: is there a place in the treatment of Cushing's disease?

Carmichael JD, Fleseriu M.

Source

Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA, john.carmichael@cshs.org.

Abstract

The purpose was to review the use of mifepristone in the treatment of Cushing's syndrome (CS) in the context of other recently published studies. We review the use of mifepristone, as published in the recent Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC). We also review the multiple case reports and case series of mifepristone use in CS. A review of other medications used in the treatment of Cushing's disease (CD), including pasireotide and cabergoline also provides context for the discussion of the role of mifepristone in the treatment of CD. The results show that the treatment of CD has been primarily surgical with medical therapy reserved for adjuvant therapy when primary treatment fails or other therapies require time for optimal efficacy. Two recent large prospective studies, using pasireotide and mifepristone provide new clinical insights to the medical treatment of CD in particular. Mifepristone has been used to treat excessive cortisol production by blocking the action of cortisol at the level of the glucocorticoid receptor. Until recently, the majority of clinical experience with mifepristone on the treatment of excess cortisol was derived from case reports and small case series. Based on the SEISMIC study, mifepristone was FDA approved for hyperglycemia associated with CS. In conclusion the role of mifepristone in the treatment of CD remains one of adjuvant therapy. Its place among other choices for medical therapy has yet to be firmly established and an evidenced-based approach toward the use of novel medications in the treatment of CD has not been made. Selection of medication depends on drug approval and availability in individual countries and requires cautious assessment of potential adverse effects, consideration of patient comorbidities, and efficacy.

 

PMID: 23192246 [PubMed - as supplied by publisher]

Magic Foundation Cushing's Conference, 2013

Dates:

Friday, April 19, 2013 - Registration and exhibits-4 PM to 9 PM

Saturday, April 20, 2013 - Educational segments

Sunday, April 21, 2013 – Educational Segments

Monday, April 22, 2013 – Departure or visiting sites of Las Vegas

 

Registration: $155 for members $190 for non-members (includes 1 yr membership)

Registration fee includes: Thursday exhibits and refreshments, Friday continental breakfast, and lunch and Saturday continental breakfast and lunch. An optional dinner will be held on Friday night for $25.00 per person.

For additional attendees in your family there will be no registration fee but a $75 charge for inclusion of the segments and meals. (optional dinner on Friday night not included in the $75 fee)

 

Accommodations:

Tuscany Suites & Casino (Just off the Las Vegas Strip)

255 East Flamingo Rd

Las Vegas, NV

Guest room costs: 

Friday and Saturday $105 per guestroom, single or double occupancy ($117.60 w/tax)

Sunday thru Thursday $65 per guestroom, single or double occupancy ($72.80 w/tax)

Reservations made after March 20, 2013 at noon will be charged the prevailing room rate if accommodations are available. To book your room you must call Tuscany Room Reservations, 877-887-2261 and ask for MAGIC Foundation group rates. You will be required to provide a major credit card for the first night’s room and tax deposit, which will be charged in order to guarantee accommodations.

Cushing's Syndrome after Hemodialysis for 21 Years

Koki Mise, Yoshifumi Ubara, Keiichi Sumida, Rikako Hiramatsu, Eiko Hasegawa, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Junichi Hoshino, Naoki Sawa, Masaji Hashimoto, Takeshi Fujii, Hironobu Sasano and Kenmei Takaichi

- Author Affiliations

Nephrology Center (K.M., Y.U., K.S., R.H., E.H., M.Y., N.H., T.S., J.H., N.S., K.T.), Surgical Gastroenterology (M.H.), Pathology (T.F.), and Okinaka Memorial Institute for Medical Research (Y.U., K.T.), Toranomon Hospital, 1058470 Tokyo, Japan; and Department of Pathology (H.S.), Tohoku University Graduate School of Medicine, 9800872 Sendai, Japan

Address all correspondence and requests for reprints to: Koki Mise, M.D., Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatu-ku, Kawasaki-shi, Kanagawa-ken, 213-0015, Japan. E-mail: kokimise@yahoo.co.jp.

Abstract

Context: Hyperkalemia and weight loss are critical clinical problems for hemodialysis patients. There have been no documented reports of adrenal Cushing's syndrome with central obesity and hypokalemia in a hemodialysis patient.

Objective: The aim of the study was to report a patient with Cushing's syndrome after chronic hemodialysis, review the published literature, and discuss the significance of hypokalemia and obesity in anuric hemodialysis patients from the perspective of cortisol metabolism.

Patient: A 61-yr-old woman who had been on hemodialysis for 21 yr presented with persistent hypokalemia and central obesity. In 2002, her dry weight was 48.1 kg, but thereafter she gained weight to 60 kg.

Results: Adrenal Cushing's syndrome was diagnosed from endocrinological findings such as increased cortisol secretion without a circadian rhythm and suppression of plasma ACTH. Spironolactone was administered (25 to 50 mg/d), and her serum potassium became normal. Then, left adrenalectomy was performed by laparoscopic surgery. The resected specimen contained a well-circumscribed adrenal adenoma expressing P450c17. After surgery, hypokalemia improved gradually without medication, and her weight gain stopped.

Conclusions: This is the first documented case of adrenal Cushing's syndrome in a patient on long-term hemodialysis, although several authors have reported a relation between hypokalemia and primary hyperaldosteronism in hemodialysis patients.

From The Journal of Clinical Endocrinology and Metabolism

Happy Thanksgiving!

What are YOU thankful for this year?

Evaluation of depression, quality of life and body image in patients with Cushing’s disease

Nilufer Alcalar, Sedat Ozkan, Pinar Kadioglu, Ozlem Celik, Penbe Cagatay, Baris Kucukyuruk and Nurperi Gazioglu

 

• Download PDF (220.3 KB)
• View HTML

Abstract

The aim of this study was to evaluate patients with Cushing’s disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls.

Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups.

When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.

Keywords  Cushing’s disease – Pituitary surgery – Depression – Quality of life – Body image

Fulltext Preview

 

 

Share Your Cushing's Story on TV

A new series on Lifetime TV's daily morning talk show, The Balancing Act is featuring Cushings Syndrome.

Producers are looking for patients to share their stories in the comments of their landing page for Unveiling the Mystery: Rare and Genetic Diseases!

http://www.thebalancingact.com/rare/

Robotic versus laparoscopic adrenalectomy in obese patients

Surgical Endoscopy, 10/23/2012 Clinical Article

Aksoy E et al. – The aim of this study is to compare perioperative outcomes of RA versus LA in obese patients. The study did not show any difference in perioperative outcomes between RA and LA in obese patients. These results suggest that the difficulties in maintaining exposure and dissection in obese patients nullify the advantages of robotic articulating versus rigid laparoscopic instruments in adrenal surgery.

Methods

• Between 2003 and 2012, 99 obese (BMI ≥ 30 kg/m2) patients underwent adrenalectomy at a tertiary academic center.
• Of these, 42 patients had RA and 57 had LA. The perioperative outcomes of these patients were compared between the RA and LA groups.
• Data were collected from a prospectively maintained, institutional review board approved database.
• Clinical and perioperative parameters were analyzed using Student t and χ2 tests.
• All data are expressed as mean ± standard error of the mean.

Results

• The groups were similar in terms of age, gender, and tumor side.
• Body mass index was lower in the robotic versus laparoscopic group (35.4 ± 1.0 vs. 38.8 ± 0.8 kg/m2, respectively, p = 0.01).
• Tumor size (4.0 ± 0.4 vs. 4.3 ± 0.3 cm, respectively, p = 0.56), skin–to–skin operative time (186.1 ± 12.1 vs. 187.3 ± 11 min, respectively, p = 0.94), estimated blood loss (50.3 ± 24.3 vs. 76.6 ± 21.3 ml, respectively, p = 0.42), and hospital stay (1.3 ± 0.1 vs. 1.6 ± 0.1 days, respectively, p = 0.06) were similar in both groups.
• The conversion to open rate was zero in the robotic and 5.2 % in the laparoscopic group (p = 0.06).
• The 30–day morbidity was 4.8 % in the robotic and 7 % in the laparoscopic group (p = 0.63).

From MDLinx

A Quarter of a Century

I had my one, and only, pituitary surgery on this date in 1987.  Of course, I was trying to get a diagnosis for several years before that.

I know it's hard to get a diagnosis now - imagine how hard it was over 30 years ago - before the Internet, Facebook, Twitter, message boards, chatrooms.  No online support - no support anywhere. 

Finding any information possible at the Public Library.  Days that you feel like death warmed over, heading out to the library to Xerox medical articles you don't understand, poring over them at home, trying to find any kernel of hope for what you have.  Then trying to convince doctors when your family doesn't even believe you.

Finally, a doctor believes you...but he's the wrong kind of doctor so he sends you away.  Another year goes by.  The endo recommends surgery but there are only 3 possibilities anywhere.  NIH - close by and free, Montreal - they speak French - and San Francisco.  

After a diagnosis, 6 weeks of inpatient testing at the NIH.

From my bio at http://www.cushings-help.com/maryos_story.htm

 

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn't walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with. While I was at NIH, I was gaining about a pound a day!

The MRI still showed nothing, so they did a Petrosal Sinus Sampling Test. That scared me more than the prospect of surgery. (This test carries the risk of stroke and uncontrollable bleeding from the incision points.) Catheters were fed from my groin area to my pituitary gland and dye was injected. I could watch the whole procedure on monitors. I could not move during this test or for several hours afterwards to prevent uncontrolable bleeding from a major artery. The test did show where the tumor probably was located. Also done were more sophisticated dexamethasone suppression tests where drugs were administered by IV and blood was drawn every hour (they put a heplock in my arm so they don't have to keep sticking me). I got to go home for a weekend and then went back for the surgery - the Transsphenoidal Resection. I fully expected to die during surgery (and didn't care if I did) so I signed my will and wrote last letters to those I wanted to say goodbye to. During the time I was home just before surgery, a college classmate of mine (I didn't know her) did die at NIH of a Cushing's-related problem. I'm so glad I didn't find out until a couple months later!

November 3, 1987, the surgeon, Dr. Ed Oldfield, cut the gum above my front teeth under my upper lip so there is no scar. He used tiny tools and microscopes. My tumor was removed successfully. In some cases (not mine) the surgeon uses a plug of fat from the abdomen to help seal the cut. Afterwards, I was in intensive care overnight and went to a neurology ward for a few days until I could walk without being dizzy. I had some major headaches for a day or two but they gave me drugs (morphine) for those. Also, I had cotton plugs in my nostrils. It was a big day when they came out. I had diabetes insipidus (DI) for a little while, but that went away by itself - thank goodness!

I had to use a foam product called "Toothies" to brush my teeth without hitting the incision. Before they let me go home, I had to learn to give myself an injection in my thigh. They sent me home with a supply of injectible cortisone in case my level ever fell too low (it didn't). I was weaned gradually off cortisone pills (scary). I now take no medications. I had to get a Medic Alert bracelet. I will always need to tell medical staff when I have any kind of procedure - the effects of my excess cortisone will remain forever.

I went back to the NIH for several follow-up visits of a week each where they did all the blood and urine testing again. After a few years NIH set me free. Now I go to my "outside" endocrinologist every year for the dexamethasone suppression test, 24-hour urine and regular blood testing.

As I get further away from my surgery, I have less and less chance that my tumor will grow back. I have never lost all the weight I gained and I still have the hair on my chin but most of my other symptoms are gone. I am still and always tired and need a nap most days. I do not, however, still need to take whole days off just to sleep.

I consider myself very lucky that I was treated before I got as bad as some of the others on my floor at NIH but think it is crazy that these symptoms are not taken seriously by doctors.

 

 

Adrenal Insufficiency - Female Patient found Unconscious with Syringe Nearby

Crew’s misdiagnosis of drug overdose could have cost patient her life

Kimberly Doran | From the October 2012 Issue |

A call comes in to 9-1-1 dispatch. “Help” is all that’s spoken before the operator hears the phone hit the floor. The 9-1-1 dispatcher calls back only to get a busy signal. Police and EMS are dispatched for a well-being call.

On arrival, the front door is found to be slightly ajar. The crew knocks, but there’s no reply. They find a young woman  lying on the floor, naked, and in a pool of vomit. A syringe with an unknown substance is on the ground nearby. Suspecting a drug overdose, the EMS crew begins treating the patient for this condition. The patient is unconscious with emesis around her head and face. Her vital signs are blood pressure 60/45, heart rate of 130 bpm and respiratory rate of 10.

The patient shows no signs of waking. The crew clears the airway and administers oxygen. An IV is established, and the patient is readied for transport. As the crew leaves the scene, one of the medics turns to shut the door and sees a vial under a chair. He retrieves it and notes that the label says Solu-Cortef (a glucocorticoid). He bags it for the emergency department (ED). Following his instinct, he looks around the area for medications and finds two bottles. One is labeled dexamethosone and the other is labeled fludrocortisone. He takes his findings and rushes out the door into the awaiting ambulance. During transport, the patient continues to deteriorate.

The medic administers 0.5 mg of narcan and a 500mL bolus of normal saline with no response. He radios ahead to let the hospital know that they’re en route. Now questioning the original diagnosis of drug overdose, he reports the medications he found on the scene in hopes it will help the receiving physician determine the cause of the patient’s condition.

Arrival at the ED
On arrival to the ED, the medic hands over the loaded syringe containing 2mL of unidentified solution, as well as the empty vial of Solu-Cortef and the bottles of dexamethosone and fludrocortisones.

As the crew arrives at the hospital, the ED physician meets the crew and informs them that he’s familiar with the medications. He says they're all used for people who have various forms of adrenal insufficiency (AI). The symptoms seen in this patient coincide with life-threatening adrenal crisis. The physician administers 100 mg of Solu-Cortef via IV and within minutes, the patient rouses. In 30 minutes, she can explain what happened in the desperate moments before her crisis.

Adrenal Insufficiency
Adrenal Insufficiency (AI) is a life-threatening in which the body is unable to produce enough cortisol to sustain life. In other words, their adrenal cortex is “asleep.” People suffering from AI take daily cortisol/glucocorticoid steroid replacement because whatever adrenal function is depleted. These patients are glucocorticoid dependent. In times of injury, dehydration, illness or surgery, they require an injection of Solu-Cortef. Solu-Cortef contains both glucocorticoid and mineralocorticoid properties, helping the body to compensate during a stress event.

The adrenal medulla (inside of the adrenal gland) secretes epinephrine and norepinephrine. The adrenal cortex (outer layer of the adrenal gland) secretes cortisol and aldosterone. Cortisol, a glucocorticoid, is often called the “stress” hormone. One of cortisol's functions is elevating blood glucose levels in times of stress. It also functions as a mediator for several inflammatory pathways.

Absence of cortisol can result in hypotension, hypoglycemia and death. Aldosterone, a mineralocorticoid, is responsible for the regulation of sodium and water. Absence of aldosterone can result in hypotension and electrolyte imbalance. AI in the prehospital setting may be difficult to recognize in the absence of a good history, including medications, to point providers in the cause of the problem. Two life-threatening conditions associated with AI include hypotension and hypoglycemia.

If not managed, these two conditions are life threatening. Prehospital treatment should include management of the patient’s airway, vascular access and fluid resuscitation. If blood glucose levels are low, the patient should receive dextrose per local protocol. It’s important to complete a thorough physical assessment and obtain a complete patient history before treating patients with this condition. Providers may confuse patients having an adrenal crisis with drug overdose patients because of their similar symptoms. Although AI is rare, it should still be considered as a potential diagnosis.

Authors’ note: Parts of the above case are taken from a true story. However, the difference is that there was no syringe on the floor, no vial under the chair and no one found the medications. The patient was treated with charcoal and diagnosed as a drug-overdose patient. She likely would have died, but her mother charged into the ED and expressed the need for Solu-Cortef. Security was called, but luckily someone listened, researched and called the patient’s treating physician. The patient was treated and released. 

From Journal of Emergency Medical Services

Use of ketoconazole in the treatment of Cushing's syndrome

An older, but still useful, abstract:

J Clin Endocrinol Metab. 1986 Dec;63(6):1365-71.

 

Loli P, Berselli ME, Tagliaferri M.

Abstract

The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period.

Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another.

The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.

From http://www.ncbi.nlm.nih.gov/pubmed/3023421

 

Cushing's, The "Gift" that Keeps on Giving

I had an eye doctor appointment yesterday. No problems, just a routine check, maybe update my contacts to a newer version.

I was completely not ready when the doctor said "cataracts" to me. Say what? I'm not that old.  He mentioned a few other things like macular degeneration but that was less distressing to me somehow than the Cataract Word.

They're not bad yet.  They're slow growing.  I won't need to do anything about them for 7-8 years.  AARRGGHH!

My mother is waiting for her cataract surgery.  Maybe we can do this together, a bonding thing.

When I got home and all the eye drops had worn off, I looked at the brochures he had given me.  One of the symptoms was light insensitivity.  So that explains why I have trouble first thing in the morning and it hurts to open my eyes and other bright lights can be painful.  It's nice to be validated but...

Then, I turned the page to find contributing factors and came upon the word STEROIDS.  Not again!  Almost all the problems in my life start with the word steroids.  I did a search of the Cushing's Help boards for "Cataracts" and came up with 84 entries.  How could I have missed this?

From Cigna.com:

The eye conditions glaucoma and cataracts also may occur in Cushing's syndrome. In Cushing's disease (tumors on the pituitary gland), your field of vision can be affected. You may have loss of side, or peripheral, vision.

Surgical Versus Medical Treatment for Cushing Disease, the New and the Old

Surgical Versus Medical Treatment for Cushing Disease the New and the Old

Novartis launches pasireotide for Cushing’s disease

Cushing’s disease patients for whom surgery is not a viable option have a new treatment alternative, in the form of the orphan medicine pasireotide.

Launched by Novartis as Signifor, the drug is a somatostatin analogue that blocks the release of excessive adrenocorticotropic hormone, thus reducing cortisol levels.

Pasireotide is available as a solution for injection that should be self-administered by the patient twice a day. Patients should be informed how to inject the drug under the skin and that using the same injection site for two consecutive injections is not recommended.

After two months of treatment, patients’ blood cortisol levels are measured to determine whether treatment should continue, and at what dose (see Panel).

Patients who experience adverse reactions may need to temporarily lower their twice-daily dose, with decrements of 0.3mg suggested in the summary of product characteristics.

Pasireotide is indicated for adults only and is contraindicated for use by patients with severe liver impairment. It should be used with caution by patients who are taking medicines that prolong the QT interval, and clinical monitoring of heart rate is recommended for patients receiving pasireotide concomitantly with bradycardic drugs.

Dose adjustments of ciclosporin, insulin and antidiabetic medicines may be required if these are taken concomitantly with pasireotide.

The EMA granted marketing authorisation for pasireotide in April 2012 on the basis that, although the proportion of patients who responded to treatment in clinical trials was small (around 15 per cent), a partial response may be of benefit to patients whose condition cannot be managed with surgery.

Product information

Class: Somatostatin analogue

Dose: 0.6mg by subcutaneous injection twice daily. After two months of treatment, patients whose urinary free cortisol levels have reduced can continue treatment for as long as they experience a benefit. The dose can be increased to 0.9mg as long as the 0.6mg dose is well tolerated. Patients who have not responded after two months of treatment should be considered for discontinuation. The recommended twice-daily dose for patients with moderate liver impairment is 0.3mg initially, up to a maximum of 0.6mg.

NHS list price: 60 x 0.3mg/ml, £2,800; 60 x 0.6mg/ml, £3,240; 60 x 0.9mg/ml, £3,240

Legal category: POM 

From PJOnline

 

Interview with Dr. Amir H. Hamrahian

Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. 

His clinical interests include pituitary and adrenal disorders.

Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland.

In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists.

Some of the questions answered in this interview October 1, 2012 include (not in this order):

 

• Can you tell me a little about you endocrine practice and your experience with Cushing’s as part of your practice?
• What are some of biggest challenges you have in treating Cushing’s?
• How do you test cyclical/episodic Cushing's?
• Can someone with cyclical/episodic Cushing's take Korlym?
• I know that Cushing's patients (those that currently have it and/or are cured/in remission can have healthy pregnancies with the right care. How do doctors support this process? Through an endocrinologist and a high-risk ob/gyn? And what sort of treatment is given throughout the pregnancy to prevent hypercortisolism.
• While many patients have a successful long term result from surgery, there are just as many that don’t. Do you find that there are any particular challenges treating patients with Cushing’s disease when pituitary surgery has already failed?
• As I understand, you were an investigator in the clinical trial for Korlym, and I think you treated 4 patients. Did these patients all have a previous surgery that had failed?
• Many Cushing’s patients are trying to understand if they might be candidates for Korlym treatment, can you tell me a little history about the types of patients you treated with Korlym?  I hear that not all patients can take Korlym. Which type of patient should not take it?
• Every past treatment for Cushing’s has always had the goal of lowering cortisol levels, but Korlym doesn’t lower cortisol levels, can you explain how it works?
• So, how do you judge success for a Cushing’s patient on Korlym?
• I lost copious amounts of hair while on Korlym, is this a known side effect?
• Are there any long term reproductive implications due to use of Korlym?

Listen to this interview at http://www.blogtalkradio.com/cushingshelp/2012/10/01/dr-amir-hamrahian-answers-our-questions or to the podcast by searching for Cushings in the iTunes podcast area or click here: http://itunes.apple.com/podcast/cushingshelp-cushie-chats/id350591438

 

 

Dr. Redmond, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Redmond, Johns Hopkins Pituitary Day

Meeting Created: September 29, 2012, 12:07 PM
Baltimore

radiotherapy indications

• recurrence
• persistent hormone secretion
• inoperable

tumors repair more slowly than normal cells

IMRT (Intensity modulated radiation therapy)

stereotactic radiosurgery

• more radiation beams, greater precision
• very small tumors 1-5 treatments
• larger 5-6 weeks
• 150-300 radiation beams target area
• Synergy machine
• for divided course of radiation

cyberknife for 1-5 treatments

• short-term 
• fatigue
• hair loss
• tearful or dry eye
• headache
• nausea
• long-term
• cataracts
• decreased hormones
• damage to vision (rare)
• second tumor (rare)
• tumor control 90%
• hormone normalization 60%

Dr. Ishii, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Ishii, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 11:41 AM

Baltimore

patient participation is most important

waiting for other doctor's computer

________________________

nasal issues pst-op

nose is good corridor to pituitary, endoscope

nose: smells, filters air, air flow

instruments

post-op care

problems

pain

smell

activity

CSF leak

tired

Dr. Gary Gallia, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Gary Gallia, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 11:11 AM

Baltimore

pituitary lesions, surgery

micro

macro

large

giant

confined to sella, outside sella

surgical risk

CSF leak

damage

incomplete

DI

recovery variable

29 YO f with Cushing's

cheerio is 13mm

cortisol below 2 after surgery

Dr. Barbara Craven, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Barbara Craven, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:49 AM

Baltimore

Cushing's, cyclical

dietician

started noticing problems early 1990s

1993 people told her she had a red face, 3 little kids

mood swings, depression

gaining weight

1997, Christmas, puffy face, tired, red face, no energy

internist, bloodwork

Epstein-barr virus high, mono.

bone biopsy - rule out cancer. bones too soft, fractured hip in 2 places falling from horse

1998, mole growing on back, removed.  then more and more, every 2 weeks mole removed, all pre-cancerous, melanoma

immune system compromised

2000, racing heart, aching in chest, cardiologist, testing for heart, beta blocker for BP

2001, getting pudgier, weight increasing, tai kwondo, still couldn't lose weight.  800 calories per day, still gaining, shrunk, hair started falling out

dermatologist, no problem.  blood test.  took cortisol and DHEA

endocrinologist (not pituitary), dex suppression test positive

MRI of pit and adrenals.

Dr. Salvatori

hard to diagnose, 9 more months of testing, UFCs, blood, symptoms but not positive tests, salivary was positive

swollen feet, chest hurting, sleeping in recliner, memory became terrible, 

depressed, anxiety, panic attacks, miserable, couldn't fly due to anxiety. Agreed to surgery

removed whole pituitary, only found soft spots.  didn't find pituitary tumor.  found 3mm ACTH tumor

hormones still messed up even though in remission

2006 feeling better

even now hormones can get out of balance. DI.  DDVAP

sodium got low. stopped DDVAP.  drink a lot of water now.

stick with it, don't give up.

Dr. Craven was our guest in the Guest Speakers Interview series.

Dr. Subramarnian, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Subramarnian, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:28 AM

Baltimore

neuro-opthalmology

diseases and surgery of the eye

vision loss

peripheral field loss

double vision

kinetic perimetry

5 case studies

craniopharingioma

can find pituitary tumor through vision

Johns Hopkins Pituitary Day

MEETING NOTES : Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:04 AM

Baltimore

Dr. Gary Wand

pituitary slides, growth hormone, ACTH

prolactin, breast milk

anterior, Oxytocin

ADH, vassopressin, sodium, diabetes insipidus

micro/macro adenoma

secretory vs nonfunctional

normal MRIs compared to tumors

compression of pituitary

• thyroid: energy, weight, mental function, skin, temp
• sex hormones, drive and function
• adrenal: light-headed, fatigue, appetite, weight, GI

Compression of surrounding structures like optic nerve

Excess hormones: prolactin, GH or cortisol

34% prolactin

36% nonfunctioning

nonfunctioning

signs from compression

diminished pituitary: sex hormones, thyroid, adrenal

visual defects

headaches

no medication

no hormone excess

surgery

prolactinoma

medication

some surgery

rarely radiation

growth hormone - acromegaly

surgery

medication

radiation

cortisol, Cushing's

symptoms

surgery

medications

tsh tumor, similar symptoms to Grave's

surgery

meds

other pit disorders

Transsphenoidal Microsurgery for Cushing’s Disease: Initial Outcome and Long-Term Results

Transsphenoidal Microsurgery for Cushing’s Disease: Initial Outcome and Long-Term Results

Dr. Amir Hamrahian Answers Our Questions About Cushing's and Korlym

October 1, 2012 at 6:30 PM eastern, Dr. Amir Hamrahian will answer our questions about Cushing's, pituitary or adrenal issues and Korlym (mifepristone) in BlogTalkRadio at http://www.blogtalkradio.com/cushingshelp/2012/10/01/dr-amir-hamrahian-answers-our-questions

 

You may listen live at the link above.  The episode will be added to the Cushing's Help podcast after the show is over.  Listen to the podcasts by searching for Cushings in the iTunes podcast area or click here: http://itunes.apple.com/podcast/cushingshelp-cushie-chats/id350591438

 

Dr. Hamrahian has had patients on Korlym for about 4 years.

 

Please submit your questions below or email them to CushingsHelp@gmail.com before Sunday, September 30.

 

From Dr. Hamrahian's bio at http://my.clevelandclinic.org/staff_directory/staff_display.aspx?doctorid=3676

 

 

Amir Hamrahian, M.D. 

(216) 444-6568

Appointed: 2000

Request an Appointment

Department:Endocrinology, Diabetes and Metabolism

Location:Cleveland Clinic Main Campus
Mail Code F20 
9500 Euclid Avenue
Cleveland, OH 44195

Appointment:(216) 444-6568

Desk:(216) 445-8538

Fax:(216) 445-1656

Department:Brain Tumor and Neuro-Oncology Center

Location:Cleveland Clinic Main Campus
Mail Code R20 
9500 Euclid Avenue
Cleveland, OH 44195

Appointment:(216) 444-6568

Desk:(216) 445-8538

Fax:(216) 445-1656

Surgeon:

No

Treats:

Adults Only

Research & Publications †

( † Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Biographical Sketch

Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. 

His clinical interests include pituitary and adrenal disorders.

Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland.

In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists.

Education & Fellowships

Fellowship - University Hospitals of Cleveland

Endocrinology
Cleveland, OH USA
2000

Residency - University of North Dakota Hospital

Internal Medicine
Fargo, ND USA
1997

Medical School - Hacettepe University School of Medicine

Ankara Turkey
1991

Certifications

• Internal Medicine
• Internal Medicine- Endocrinology, Diabetes & Metabolism

Specialty Interests

Cushing syndrome, acromegaly, pheochromocytoma, prolactinoma, primary aldosteronism, pituitary disorders, adrenal tumor, adrenocortical carcinoma, MEN syndromes, adrenal disorders

Awards & Honors

• Best Doctors in America, 2007-2008 

Memberships

• Pituitary Society
• Endocrine Society
• American Association of Clinical Endocrinologists
• American Medical Association

Treatment & Services

• Radioactive Iodine Treatment
• Thyroid Aspiration
• Thyroid Ultrasound

Specialty in Diseases and Conditions

• Acromegaly
• Addison’s Disease
• Adrenal disorders
• Adrenal insufficiency
• Adrenal Insufficiency and Addison’s Disease
• Adrenal Tumors
• Adrenocortical Carcinoma
• Adrenoleukodystrophy (ALD)
• Amenorrhea
• Androgen Deficiency (Low Testosterone)
• Androgen Excess
• Calcium Disorders
• Carcinoid Syndrome
• Conn's Syndrome
• Cushing's Syndrome
• Empty sella
• Erectile Dysfunction
• Familial Multiple Endocrine Neoplasia
• Fasting hypoglycemia
• Flushing Syndromes
• Galactorrhea
• Goiter
• Growth hormone deficiency
• Growth hormone excess
• Gynecomastia
• Hirsutism
• Hyperaldosteronism
• Hyperandrogenism
• Hyperprolactinemia
• Hypertension - High Blood Pressure
• Hyperthyroidism
• Hypocalcemia
• Hypoglycemia
• Hypogonadism
• Hypoparathyroidism
• Hypophysitis
• Hypopituitarism
• Hypothyroidism
• Mastocytosis
• Menopause, Male
• Menstrual Disorders
• Paget's Disease
• Panhypopituitarism
• Parathyroid Cancer
• Parathyroid Disease and Calcium Disorders
• Pheochromocytoma
• Pituitary Cysts
• Pituitary Disorders
• Pituitary stalk lesions
• Pituitary Tumors
• Premenstrual Syndrome (PMS)
• Primary Hyperaldosteronism
• Primary Hyperparathyroidism
• Prolactin Excess States
• Prolactinoma
• Thyroid and pregnancy
• Thyroid Cancer
• Thyroid Disease
• Thyroid Nodule