Thursday, March 31, 2011

Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease

To the Editor:

 

Cushing's disease, which is caused by an adrenocorticotropin-secreting pituitary adenoma, is associated with increased morbidity and mortality.1 Currently, there is no effective medical therapy for Cushing's disease. However, recent studies identified the somatostatin-receptor subtype 5 and dopamine-receptor subtype 2 as potential therapeutic targets in Cushing's disease.2

Pasireotide is a new somatostatin analogue that binds with high affinity to somatostatin-receptor subtypes 1, 2, and 3, and it especially has high-affinity binding to somatostatin-receptor subtype 5.3 In a recent 15-day pilot study, pasireotide normalized the excretion of urinary free cortisol in 17% of patients with Cushing's disease.4 Cabergoline, a dopamine-receptor subtype 2 agonist, can also normalize levels of urinary free cortisol in Cushing's disease, but this effect is often not maintained during prolonged treatment.5 Because the majority of adrenocorticotropin-secreting adenomas simultaneously express somatostatin-receptor subtype 5 and dopamine-receptor subtype 2,2 we hypothesized that pasireotide and dopamine-receptor subtype 2 agonists may have synergistic effects in the treatment of Cushing's disease. Finally, ketoconazole suppresses cortisol production at the adrenal level through inhibition of steroidogenic enzymes.1 In a prospective, open-label, multicenter trial, we used a stepwise approach for the medical treatment of Cushing's disease, with pasireotide as the initial form of treatment and the sequential addition of cabergoline and low-dose ketoconazole.

Seventeen patients with Cushing's disease (mean age, 45.7 years; 13 women) were included in an 80-day trial with normalization of levels of urinary free cortisol as the main outcome measure. All patients began treatment with 100 μg of pasireotide subcutaneously three times daily; this dose was increased to 250 μg subcutaneously three times daily at day 15 if the level of urinary free cortisol had not normalized. At day 28, cabergoline was added to pasireotide at a dose of 0.5 mg every other day (this dose was increased to 1.0 mg every other day after 5 days and 1.5 mg every other day after 10 days) if the level of urinary free cortisol remained elevated. If the level of urinary free cortisol had not normalized at day 60, ketoconazole was added at a dose of 200 mg thrice daily.

Pasireotide monotherapy induced sustained normalization of the level of urinary free cortisol in 5 of 17 patients (29%) (Figure 1A  
(Figure 1A Levels of Urinary Free Cortisol after Treatment for Cushing's Disease.).

 

The addition of cabergoline normalized urinary free cortisol values in an additional 4 of 17 patients (24%). At day 60, a total of 8 of 17 patients (47%) still had elevated urinary free cortisol levels with pasireotide–cabergoline combination therapy, although a trend toward normalization of levels of urinary free cortisol was observed in all but one patient, with a mean (±SE) decrease of 48±6% in the level of urinary free cortisol. The addition of low-dose ketoconazole induced biochemical remission in six of these eight patients at day 80, increasing the number of patients with a complete response to 88%.

Figure 1B shows the effects of 28 days of pasireotide monotherapy in relation to the severity of hypercortisolism at baseline. In patients with mild hypercortisolism and those with severe hypercortisolism, significant reductions in the level of urinary free cortisol of up to 67% of the baseline value were observed.

Along with the normalization of the level of urinary free cortisol, the clinical features of Cushing's disease improved, including a decrease in body weight (−2.4±0.9 kg), waist circumference (−4.2±1.3 cm), systolic blood pressure (−12±4 mm Hg), and diastolic blood pressure (−8±3 mm Hg). Adverse events included disturbance of glucose homeostasis (glycated hemoglobin level, 5.8±0.2% to 6.7±0.3%; P<0.01) and a decrease in levels of serum type I insulin-like growth factor to below the lower limit of the normal range in 9 of 17 patients.

Thus, stepwise medical therapy for Cushing's disease with the use of three drugs that differentially target somatostatin-receptor subtype 5 and dopamine-receptor subtype 2 receptors in the adrenocorticotropin-secreting adenoma and steroidogenic enzymes in the adrenal cortex resulted in biochemical control in nearly 90% of patients.

Richard A. Feelders, M.D., Ph.D.
Christiaan de Bruin, M.D., Ph.D.
Erasmus Medical Center, Rotterdam, the Netherlands

Alberto M. Pereira, M.D., Ph.D.
Johannes A. Romijn, M.D., Ph.D.
Leiden University Medical Center, Leiden, the Netherlands

Romana T. Netea-Maier, M.D., Ph.D.
Ad R. Hermus, M.D., Ph.D.
Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands

Pierre M. Zelissen, M.D., Ph.D.
University Medical Center Utrecht, Utrecht, the Netherlands

Ramona van Heerebeek
Frank H. de Jong, Ph.D.
Aart-Jan van der Lely, M.D., Ph.D.
Wouter W. de Herder, M.D., Ph.D.
Leo J. Hofland, Ph.D.
Steven W. Lamberts, M.D., Ph.D.
Erasmus Medical Center, Rotterdam, the Netherlands

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

5 References

From http://www.nejm.org/doi/full/10.1056/NEJMc1000094

(Cushing's patient) Zumba becomes more than a dance, it's a way of coping

By Christine Young
Intermountain Catholic

RIVERTON - Karla Padilla began what she calls a Zumba journey as a way of reclaiming her Latino identity and later learned it became a way of coping with and healing from Cushing's disease.


Padilla, a member of Saint Andrew Parish, started doing Zumba after her husband, Duane, suggested it. She did not expect Zumba to become a career. She graduated with a bachelor's degree in public relations from the University of Utah and earned a master's degree in organizational management from the University of Phoenix. She worked as a human resource manager at Marriott International for eight years before deciding to become a full-time mother to her 4-year-old daughter, Anavaleska, whom she adopted from Guatemala. She and her husband also have a son, Carlos, 10.


"I was really inspired by my Zumba instructor and became a certified teacher," Padilla said. "This was a huge step for me because I had a difficult time growing up as a Latina in Utah. I always loved to dance, but was never selected for dance clubs in school. Once I started Zumba and heard the Latin music, my Latino roots were awakened and I gained a new self-confidence. Zumba is dancing the salsa, cumbia, merengue, reggaeton and belly dancing blended together with the bhangra, samba, Brazilian or African dances. These dances are put together in a routine, or a powerful combination, where you exercise in disguise because you feel like you are dancing. It is a way of building friendships and camaraderie with others while dancing."


Zumba also helped Padilla heal from Cushing's disease after she was diagnosed in June 2009. Cushing's disease is a disorder resulting from prolonged exposure of the body's tissues to high levels of the hormone cortisol, which is released from the pituitary gland.


"We need cortisol, but when it is in excess, it becomes dangerous because it eats away at our muscles and bones," said Padilla. "It also causes acne, dry skin, thin arms and a large upper body, fatigue, unexplained bruises and an occasional moon face."


Padilla said she and her family became one with her community to help them get through the trial of this disease; race and religion did not matter. She had to have brain surgery to help heal from the condition. "If I did not have the surgery, my body would have deteriorated," she said. "With two young children and a husband, I had to do something. My faith got me through this. God put special people in my life like my neighbors, who are mostly members of the Latter-day Saints faith, to help with my children and instructors to take over and hold my classes until I could return. My mom and my husband prayed with me to ask for guidance, especially the day we thought I was going to have to have more surgery."


Padilla also started meditating, visualizing her body healing and reading the Bible. "Luke became important to me because he spoke about being strong," Padilla said. "All of this with prayer and Zumba helped me to the point that the doctors were amazed. They expected me to be big and overweight and in bed without any energy. I told them I run and do Zumba. The music is happy and helps me let go of my problems. I give them to God. I realized exercise is so important for my mental and physical well-being. I also learned I needed to slow down and enjoy life and my family, which was difficult after having a career."

From http://www.icatholic.org/article/zumba-becomes-more-than-a-dance-its-a-way-of-coping-6271073

Tuesday, March 29, 2011

(Cushing's patient) Durham woman plans prom for ill, disabled youth

A Durham woman waiting on a double lung transplant is trying to help inspire young adults and teens in a similar situation. 

After seeing a teen in a wheelchair turned away at a dress shop, Naomi Sjostedt-Smith, 28, decided to throw her own prom for teens with disabilities and illnesses that might keep them from a typical school dance.

The "Dance Like No One is Watching Gala" is for people ages 14 to 21 who are too ill or have life-altering, emotional disabilities that might prevent them from attending a regular prom.

In high school, Sjostedt-Smith was diagnosed with Cushing's disease, which causes fluid to build up in her brain and lungs. The disease kept her from going to her own prom. 

"I remember how hard it was as a teen to not be able to do the same things that my friends were doing," she said. 

Planning the May 27 event has been difficult for Sjostedt-Smith, who has been waiting for a year for a double lung transplant. She has seizures and is assisted by a service dog. Her mother is also battling terminal breast cancer. 

"What better person to organize and help with this than somebody that knows what they are going through?" she said. 

Though the date is set, the group has yet to find a venue. Sjostedt-Smith said she had been speaking with one venue, but it burned down.

The group is also seeking caterers, evening gowns, tuxedos and the help of any vendors able to donate services.

"We are working on a budget of zero," Sjostedt-Smith said. "We’re working on a budget of compassion."

From http://www.wral.com/news/local/noteworthy/story/9326227/

(Clinical Trial) Versartis starts test of growth hormone therapy

Versartis Inc. started a Phase I clinical trial of a treatment for growth hormone deficiency.

The Mountain View company is testing the safety and efficacy of VRS-317, a once monthly form of recombinant human growth hormone meant to be easier to use than current daily treatments.

A Phase I trial is typically done with just a handful of patients to make sure a treatment is safe, although data is also collected on how well a treatment works. This test will use about 50 patients in the United States and Europe.

Jeffrey Cleland, who started Versartis, is its CEO.

From http://www.bizjournals.com/sanfrancisco/news/2011/03/28/versartis-growth-hormone-test.html

Pituitary Adenomas

Pituitary adenomas are common benign tumors of the pituitary gland. It is said that up to 10% of people will have a pituitary adenoma (which might never have caused a problem) by the time of their death. Some tumors secrete one or more hormones in excess. Such so-called secretory pituitary adenomas are usually found due to hormonal imbalances that affect bodily functions. They may be relatively small when detected.

People can develop pituitary adenomas at any age. Most pituitary adenomas are in the front part (anterior lobe) of the pituitary gland.

pituitary macroadenoma pre-op
Pre-op image of pituitary macroadenoma
pituitary macroadenoma post-op
Post-op image of pituitary macroadenoma

Types of pituitary adenomas:

There are multiple types of adenomas, classified by size and whether they produce hormones.

Secreting tumors, functioning tumors, or endocrine-active tumors
About 50% of adenomas produce too much of one of the hormones. These adenomas are called secreting tumors, functioning tumors or endocrine-active tumors.

Non-functioning or endocrine-inactive pituitary tumors
Some secreting tumors produce more than one type of hormone, causing hypeprolactinemia, acromegaly or Cushing's disease. Non-secreting pituitary tumors do not make extra hormones. They are also called non-functioning or endocrine-inactive pituitary tumors.

Pitutary adenomas have specific signs and symptoms that are primarily related to the endocrinopathies produced by hypersecretion.

  • The prolactin-secreting pituitary adenomas are the most common, and account for approximately 30% of all pituitary tumors. The clinical findings are galactorrhea and reproductive dysfunction.
  • The endocrinopathy of excess growth hormone results in enlargement of the extremities, face and the soft tissues, producing a characteristic appearance called acromegaly. Acromegaly can be associated with hypertension, diabetes mellitus and cardiovascular disease. Further, aromegaly is associated with decreased life expectancy.
ACTH Producing Tumor (Cushing&rsquo;s Disease)
ACTH Producing Tumor
(Cushing’s Disease)
Growth Hormone Producing Tumor (Acromegaly)
Growth Hormone Producing Tumor
 (Acromegaly)

prolactinoma
a coronal image demonstrates a
prolactinoma on the left side of
the pituitary gland

Prolactinoma: prolactin-secreting pituitary adenoma

Prolactinoma is a type of pituitary tumor that produces prolactin. The prolactin hormone stimulates milk production from the breasts. Prolactinomas may present with visual symptoms due to compression of the optic chiasm if the tumor is large. Prolactin levels in the blood help to make the diagnosis as these levels can be very high. The levels of prolactin are useful to monitor the success of treatment (prolactin levels decrease after treatment).

Microadenoma: <10mm

A pituitary adenoma that is smaller than 10 mm in diameter (about three-fourths of an inch across) is called a microadenoma.

Macroadenoma: >10mm

A pituitary adenoma equal to or larger than 10 mm is called a macroadenoma.

Pre-operative images of patient with non-functional pituitary macroadenoma
pre-op non-functional macroadenoma pre-op non-functional macroadenoma
Post-operative images of patient with non-functional pituitary macroadenoma who underwent endonasal transphenoidal endoscopic-assisted resection
post-op non-functional macroadenoma post-op non-functional macroadenoma

Symptoms of an adenoma:

The most common symptoms include:

  • Headaches
  • Vision problems that cannot be easily explained
  • Menstrual cycle changes in women
  • Mood swings or behavior changes
  • Erectile dysfunction
  • Weight change

Diagnosis of an adenoma:

Blood and urine tests to measure hormone levels and medical imaging provide the best means of diagnosing pituitary tumors. Diagnosistic imaging may include a high-resolution, T1 weighted, gadolinium enhanced MRI. In addition, blood and urine tests to obtain endocrine diagnostics may be peformed to establish basal levels of PRL, GH, IGF-1, free thyroxine, cortisol, and testosterone (in males) levels.

Treatment of an adenoma:

Specific treatment for adenomas is coordinated by a neurosurgeon and endocrinologist (hormonal disorder specialist) on the Pituitary Tumor team. Treatment may include surgery, including surgical removal via a procedure called endonasal transphenoidal endoscopic surgery, medical therapy, radiation therapy, hormone therapy, and/or observation.

For more information, contact the Johns Hopkins Pituitary Tumor Center at 410-955-GLAN (4526).

From http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/pituitary_center/pituitary-tumor/types/pituitary-adenoma.html

Wednesday, March 23, 2011

Adult Growth Hormone Deficiency: Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency

Nicholas A. Tritos, Susan L. Greenspan, Donna King, Amir Hamrahian, David M. Cook, Peter J. Jönsson, Michael P. Wajnrajch, Maria Koltowska-Häggstrom and Beverly M. K. Biller

Neuroendocrine Unit (N.A.T., B.M.K.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Medicine (S.L.G.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260; Department of Endocrinology, Diabetes, and Metabolism (A.H.), Cleveland Clinic, Cleveland, Ohio 44195; Department of Endocrinology (D.M.C.), Oregon Health & Science University, Portland, Oregon 97239; KIMS Medical Outcomes (P.J.J., M.K.-H.), Pfizer Endocrine Care, 191 90 Sollentuna, Sweden; and Pfizer Inc. (D.K., M.P.W.), New York City, New York 10017

Address all correspondence and requests for reprints to: Nicholas A. Tritos, M.D., D.Sc., Neuroendocrine Unit, Massachusetts General Hospital, Zero Emerson Place, Suite 112, Boston, Massachusetts 02114. E-mail: ntritos@partners.org.

Context: GH deficiency (GHD) is associated with low bone mineral density (BMD). Risk factors for lower BMD in this GHD population have not been fully elucidated. In particular, there are limited published data in GH-naïve subjects.

Objective: The objective of the study was to identify endocrine correlates of low BMD in treatment-naïve adult GHD subjects.

Design: This was a retrospective analysis of data extracted from the (Pfizer International Metabolic Study) KIMS database.

Setting: The study was an international epidemiological survey of more than 15,000 adult GHD patients from 31 countries.

Patients: A total of 1218 subjects with stringently defined GHD of adult onset (641 women and 577 men) who were GH naïve and had BMD measured in the posterior anterior lumbar spine and femoral neck by dual-energy X-ray absorptiometry.

Main Outcome Measures: Variables associated with standardized BMD (sBMD) in adult-onset GHD were examined.

Results: In the LS, body mass index (r = 0.13, P < 0.01), unreplaced sex steroid deficiency (r = –0.17, P < 0.0001), and corticotropin deficiency (r = –0.11, P < 0.01) were independently associated with sBMD. In the FN, age (r = –0.19, P < 0.0001), female gender (r = –0.18, P < 0.0001), body mass index (r = 0.21, P < 0.0001), and decreased IGF-I SD scores (r = 0.10, P < 0.001) were independently associated with sBMD.

Conclusions: Hormone variables associated with lower sBMD in patients with adult-onset GHD include unreplaced sex steroid deficiency and corticotropin deficiency in the LS and lower IGF-I SDS in the FN.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2662v1

Sunday, March 20, 2011

I Was Diagnosed with a Pituitary Tumor…Now What?

Join Johns Hopkins neurosurgeon and surgical director of the Pituitary Center, Alfredo Quinones-Hinojosa, M.D., for a free online seminar about what people diagnosed with a pituitary brain tumor, their family members and caregivers should know about this condition, the latest treatment options available and what to expect after treatment.

DATE/TIME:
April 5, 2011 - 7 p.m. to 8 p.m. (EST)

REGISTRATION & MORE INFO:
www.hopkinsmedicine.org/healthseminars

US Residents: Register here
International Residents: Register here

Friday, March 18, 2011

Thinking about Kidney Cancer again...


This month is Kidney Cancer Awareness month so yesterday, for St. Patrick's day, I wore one of my kidney cancer awareness shirts with the image above.

I've been thinking a bit about my cancer lately because it seems to be tied up with Sue's death, at least in my mind. Five years ago this month she died from lung cancer. Five years ago next month, I found out I had kidney cancer.

I need to make an appointment with my endo (Dr. Salvatori). Since it will be 5 years, he says I can go back on growth hormone but I'll have to weigh that very carefully.

Did the GH help/contribute to my cancer in the first place? Did it even help me with my post-Cushing's issues? Would my kidney cancer surgeon even agree to let me take GH again? it might harm my remaining kidney.

When my kidney was removed, my left adrenal was, too, causing problems for my post-op Cushing's issues. Today, this news item came up in my Google Alerts - so I joined the http://urotoday.com website to read the whole article.
Routine adrenalectomy is unnecessary during surgery for large and/or upper...
UroToday
We evaluated the radiographic and pathological incidence of adrenal involvement in patients undergoing renal surgery for renal cell carcinoma 7 cm or greater. Patients who underwent renal surgery for tumors 7 cm or greater between 1999 and 2008 were...
I sure wish that they had known that back "in my day" and I still had that adrenal gland.

A day late for this signature but I'll use it anyway since the color works :)

Thursday, March 17, 2011

In the UK? Medical research volunteers wanted

A medical market research company called Semantics, in London, is looking for a total of 5 people with Growth hormone deficiency: these can be either adults who self-inject or the parents/guardians of children/teenagers.

We are also looking for 3 people with Acromegaly: either self-injecting or not.

The aim of the study is to assess the usability of a range of 6 prototypes for a new range of platform injection devices. During the sessions, participants will be asked to perform a series of tasks with the device.

The location of the interviews is in Hammersmith and we can schedule respondents at various times in the first two weeks of April. Once you contact us we can accommodate the exact time to fit your needs and you will be sent exact location details after that.
£60 will be paid to each participating individual.

Note: This is not a clinical trial. Respondents will only be asked to interact with certain features of the device and express their subjective feedback. They will not be asked to inject any drug into the body and there will be no actual medication in use.

Please contact: Urte Jakimaviciute (Project Coordinator)
Direct Line: 0208 326 5613
Mobile: 07545 501 623
Email: urte.j@semantics-mr.com

From http://www.pituitary.org.uk/content/view/570/105/

Effects of Once-Weekly Sustained-Release Growth Hormone: A Double-Blind, Placebo-Controlled Study in Adult Growth Hormone Deficiency

 The Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2010-2819

Beverly M. K. Biller, Hyi-Jeong Ji, Hyunji Ahn, Conrad Savoy, E. Christine Siepl, Vera Popovic, Mihail Coculescu, Josefine Roemmler, Catalin Gavrila, David M. Cook and Christian J. Strasburger

Massachusetts General Hospital (B.M.K.B.), Boston, Massachusetts 02114; LG Life Sciences, Ltd. (H.-J.J., H.A.), Seoul 150-721, Korea; Biopartners, GmbH (C.S., E.C.S.), CH-6340 Baar, Switzerland; Institute of Endocrinology (V.P.), HU-11000 Belgrade, Serbia; Institute of Endocrinology (M.C.), C.I. Parhon, 011863 Bucharest, Romania; University of Munich (J.R.), 80336 Munchen, Germany; SANA Medical Center (C.G.), 011025 Bucharest, Romania; Oregon Health and Science University (D.M.C.), Portland, Oregon 97239; and Division of Clinical Endocrinology (C.J.S.), Department of Medicine, Campus Charite, Mitte, 10117 Berlin, Germany

Address all correspondence and requests for reprints to: Beverly M. K. Biller, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: bbiller@partners.org.

Background: A sustained-release recombinant human GH formulation, LB03002, has been recently developed, with pharmacokinetics and pharmacodynamic activity appropriate for once-weekly administration. LB03002 is a long-acting GH that is administered once a week by sc injection.

Objective: This study evaluated efficacy and safety of LB03002 in adult patients with GH deficiency.

Patients and Methods:
A total of 152 patients were randomized to receive LB03002 or placebo once weekly for 26 wk. Changes in body composition were evaluated from DXA (dual-energy x-ray absorptiometry). IGF-I was assessed at each study visit. Safety was assessed from adverse events, glucose homeostasis, and antibody development.

Results: IGF-I increased significantly (P < 0.001) with LB03002 and remained unchanged with placebo. Mean fat mass (FM) decreased by 1.052 kg [95% confidence interval (CI) = –1.614 to –0.491] in the LB03002 group vs. an increase of 0.570 kg (95% CI = –0.205–1.345) in the placebo group; treatment difference was 1.622 kg (95% CI = –2.527 to –0.717; P < 0.001). FM change was mainly due to decreased trunk fat. Least square mean treatment difference was 1.032 kg (95% CI = –1.560 to –0.515; P < 0.001). LBM (lean body mass) was significantly increased with LB03002 vs. placebo (least square mean difference was 1.393 kg; 95% CI = 0.614–2.171; P < 0.001). No concerning safety issues arose during the study.

Conclusions: Weekly GH replacement with the sustained-release preparation LB03002 in adults significantly reduced FM over 6 months and was well tolerated.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2819v1

Tuesday, March 15, 2011

(Book) Cushing's Disease

Series: Endocrine Updates, Vol. 31

Swearingen, Brooke; Biller, Beverly M. K. (Eds.)

1st Edition., 2011, 378 p. 33 illus., 7 in color., Hardcover

ISBN: 978-1-4614-0010-3

Not yet published. Available: August 15, 2011

In Cushing’s Disease, leading authorities in the field offer a thorough review of the pathogenesis, diagnostic algorithm and treatment options for this complex disease.   Beginning with a fascinating history of Cushing's disease that outlines its historical significance to both endocrinology and neurosurgery, the book goes onto  to cover the full range of important issues, including the molecular pathogenesis of Cushing’s,  anatomic pathology,  the diagnosis of Cushing's syndrome,  the differential of pseudo-Cushing's syndromes,  hypercortisolemia, surgical removal of the corticotroph adenoma, post-operative management and assessment of remission, radiotherapeutic options,  and the exciting developments in medical therapy.   In addition, the book also addresses  Cushing's disease in the pediatric population, given that its clinical manifestations and impact on growth can be severe;  silent corticotroph adenomas as a distinct clinical entity;  diagnosis and management of Cushing's disease during pregnancy, bilateral adrenalectomy, and, finally, the long-term psychological manifestations of hypercortisolemia.   Comprehensive and an invaluable addition the literature, Cushing’s Disease is an essential reference for enhancing diagnosis and treatment of this debilitating disorder.

 

Content Level » Professional/practitioner

Keywords » Nelson's syndrome - Pituiitary imaging - adenomas - radiation

Related subjects » Internal Medicine - Surgery

Table of contents 

Preface

 

Contributors

 

Chapter 1: Cushing's Disease: An Historical Perspective.

Chapter 2: Molecular Biology of Cushing’s Disease.

Chapter 3: Pathology of Cushing’s Disease.

Chapter 4: Clinical Diagnosis of Cushing’s Syndrome.

Chapter 5: Pseudo-Cushing’s Syndrome.

Chapter 6: Cyclical Cushing’s Disease.

Chapter 7: Differential Diagnosis of Cushing’s Syndrome.

Chapter 8: Radiologic Imaging Techniques in Cushing’s Disease.

Chapter 9: Surgical Treatment of Cushing’s Disease.

Chapter 10: Postoperative Management and Assessment of Cure.

Chapter 11: Radiation Therapy in the Management of Cushing’s Disease.

Chapter 12: Medical Management of Cushing’s Disease.

Chapter 13:  Recurrent Cushing’s Disease

Chapter 14: Diagnosis and Treatment of Pediatric Cushing’s Disease.

Chapter 15: Silent Corticotroph Adenomas.

Chapter 16: Cushing’s Syndrome in Pregnancy.

Chapter 17: Nelson’s Syndrome: Corticotroph Tumor Progression after Bilateral Adrenalectomy in Cushing’s Disease.

Chapter 18: Psychosocial Aspects of Cushing’s Disease.

Index

From http://www.springer.com/medicine/internal/book/978-1-4614-0010-3

Book explains adrenal dysfunction

Adrenal Glands

Another dysfunction

Are You Tired and Wired?” (Hay House, $24.95, Amazon price, $16.47)

Simultaneous feelings of exhaustion and being “keyed up” characterize early adrenal dysfunction, the subject of nurse practitioner Marcelle Pick’s self-help book. The adrenal glands are responsible for providing the fight-or-flight hormones in response to stress. If they’re under-producing, that’s Addison’s disease, and if they’re overproducing, that’s Cushing’s syndrome. “But if your adrenal imbalance is less extreme — as is true for hundreds of thousands of U.S. women — your practitioner is unlikely to recognize your condition,” Pick writes. She suggests a 30-day plan to solve adrenal dysfunction, including dietary supplements, exercise, stress-reduction techniques and, the biggie, an adrenal-friendly diet with regular meal times and no processed foods.

From http://www.washingtonpost.com/national/book-explains-adrenal-dysfunction-vegan-magazine-applauds-herbivore-heroes/2011/02/24/ABKaGxV_story.html

Monday, March 14, 2011

Cushing's Syndrome due to a Pancreatic Neuroendocrine Tumor Metastatic to the Ovaries

Summary

We report the case of a 36-year-old woman with Cushing's syndrome caused by a malignant unresectable neuroendocrine carcinoma of the pancreas that developed bilateral ovarian metastases 7 years after diagnosis.

In November 2001, because of abdominal pain and jaundice, the patient underwent radiological investigations and exploratory laparotomy that demonstrated the presence of a 3-cm mass of the head of the pancreas, infiltrating the superior mesenteric vein, associated with enlargement of multiple abdominal lymph nodes and with a liver nodule. Histological examination of one lymph node and of the liver nodule demonstrated the presence of metastases from a well-differentiated neuroendocrine carcinoma showing corticotropin immunoreactivity.

A few months later, the patient started to show the clinical symptoms of Cushing's syndrome and underwent steroid-blocking ketoconazole therapy. The clinical endocrine picture was controlled until the end of 2008, when the endocrine symptoms of the Cushing's syndrome worsened and bilateral ovarian tumors appeared. Hysteroannexectomy was performed and ovarian tumors were found to be metastases from a well-differentiated neuroendocrine carcinoma with morphological and immunohistochemical features overlapping those observed in 2002.

The clinical situation worsened and the patient died in November 2009. The clinical aspects and the problems in the differential diagnosis are discussed.

Affiliation

Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100, Varese, Italy, stefano.larosa@ospedale.varese.it.

Journal Details

Name: Endocrine pathology
ISSN: 1559-0097
Pages:

Links

From http://www.bioportfolio.com/resources/pmarticle/155008/Cushing-s-Syndrome-Due-To-A-Pancreatic-Neuroendocrine-Tumor-Metastatic-To-The.html

High prevalence of subclinical hypercortisolism in patients with bilateral adrenal incidentalomas: a challenge to management

Authors: Vassiliadi, Dimitra A.; Ntali, Georgia; Vicha, Eirini; Tsagarakis, Stylianos

Source: Clinical Endocrinology, Volume 74, Number 4, April 2011 , pp. 438-444(7)

Abstract:

Summary Objective  The prevalence of subclinical hypercortisolism (SH) in unilateral incidentalomas (UI) has been extensively studied; however, patients with bilateral incidentalomas (BI) have not been thoroughly investigated. We therefore aimed to describe the characteristics of patients with BI compared to their unilateral counterparts. The surgical outcome in a small number of patients is reported.

Design  Observational retrospective study in a single secondary/tertiary centre. Patients  One hundred and seventy-two patients with adrenal incidentalomas (41 with BI).

Measurements  Morning cortisol (F), ACTH, dehydroepiandrosterone sulphate (DHEA-S), midnight F, 24-h urine collection for cortisol (UFC), low-dose dexamethasone suppression test (LDDST), fasting glucose, insulin, and oral glucose tolerance test (OGTT). Primarily, SH was defined as F-post-LDDST>70 nmol/l and one more abnormality; several diverse cut-offs were also examined.

Results  No difference was noted in age, body mass index, or prevalence of diabetes and impaired glucose tolerance between patients with UI and those with BI. Patients with BI had higher F-post-LDDST (119·3 ± 112·8 vs 54·3 ± 71·5 nmol/l, P < 0·001) and lower DHEA-S (1·6 ± 1·5 vs 2·5 ± 2·3 μmol/l, P = 0·003) but similar UFC, ACTH and midnight F levels, compared to UI. SH was significantly more prevalent in BI (41·5%vs 12·2%, P  < 0·001). Fourteen patients were operated on; four underwent bilateral interventions. In 10 patients, unilateral adrenalectomy on the side of the largest lesion resulted in significant improvement in F-post-LDDST (P = 0·008) and a decrease in midnight F (P = 0·015) levels.

Conclusions  Subclinical hypercortisolism is significantly more prevalent in bilateral incidentaloma patients, posing great dilemmas for its optimum management.

Document Type: Research article

DOI: 10.1111/j.1365-2265.2010.03963.x

Publication date: 2011-04-01

From http://www.ingentaconnect.com/content/bsc/cend/2011/00000074/00000004/art00005

Saturday, March 12, 2011

I can't believe it's been 5 years since we lost Sue :(

It's been another year. Not a day goes by that I don't miss Sue.

I'm sure that many of the new folks here never got to meet her, but you would go well to go back and read some of her old posts. She was always so encouraging to all of us.

RIP, Sue

View PostMaryO, on 12 March 2007 - 11:19 AM, said:

When I opened up my PDA this morning, I saw the reminder that this is the anniversary of Sue's passing. She was such a good friend to so many here and so many Cushies world wide.

We miss you, Sue!

From http://www.cushings-help.com/memoriam_koziol.htm

CUSH Founding President, Sue Ann Koziol (SuziQ)

CUSH Founding President, Sue Ann Koziol (SuziQ)

Sue was born in Michigan on August 08, 1946 and passed away on March 12, 2006 at the age of 59.

She was a very special friend to Cushies world-wide. We will remember her always.

There was an online memorial for Sue during the Cushing's Awareness Day Medical Forum in Oklahoma, April 5-8, 2006. For more information, please visit this topic on the message boards

To light a candle or post a tribute for Sue, please go here: http://suziq.memory-of.com

To read more about Sue's journey, please click here: http://cushings.invisionzone.com/index.php?showtopic=14655

Did King Henry the VIII Have Cushing's?

King Henry VIII's Madness Explained

By Emily Sohn
Fri Mar 11, 2011 08:35 AM ET

THE GIST

  • Henry VIII may have had two rare medical conditions that could explain both his health issues later in life and the miscarriages of two of his wives.
  • An X-linked genetic disease might have caused Henry to become paranoid and anxious after his 40th birthday.
  • An unusual blood type might have caused the bodies of his wives to attack their fetuses.

Among a long list of personality quirks and historical drama, Henry VIII is known for the development of health problems in mid-life and a series of miscarriages for two of his wives. In a new study, researchers propose that Henry had an X-linked genetic disorder and a rare blood type that could explain many of his problems.

By suggesting biological causes for significant historical events, the study offers new ways to think about the infamous life of the notorious 16th-century British monarch, said Catarina Whitley, a bioarchaeologist who completed the research while at Southern Methodist University.

"What really made us look at Henry was that he had more than one wife that had obstetrical problems and a bad obstetrical history," said Whitley, now with the Museum of New Mexico. "We got to thinking: Could it be him?"

Plenty of historians have written about Henry's health problems. As a young man, he was fit and healthy. But by the time of his death, the King weighed close to 400 pounds. He had leg ulcers, muscle weakness, and, according to some accounts, a significant personality shift in middle age towards more paranoia, anxiety, depression and mental deterioration.

Among other theories, experts have proposed that Henry suffered from Type II diabetes, syphilis, an endocrine problem called Cushing's syndrome, or myxedema, which is a byproduct of hypothyroidism.

All of those theories have flaws, Whitley said, and none address the monarch's reproductive woes. Two of his six wives -- Ann Boleyn and Katherine of Aragon -- are thought to have suffered multiple miscarriages, often in the third trimester.

To explain those patterns, Whitley and colleague Kyra Kramer offer a new theory: Henry may have belonged to a rare blood group, called Kell positive. Only 9 percent of the Caucasian population belongs to this group.

When a Kell positive man impregnates a Kell negative woman, there is a 50 percent chance of provoking an immune response in the woman's body that attacks her developing fetus. The first baby of a Kell positive father and Kell negative mother is usually fine. But some of the baby's blood will inevitably get into the mother's body -- either during development or at birth, leading her to produce antibodies against the baby's Kell antigens.

As a result, in subsequent pregnancies, babies may suffer from extra fluid in their tissues, anemia, jaundice, enlarged spleens, or heart failure, often leading to miscarriage between about 24 and 28 weeks of pregnancy.

Ann Boleyn is a classic example of this pattern, Whitley said. According to some accounts (and there is still much dispute about the details, including how many pregnancies there actually were), Elizabeth -- Anne's first daughter with Henry -- was born healthy and without complications. But her second and third pregnancies miscarried at about month six or seven.

Katherine of Aragon carried as many as six pregnancies. Only her fifth led to the birth of a live and health baby, a daughter named Mary.

In addition to Henry's problematic blood type, the researchers propose that he also had a rare genetic disorder called McLeod syndrome. Carried on the X-chromosome, the disease generally affects only men and usually sets in around age 40 with symptoms including heart disease, movement disorders and major psychological symptoms, including paranoia and mental decline.

The disease could explain many of Henry's physical ailments, the researchers propose. It could also explain why he may have become more despotic as he grew older and why he shifted from supporting Anne to having her beheaded.

"This gives us an alternative way of interpreting Henry and understanding his life," Whitley said. "It gives us a new way to look at the reasons he changed."

Without any genetic evidence, however, there's no way to know for sure whether the new theories are right, said Retha Warnicke, a historian at Arizona State University and author of The Rise and Fall of Anne Boleyn: Family Politics at the Court of Henry VIII.

Other conditions could explain the miscarriages, she said. Until the late 19th-century, midwives did not wash their hands. And in Henry's time, up to half of all children died before age 15.

As for Henry's woes, dementia could explain his personality shifts, she added. Lack of exercise -- after an active youth -- combined with a hearty appetite could have led to his obesity and related ills.

"Could is the big word," Warnicke said. "It's an interesting theory and it's possibly true, but it can't be proven without some clinical evidence, and there is none."

From http://news.discovery.com/history/henry-viii-blood-disorder-110311.html


By Philippa Gregory
Last updated at 9:55 PM on 02nd February 2009

King size! Henry VIII's armour reveals he had a 52in girth - for which he paid a terrible price

He was an immense figure in the history of England. Just how immense, however, has finally been revealed after a study of his body armour exposed Henry VIII's extraordinary vital statistics.

It found that by the end of his reign the 6ft 1in Tudor king had a whopping 52in waist and 53in chest - enough to make him severely obese by modern standards.

The study by the Royal Armouries coincides with a forthcoming exhibition of his supersized battle dress at the Tower of London to mark the 500th anniversary of him taking the throne. Here, Philippa Gregory reveals the heavy price he paid for being a very tubby Tudor.

He was a lithe and handsome lothario who went on to acquire a truly legendary waistline.

Until now, however, we haven't quite appreciated just how much larger than life Henry VIII really became.

But as we approach the 500th anniversary of his coronation, new research by the Royal Armouries in Leeds reveals the full scale of his gargantuan girth.

Analysing his suits of armour, many of which will be brought together in a new exhibition at the Tower of London in April, the researchers discovered that by the final years of his life, the 6ft 1in Tudor boasted a whopping 52in waist.


In other words, the one-time royal pin-up was now barely taller than he was round.

henry Viii

New research has shown that by the age of 45, Henry VII's weight had started to balloon as he suffered increasingly from chronic constipation and his body succumbed to hideous sores and repeated infections

Of course, years earlier, life had started rather well for young Hal.

The twentysomething Henry VIII was tall, muscle-bound and supremely fit - a talented athlete and a courageous jouster at the grand tournaments of the age.

His armour from that period reveals some impressive dimensions: a 32in waist and a 39in chest.

According to the Venetian Ambassador, he was 'the handsomest potentate I ever set eyes on, with an extremely fine calf to his leg . . . and a round face so very beautiful that it would become a pretty woman'.

But not even Henry, who believed himself directly favoured by God, could stay young for ever.

Indeed, physically and mentally, the final 15 years of his life saw the most astonishing deterioration.

The golden Prince Hal became old, very likely mad  -  and monstrously fat.

By his late 40s, he measured 48 inches around the middle and soon expanded to the colossal measurements of his twilight years.

Peter Armstrong, the director of the Royal Armouries, describes him simply as 'an absolute monster'.

Not that you would have known that from his portrayal by Jonathan Rhys Meyers in the recent hit TV series The Tudors.

The final episode reached the mid-1530s, which meant that Henry was in his mid-40s and courting his future third wife, Jane Seymour, while still married to his second, the doomed Anne Boleyn.

Expanding waistline: A suit of armour worn by the king in his early 20s

Suit of armour worn by King Henry VIII approximately 1540

Expanding waistline: A suit of armour worn by the king in his early 20s, left, is noticeably slimmer than one he used in about 1540, right

But Rhys Meyers looked as slim and fresh-faced as he had at the start of the first series.

In the 16th century, the life expectancy of the average man was 45.

As for Henry, the new research confirms, by this age his weight had started to balloon as he suffered increasingly from chronic constipation and his body succumbed to hideous sores and repeated infections.

Mentally, he was also beginning to show the first signs of madness.

However, he probably did not have syphilis, as is often alleged. Nor is there any record of him being prescribed mercury, the highly toxic metal that was used to treat the disease.

But he may have had Cushing's syndrome (a rare hormonal disorder) which could account for the obesity and the mental instability.

And there were a host of other problems, too. I would think it likely that Henry was also experiencing bouts of impotence during his marriage to Anne Boleyn; certainly, she is said to have complained of such a problem to her brother.

And while he successfully sired a son  -  the future Edward VI  -  with Jane, he never managed intercourse with wife number four, Anne of Cleves.

Not surprisingly, his next marriage  -  to the young and sexually active Catherine Howard  -  was said to have rejuvenated and exhausted him. But she was executed by him for no good reason other than malice in little over a year.

By this time, the King weighed more than 20st, was enduring regular and very painful enemas and had a foul-smelling open wound on his leg that the royal physicians  -  based on the then accepted medical knowledge  -  refused to let heal, believing that illness must be allowed to flow out of the body.

Whenever it threatened to close up, the wound would be cut open, the flesh pulled apart and tied open with string and the abscess filled with gold pellets to keep the sore running.

henry viii

Jonathan Rhys Meyers played Henry VIII in the hit TV series The Tudors

The constant pain must have been unimaginable and certainly goes some way to explaining the legendary royal rages that characterised Henry's later years.

Armed with modern medical knowledge, historians now believe this wound, which marked the onset of Henry's long decline into chronic ill health, was the result of a varicose ulcer he developed on his left thigh in his mid-30s, probably brought on by his habit of wearing tight garters on his famously handsome legs.

Alternatively, it could have been caused by a condition called chronic osteitis, a bone infection that certainly fits reports of constant ulcers opening up.

In 1536, Henry also suffered a particularly nasty fall from a horse while participating in one of the tournaments he so enjoyed. He was unconscious for about two hours  -  a period long and worrying enough for Anne Boleyn later to blame for the miscarriage she suffered soon afterwards.

Some medical historians now believe his head injury was severe enough to cause permanent brain damage.

Certainly, from that time, Henry's furious temper and unpredictability got even worse.

He would issue orders in the morning and then countermand them in the afternoon  -  then plunge into an ever darker rage on discovering his instructions had already been carried out.

My own research makes me believe that some sort of brain damage also goes a long way to explaining his persecution of Anne Boleyn  -  accusing her of adultery (not with just one man but five), witchcraft, treason and even incest, and then insisting on her execution when almost everyone, Anne included, expected her to be granted a royal pardon.

Typically, at the hour of the execution of the woman he had so adored, the King was dancing with Jane Seymour.

Just a few years later, in 1540, the onset of madness could also explain the savage humiliation and botched execution (carried out by a nervous teenager with a blunt axe) of Thomas Cromwell, once the King's closest adviser.

Within months, Henry bitterly regretted the execution  -  an irrational about face that was becoming all too common. By this time, Henry was becoming a tyrant.

In writing my historical novels, I apply very strict rules of accuracy to facts when they are known. But when it comes to Henry VIII, there's just no need to invent or significantly change events to improve the story.

We are faced with this extraordinarily charismatic king who married six times, who broke with the Roman Catholic Church and then went mad, all before his death at the age of 55.

Indeed, it is the question of human mortality that makes history so interesting.

The true story of Henry VIII is a parable of the corruption of power and the frailty of the body. He got old, he became disgusting and dangerous and he grew enormously fat.

But in many ways, England's most enigmatic king remains all the more interesting for his viler features.

Philippa Gregory is author of The Other Boleyn Girl (HarperCollins).

 * Henry VIII: Dressed to Kill opens to the public on April 3 at the Tower of London.

From http://www.dailymail.co.uk/news/article-1134222/King-size-Henry-VIIIs-armour-reveals-52in-girth--paid-terrible-price.html

Friday, March 11, 2011

Pituitary Tumor Video

John Atkinson, M.D., a Mayo Clinic neurosurgeon, describes diagnosis and treatment options for pituitary tumors.

Addison Disease Video

Date: 04 Oct 2009
Uploader: Melvin Koplow
Lenght: 2m 7s
Specialty: Endocrinology   Pediatrics  

Henry Anhalt DO FAAP FACOP FACE CDE Pediatric Endocrinology http://www.TheDoctorsVideos.com Dr. Anhalt completed his post-doctoral fellowship in pediatric endocrinology the Lucille Salter Packard Children's Hospital at Stanford University

 

 

From http://www.symposier.com/library_detail/4708/Addison-Disease

Pituitary Terms

ACTH

ACTH is important in controlling the adrenal gland’s secretion of cortisol and androgens (male hormones). Too much ACTH causes a disease called Cushing’s disease and too little ACTH causes adrenal insufficiency. Symptoms of adrenal insufficiency include weight loss, decrease in appetite, abdominal pain, and muscle aches. Please see the additional patient education material on this Web site for further information. 

ADH

ADH is a critical hormone that regulates water balance in the body by controlling how much water the kidneys release into the urine. Too much ADH secretion by the pituitary causes the syndrome of inappropriate antidiuretic hormone (SIADH), in which the salt levels in the body can drop dangerously low due to holding on to too much water. Treatments may include fluid restriction and salt supplementation. Too little ADH results in diabetes insipidus (DI), in which the body constantly produces a clear high volume of urine accompanied by extreme thirst. The treatment is fluids and a medicine called DDAVP. Additional information regarding diabetes insipidus may be found in patient education material on this Web site.

Acromegaly

A rare disorder called acromegaly occurs when a person’s pituitary gland secretes too much growth hormone, usually from a pituitary tumor. Symptoms of this disorder may include broadening of the lips and nose, irregular menstrual periods, excessive sweating and increasing ring and shoe size. Surgery is generally indicated for the treatment of acromegaly. There are several medications that are frequently used in addition to surgery to control acromegaly, and, occasionally, radiation therapy is required as well.

Cushing's Disease

Too much ACTH secretion is rare and may be from a pituitary tumor; this is called Cushing’s disease. Symptoms of too much ACTH include weight gain, a round and red face, increased acne, purple stretch marks, hair growth and muscle weakness. Special testing is necessary to make the diagnosis. Surgery is generally indicated for the treatment of Cushing’s disease. Medications are also available to lower cortisol production, and radiation therapy is sometimes required as well.

Gonadotropins

The gonadotropins are responsible for the initiation and maintenance of sexual characteristics and fertility (ability to have children). LH and FSH act on the gonads (ovaries and testes) to cause production of estrogen and testosterone and ultimately make eggs and sperm. Too little secretion of LH and FSH can cause infertility and hypogonadism, manifesting primarily as erectile dysfunction in men and irregular or absent menstrual periods in women as well as low sex drive in both. Treatment includes various forms of testosterone or estrogen replacement.  Fertility can be possible with the assistance of injectable forms of gonadotropins.

Growth Hormone

As its name implies, growth hormone is important for childhood growth. In adults, it is also important in order to maintain bone mass and normal body composition. Symptoms of growth hormone deficiency include fatigue, an increase in fat around the abdomen, decreased ability to exercise and poor sense of well-being. Treatment includes subcutaneous injections of growth hormone.

Oxytocin

Oxytocin is a hormone that is important for uterine contractions during childbirth and for release of milk during breastfeeding. It is, therefore, frequently used in the induction of labor.

Pituitary

The pituitary is a pea-sized gland located at the base of the brain in the middle of the head and right below the optic nerves. It serves as the “master gland” that regulates the secretion of the majority of hormones in the body from all of the other glands, such as the thyroid and adrenal glands, as well as the ovary and testicles. The pituitary gland is divided into the anterior and posterior lobes, both of which secrete different hormones that have unique functions in the body. The anterior pituitary secretes prolactin, growth hormone and the gonadotropins, which include luteinizing hormone (LH) and follicle stimulating hormone (FSH), adrenocorticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH). The posterior pituitary makes antidiuretic hormone (ADH) and oxytocin. The secretion of the hormones from the pituitary gland itself is also controlled by hormones coming from part of the brain directly above the pituitary called the hypothalamus. The hypothalamus and the pituitary gland are connected by the pituitary stalk.

Pituitary tumors result from a single cell losing the ability to control its growth. These tumors are almost always benign or non-cancerous. Very rarely can a pituitary tumor become malignant or cancerous. A tumor that is less than 1 cm in size is called a microadenoma, and a tumor that is larger than 1 cm is a macroadenoma.

Microadenomas usually do not cause symptoms related to their size, but macroadenomas can cause headaches as well as visual loss secondary to compression of the optic nerves. In addition, the normal pituitary tissue can be compressed by a macroadenoma, so deficiencies of anterior pituitary hormones can be identified on blood tests and based on symptoms. Pituitary tumors are also categorized according to their ability to make hormones and cause symptoms. 

The functional tumors include those that secrete prolactin (prolactinomas), ACTH (Cushing’s disease), growth hormone (acromegaly) and TSH. Tumors that do not secrete functional hormones are called non-functioning pituitary tumors. The most common tumors in adults are prolactinomas followed by non-functioning tumors, ACTH-secreting tumors, GH-secreting tumors and TSH-secreting tumors. In children, the most common tumor is also a prolactin-secreting tumor followed by ACTH-secreting tumors, GH-secreting tumors, non-functioning tumors and TSH-secreting tumors. 

Prolactin

Prolactin is a hormone that is important for the production of breast milk. 

Prolactinoma

A pituitary tumor that secretes prolactin is called a prolactinoma. In women, too much prolactin is associated with milk production outside of pregnancy and irregular menstrual periods or a lack of periods altogether. In men, excess prolactin levels cause low testosterone levels, which will typically manifest as low sex drive. Medical treatment with a pill is available for a prolactinoma. Women with too little prolactin production will be unable to make breast milk but otherwise there are no obvious symptoms of prolactin deficiency.

TSH

Thyroid stimulating hormone (TSH) directs the thyroid gland to produce thyroid hormones, which are important in regulating the body’s metabolism. Rarely, a pituitary tumor can secrete too much TSH. This would cause hyperthyroidism, as manifested by increased sweating, intolerance to heat, tremors, fast heart rate, heart palpitations, anxiety and/or weight loss. Treatment includes medications and surgery. Too little TSH results in hypothyroidism, a condition in which a person would have intolerance to cold, fatigue, dry skin, constipation, a slow heart rate and/or weight gain due to water retention. Treatment includes taking daily thyroid hormone.

From http://www.mdanderson.org/patient-and-cancer-information/care-centers-and-cli...

Thursday, March 10, 2011

Can you help?

Can anyone help Karen - she posted on Facebook at http://www.facebook.com/permalink.php?story_fbid=10150119434213954&id=146... and wrote: "I am the mother of a 12 yr old recently diagnosed with Cushings, still awaiting cause (ACTH results, imaging) Is there anyone out there that can offer words of wisdom in respect to kids and Cushings? Ive red so much, but would love to hear from the family member or young post-treatment "survivor" Thanks."

Please respond at the link I posted, not to me.  Thanks!

Wednesday, March 9, 2011

Corcept Therapeutics Announces Fourth Quarter Results and Corporate and Development Update

MENLO PARK, CA--(Marketwire - March 9, 2011) - Corcept Therapeutics Incorporated (NASDAQ: CORT), 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 fourth quarter ended December 31, 2010, and updated its corporate progress.

"We are very proud of our accomplishments during the fourth quarter and throughout 2010, most significantly the completion of our Phase 3 study of CORLUX for the treatment of patients with Cushing's Syndrome and the positive results from that study," said Joseph Belanoff, M.D., Chief Executive Officer of Corcept. "With the Phase 3 study complete, we look forward to submitting our NDA for CORLUX to the FDA by the end of March 2011, and, if approved by the FDA, providing an important treatment option to patients suffering from Cushing's Syndrome." 

Corporate and Development Highlights

  • Announced positive top-line results from the primary endpoints in our Phase 3 study of CORLUX for the treatment of Cushing's Syndrome in December 2010. In the trial, 60% of the patients with glucose intolerance and 38% of the patients with hypertension met the categorical response hurdle. Although only one endpoint needed to be positive for the study to be deemed positive, both of the endpoints were met with statistical significance.

  • Announced positive top-line results from the key secondary endpoint in our Phase 3 study of CORLUX for the treatment of Cushing's Syndrome in January 2011. In the trial, 87% of the patients had a clinically significant improvement in the signs and symptoms of Cushing's Syndrome over the course of the study, as measured by the assessment of a panel of three independent Cushing's Syndrome experts. These results were statistically significant.

  • Enrolled 88% of the patients who completed the six-month Phase 3 study of CORLUX for Cushing's Syndrome in the long-term extension study of the treatment. We now have patients treated with CORLUX through our Phase 3 and extension studies for over two years.

  • Initiated a Phase 1b/2a multi-dose safety and proof of concept study of CORT 108297 in December 2010. The study is evaluating the compound in models of antipsychotic induced weight gain and changes in biomarkers induced by prednisone, a steroid.

  • Raised approximately $45 million in gross proceeds in an underwritten public offering of common stock in January 2011, which we believe is sufficient to operate the company into the third quarter of 2012.

In addition, we continued to make progress on:

  • Preparing for an end of first quarter 2011 submission of our NDA for CORLUX in Cushing's Syndrome.

  • Planning for the commercialization of CORLUX in the United States. 

  • Enrolling patients in our double-blind placebo controlled Phase 3 trial of CORLUX in patients with psychotic depression.

  • Advancing our second selective GR-II antagonist, CORT 113083, towards an IND submission in 2011.

  • Identifying additional compounds from among our three proprietary series of selective GR-II antagonists to advance toward an IND submission.

Fourth Quarter Financial Results

For the fourth quarter of 2010, Corcept reported a net loss of $7.1 million, or $0.10 per share, compared to a net loss of $5.2 million, or $0.09 per share, for the fourth quarter of 2009.

Total operating expenses increased to $7.8 million for the fourth quarter of 2010, from $5.2 million for the same period in 2009. In the fourth quarter of 2010 research and development expenses increased to $4.7 million from $3.8 million in the fourth quarter of 2009. This increase in research and development expenses was due primarily to increased costs associated with clinical trials for CORLUX for the treatment of Cushing's Syndrome, the conduct of drug-drug interaction studies for CORLUX and other NDA supportive activities, and our selective GR-II antagonist program, including a Phase 1 study of CORT 108297 and the initiation of a Phase 1b / 2a study with this compound. General and administrative expenses increased to $3.2 million for the fourth quarter of 2010 from $1.4 million for the same period in 2009 due to the payment of cash bonuses in connection with corporate achievements during 2010 and additional resources focused on commercial planning for the potential launch of CORLUX in Cushing's Syndrome.

Our cash balance as of December 31, 2010 was $24.6 million, up from $23.9 million at December 31, 2009. "We anticipate that our current cash balance is sufficient to fund the company into the third quarter of 2012," said Caroline Loewy, Chief Financial Officer of Corcept.

Anticipated Milestones for 2011

We are focusing our efforts on advancing CORLUX toward approval and commercialization for the treatment of Cushing's Syndrome. In that vein, we are working to submit our NDA to the FDA by the end of the first quarter of 2011. We plan to request a priority (six-month) review of our application at that time. Concurrently, we are developing plans and engaging third-party vendors to support a commercial launch of CORLUX in the United States, if approved by the FDA. We also expect to make detailed data from our Phase 3 trial of CORLUX in Cushing's Syndrome available to the endocrinologists who treat the disorder at the Endocrine Society Annual Meeting (ENDO), June 4-7 in Boston.

"The past year has been transformational for Corcept, driven by the achievement of several important milestones, particularly in our Cushing's Syndrome program. We are well underway preparing for our next steps: working toward the NDA submission and potential approval of CORLUX and its commercial launch. The FDA has granted us Orphan Drug Designation for CORLUX for the treatment of endogenous Cushing's Syndrome, which provides seven years of marketing exclusivity from the date of approval. We look forward to having the chance to help patients with this life-threatening disease," concluded Dr. Belanoff.

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 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 CORLUX

Corcept's first-generation compound, CORLUX, 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 CORLUX. Corcept retains worldwide rights to its intellectual property related to CORLUX.

About CORT 108297 and CORT 113083

CORT 108297 and CORT 113083 are two of the potent, selective antagonists 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 neither of these compounds have 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 CORLUX for the treatment of Cushing's Syndrome, and has an ongoing Phase 3 study of CORLUX for the treatment of the psychotic features of psychotic depression. Corcept also has a Phase 2 program for CORT 108297 and an IND-enabling program for CORT 113083. 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 Corcept's clinical development and research programs, the timing of the NDA submission and introduction of CORLUX and future product candidates, including CORT 108297 and CORT 113083, estimates of the timing of enrollment or completion of our clinical trials and the anticipated results of those trials, the ability to create value from CORLUX or other future product candidates and our estimates regarding our capital requirements, spending plans and needs for additional financing. 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 CORLUX, CORT 108297, CORT 113083 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)
  December 31,
2010
  December 31,
2009
 
  (Unaudited)   (Note)
ASSETS:          
Current assets:          
  Cash and cash equivalents $ 24,578   $ 23,867
  Other current assets   418     553
    Total current assets   24,996     24,420
           
Other assets   108     91
    Total assets $ 25,104   $ 24,511
           
LIABILITIES AND STOCKHOLDERS' EQUITY:          
Current liabilities:          
  Accounts payable $ 817   $ 1,270
  Other current liabilities   3,043     1,149
    Total current liabilities   3,860     2,419
           
Total stockholders' equity   21,244     22,092
           
    Total liabilities and stockholders' equity $ 25,104   $ 24,511
               

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
December 31,
    Year Ended
December 31,
 
 
  2010     2009     2010     2009  
                               
Collaboration revenue $ --     $ --     $ --     $ 29  
                               
Operating expenses:                              
  Research and development*   4,663       3,750       18,949       14,402  
  General and administrative*   3,160       1,414       8,488       5,877  
    Total operating expenses   7,823       5,164       27,437       20,279  
                               
Loss from operations   (7,823 )     (5,164 )     (27,437 )     (20,250 )
                               
Interest and other income, net   737       5       1,496       101  
Other expense   (8 )     (11 )     (25 )     (17 )
    Net loss $ (7,094 )   $ (5,170 )   $ (25,966 )   $ (20,166 )
                               
                               
Basic and diluted net loss per share $ (0.10 )   $ (0.09 )   $ (0.38 )   $ (0.38 )
Shares used in computing basic and diluted net loss per share   72,354       60,390       68,336       52,443  
                               
*Includes non-cash stock-based compensation of the following:                              
    Research and development $ 49     $ 65     $ 220     $ 263  
    General and administrative   536       394       1,896       1,552  
      Total non-cash stock-based compensation $ 585     $ 459     $ 2,116     $ 1,815  
                               

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