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

Expanding treatment options for Cushing disease

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

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

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

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

AUTHOR CONTACT:

Shlomo Melmed

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

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

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

AUTHOR CONTACT:

Fredric E. Wondisford

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

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

By: Zacks Equity Research

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

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

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

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

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

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

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

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

Our Recommendation

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

Read the full analyst report on NVS

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

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

for people with Cushing’s Syndrome 

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

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

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

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

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

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

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

How do I find out more?

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

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

E-mail: cushing@compasshc.com 

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

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

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

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

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

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

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

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

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

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

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

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

About Cushing's disease

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

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

About pasireotide

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

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

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

Important Safety Information about pasireotide

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

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

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

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

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

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

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

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

About Novartis

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

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

References

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

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

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

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

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

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

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

# # #

Novartis Media Relations

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

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

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

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

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

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

Category: Tumor Biology

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

Pages: 101

Price: US$48.00

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

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

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

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

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

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

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

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

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

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

The full list of EMA orphan drug recommendations

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

Download PDF

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

Publication Date: 11 Jan 2012

Journal: Clinical Medicine Insights: Oncology

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

doi: 10.4137/CMO.S6198

Abstract

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

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

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

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

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

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

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

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

$5,000 in prizes!

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

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

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

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

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

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

Posted on EndocrineToday.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

What doctors found

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

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

Under the knife

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

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

'Hoping for normalcy'

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

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

Cushing's syndrome

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

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