Friday, July 30, 2010

Nelson’s Syndrome

Thomas M Barber, Emily Adams, Olaf Ansorge, James V Byrne, Niki Karavitaki and John Wass
T Barber, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
E Adams, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
O Ansorge, Department of Pathology, University of Oxford, Oxford, United Kingdom
J Byrne, Department of Radiology, University of Oxford, Oxford, United Kingdom
N Karavitaki, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
J Wass, Endocrinology, Oxford University, Oxford, OX3 7LJ, United Kingdom
Correspondence: John Wass, Email:

Nelson’s Syndrome is a potentially life-threatening condition that not infrequently develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s Disease. In this review article, we discuss some controversial aspects of Nelson’s Syndrome including diagnosis, predicitve factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre.
Definitive diagnostic criteria for Nelsons’s Syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson’s Syndrome should be diagnosed in any patient with prior TBA for Cushing’s Disease and at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800hrs plasma level of ACTH (>500ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson’s Syndrome post-TBA, current evidence favours: the presence of residual pituitary tumour on MRI post-TSA; an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSA samples); lack of prophylactic neo-adjuvant pituitary radiotherapy at the time of TBA, and; a rapid rise of ACTH levels in year one post-TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson’s Syndrome, including the alkylating agent, temozolomide which holds promise as a novel and effective therapeutic agent in the treatment of associated aggresive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.


Sunday, July 25, 2010

A Really Great Book on Patient Empowerment

I'm really enjoying this new book “Laugh, Sing, and Eat Like a Pig”  by "e-Patient Dave".


"e-Patient Dave" deBronkart was diagnosed in 2007 with renal cell carcinoma (kidney cancer) (MaryO’Note: my cancer!) at a very late stage. His median survival was just 24 weeks; with tumors in both lungs, several bones, even in muscle, his prognosis was "grim," as one web site put it.

Online since 1989, Dave used every resource at his disposal: a strong mental attitude, online research, great treatment at Boston's Beth Israel Deaconess, online medical records, an online journal for family and friends, and online forum of kidney cancer patients. He beat the disease in less than a year, then discovered "e-patients," who participate actively in their healthcare. He began blogging as e-Patient Dave.

An accomplished speaker and writer before his illness, today Dave is engaged in opening health information directly to patients, as public speaker, policy consultant, and Founding Co-chair of the Society for Participatory Medicine. He's testified in Washington, appeared in Time, US News & World Report, the Boston Globe, and was named to the HealthLeaders "20 People Who Make Healthcare Better."

"This is the first time in my life I've felt I have a calling," says Dave, "something I can't get away from: it's what I need to do. I've had plenty of fulfilling jobs in a great career, but not a calling. This is it."

I’ve been “following” Dave on Twitter and elsewhere for over a year.  When I was participating on my kidney cancer message boards (ACOR) a little more actively, Dave’s information was always the best, and he shared his experiences so honestly and openly.

I was so glad when he compiled those experiences and knowledge into this book. 

I understand what he means about a calling.  I’ve often felt that Cushing’s was my calling, too.  I’m too shy to get out there and testify but I can sure use my computer to get info out there.

Hopefully, more and more people will become empowered and take control of their own health.

I’m about halfway though this book.  My favorite quote (so far) is Reality is what it is,
regardless of what we think
and whether we know it or not.


To find Dave: 

Wednesday, July 21, 2010

10 Years of Cushing’s Help. Who Would Have Guessed?


Ten years ago yesterday I was talking with my dear friend Alice, who runs a wonderful menopause site, Power Surge, wondering why there weren't many support groups online (OR off!) for Cushing's and I wondered if I could start one myself.  We decided that I could.

This website ( first went "live" July 21, 2000 and the message boards September 30, 2000. Hopefully, with this site, I’ve made  some helpful differences in someone else's life.

Who could have known how this site – now sites – could have grown and grown.

It started as a one-page bit of information about Cushing’s  In people, not dogs, horses, ferrets…

Then, it started growing and growing, taking on a life of its own.  To truly emulate Alice, I added message boards in September.  They were really low-quality, a type put together by an old HTML editor but we had members and actually had discussions.

Not too long after, a real board was opened up and things really started happening.  Then we outgrew that board and ended up in our current home.

The message boards are still very active and we have weekly online text chats, live interviews, local meetings, email newsletters, a clothing exchange, a Cushing's Awareness Day Forum, podcasts, phone support and much more.

Whenever one of the members of the boards gets into NIH, I try to go to visit them there. Other board members participate in the "Cushie Helper" program where they support others with one-on-one support, doctor/hospital visits, transportation issues and more.

Things have changed over the years, though.  The original Cushings-Help site is still updated with new bios, new Helpful Doctor listings, meetings and more but all new articles have moved to a new site - – which is much easier to maintain than the older strictly-HTML site.

Also new are a CushieWiki, a site for the Cushing’s Help Organization, several blogs (of which this is one), three Facebook entities (Cushing's Help Cause; Cushing's Help and Support Group; and the Cushings Help Organization, Inc.); a Twitter stream and much more.

New recently:

NEW! Daily News Summary at Cushing's Daily News

NEW! is now optimized for viewing on PDAs and mobile phones

NEW!  Medical Centers. These are centers which specialize in Cushing's, pituitary or adrenal patients.  If you, as a patient, have one that you'd like to have added, please send any info you may have to Mary O'Connor (MaryO).  Thank you!

Occasional Newsletters are Back: Members of will automatically receive these occasional newsletters. Of course, you may opt-out at any time. Thank you for your interest.  Non-members may subscribe through the Newsletter Subscription module on the left side of this page.

Cushie Toolbar: Be the first to know! The Cushie Toolbar features a Google search box, the 911 Adrenal Crisis! page, the Cushie Reads book recommendations page, Cushie Calendar, all the bios, arranged by diagnosis type or date, add (or update) your bio, our locations around the world, the message boards and chatroom, Helpful Doctors list, add (or update) your Helpful Doctor, support page, scrolling message area for Cushing’s news, Cushing’s blogs, NIH Clinical trials for Cushing’s, pituitary and adrenal, the Cushings Help Organization cause on Facebook, Staticnrg and Cushings on Twitter, new CushieWiki and listen to the Cushing’s podcasts right from this toolbar.

CushieWiki: Please feel free to contribute! The CushieWiki is an ever-changing, ever-growing body of Cushing's knowledge provided by *YOU* and other patients.

Members of the site have additional features:

We’ve grown out of control from that simple one-page info sheet to way more than I could have ever imagined in that phone conversation with my friend.  I would never have thought that I could do any of this, provide these services and touch the lives of so many others.

I also never thought that I would spend hours a day updating, adding, improving, helping, emailing, phoning, paperwork, writing…

But it’s all worth it if the lives of other Cushies are made better.

Here’s to another 10 years…

Friday, July 9, 2010

Role of adrenalectomy in recurrent Cushing’s disease

DING Xue-fei, LI Han-zhong, YAN Wei-gang, GAO Ying, LI Xiao-qiang

Free Full Text [ Fulltext HTMLHTML | Full PDFPDF(100K) ] Abstract download [TXT | XML]

Keywords: adrenal gland·Cushing’s disease·adrenalectomy·laparoscopy


Background  Cushing’s disease is a pituitary-dependent type of Cushing’s syndrome. Treatment consists of pituitary surgery or radiotherapy, but the recurrence rate at 10 years is as high as 40%. Adrenalectomy is considered an effective treatment to refractory Cushing’s disease. The objective of this study was to examine the efficacy of laparoscopic adrenalectomy and open adrenalectomy in Cushing’s disease, focusing on reversing the sequelae of hypercortisolism and improving patients’ quality of life.

Methods Forty-three patients (29 women, 14 men) with recurrent Cushing’s disease after transsphenoidal operation underwent laparoscopic (n=32) or open (n=11) adrenalectomy from 2000 to 2008. Surgical results were evaluated for all the 43 patients. Patients completed a follow-up survey, including the short-form 36-item (SF-36) health survey.

Results All the 43 patients achieved clinical reversal of hypercortisolism after adrenalectomy. Time to symptom resolution varied from a few weeks to up to 3 years. Most physical changes had resolved by a mean of 8 months after surgery. These conditions were not significantly different between the laparoscopy and open groups. Median length of hospital stay was shorter in the laparoscopy group (4 vs. 9 days; P <0.001).

Median follow-up was 48.5 months. Of the 34 (79%) patients available for follow-up, 22 (65%) had adrenocorticotropic hormone levels >200 ng/ml and 6 (27%) had clinical Nelson syndrome. Four patients died by 75 months after surgery. Using SF-36, 30 (88%) patients reported they felt their health status was good to excellent compared with 1 year before adrenalectomy; however, they showed significantly lower scores in all the 8 SF-36 parameters compared with the general population. No significant difference emerged in SF-36 scores between the laparoscopy and open groups.

Conclusions Adrenalectomy showed high survival and clinical benefits in recurrent Cushing’s disease patients. Despite patient-reported improvement in health after adrenalectomy, patients continue to experience poor health status compared with the general population.

Chinese Medical Journal 2010;123(13):1658-1662

Free Full Text [ Fulltext HTMLHTML | Full PDFPDF(100K) ] Abstract download [TXT | XML]

DING Xue-fei Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China; LI Han-zhong Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China; YAN Wei-gang Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China; GAO Ying Department of Obstetrics and Gynecology, Affiliated Hospital of North China Coal Medical College, Tangshan, Hebei 063000, China; LI Xiao-qiang Department of Urology, Affiliated Hospital of North China Coal Medical College, Tangshan, Hebei 063000, China
Correspondence to: LI Han-zhong  Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China  (Tel:86-10-65296073 Fax:86-10-65296073 )


Tuesday, July 6, 2010

Endocrinology Workup of Cushing’s Syndrome


The patient has evidence of excess cortisol production based upon the 2300 hrs salivary cortisol test. Cortisol is cyclically produced, with nadir of ACTH and cortisol near midnight. This diurnal variation is lost early in the course of autonomous ACTH/cortisol production. Midnight serum cortisol is elevated in Cushing’s syndrome; however, hospitalization for collection of serum may be stressful and cause false positive results. Salivary cortisol is unbound and reflects the normal serum nadir – with ease of outpatient collection. False-positive results may occur, including contamination with corticosteroid-containing ointments. Many experts therefore recommend two or more screening tests, as in this patient.

The patient’s ACTH is within the normal range, which may indicate that the source of ACTH is a corticotrope adenoma, or may reflect ectopic production by a tumor. Extremely elevated ACTH concentrations would suggest ectopic sources; however, this is not a reliable discriminator. Ectopically produced ACTH molecules are often partially formed and are excluded from detection by current assays.

ACTH-dependent Cushing’s syndrome should be differentiated using one of several tests. The dexamethasone 8-mg (high-dose) overnight suppression test is performed as an outpatient. If the source of ACTH is a corticotrope in the pituitary gland, high-dose dexamethasone will suppress ACTH and cortisol production by at least 68%. If the source of ACTH is ectopic, suppression is negligible.

Another noninvasive test is the CRH stimulation test. Corticotrope adenomas respond to CRH, increasing ACTH by 35% to 50% over baseline. Cortisol concentrations rise by 20% to 50%. Nonpituitary tumors producing ectopic ACTH do not respond.

Localizing studies (MRI, scintigraphy, inferior petrosal sinus sampling) should never be performed before hormonal excess is confirmed. Incidentalomas in the pituitary (as common as 10% of studies) and / or adrenals (as many as 5% of studies) will confound the diagnosis.


Monday, July 5, 2010

A Nonlinear Relationship of Generalized and Central Obesity with Diurnal Cortisol Secretion in the Whitehall II Study

Meena Kumari*, Tarani Chandola, Eric Brunner,  and Mika Kivimaki

Department of Epidemiology and Public Health (M.Ku., T.C., E.B., M.Ki.), London, WC1E 6BT, United Kingdom

* To whom correspondence should be addressed. E-mail:

Context: Evidence for an association of measures of generalized and central obesity with salivary cortisol secretion is equivocal.

Objective: The objective of this study was to assess the relationship between body mass index (BMI), waist circumference, and salivary cortisol.

Design: The design was a cross-sectional study of BMI, waist circumference, and salivary cortisol from phase 7 (2002–2004) of the Whitehall II study.

Setting: The occupational cohort was originally recruited in 1985–1988.

Participants: Participants included 2915 men and 1041 women aged 50–74 yr with complete information on height, weight and waist circumference, and cortisol secretion.

Outcome Measures: Saliva samples were taken on waking, waking plus 0.5, 2.5, 8, and 12 h, and bedtime for the assessment of cortisol. The cortisol awakening response and slope in diurnal secretion were calculated.

Results: After adjustment for age, sex, social position, waking time, and time since waking of sample collection, increasing central and generalized obesity was associated with lower waking cortisol (P = 0.001). U-shaped associations were apparent between diurnal slope in salivary cortisol and both BMI and waist circumference (P < 0.0001 for quadratic term). For example, the shallowest (most adverse) slopes in salivary cortisol were associated with highest (>31 kg/m2) and lowest (<21 kg/m2) levels of BMI, and the steepest slopes were apparent for those with BMI of 26 kg/m2, independently of the 12 covariates examined. No associations were apparent for the cortisol awakening response (P > 0.05).

Conclusion: The associations of measures of generalized and central obesity with diurnal slope in salivary cortisol are not linear in older adults. These nonlinear associations may explain previously described mixed findings.

The diagnosis and treatment of growth hormone deficiency in adults

Current Opinion in Endocrinology, Diabetes & Obesity:
August 2010 - Volume 17 - Issue 4 - p 377–383
doi: 10.1097/MED.0b013e32833b6bc7
Neuroendocrinology: Edited by William H. Ludlam

Clemmons, David R


Purpose of review: This review summarizes the recent published information regarding efficacy and complications of growth hormone replacement therapy. Several recent reports have monitored patients for periods of up to 10 years. Additionally, a consensus conference has been held regarding needed improvements in diagnostic testing and the recommendations of consensus panels regarding diagnostic criteria and laboratory test utilization are summarized.

Recent findings: Long-term studies show growth hormone can be administered safely and that muscle strength and function as well as lipoprotein abnormalities and low-bone mineral density show sustained improvement over extended periods of time. The complications that occur are generally dose-dependent and once attenuated do not tend to recur. Long-term safety studies regarding improvement in cardiovascular mortality and/or worsening prognosis for patients who develop malignancies are available only in the form of observational studies and randomized controlled long-term trial information is not yet available. The studies reported provide a means for clinicians to ascertain the patients who are likely to derive the greatest benefit from growth hormone when the appropriate diagnostic testing and treatment paradigms are utilized.

Summary: The studies that are summarized provide useful information for assessing the response to treatment, selecting patients who are candidates for long-term replacement therapy and for selecting those in whom the need for therapy may need to be reassessed.

© 2010 Lippincott Williams & Wilkin



Thursday, July 1, 2010

Cushing’s Syndrome and Receiving Social Security Disability


Cushing’s syndrome is an endocrine disorder. Cushing’s syndrome is a condition that occurs when your body is exposed to high levels of the hormone cortisol for a prolonged period of time.

It is a disease that happens when your body produces too much of the hormone cortisol. This happens when your adrenal glands, located above your kidneys, make too much cortisol. It may also occur if you take too much cortisol or other steroid hormones.

Cushing’s syndrome is a relatively rare disorder. It usually happens to adults between the ages of 20 and 50. An estimated 10 to 15 out of every million people in the United States are affected by it each year.

Cushing’s syndrome gets its name from American doctor Harvey Cushing who described and reported the disorder in 1932. It is also known as hypercortisolism.

The effects caused by Cushing’s syndrome are varied. Usually, however, you may have an increased amount of fat around your neck, upper body obesity, thinning arms and legs, and a rounded face.

There are other signs and symptoms that show up in your skin. Your skin heals poorly and bruises easily. It becomes thin and fragile. You may see purplish pink stretch marks appear on your thighs, buttocks, abdomen, breasts and arms.

Your bones get weaker. Normal, routine activities like rising or lifting from a chair or bending can result in rib and spinal column fractures and backaches.

Other effects that you may experience are:

  • Weak muscles
  • High blood pressure
  • Severe fatigue
  • High blood sugar
  • Anxiety and depression
  • Irritability
  • Women may have menstrual periods stop or become irregular
  • Women may also experience excessive hair growth on their thighs, abdomen, chest, neck and face.
  • Men may experience decreased fertility and an absent or diminished desire for sex.

The effects of Cushing’s syndrome and/or conditions resulting from or in connection with it can become incapacitating. It may be the cause of you or a loved one’s disability.

Do you or your loved one need help because of your disability? Do you need financial help?

Have you or your loved one applied for Social Security disability benefits or disability benefits from the Social Security Administration because of the disability caused by Cushing’s syndrome and/or conditions resulting from or along with it? Were you or your loved one denied?

You or your loved one may be thinking about appealing the denial by the Social Security Administration. If you do, remember this.

You or your loved one may need a  disability lawyer like the one you will find at here to counsel you in what can be a long and trying process. The reason for this being true is because people who are aided and represented by a disability attorney are approved more often than those people who do not have a lawyer.


Tags: Adrenal gland, Cortisol, Cushing's syndrome, Disease, Endocrine system, Harvey Cushing, social security administration, United States