Saturday, May 29, 2010

Cushing’s Disease: Fighting back to fitness

Cushing's Disease

Sian Fletcher was overweight, unfit and depressed after undergoing brain surgery, but was helped to recover by a gym instructor. Now she has qualified to become a fitness instructor herself. Suzanne Savill reports

Tears were rolling down Sian Fletcher's face as she stood on the treadmill at the Fitness First gym on Bristol Harbourside.

"I just broke down and started crying because I felt so hopeless," she recalls.

"I'd only managed to do about 15 minutes. I was overweight, exhausted and depressed.

"At that point it would have been very easy for me to have given up going to the gym altogether."

About a month earlier, Sian had undergone brain surgery for a tumour on her pituitary gland that had caused her years of mysterious health problems.

But as she staggered off the treadmill, it seemed that her health problems were going to continue despite the operation. However, her personal trainer Phil would not let her give up.

"He told me that I was doing a fantastic job by even getting on the treadmill after the operation I'd just had," says Sian, 23, who lives in Whitchurch with her husband Andy.

"Phil was very professional and managed to encourage me to keep going."

At that time, Sian – who is just five feet tall – weighed about 10 stones. Today, she is seven stones and she is also a qualified fitness instructor, and studying to become a personal trainer.

"I trained as a chef, and I'd worked at some of the best restaurants in Bristol, such as Quartier Vert, Bordeaux Quay and Taste in St Nicholas Market," she says.

"But I wanted to give something back to people like me, just as Phil did for me. He made me see that I could get through it, and that it just took time."

Sian first began feeling ill in 2007, when she suddenly developed stretch marks on her abdomen, legs, and arms.

She says: "I was getting a little 'round' in the middle and I was just not feeling well, but when I went to the doctor I was told that some people do develop stretch marks for no reason.

"Later that year I went back to the doctor, complaining that I was very thirsty in the morning and also kept having headaches that would turn into painful migraines on the right side of my head.

"They gave me some blood tests to rule out diabetes and some other routine tests. When they came back they said I had low potassium levels and my B12 vitamins were low. They recommended eating a banana a day. I accepted this and bought a bunch of bananas!"

But Sian's health continued to deteriorate. She was still putting on weight, and noticeable hair had begun to appear on her upper lip and neck.

"I felt horrible and totally unfeminine, although my boyfriend Andy – who is now my husband – was lovely and just accepted me as I was," she says.

"I was quite big by then, and a friend very kindly told me that she had a free pass to the Fitness First gym at Bristol Harbourside and asked me if I'd like to use it.

"I wasn't too sure, as I was never one to play sport or do exercise in school. In fact I'd be the one forging notes or faking illness injury so I didn't have to take part!

"But when I went and loved it, I thought it would solve all my health problems, and I did manage to lose around half a stone, but then that was it.

"After several months of not losing any more weight I went back to the doctor. He said that I just had to be persistent with my diet and exercise."

The first signs that something was seriously wrong came after Christmas 2008, when Sian visited her GP for a routine check-up for her contraceptive pill. Her blood pressure was so high that her doctor switched her to an oestrogen-only pill.

Just over a week later, Sian had a motorcycle accident as she made her way home from her job at Chef Direct on the A38 Bridgwater Road.

Her Kawasaki 500 GPZ motorcycle collided with the back of a car, and she hit her head which resulted in a large gash on her nose.

Sian says: "My face was covered in blood. An ambulance arrived and I was put on a stretcher while they checked my pulse and blood pressure.

"I told the paramedic that my doctor had changed my pill about a week ago so my blood pressure would still be high. He said it should have dropped down by now, but it hadn't and I should go back as soon as possible."

Sian's doctor sent her to see an endocrine specialist in case she had a problem with her kidneys, and she also had to have an MRI scan.

By now her blood pressure was very high, at 163 over 98, her skin was bruising easily from the blood tests and her face was bright red and puffy.

Meanwhile, she had begun exercising with a personal trainer at Fitness First Harbourside, called Philip Shoyer.

"Little did I know that he would be so much help to me over the coming 18 months," she says. The tests and MRI scan revealed that Sian had a rare condition called Cushing's Disease, caused by a small tumour the size of a pea on the right side of her pituitary gland.

Sian says: "I was booked to have key hole surgery to remove the tumour in August 2008, but I was terrified of what was going to happen to me. I'd been told I may lose some of my vision and my fertility, and that I might not be the same as I was before."

"Phil pointed out that if I didn't have the surgery I could only get worse. I listened to his advice and decided to have the operation."

When Sian woke up at Frenchay Hospital after the operation she felt worse instead of better.

"I felt drained and tired. I was dizzy, I had a headache and I just wanted to sleep," she says.

Even after five days in hospital, during which time she had blood tests which showed she was cured of Cushing's Disease and no longer needed to take hydrocortisone, she was still feeling ill.

"I wasn't allowed to go back to work for six weeks, I couldn't lean forward, swim, or sneeze. I hated it," she says.

"Four weeks after the operation I had my first personal training session with Phil following the surgery. I lasted around 20 minutes before I broke down in tears because I couldn't do any more.

"He told me it was fine, and reminded me that I'd had major surgery only a few weeks ago, and we would just have to take it slowly until I felt better."

Instead of feeling better, however, Sian was diagnosed with depression just before Christmas 2009, and put on anti-depressants.

She recalls: "I felt ashamed. I didn't want to be depressed. I wanted to be normal – the person I was before. I wanted to go kickboxing and train five days a week like I used to. But I could barely stay awake on the bus after six hours' work.

"I was very unhappy and was beginning to wish I'd never had the surgery."

However, the anti- depressants began to work, and within weeks, Sian began to feel much better. She managed to lose two and a half stone by February and her body fat went from 33 per cent to 18 per cent, while her blood pressure became normal and she started to feel better.

By April she was back to training with Phil for an hour at the gym five days a week, and in September she took part in her first kickboxing tournament and won gold. She has now reached third kuy belt standard.

Fitness First holds an award ceremony for members, and earlier this year Sian was one of 12 members from around the UK selected to attend the final in London.

"I didn't win the award for Fitness First but was so proud to be there. I was finally realising that what I had gone through was a big deal and I had actually managed to push through it," she says.

Sian is now working towards her black belt in kickboxing and training to become a personal trainer, so that she can help other people in the way Phil helped her.

"I know I'll always be a pituitary patient and it will always be with me. But I believe that with people like Phil who give their time and patience to people like me, we can get better and feel 'normal'," she says.

"Without him and all the staff at Fitness First, plus my wonderfully supportive husband Andy, I would never be where I am today."

Cushing's syndrome develops when the body makes too much of the hormone cortisol, which helps to regulate blood pressure and blood sugar levels, and helps the body cope with stress.

The commonest cause of spontaneous Cushing's Disease is a small, benign tumour of the pituitary gland at the base of the brain.

Treatment usually requires an operation in which a surgeon makes a small cut in front of the upper teeth behind the upper lip, or inside the nose.

After the operation, patients need to take a replacement cortisol called hydrocortisone in a tablet form, as the body's normal production of cortisol will have been affected by Cushing's.

Sian no longer needs to take hydrocortisone for daily function, although she will need to take it again if she becomes stressed or ill.

For further information about Cushing's, contact The Pituitary Foundation, which is based in Bristol and can be contacted on 0845 450 0375. The foundation's website is


Thursday, May 27, 2010

Endonasal transsphenoidal approach to pituitary surgery: experience of 55 cases

Bangladesh Journal of Otorhinolaryngology, Vol 15, No 2 (2009)

Forhad Hossain Chowdhury, Md Raziul Haque, Md Shafiqul Islam, Mani Lal Aich, Khandkar Ali Kawsar, Momtazul Haque, Mainul Haque Sarkar


Transsphenoidal approach to sella is not a new approach. In the last 100 years it has gone numerous changing refinements from using headlight to microscope and more recently the sensitive endoscope. In this prospective study, all patients with pituitary tumor who underwent endonasal transsphenoidal pituitary surgery during the period of January 2006 to July 2009 in the department of neurosurgery, Dhaka Medical College Hospital and Islami Bank Central Hospital, Dhaka, Bangladesh were included. Among the 55 patients 36 cases were operated by combined endoscopic and microscopic techniques and 19 cases were operated by endoscope only. Total 73 procedures were done in 55 patients. Age range was 17 years to 70 years. Follow up period was 03 months to 42 months (mean 14.2 months) .Male: female was almost 1:1. Clinical features were pituitary apoplexy, pituitary apoplexy with 3rd/+6th cranial nerve palsy, headache, amenorrhea, loss of libido, galactorrhoea, gynecomastia, weight gain and psychosis. Visual impairment was in 35 cases. Functioning adenoma was 21 and non functioning adenoma was 34 cases. Among the functioning adenoma acromegaly was seen in 12 cases, gigantism in 01 case, prolactinoma in 05 cases, Cushing's disease 03 cases. Purely sellar tumor was 15, sellar & suprasellar 35 and sellar & parasellar 11 cases.

Microscopic plus endoscopic techniques used in 54 procedures. Purely endoscopic procedures were 19. Complete removal of tumor in single stage was done in 33 cases. Complete removal with more than one stage surgery in 13 cases. In our initial cases of the series, we exposed the sella endonasally with endoscope then we used microscope for the rest of the surgery. In the later part of the series we gained experience and confidence for removal of pituitary tumor with an endoscope completely. The rate of diabetes insipidus occurred in 11(20%) cases and all are transient. Postoperative CSF leak was noted in 10(18%) cases. Patient with ocular palsy improved post operatively within 6 weeks. Among non functioning adenoma that were removed completely (30 cases) recurrence occurred in three cases. Eleven patients were stable in vision as preoperative. Other showed visual improvement to variable extents.

Key words: Pituitary surgery; Endonasal; Transsphenoidal; Microsurgery; Endoscopic surgery.

DOI: 10.3329/bjo.v15i2.5056

Bangladesh J Otorhinolaryngol 2009; 15(2): 45-49

Full Text: PDF

Bangladesh Journal of Otorhinolaryngology ISSN 1728-8835

BanglaJOL is supported by INASP


NIH: Undiagnosed Diseases Program

Some patients wait years for a definitive diagnosis. Using a unique combination of scientific and medical expertise and resources at the National Institutes of Health (NIH), the Undiagnosed Diseases Program pursues two goals:

  • To provide answers to patients with mysterious conditions that have long eluded diagnosis
  • To advance medical knowledge about rare and common diseases

The program is trans-NIH in scope. It is organized by the National Human Genome Research Institute (NHGRI), the NIH Office of Rare Diseases Research (ORDR) and the NIH Clinical Center. Many medical specialties from other NIH research centers and institutes will contribute expertise needed to conduct the program, including endocrinology, immunology, oncology, dermatology, dentistry, cardiology, and genetics, which are represented among the dozens of participating senior attending physicians who may participate in the program's clinical research.

Any longstanding medical condition that eludes diagnosis by a referring physician can be considered undiagnosed and may be of interest to this clinical research program. Of the total number of cases that may be referred to this program, a very limited number will be invited to proceed in the study at the discretion of the program’s medical team.

For more information please call (866) 444-8806

Please do not send Undiagnosed Diseases Program-related email or submit medical records to the NIH Office of Rare Diseases. All communication should be handled through the Undiagnosed Diseases Program staff at the NIH Clinical Center.

Program Information

Frequently Asked Questions (FAQ)

Information for patients (PDF - 90 KB)

Information for health-care providers (PDF - 93 KB)


Press Release (PDF - 51KB)

Place for Hope

Audio recording media telebriefing (MP3 - 10,799 KB)

Audio recording patient advocacy teleconference (MP3 - 18,905 KB)

Transcript: Undiagnosed Diseases Program Media Tele-Briefing (PDF - 79 KB)

NY Times Magazine describes the experiences of a UDP patient

Patient Support

In Need of Diagnosis, Inc. (INoD)

Syndromes Without A Name- USA (SWAN-USA)


NIH recognizes undiagnosed diseases

By Ricki Lewis
If TV’s Dr. House, diagnostician extraordinaire, is ever truly stumped, he can refer his patient to the National Institutes of Health’s new "Undiagnosed Diseases Program."

Health care providers will refer patients whose symptoms do not fit any known pattern, and the agency will invite some of them for a work-up at the NIH’s Clinical Center in Bethesda. After examinations by dozens of medical specialists, patients might be enrolled in one of the existing 1,500 ongoing clinical trials or perhaps inspire a new investigation. In addition to attempting to diagnose the undiagnosable, the program will also identify subtypes of more common illnesses, leading to a “catalog of descriptions of conditions – a phenotype atlas that will provide new information for textbook diagnoses,” said William A. Gahl, MD, PhD clinical director at the National Human Genome Research Institute, who was one of a panel of speakers at a telephone news conference today announcing the program.

Amanda Young, a 26-year-old from Georgia, represented the type of patient who might take advantage of the new program. “I had horrible infections, and no one knew how to stop them. All they knew was that I had a low white blood cell count. By age 3 1/2 I’d had meningitis 3 times, seizures, and an abscess on my abdomen the size of a cantaloupe.” At age 8, a scratch on a leg turned into a raging infection, and gas gangrene led to amputation up to the hip. At age 9, she went to the NIH, and on May 13, 2003, her disease finally received a name: IRAK4 deficiency. She inherited a mutation from each parent, profoundly impairing her innate immunity.

The Undiagnosed Diseases Program anticipates 1-2 referrals a week for the first year, and hopefully many of them will hear “magic words” like Amanda Young did – a name for their diseases. More importantly will be the explanations that the names symbolize. For example, IRAK4 is an enzyme that participates in the Toll-like receptor pathway – discovered in the fruit fly Drosophila melanogaster.

As a former Drosophila geneticist, I was thrilled at the reference during the NIH phone conference to my old six-legged friends. I worked with homeotic mutants – flies that had legs in place of their antennae and mouthparts (that's a picture of one on the right). One reason that I left science for journalism was my oh-so-wrong feeling that flies with mixed up body parts mattered only to other flies. Months after I got my PhD, others in my lab discovered the homeobox – the genetic instructions for where organs end up in the embryo. Homeoboxes would eventually be found everywhere in the living world, from chickens to trees. And over the years, the mutations I’d worked with turned up behind a host of human diseases, from cancers, to birth defects, to curiously fused toes.

NIH’s Undiagnosed Diseases Program is a boon to desperately sick people, a fitting celebration of the 25 year anniversary of the Orphan Drug Act, and at the same time a vindication of basic research.

Lewis, R. Confessions of an ex-fly pusher. The Scientist 14(9):10, 2000.

Ricki Lewis is the author of the novel Stem Cell Symphony and the textbook Human Genetics: Concepts and Applications, now in its 8th edition. She is a fellow of the Alden March Bioethics Institute.


Tuesday, May 25, 2010

Pituitary apoplexy following endoscopic sinus surgery

The Journal of Laryngology & Otology (2010), 124:677-679 Cambridge University Press

Copyright © JLO (1984) Limited 2009



G Fyrmpasa1 c1, J Constantinidisa1, N Forogloua2 and P Selviaridisa2

a1 Department of Otolaryngology Head and Neck Surgery, AHEPA Hospital, Aristotle University of Thessaloniki, Greece

a2 Department of Neurosurgery, AHEPA Hospital, Aristotle University of Thessaloniki, Greece



Objective: To highlight the possibility of pituitary apoplexy after functional endoscopic sinus surgery for elimination of sinonasal infection, an important preparatory step for safe trans-sphenoidal access to the pituitary fossa.

Case report: A 67-year-old man with a known pituitary macroadenoma developed headache, diplopia and reduced vision after endoscopic middle meatal antrostomy and ethmoidectomy for rhinosinusitis with polyps. Magnetic resonance imaging showed pituitary haemorrhage. The patient underwent emergency endoscopic trans-sphenoidal resection of the tumour, with significant symptomatic improvement. Despite mild right eyelid ptosis and persistent diabetes insipidus, the patient resumed normal activities in a few weeks. To our knowledge, this is the first report of pituitary apoplexy after a nasal operation.

Conclusion: Pituitary apoplexy is a rare and potentially life-threatening event in high risk patients with pituitary adenomas; it may occur spontaneously or after surgical procedures. Early, combined surgical intervention by rhinologists and neurosurgeons is recommended. The endoscopic trans-sphenoidal approach is a safe and effective technique for the acute management of pituitary apoplexy.

(Accepted July 15 2009)

(Online publication November 25 2009)

Key words: Pituitary Gland; Paranasal Sinuses; Endoscopy; Complications


c1 Address for correspondence: Dr Georgios Fyrmpas, Department of Otolaryngology Head and Neck Surgery, Aristotle University of Thessaloniki, AHEPA Hospital, Kiriakidi 1, 546 36 Thessaloniki, Greece. Fax: 00302310994916 E-mail:


Dr G Fyrmpas takes responsibility for the integrity of the content of the paper.

Competing interests: None declared


Monday, May 17, 2010

Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients.First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations.

Patients with resistance to dopamine agonists may require other treatment.First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease.
Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients.

The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery.In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures.

Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to surgery and other medical therapy, although there are regional differences in when it is prescribed.In conclusion, the treatment of patients with pituitary adenomas requires a multidisciplinary approach.

Dopamine agonists are an effective first-line medical therapy in most patients with a prolactinoma, and somatostatin analogues can be used as first-line therapy in selected patients with acromegaly. Current medical therapies for Cushing's disease primarily focus on adrenal blockade of cortisol production, although pasireotide and cabergoline show promise as pituitary-directed medical therapy for Cushing's disease; further long-term evaluation of efficacy and safety is important.

Author: Beverly Biller
Annamaria Colao
Stephan Petersenn
Vivien Bonert
Marco Boscaro
Credits/Source: BMC Endocrine Disorders 2010, 10:10


Thursday, May 13, 2010

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

Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

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 . .

[Full Text of this Article]

Gamma-Knife Radiosurgery Is Promising for Patients With Pituitary Adenoma: Presented at AANS

By Liz Meszaros

PHILADELPHIA -- May 5, 2010 -- Gamma-knife radiosurgery may effectively achieve tumour control in patients who have recurrent residual pituitary adenoma, researchers stated here at the 2010 Annual Meeting of the American Association of Neurological Surgeons (AANS).

"Radiosurgery is an excellent treatment option for patients with recurrent or residual pituitary tumours," noted investigator Jason P. Sheehan, MD, PhD, University of Virginia, Charlottesville, Virginia, speaking here on May 3. "It offers a high rate of tumour and endocrine control. As such, it allows most patients to avoid repeat open surgery or lifelong, expensive medical management."

Dr. Sheehan and colleagues conducted a single-centre retrospective study of the largest group of radiosurgery patients with a pituitary adenoma to date. In all, 418 patients who had undergone gamma-knife radiosurgery were followed for a minimum of 6 months (median 31 months). Factors related to endocrine remission, control of tumour growth, and development of pituitary deficiency were analysed.

Tumour control was achieved in 90.3% of patients, and higher radiation doses significantly resulted in tumour shrinkage. In patients with secretory pituitary adenoma, such as seen in Cushing's disease or acromegaly, median time to endocrine remission was 48.9 months.

Tumour-margin radiation dose was inversely correlated with time to achievement of endocrine remission (P < .05). Smaller adenoma size correlated with improved endocrine response in patients with secretory adenomas.

"Smaller tumour size improves the chances of endocrine control and lowers the risk of new pituitary hormone deficiency following stereotactic radiosurgery. A higher radiosurgical dose offers a greater chance of endocrine and tumour control," Dr. Sheehan noted.

New-onset pituitary hormone deficiency following surgery was seen in 24.4% of patients. There were no cases of panhypopituitarism, and 1 case of posterior pituitary insufficiency. Treatment with pituitary-hormone suppressive medication at the time of surgery was related to a loss of pituitary function (P < .05).

"Radiosurgery has become an increasingly important technique for the treatment of recurrent or residual pituitary adenomas. It affords effective growth control, hormonal normalisation, and an acceptable risk of delayed endocrinopathy," concluded Dr. Sheehan.

Dr. Sheehan was presented with the Synthes Skull Base Award for this research.

[Presentation title: Gamma Knife Radiosurgery for Pituitary Adenomas: Factors Related to Radiologic and Endocrine Outcomes in a Series of 400+ Patients.]


Comparison of pituitary function recovery 3 and 12 months post surgery

The insulin tolerance test (ITT) is considered the gold standard for assessment of GH and ACTH reserve in patients with pituitary disease following pituitary surgery and is usually performed after 6–12 weeks.

Berg et al. conducted a study to evaluate dynamic testing 3 and 12 months after transsphenoidal pituitary surgery. Serial dynamic testing was performed in 36 patients (13 women, age 18–78) at 3 and 12 months after transsphenoidal surgery.

They found that there was a significant increase in median GH and cortisol peak levels during ITT after l2 months compared with the 3-month results. This is the first study showing that in the late-postoperative phase after pituitary surgery, there is ongoing recovery of pituitary function demonstrated by a significant improvement of GH and cortisol peak levels in ITT during follow-up. They found that dynamic re-testing at 12 months after pituitary surgery in comparison to a single ITT at 3 months detects a recovery from ACTH and GH insufficiency, in each by 11%. Berg et al. (2010), European Journal of Endocrinology 162.

Read the full article at: DOI: 10.1530/EJE-09-0997

Monday, May 10, 2010

Four Years Post-Op Kidney Cancer Surgery

Yesterday was my 4-year surgery anniversary.  Amazing how time flies.  If anyone had told me then that I’d have four years to live, it wouldn’t have seemed like “enough”, though.

Four years ago yesterday was also the first (and only!) Cushie Cruise, leaving for Bermuda on Mother’s Day.  I wasn’t able to go due to financial reasons, but a very kind Cushie Angel made it possible.  I got new clothes, and was very excited.  I’d never been to Bermuda.

So, along comes this surprise cancer.  I told my surgeon-to-be while still in the ER about this cruise and he said no way could I go.

I ended up getting out of the hospital the day before the cruise, the day before Mother’s Day, and the doctor was right.  There would have been no way I could have gone and enjoyed this cruise.  It was a few weeks before I could even walk, and several days before I could consider getting off pain meds.

Another lucky Cushie got to go in my place, so all was not lost.  I got to use my new clothes on a “second chance” cruise and I’m now 4 years cancer free!

Happy endings all around!

Here’s a review of the cruise by other non-Cushies with lots of pictures:

If you’re a member of the Cushing’s Help message boards, you can see cute pictures of “Penelopee Cruise” at  Penelopee was made from someone’s 24-hour UFC jug.  The pictures and captures are a real hoot.

At four years post-op, I have no signs of my cancer returning or showing up in another organ.  (Hooray!)  I do have an enlarged lymph node between my lungs but that seems stable at this time.

Energy levels are still very low thanks to the combination of post-pituitary surgery panhypopituitarism, the removal of one adrenal during kidney surgery and low-functioning remaining adrenal.  Beats the alternative, though!

Daily (l-o-n-g) naps are a must and, I guess, will always be.  Doctors haven’t seem to come up with any ideas for extra energy for me.

I don’t have any lingering symptoms from my bout with cancer, so it’s all good.

As I learned to say in church yesterday, despite my illnesses, “I am blessed!”

Thursday, May 6, 2010

Adrenocortical Zonation in Humans under Normal and Pathological Conditions

Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-2010
The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 5 2296-2305
Copyright © 2010 by The Endocrine Society

Koshiro Nishimoto, Ken Nakagawa, Dan Li, Takeo Kosaka, Mototsugu Oya, Shuji Mikami, Hirotaka Shibata, Hiroshi Itoh, Fumiko Mitani, Takeshi Yamazaki, Tadashi Ogishima, Makoto Suematsu and Kuniaki Mukai

Departments of Urology (K.Ni., K.Na., T.K., M.O.), Biochemistry and Integrative Medical Biology (D.L., F.M., M.S., K.M.), and Internal Medicine (H.S., H.I.), School of Medicine, Keio University, and Division of Diagnostic Pathology (S.M.), Keio University Hospital, Tokyo 160-8582, Japan; Laboratory of Molecular Brain Science (T.Y.), Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan; Department of Chemistry (T.O.), Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan; and Department of Urology (K.Ni.), Federation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, Tokyo 190-8531, Japan

Address all correspondence and requests for reprints to: Kuniaki Mukai, Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail,

Context: Aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiation of human adrenocortical cells. Little is known, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions.

Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other.

Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster, and a CYP11B1-expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing’s syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system.

Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.



Tuesday, May 4, 2010

Radiotherapy in paediatric Cushing’s disease: efficacy and long term follow up of pituitary function

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Radiotherapy in paediatric Cushing’s disease: efficacy and long term follow up of pituitary function

Shrikrishna V. Acharya1 Contact Information, Raju A. Gopal1, Joe Goerge1, Padma S. Menon1, Tushar R. Bandgar1 and Nalini S. Shah1

Department of Endocrinology, Seth G S Medical College and KEM Hospital, Mumbai, 12, Maharashtra, India

Published online: 22 April 2010


Pituitary radiotherapy (RT) is an effective second-line treatment for paediatric Cushing’s disease (CD). We report long-term efficacy and anterior pituitary function in a cohort of paediatric CD patients treated with RT. Between 1988 and 2008, from our cohort of 48 paediatric CD patients, eight paediatric CD patients (5 males and 3 females) underwent second-line pituitary RT (45 Gy in 25 fractions), following unsuccessful transsphenoidal surgery. Out of eight whose long term follow up is available, four patients were cured by RT. Minimum follow up of 2 years is available for all patients. Four patients achieved cure after RT. Two patients were not cured even after follow up of 60 and 132 months, respectively. Out of four uncured patients, two of them had suppressible low dose dexamethasone cortisol with altered circadian rhythm suggesting possibility of response in near future with follow up of just 26 months. Five patients were hypogonadal and one patient was hypothyroid. All patients were below their target height at the time of last follow up. None of the patients had posterior pituitary dysfunction. This series of patients illustrates the efficacy and long-term follow up of pituitary function in children with CD treated with RT. This study also emphasizes the need of growth hormone statues assessment and timely intervention.

Keywords  Radiotherapy - Cushing’s disease - Panhypopituitarism

Contact Information
Shrikrishna V. Acharya

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Gamma Knife Radiosurgery Yields Promising Results in Patients with Pituitary Adenomas

Source: American Association of Neurological Surgeons (AANS)

Newswise — In 2009, it was estimated that a total of 22,070 new cases of brain and other CNS tumors were diagnosed. Pituitary adenomas represent one of the most common brain tumors. Large studies report that approximately 10-20 percent of the population harbors a pituitary tumor. According to the Central Brain Tumor Registry of the United States, 13.4 percent of all brain and CNS tumors diagnosed in 2009 were located in the pituitary. Although surgical resection and medical management can be used to treat certain types of pituitary tumors, recurrent or residual tumors are not uncommon and frequently require treatment with stereotactic radiosurgery.

Swedish physician and professor of neurosurgery at the Karolinska Institute in Stockholm, Lars Leksell treated the first pituitary adenoma patient with the Gamma Knife® in 1968. Since then, Gamma Knife radiosurgery (GKRS) has been used to treat thousands of patients with a recurrent or residual pituitary adenoma. Many single center, retrospective studies have documented its efficacy. Unfortunately, most reports consist of fewer than 100 patients, making statistical analysis of such small groups problematic.

Researchers at the University of Virginia Health Science Center in Charlottesville, Va. and Brigham and Women’s Hospital in Boston, evaluated the efficacy of GKRS in a total of 418 radiosurgery patients. The results of this study, Gamma Knife Radiosurgery for Pituitary Adenomas: Factors Related to Radiologic and Endocrine Outcomes in a Series of 400+ Patients, will be presented by Jason P. Sheehan, MD, PhD, 5:01 to 5:15 pm, Monday, May 3, 2010, during the 78th Annual Meeting of the American Association of Neurological Surgeons in Philadelphia. Co-authors are Nader Pouratian, MD, PhD, Edward R. Laws Jr., MD, and Mary Lee Vance, MD. Dr. Sheehan will be presented with the Synthes Skull Base Award for this research.

The current study evaluates the largest group of radiosurgery patients with a pituitary adenoma, to date, analyzing factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency. Included in this study were patients with a minimum follow-up of 6 months (median 31 months). Statistical analysis was performed to evaluate for significant factors (p<0.05) related to treatment outcomes. The following results were noted:

•In 90.3 percent of patients, there was tumor control (i.e. no growth or tumor shrinkage). A higher radiation dose significantly resulted in tumor shrinkage.

•In patients with a secretory (i.e. functioning) pituitary adenoma such as in Cushing’s disease or acromegaly, the median time to endocrine remission was 48.9 months. A higher radiation dose correlated with a faster time to endocrine remission.

•Smaller adenoma size correlated with improved endocrine response in those patients with secretory adenomas. Temporarily halting pituitary suppressive medications at the time of radiosurgery led to an improvement in endocrine response.

•New onset of a pituitary hormone deficiency following radiosurgery was seen in 24.4 percent of patients. These patients were placed on hormone supplementation as required. The two most common hormone deficiencies following radiosurgery were thyroid and growth hormone.

“Smaller tumor size improves the chances of endocrine control and lowers the risk of new pituitary hormone deficiency following stereotatic radiosurgery. A higher radiosurgical dose offers a greater chance of endocrine and tumor control,” remarked Dr. Sheehan.

“Radiosurgery is an excellent treatment option for patients with recurrent or residual pituitary tumors. It offers a high rate of tumor and endocrine control. As such, it allows most patients to avoid repeat open surgery or lifelong, expensive medical management,” concluded Dr. Sheehan.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,600 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.

Disclosure: the author reports no conflicts of interest.

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Monday, May 3, 2010

Active Cushing's Disease Is Associated With Subtle Cognitive Impairment: Presented at ECE

By Karen Dente

PRAGUE, Czech Republic -- April 29, 2010 -- Researchers have found a correlation between Cushing's disease and cognitive impairments long after Cushing's was cured.

Results of a study were presented here during an oral session at the 12th European Congress of Endocrinology (ECE).

"We hypothesised that previous hypercortisolism in patients with Cushing's disease results in irreversible impairments in cognitive functioning," said Jitske Tiemensma, Leiden University Medical Center, Leiden, Netherlands, on April 25.

The study was designed to assess cognitive functioning using 11 tests looking at memory, global cognitive functioning, and executive functioning.

A total of 74 patients cured of Cushing's disease were matched with 74 controls. More than 80% of the patients were female and the mean age was 52 years.

Another 54 patients who were previously treated for non-functioning pituitary macroadenomas (NFMA) along with 54 matched controls were included as well.

In contrast to the NFMA patients, those cured from Cushing's disease had lower scores on the Mini-Mental State Examination (P = .001) and on the Wechsler Memory Scale (P = .050).

Patients with previous Cushing's also tended to recall fewer words on the imprinting trial (P = .013), the immediate recall trial (P = .012), and the delayed recall trial (P = .003) of the Verbal Learning Test of Rey. They also recalled more intrusions on all trials of this test (P = .002, P = .003, and P = .003, respectively).

"The results from our study indicated that irreversible effects from previous hypercortisolism remain on cognitive function, and, thus on the central nervous system," said Dr. Tiemensma.

These observations may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

[Presentation title: Subtle Cognitive Impairments in Patients With Long-Term Cure of Cushing's Disease. Abstract H2.3]


(Adrenal Cushing’s) Hormone May Ward Off Osteonecrosis

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: April 29, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner


Action Points  

  • Explain to interested patients that long-term glucocorticoid treatment may be part of the therapy for asthma, ulcerative colitis, kidney diseases, and rheumatologic disorders.


Patients on chronic glucocorticoid therapy often develop osteonecrosis of the hip, but injections of adrenocorticotropic hormone (ACTH) might prevent that devastating complication, a preclinical study showed.

Rabbits treated with depot methylprednisolone acetate (Depo Medrol) showed half as much necrotic surface area on the femoral head when also given the synthetic cosyntropin (Cortrosyn) form of ACTH (P<0.05), Mone Zaidi, MD, PhD, of the Mount Sinai School of Medicine in New York City, and colleagues found.

The protective effect weakened for deeper bone, with all rabbits in both groups showing focal necrotic spots.

But these deeper areas of necrosis were smaller and generally not consolidated in ACTH-treated rabbits compared with prominent consolidated areas of necrosis in those that got only the glucocorticoid, Zaidi's group reported online in the Proceedings of the National Academy of Sciences.


These results provide a rationale for extended use of cosyntropin to decrease the risk of osteonecrosis for human patients who have to be on long-term glucocorticoid treatment, they suggested.


"The results are very promising because this is the first proof-of-concept of any medical therapy" in this setting, Zaidi said in an interview.


The only treatment for this debilitating, painful condition has been surgical debridement, the researchers explained.


The rate of osteonecrosis of the hip induced by long-term glucocorticoid use isn't clear, but it is thought to account for about 10% of hip replacements in the U.S. each year, Zaidi noted.

The mechanism appears to be different than with osteoporosis from long-term glucocorticoid treatment, which occurs largely due to osteocyte apoptosis, his group wrote.


The researchers started looking into the the role of ACTH after noting that ACTH-producing adenomas result in a profound glucocorticoid excess but not osteonecrosis.


They gave rabbits 10 mg/kg depot methylprednisolone acetate, which consistently produced damage to bone in the femoral head within 28 days.


Half the rabbits also received 0.2 μg/kg ACTH in the form of subcutaneous cosyntropin injections daily, which normalized ACTH serum levels for about three hours.


Bone scans showed a small effect of ACTH on density of the femoral head: it was 10% greater with the hormone.


There was a highly significant approximately 50% reduction in the necrotic surface area in femora from the rabbits treated with MPA plus ACTH compared with those given the glucocorticoid alone.


The explanation for this and the other morphological results appeared to be that ACTH supported osteoblast activity, the researchers wrote.


Quantitative PCR indicated significantly greater vascular endothelial growth factor (VEGF) mRNA expression in bone marrow of rabbits that got ACTH compared with those on methylprednisolone alone.


VEGF might maintain viability of components of the bone matrix given its central role in bone development and homeostasis, Zaidi's group noted.


"The femoral head is a site of high bone turnover, with formation and resorption occurring continuously over a large fraction of the total surface area," they explained in the paper. "This surface area is also embedded with an extensive capillary network; this means that the maintenance and regeneration of capillaries requires support by molecules such as VEGF."


Further testing suggested that ACTH stimulated production of VEGF in osteoblasts, not monocytes, and that the glucocorticoid dexamethasone profoundly inhibited monocyte-induced VEGF production, "probably as one of several mechanisms that initiate osteonecrosis," the researchers wrote.


The effect of ACTH appeared VEGF-dependent in cell line experiments with ACTH-stimulated VEGF production apparently through the ACTH receptor MC2R.


The investigators didn't look at whether this mechanism is a normal feature of bone mass regulation in the absence of glucocorticoid treatment. They noted, though, that results from patients with familial glucocorticoid deficiency and adrenal Cushing's syndrome support "at least a small anabolic effect of ACTH, which seemingly counteracts the bone loss due to cortisol."


Zaidi said that because synthetic ACTH would be dosed to restore the naturally occurring hormone levels and is already in clinical use for testing adrenal sufficiency there shouldn't be any safety concerns with long-term use in patients on glucocorticoids.


However, the protective effect wouldn't extend to patients who already have developed osteonecrosis, he told MedPage Today.


"The idea is to prevent," he said in the interview. "Once that part of the bone is dead, I can't see any logical way to bring it back to life again."


The study was supported by grants from the National Institutes of Health and by the American Federation for Aging Research.


Primary source: Proceedings of the National Academy of Sciences
Source reference:
Zaidi M, et al "ACTH protects against glucocorticoid-induced osteonecrosis of bone" Proc Natl Acad Sci 2010; DOI:10.1073/pnas.0912176107