News Items:

General Cushing's Info:

From http://jcem.endojournals.org/cgi/content/abstract/79/3/887

Patient's age is a simple predictive factor for the development of Nelson's syndrome after total adrenalectomy for Cushing's disease

L Kemink, G Pieters, A Hermus, A Smals and P Kloppenborg
Department of Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.

Reportedly between 8-38% of patients who receive bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. We investigated which factors may predict the development of the syndrome. Eight of 48 patients, bilaterally adrenalectomized for pituitary-dependent Cushing's syndrome 1-30 yr previously, developed Nelson's syndrome 1.5-13 yr (6.6 +/- 4.3 yr) after adrenalectomy. The mean age at adrenalectomy in the group of patients who developed Nelson's syndrome was significantly lower than that in the group without the syndrome (mean +/- SD, 26.0 +/- 6.0 and 35.6 +/- 11.7 yr, respectively; P < 0.02). In the patients adrenalectomized before the age of 35 yr, 8 of 27 (30%) developed Nelson's syndrome, whereas in the patients older than 35 yr, no one did (P < 0.02). No statistically significant differences between the two groups were found in sex ratio, duration of disease before adrenalectomy, or duration of follow-up thereafter. There were no statistically significant differences between the two groups in mean plasma cortisol and ACTH levels before adrenalectomy, cortisol suppressibility after the administration of 8 and 16 mg dexamethasone, or cortisol responses to CRH, TRH, and LH- releasing hormone before adrenalectomy. We conclude that age at the time of adrenalectomy is an important predictive factor for the development of Nelson's syndrome.

Full PDF: here

From http://www.eje-online.org/cgi/content/full/153/4/503?ck=nck

European Journal of Endocrinology, Vol 153, Issue 4, 503-505
Copyright © 2005 by Society of the European Journal of Endocrinology

Rosiglitazone for prevention or adjuvant treatment of Nelson’s syndrome after bilateral adrenalectomy

Mikkel Andreassen and Lars Østergaard Kristensen

Department of Endocrinology and Internal Medicine, J 106, Herlev Hospital, University of Copenhagen, Herlev Ringvej, 2730 Herlev, Denmark

(Correspondence should be addressed to M Andreassen; Email: andreassenmikkel@hotmail.com)

Abstract

Objective: To investigate the effect of Rosiglitazone in three patients treated with bilateral adrenalectomy followed by hyperpigmentationand hypersecretion of ACTH.

Patients and methods: One patient had increasing ACTH after previous transsphenoidal surgery for Nelson’s syndrome,and two patients without pituitary adenomas had recurrence of Cushing’s disease after primary and repeated transsphenoidal surgery with need for bilateral adrenalectomy. The patients developed hyperpigmentation and increasing ACTH at nadir 2–4h after morning hydrocortisone dose. ACTH during Rosiglitazone therapy (4 mg/day for 4 weeks and then 8 mg/day) was measuredat regular intervals 24 h after the latest dose of hydrocortisone.

Results: In two patients there was a decrease in ACTH by 40% after 5 months. The first of these patients showed an escape with increasing ACTH to the initial value after 11 months. In the third patient no effect was observed. Tumour development or progression on magnetic resonance imaging was not observed.

Conclusion: Rosiglitazone might represent an adjuvant therapy in patients with ACTH hypersecretion. Larger long-term studies are needed.

Introduction

Bilateral adrenalectomy is an option of treatment after unsuccessful transsphenoidal surgery (TSS) and recurrence of Cushing’s disease. A considerable fraction of these patients need bilateral adrenalectomy (1). A complication of bilateral adrenalectomyis Nelson’s syndrome with adrenocorticotrophin (ACTH)hypersecretion, hyperpigmentation and possibly development ofpituitary tumour. Radiotherapy is partially prophylactic, butimplicates the risk of pituitary insufficiency and also damageof the optic chiasma. Therefore, the recent suggestion for treatmentis TSS in cases with tumour, but tumour is not always present.An acute effect of bromocriptine in Nelson’s syndromehas been observed (2) and long-term remission with cabergolinehas been reported in a single patient (3).

Peroxisome proliferator-activating receptor- (PPAR-) is a memberof the nuclear hormone receptor superfamily (4, 5). PPAR- receptorsare predominantly expressed in adipose tissue (6, 7). Importantlyin this context it has recently been shown that PPAR- is alsoexpressed in normal ACTH-secreting cells and abundantly in ACTH-secretingtumour cells (8).

Rosiglitazone is a PPAR- ligand. It is a member of the thiazolidinedioneclass of insulin-sensitizing drugs. In vitro treatment of human ACTH-secreting pituitary tumour cells with Rosiglitazone leadsto enhanced apoptosis and decreased cell division and in vivo studies reveal that Rosiglitazone is able to inhibit ACTH secretion and tumour growth in mice (8). Furthermore, Rosiglitazone hasbeen used as short-term therapy in Cushing’s disease inhumans (9). Based on these observations we have employed Rosiglitazonein three patients with Nelson’s syndrome.

Patients and methods

Patients

Patient 1 was a 67-year-old female with Cushing’s disease diagnosed in 1970. Primary treatment was bilateral adrenalectomy. Gradually increasing ACTH and hyperpigmentation was observedfrom about 1990. In 1998 magnetic resonance imaging (MRI) showeda pituitary adenoma with suprasellar extension close to theoptic chiasma. TSS was performed with temporary improvement,but in 2002 there was recurrence of Nelson’s syndromewith increasing ACTH and relapse of a small (7 x 7 x 3 mm) pituitaryadenoma.

Patient 2 was a 74-year-old male with Cushing’s disease diagnosed in 1993. Initially successful treatment with TSS was performed, but in 1999 recurrence was diagnosed. Another TSSwas attempted without success, and in 2000 bilateral adrenalectomy was performed. 2 years later hyperpigmentation and increasing ACTH occurred. There was no visible tumour on MRI.

Patient 3 was a 37-year-old female with Cushing’s disease diagnosed in 2002. TSS was performed as a primary treatment without cure and a second TSS was also ineffective, whereafter laparascopically bilateral adrenalectomy was done. Due to residual disease activity a second open operation was performed on the left adrenal gland. Clinically the patient was cured and hydrocortisone-replacementtherapy was initiated but, apparently, low endogenous cortisolproduction was still present. Since 2003 the patient has shownhyperpigmentation and increasing ACTH, but there is no visibletumour on MRI.

All patients received hydrocortisone-replacement therapy of 20–30 mg/day divided into two or three doses.

Methods

During Rosiglitazone therapy (4 mg/day for 4 weeks and then8 mg/day) ACTH was measured at regular intervals 24 h afterthe latest dose of hydrocortisone at nadir cortisol, when zenithACTH could be expected.

Plasma ACTH was measured with a high-detectability immunoradiometric assay (DYNOtest; BRAHMS Diagnostica GmbH, Berlin, Germany). The normal range is 1.8–12 pM. Serum cortisol was measuredwith RIA (Diagnostic System Laboratories, Webster, TX, USA);the lower limit of detection was 10 nM.

No side effects were reported, including any episodes of hypoglycaemia. Liver-function tests were performed at every visit and remained normal during the study. This retrospective report was approved by the Danish Data Protection Agency, Copenhagen.

Results

Figure 1 shows ACTH during Rosiglitazone treatment. Patients1 and 2 showed a gradual decrease in ACTH by 40% after 3–6months (patient 1 from 1290 to 765 pM and patient 2 from 478to 289 pM). However, in patient 1 there was an escape after5 months of treatment, with ACTH increasing to the initial value,and the treatment has now been paused. Patient 3 received Rosiglitazone for 1 year, during which time no effect on ACTH was observed,and the treatment has recently been stopped and so far no increasein ACTH has been observed. Hyperpigmentation did not improvein any of the patients.
 

View larger version (17K): [in this window] [in a new window]  Figure 1 Plasma ACTH (pM) during Rosiglitazone treatment. Measurements of ACTH were taken 24 h after the latest hydrocortisone dose.

MRI of the pituitary showed no evidence of tumour progression in patient 1 and no development of tumours in patients 2 and3.

Discussion

Hypersecretion of ACTH with hyperpigmentation is the key characteristic of Nelson’s syndrome and an obvious pituitary tumour isnot always present (10). According to this criterion there isno doubt that our three patients had Nelson’s syndrome.

In two of the patients Rosiglitazone treatment lead to a significant decrease in ACTH, assumed to reflect secretion, but in one of these patients there was an escape of the effect. The third patient did not respond. This patient had low residual endogenous cortisol production, which might be of some importance in reducing corticotrophic ACTH secretion and cell proliferation. Concerning cell proliferation it should be noted that the residual tumour in one patient did not progress and that tumour development was not observed in the other two patients.

In order to separate potential responders from nonresponders it would have been of interest to evaluate PPAR- receptor expressionin tumours already removed, but such an analysis was not performed.However, Ambrosi et al. (9) observed no correlation betweenPPAR- expression and response to Rosiglitazone in patients with Cushing’s disease.

Rosiglitazone did not lead to normalization of ACTH in any of our patients. However, it seems worthwhile to consider an attempt of such treatment in patients with Nelson’s syndrome without obvious tumours and possibly in patients after unsuccessfulTSS for a pituitary adenoma hypersecreting ACTH. Furthermore,the medical treatment might be used in concert with radiotherapy during the time period awaiting the effect of radiation.

PPAR- is also expressed in a variety of other pituitary tumours(6). This current information and the present results pointto the possibility that thiazolidinedione represents an optionof treatment for Nelson’s syndrome and, potentially, otherpituitary tumors. Larger long-term studies are needed to elucidatethe answers to these questions. A new generation of thiazolidinediones developed selectively for this specific purpose would be of considerable interest. This may bring about a change in the strategy towards medical treatment of a variety of pituitary tumors, analogous to the well-established first-line medical treatment of prolactinomas with dopamine agonists.

Acknowledgements

We thank chief laboratory technician Ulla Kjerulff-Hansen and her team for skilled technical assistance.

References

1. Rees DA, Hanna FWF, Davies JS, Mils RG, Vafidis J & Scanion MF. Long-term follow-up results of Cushing’s disease in a single centre using strict criteria for remission. Clinical Endocrinology 2002 56 541–551.
2. Leilani B, Mercado-Asis LB, Yanovski JA, Tracer HL, Chik CL & Cutler CB. Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson’s syndrome. Journal of Clinical Endocrinology and Metabolism 1997 82 514–517.
3. Pivonello R, Faggiano A, Di Salle F, Filippella M, Lombardi G & Colao A. Complete remission of Nelson’s syndrome after 1-year treatment with cabergoline. Journal of Endocrinological Investigation 1999 11 860–865.
4. Spiegelman BM. PPAR-: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998 47 507–514.
5. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P & Evans RM. The nuclear receptor superfamily: the second decade. Cell 1995 83 835–839.
6. Heaney AP. Novel pituitary ligands: peroxisome proliferator activating receptor-. Pituitary 2003 6 153–159.
7. Heaney AP, Fernando M & Melmed S. PPAR- receptor ligands: novel therapy for pituitary adenomas. Journal of Clinical Investigation 2003 111 1381–1388.
8. Heaney AP, Fernando M, Yong WH & Melmed S. Functional PPAR- receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nature Medicine 2002 8 1281–1287.
9. Ambrosi B, Dall’Asta C, Cannavo S, Libé R, Vigo T, Epaminonda P, Chiodini I, Ferrero S, Trimarchi F, Arosio M & Beck-Peccoz P. Effects of chronic administration of PPAR- ligand rosiglitazone in Cushing’s disease. European Journal of Endocrinology 2004 151 173–178.
10. Kelly PA, Samandouras G, Grossman AB, Afshar F, Besser GM & Jenkins PJ. Neurosurgical treatment of Nelson’s syndrome. Journal of Clinical Endocrinology and Metabolism 2002 87 5465–5469.

Full PDF: Full Text (PDF)

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From http://www.emaxhealth.com/24/8215.html

Google Helping Doctors Diagnose Difficult Cases
Google For A Diagnosis

Searching with Google may help doctors to diagnose difficult cases, finds a study from Australia published on bmj.com today.

Doctors have been estimated to carry two million facts in their heads to help them diagnose illness, but with medical knowledge expanding rapidly, even this may not be enough. Google is the most popular search engine on the world wide web, giving users quick access to more than three billion medical articles.

So, how good is Google in helping doctors diagnose difficult cases?

Doctors at the Princess Alexandra Hospital in Brisbane identified 26 difficult diagnostic cases published in the New England Journal of Medicine in 2005. They included conditions such as Cushing's syndrome and Creutzfeldt-Jakob disease.

They selected three to five search terms from each case and did a Google search while blind to the correct diagnoses.

They then selected and recorded the three diagnoses that were ranked most prominently and seemed to fit the symptoms and signs, and compared the results with the correct diagnoses as published in the journal.

Google searches found the correct diagnosis in 15 (58%) of cases.

The authors suggest that Google is likely to be a useful aid for conditions with unique symptoms and signs that can easily be used as search terms.

However, they stress that the efficiency of the search and the usefulness of the retrieved information depend on the searchers' knowledge base.

Doctors and patients are increasingly using the internet to search for health related information, and useful information on even the rarest medical syndromes can now be found and digested within a matter of minutes, say the authors.

"Our study suggests that in difficult diagnostic cases, it is often useful to google for a diagnosis."

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From http://www.abc.net.au/news/newsitems/200611/s1785466.htm

Doctors use Google to diagnose disease: study
By Anna Salleh, ABC Science Online

It is not just patients who are frantically plugging their symptoms into Google to see what disease they might have, Australian researchers say doctors are doing it too.

Dr Hangwi Tang and Dr Jennifer Ng of the Princess Alexandra Hospital in Brisbane have reported their findings online in the British Medical Journal.

Dr Tang says the study was driven by personal curiosity after noticing how patients and doctors alike were using Google to diagnose difficult cases.

In one example he had a patient whose father used the search engine to correctly diagnose that his son had the rare circulatory condition -Paget-von Schrötter syndrome.

Dr Tang and Dr Ng selected 26 difficult cases presented in the New England Journal of Medicine, including Cushing's syndrome, Creutzfeldt-Jakob disease, encephalitis and cirrhosis.

They then plugged the symptoms of each case into the search engine to come up with a diagnosis.

When these diagnoses were compared with the correct published diagnoses, the researchers found that Google got it right 58 per cent of the time.

They say an online search is likely to be more effective at helping to diagnose conditions with unique symptoms that can be used as search terms.

Dr Tang says part of the challenge in using Google is to be able to efficiently sift through the many pages of links that you get from an online search.

He thinks that doctors are better placed than patients at doing this because they are better at selecting relevant links.

"I don't think Google can replace doctors, in other words," said Dr Tang. Millions of facts

Doctors have been estimated to carry 2 million facts in their heads to help them to diagnose disease, the researchers say.

But search engines allow them to get quick access to an ever increasing medical knowledge base that might be impossible to hold in their head.

Google in particular gives access to more than 3 billion articles, they say, with Google Scholar restricting searches to peer reviewed articles.

Dr Tang says while there are a number of other search engines that clinicians can use, they often prefer Google because it is so easy to use and freely available. Other studies

Professor Johanna Westbrook of the Centre for Health Informatics in Sydney says the findings are consistent with her own.

Her team looked at how specialised search engines could help clinicians to both diagnose and treat patients, using the best available evidence.

The study found clinicians were 21 per cent more likely to give the correct answers when they used online search engines.

Interestingly though, a few clinicians got the wrong answers using the search engines, although they got the right answers without them.

Professor Westbrook says this underscores the importance of learning how to interpret complex evidence.

Another interesting finding was that clinical nurse consultants using the search engines were just as accurate as doctors.

Professor Westbrook says this suggests search engines might help such nurses to diagnose and treat patients in rural areas where there are fewer doctors.

"[An online search engine is] available 24 hours a day," she said.

"Whereas you can't get a clinician 24 hours a day. You can't get to a hospital library 24 hours a day."

Professor Westbrook says that while Google might be good for helping find information about diseases with unique symptoms, more sophisticated search engines would be required for more complex diseases.

Is Google Really The New GP Service?
Life Style Extra - UK
... 26 difficult diagnostic cases published in the New England Journal of Medicine last year, including obscure conditions such as Cushing's syndrome and ...

GPs should Google diagnosis: study
Ninemsn - Sydney,New South Wales,Australia
... The doctors collected journal articles about 26 rare diseases like endocrine condition Cushing's syndrome and the fatal brain disorder Creutzfeldt-Jakob disease ...

'Googling' may help doctors diagnose
Irish Health - Ireland
... They included conditions such as Creutzfeldt-Jakob disease - a very rare form of dementia - and Cushing's syndrome, which is a rare hormonal disorder. ...

Doctors turn to Google for tricky cases
Guardian Unlimited - UK
... The conditions correctly diagnosed by Google included Creutzfeldt-Jakob disease, the hormonal disorder Cushing's syndrome, acute chest syndrome - a ...

Will Your Doctor Google You?
Blogcritics.org - Aurora,OH,USA
... The two they used (of 26 “hard-to-diagnose” cases), found in the New England Journal of Medicine, were Cushing's syndrome and CJD (Creutzfeldt-Jakob disease ...

Adrenal:

From http://thyroid.about.com/od/drsrichkarileeshames/a/thyroidadrenal.htm

From Richard Shames, MD and Karilee Shames, PhD, RN

Very few conditions are as frustrating as a combined thyroid/adrenal challenge. Frequently, the adrenal insufficiency is undiagnosed. If you have been fortunate enough to be diagnosed and treated for thyroid problems, but this treatment hasn't been fully successful, there may be additional information you need in order to feel well.

The thyroid/adrenal issue was given one chapter in our previous book THYROID POWER. Based on responses of patients and readers, our new book FEELING FAT, FUZZY, OR FRAZZLED gives equal weight to thyroid, adrenal, and sex hormone interrelations. We have found that this new approach has tremendous benefitted people who had otherwise been struggling for years, despite regular thyroid care -- sometimes even very good thyroid care by top practitioners.

Whether thyroid treatment -- be it alternative, over-the-counter, or by prescription -- works properly is entirely dependent on your adrenal function.

Many people with low thyroid -- standard hypothyroidism -- have the same immune difficulty with their adrenal gland as they do with the thyroid, an adrenal fatigue situation.

Most all low thyroid is due to Hashimoto's autoimmune thyroiditis. A frequent co-existent condition with thyroiditis is adrenalitis. It is generally mild enough to go undetected, yet serious enough to interfere with thyroid hormone's function in your tissues.

You might be dealing with a combined thyroid/adrenal problem if you are a thyroid sufferer and:

• you have particularly low stamina for stress
• you have excess mood responses after eating carbs (hypoglycemia)
• you have particularly low blood pressure (momentary lightheadedness upon standing up)
• you have chronic allergies
• you are feeling "tired but wired"
• you have your best energy when others are getting ready for bed
• you have poor resistance to respiratory infections
• you have cystic breasts
• you have difficulty recuperating from extra exertion or jet lag

In fact, in our new book we refer to this as the "emotional (adrenal-driven) endo-type", a low adrenal situation compounded by low thyroid.

The main way you can help your practitioner succeed with combined therapy of any sort is to realize that you need to alternate interventions (much like climbing a ladder, left foot, right foot alternating). This means starting with a very small amount of adrenal support first (natural, OTC, or prescription in very minute dosage). After that initial support for a week, there is frequently needed a slight boost in thyroid support for another week. Then, a small addition to the adrenal support for the next week; after that, a further small increase in thyroid support.

This dual upward titration approach (what our colleagues have called "The Shames Ladder") is often successful when other types of intervention have failed. This is because a mixed thyroiditis/adrenalitis is a very sensitive situation. Each gland needs the other for support. You can't simply boost one without also boosting the other, and can't do it well by giving big doses of either at any one time. The glands need to gradually adapt to the new environment of expanded function.

Details of exactly how this dual therapy approach would best be accomplished are available in our books, websites, and through individual coaching sessions. The point we want to make here is that if you have been struggling to reach more optimal thyroid balance, this new process has been amazingly gratifying to us and our patients. We offer it to you with the hope that you can personalize it to reach your highest potential, and to live your fullest life.

Richard Shames MD
Karilee Shames PhD, RN
www.FeelingFFF.com
For more information, please send an email to keepmeposted@feelingfff.com

Upcoming Conventions, Meetings and Seminars:

December 7-10, 2006, "December in the Desert 2006" Conference, Rancho Mirage, California.
More info here 

December Dec 13, 2006, Pittsburg, PA, More info on the message boards.
Click for map and directions.

December Dec 13, 2006, UCLA (CA) Bi-monthly Pituitary Patient Support Group, more info and directions here

February 9 to 11, 2007, MAGIC Foundation (Growth Hormone) Adult Educational Convention, Las Vegas, NV, More info.

June 2-5, 2007, ENDO 2007, Toronto, Canada, Metro Toronto Center. More info as it becomes available.

More upcoming local meetings are listed here