Pancreatic islet cell carcinoma presenting with concurrent Cushing's and Zollinger-Ellison syndromes: case series and literature review

European Journal of Gastroenterology & Hepatology:

February 2010 - Volume 22 - Issue 2 - pp 246-252

doi: 10.1097/MEG.0b013e3283314827

Case Reports

Said, Rabih

Cushing's syndrome and Zollinger–Ellison syndrome occur occasionally as a result of neuroendocrine cancers. The concurrence of the two syndromes has been considered to confer a poor clinical and therapeutic outcome.

In this study, we are reviewing two patients with pancreatic islet cell carcinomas and with both Zollinger–Ellison and Cushing's syndromes, one followed up for more than 5 years, and the other still receiving therapy, 5 years since diagnosis. A literature review showed that surgery has limited utility as the majority of these patients had metastases at the time of diagnosis.

Proton-pump inhibitors, ketoconazole, and somatostatin antagonists have a major role in controlling symptoms. Interferon and systemic chemotherapeutic agents play a role in the management of metastatic and fast-growing cases. Chemoembolization and bland embolization show encouraging results in controlling liver metastases. The latter was used effectively and more than once in the two patients presented herein.

On the basis of recent molecular genetics studies, target therapy may be helpful, however, ongoing trials will define it's utility. As the data confers a worse prognosis versus other pancreatic neuroendocrine tumors, the relatively favorable outcome of the two patients reported herein may reflect the impact of multiple therapeutic modalities.

From http://journals.lww.com/eurojgh/Abstract/2010/02000/Pancreatic_islet_cell_carcinoma_presenting_with.20.aspx

Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma

E Pimenta, R D Gordon, A H Ahmed, D Cowley, D Robson, C Kogovsek and M Stowasser

 

Abstract

Experimental and human data suggest that adverse cardiovascular (CV) and renal effects of aldosterone excess are dependent on concomitant dietary salt intake.

Increased urinary protein (Uprot) is an early sign of nephropathy independently associated with CV risk. We have previously reported a positive association between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but not in patients with normal aldosterone levels.

 

We aimed to determine whether Uprot is related to UNa in patients with aldosterone-producing adenoma (APA) and whether the degree of Uprot and strength of this relationship is reduced following correction of hyperaldosteronism. Subjects with APA (n=24) underwent measurement of 24 h Uprot and UNa before and after unilateral adrenalectomy (follow-up 15.0±11.9 months).

 

Following surgery, mean clinic systolic blood pressure fell (150.4±18.2 vs 134.5±14.5 mm Hg, P=0.0008), despite a reduction in number of antihypertensive medications, and Uprot (211.2±101.6 vs 106.0±41.8 mg per day, P<0.0001) decreased. There was a positive correlation between Uprot and UNa both before (r=0.5477, P=0.0056) and after (r=0.5097, P=0.0109) adrenalectomy. Changes in UNa independently predicted Uprot reduction (P=0.0189).

 

These findings suggest that both aldosterone levels and dietary salt contribute to renal damage, and that once glomerular damage occurs it is not completely resolved following correction of hyperaldosteronism. Our study suggests that treatment strategies based on reduction of aldosterone effects, by adrenalectomy or mineralocorticoid receptor blockade, in conjunction with low-salt diet would provide additional target-organ protection in patients with primary aldosteronism.

 

From http://www.nature.com/jhh/journal/vaop/ncurrent/full/jhh2010102a.html

Art Russell's Free PDF book on Cushing's

We all face hard times at one point in our lives. But the times when we question our faith, and question our ability to move on are especially important. Do we trust in God? Do we trust in ourselves?

Something as bad as a fatal illness can cause fear, doubt, and questions about what you are doing on this earth. Pain takes over and renders us helpless and willing to throw in the towel and give up. But God tells us that He will sustain us. He will lift us up.

Art Russell shares the powerful story of his struggle with Cushing's Disease. Although unfamiliar to most people, Cushing's is a potentially fatal disease that strips the victim's life away piece by piece. As you read, you will get an up close and personal look into the life of someone plagued with Cushing's disease and his daily struggles. Discover Scriptural passages he surrounded himself with.

Read his honest, open cries to God and discover how in the midst of pain and uncertainty, he fights to keep his faith strong and find rest in God.

Read Art's book free in PDF format

Potassium & Cushing's Disease

Overview

Cushing's disease is a hormonal disorder. In this syndrome, there are excessive amounts of the hormone cortisol in the body. Cortisol is made in the adrenal glands and is released in response to stress. It has many effects on the body, including lowering potassium levels, which can cause more symptoms and problems.

Causes

According to "Harrison's Principles of Internal Medicine" by Dr. Anthony Fauci, the most common cause of Cushing's syndrome is the administration of cortisol-like drugs, called corticosteroids or just steroids. These drugs are prescribed for numerous conditions involving inflammation, such as asthma or rheumatoid arthritis. They are usually not taken chronically in high doses due to the risk of developing Cushing's. Tumors in the pituitary, a gland below the brain, or in the adrenal glands above the kidneys can also cause the disease, as can some tumors elsewhere in the body that make hormones stimulating the adrenal glands. Some hereditary conditions also can cause the disorder.

Mechanism

The hormone aldosterone is also produced by the adrenal glands. One effect it has is to lower the level of potassium in the body by binding to receptors in the kidney. Cortisol has similar structure to aldosterone and also binds to these kidney receptors, though not as strongly. The result is that cortisol also causes the kidneys to get rid of potassium through the urine, though to a lesser degree than aldosterone. This leads to lower potassium in the blood.

Symptoms and Signs

Cushing's disease produces multiple symptoms and signs. If it causes the potassium to get too low, this will also produce further problems. According to "William's Textbook of Endocrinology" by Dr. Henry M. Kronenberg, common signs of Cushing's include redistribution of fat such that the abdomen, upper body, face and neck tend to be fat relative to the arms and legs. The skin will be fragile and bruise easily. Fatigue, weakness, high blood sugar and blood pressure, mood swings and increased thirst are also common. In addition, sexual desire and fertility may be adversely affected. Low potassium may be without symptoms but can cause weakness and abnormal heart rhythms.

Diagnosis

Cortisol can be tested for in the urine, blood and saliva. Usually, urine cortisol is tested by collecting 24 hours of worth of urine. Blood and saliva are typically tested late at night because that is when the cortisol levels are naturally lowest but will be elevated in people with the disease. Another approach is too give a powerful drug that normally suppresses cortisol production, called dexamethasone, to monitor if the levels of cortisol stay elevated, indicating Cushing's. The diagnosis of low potassium is made by a blood test.

Treatment

Treatment of Cushing's syndrome depends on the cause. Tumors will need to be removed. Inoperable tumors may require radiation or chemotherapy. Low potassium caused by Cushing's disease is ultimately treated by correcting the Cushing's. While the potassium is low, however, oral or IV potassium can be given.

References

• "Harrison's Principles of Internal Medicine"; Anthony S. Fauci et al; 17th Ed.; 2008
• "Williams Textbook of Endocrinology"; Henry M. Kronenberg et al; 11th Ed.; 2007

Read more: http://www.livestrong.com/article/303872-potassium-cushings-disease/#ixzz15BWUEXlM

Adrenal Crisis Tips

From Ellen, on the Cushing's Help Message Boards

I have a very good friend who has had more adrenal crises than anyone care to count (more than 20). She has tried hard to teach me some important things for the day I should ever have a crisis. Among them is the reality that (as before surgery) success of your care depends on YOU getting everything prepared for the worst as best you can. We can no more depend on the ER staff than any other doc out there who isn't a specialist in pituitary medicine. You all have already done much of preparing by having your medic alert bracelets on, your injectable Cortef (bring it with you in case they don't have it there) and your letter from Dr. F. But that isn't enough much of the time as you have painfully discovered.

1) Prevention is the key. You, Mary, are SO overdoing it, I don't know what to say. You shouldn't even be leaving your house right now, let alone taking on the care of small children. You need a good talking to, missy. Perhaps you can choose to do ONE easy task a day but overall-you should be bored out of your gourd sitting on your tuckus. The more you do, the more you risk events like this. The hardest part is understanding that recovery is not a linear improvement every day. You are going to have weeks or maybe months where you can do no more than you did the first week after surgery. This recovery takes a long time when surgery works. Each tiny task you accomplish depletes you in an additive way. It might not have seemed much at the time to unload the dishwasher but you better believe it counts when you add in each additional task you want to accomplish.

2) Everything is additive. It isn't just what you did today but also what you did the last three, four or five days. You may have felt good the first day but each successive day my guess is you could feel your body pushing a bit. I find I say things like, "If I could just get this ONE more job done, then I will rest" before I am off to the next job. Before I know it, it is too late. Think hard about the twinges you feel the days before this happened this time around, when you were tired. How do you feel in the evenings after a day of activity? Those are the signs to look for and treat early the next time. You are having to listen to your body in a whole new way. Learn your earliest signs.

3) Take more Cortef when you first get those twinges above--the days before a crisis might strike.

4) Everyone in your household needs to be trained to give you Cortef. Teach them that confusion on your part indicates a crisis coming on-if you aren't making sense they need to understand that YOU are not able to help yourself. In most cases the oral cortef will keep you out of the ER if someone else makes sure you take it. Don't hesitate, don't let yourself talk them out of helping you-just take it-it is better to err high than low with your history of crises right now.

5) Knowing that in spite of all of this you need ER care potentially, consider calling the liason in person and talking real-time about your needs for future visits-explaining how quickly things become life threatening. They need to have something about your history in the computer already-a copy of that letter from Dr. F plus their own notes that it is on the up and up along with the note to please page your doctor. Give them a recipe to follow that they have pre-approved and it will help greatly. Most ER doctors will never see an adrenal crisis patient in their ER. Doctors have limits on their abilities just as everyone else does. I can read English really well but if you handed me a book written by someone in 1610, I would likely take longer to get through it because I am not as familiar with the format...the 'wherefore art thous' are English but they sure slow you down. That is what happens in the ER to Addisonians...doctors eventually get there but it takes longer because it is unfamiliar. Help them out by giving them the Cliff-Notes before you ever get there.

5A) Also insist that for now they order and keep Solu-Cortef on the shelves for you. Many (most?) hospitals do NOT have it stocked, as my friend discovered over and over again when she went to the ER. It took hours for them to track some down and give it to her. In the meantime, she was getting sicker and sicker. She finally asked the liason to help be certain they had it for her, ready to go. Now, they have it ready for her, they know her and they know what to do. She is often out of there in about 3 hours.

6) If you are vomiting/collapsed clearly in serious trouble, by the time you head off to the ER, call 911/ambulance so you get taken in and cared for without waiting. Your life is at risk by that stage and you need immediate care. It is justified and potentially life-saving.

7) Always have a trained advocate with you, have several back ups in your life. My friend has her husband but she also has me ready to go-have the hospital list several people to call ahead of time in case you arrive on your own and they can't reach your primary person. Your advocates need to know what to do independently of you. They need to know what to say and how to push the ER staff to get things done on your behalf. We, as patients struggling with Cushing's, are used to having to push but most people are very intimidated by medical personnel and often hang back, figuring they must know what to do. Make sure they understand this just isn't the case sometimes and that your life may depend on what they say or get the staff to do. It is critical they contact your endocrinologist-have your advocate INSIST they do this. If they won't, have your advocate page the doctor for you. Be sure you go over a plan with your advocate periodically or answer their questions about what may happen. I went over much of my plan with my husband prior to my surgery but discovered that within days of surgery, he had forgotten most of what I said. He really wanted to help but just hadn't taken in the medical stuff because it was overwhelming and scary. Keep going over it until they are comfortable.

I really hope these are the last ER visits for you all. I have agonized each time my friend goes into another crisis. I know that in spite of everything you do (or don't do) to prevent a crisis, they still happen. Hopefully the next time around, everything will be in place for you all to have a smooth experience.

So, sit down, turn on that television and get comfy girls. TAKE IT EASY!!

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma-knife?

Josef Marek, Jana Jezkova, Vaclav Hana, Michal Krsek, Lubomira Bandurova, Ladislav Pecen, Vilibald Vladyka and Roman Liscak

J Marek, 3 Dept. of Medicine, Charles University in Prague, Prague, 128 08, Czech Republic
J Jezkova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha 2, 12802, Czech Republic
V Hana, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
M Krsek, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Bandurova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Pecen, Institute of Informatics of the Czech Academy of Science, Praha, Czech Republic
V Vladyka, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic
R Liscak, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic

Correspondence: Jana Jezkova, Email: fjjezek@cmail.cz

Objective: Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism.

Design and methods: We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary < 15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001- 2009 (40 patients), irradiated with a mean dose to pituitary > 15 Gy. Serum TSH, free thyroxine, testosterone or 17?–estradiol, IGF 1, prolactin and cortisol levels were evaluated before and every six months after LGN irradiation.

Results: Hypopituitarism after LGK irradiation developed only in one out of 45 (2.2%) patients irradiated with a mean dose to pituitary < 15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose 17 Gy.

Conclusion: Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

 

From http://www.eje.org/cgi/content/abstract/EJE-10-0733v1

Regulation of Placental Growth by Aldosterone and Cortisol

Endocrinology, doi:10.1210/en.2010-0525

Carine Gennari-Moser, Eliyahu V. Khankin, Simone Schüller, Geneviève Escher, Brigitte M. Frey, C.-Bettina Portmann, Marc U. Baumann, Andrea D. Lehmann, Daniel Surbek, S. Ananth Karumanchi, Felix J. Frey, and Markus G. Mohaupt*

Departments of Nephrology/Hypertension (C.G.-M., S.S., G.E., B.M.F., F.J.F., M.G.M.) and Obstetrics and Gynecology (C.-B.P., M.U.B., D.S.), University Hospital Bern, Inselspital, 3010 Berne, Switzerland; Division of Vascular and Molecular Medicine (E.V.K., S.A.K.), Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; and Division of Histology (A.D.L.), Institute of Anatomy, University of Bern, 3000 Berne, Switzerland

* To whom correspondence should be addressed. E-mail: markus.mohaupt@insel.ch.

During pregnancy, trophoblasts grow to adapt the feto-maternal unit to fetal requirements. Aldosterone and cortisol levels increase, the latter being inactivated by a healthy placenta. By contrast, preeclamptic placental growth is reduced while aldosterone levels are low and placental cortisol tissue levels are high due to improper deactivation. Aldosterone acts as a growth factor in many tissues, whereas cortisol inhibits growth.

We hypothesized that in preeclampsia low aldosterone and enhanced cortisol availability might mutually affect placental growth and function. Proliferation of cultured human trophoblasts was time- and dose-dependently increased with aldosterone (P < 0.04 to P < 0.0001) and inhibited by spironolactone and glucocorticoids (P < 0.01). Mineralo- and glucocorticoid receptor expression and activation upon agonist stimulation was verified by visualization of nuclear translocation of the receptors.

Functional aldosterone deficiency simulated in pregnant mice by spironolactone treatment (15 ?g/g body weight/day) led to a reduced fetal umbilical blood flow (P < 0.05). In rat (P < 0.05; R2 = 0.2055) and human (X2 = 3.85; P = 0.0249) pregnancy, placental size was positively related to plasma aldosterone.

Autocrine production of these steroid hormones was excluded functionally and via the absence of specific enzymatic transcripts for CYP11B2 and CYP11B1. In conclusion, activation of mineralocorticoid receptors by maternal aldosterone appears to be required for trophoblast growth and a normal feto-placental function.

Thus, low aldosterone levels and enhanced cortisol availability may be one explanation for the reduced placental size in preeclampsia and related disorders.

 

From http://endo.endojournals.org/cgi/content/abstract/en.2010-0525v1

(Corlux) Corcept 3Q loss widens as research costs rise

Drug developer Corcept Therapeutics Inc. said Wednesday its third-quarter loss widened as expenses rose in part due to late-stage clinical research.

The Menlo Park, Calif., company lost $7.1 million, or 10 cents per share, in the three months that ended Sept. 30. That compares with a loss of $4.7 million, or 9 cents per share, in the same quarter last year. The company reported no revenue from either quarter.

Analysts polled by Thomson Reuters expected, on average, a loss of 10 cents per share on no revenue.

Corcept is running a late-stage trial of its drug candidate Corlux, and it expects to report results by the end of the year. It is studying the drug as a treatment for the hormone disorder Cushing's syndrome and also enrolling patients in a trial testing Corlux as a treatment for psychotic depression.

Cushing's syndrome is caused by overproduction of the hormone cortisol, or overexposure to cortisol. Its symptoms can include high blood sugar, high blood pressure, fatigue, and weak muscles.

The company said the Food and Drug Administration has granted an orphan drug designation for Corlux for the treatment of Cushing's syndrome. That will provide seven years of marketing exclusivity from the date of approval. Corcept expects to submit a new drug application to the Food and Drug Administration in the first quarter of 2011.

Corcept said its operating expenses climbed 52 percent to $7.1 million, as research and development expenses rose. General and administrative expenses also climbed, as the company planned for the possible Corlux launch.

The company said it anticipates its cash balance, which was $29 million at the end of September, will be enough to fund the company into next year's third quarter.

Shares rose a penny to $3.62 in morning trading.

From http://www.businessweek.com/ap/financialnews/D9JDCD402.htm

The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults

Zuleyha Karaca, Ayhan Lale, Fatih Tanriverdi, Mustafa Kula, Kursad Unluhizarci and Fahrettin Kelestimur

 

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Abstract

Evaluation of the HPA axis is still a challenge; due to different sensitivities and stimulation efficiencies of dynamic tests, lack of standard assays for cortisol measurement and lack of data regarding the effects of age and gender on the results of the HPA axis evaluation with different dynamic tests. This study was performed to compare 1 μg ACTH, 250 μg ACTH and glucagon tests in the evaluation of HPA axis. The study was carried out on 55 healthy individuals (28 men, 27 women). 10–12 volunteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 μg ACTH), standard dose short synacthen test (250 μg ACTH) and glucagon tests were performed consecutively. The mean peak cortisol response to standard dose ACTH stimulation test was found to be significantly higher than the low dose ACTH and glucagon stimulation tests. The mean peak cortisol responses to low dose ACTH and the glucagon stimulation tests were not significantly different. The mean peak cortisol responses did not differ significantly between different age or sex groups. The lowest peak cortisol responses obtained after low dose ACTH and glucagon stimulation tests were 12.5 and 9.1 μg/dl respectively in the volunteers who all had cortisol responses higher than 20 μg/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 μg ACTH, 1 μg ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 μg/dl in a known group of healthy people. So the consideration of appropriate hormonal cut-off levels for each test seems reasonable. The age, sex and body mass indeces were not shown to affect the cortisol response to dynamic stimulation tests.

Keywords  Glucagon stimulation test - ACTH stimulation test - HPA axis - Healthy adults

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From http://www.springerlink.com/content/135321p5272g4385/

Extended endoscopic endonasal approach for selected pituitary adenomas: early experience

November 10th, 2010 | Source: J Neurosurg

J Neurosurg. 2010 Nov 5;

Authors: Di Maio S, Cavallo LM, Esposito F, Stagno V, Corriero OV, Cappabianca P

Object Whereas most pituitary adenomas are removable via the transsphenoidal approach, certain cases, such as dumbbell-shaped or suprasellar adenomas and recurrent and/or fibrous tumors, remain difficult to treat. The authors present their experience with the extended endoscopic endonasal approach to the suprasellar area in managing this subset of tumors, which are classically treated through a transcranial route.

Methods From June 1997 to December 2008, 615 patients underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas in the Department of Neurosurgery of the Università degli Studi di Napoli Federico II. Of this group, 20 patients with pituitary adenomas needed an extended endoscopic endonasal transtuberculum/transplanum approach for tumor removal. Two surgical corridors were used during the transsphenoidal approach: 1) the conventional endosellar extraarachnoidal corridor and 2) a suprasellar transarachnoidal corridor.

Results The extent of resection was gross total in 12 (60%) of the 20 patients, near total in 4 (20%), subtotal in 3 (15%), and partial in 1 (5%). Postoperative CSF leakage occurred in 1 patient. One patient experienced worsening of temporal hemianopsia.

Conclusions The authors’ initial results with the extended endoscopic approach to the suprasellar area for selected pituitary adenomas are promising and may justify a widening of the current classical indications for transsphenoidal surgery.

PMID: 21054140 [PubMed - as supplied by publisher]

From http://medicine.journalfeeds.com/surgery/j-neurosurg/extended-endoscopic-endonasal-approach-for-selected-pituitary-adenomas-early-experience/20101110/

A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials of DHEA Treatment Effects on Quality of Life in Women with Adrenal Insufficiency

Aziz A. Alkatib, Mihaela Cosma, Mohamed B. Elamin, Dana Erickson, Brian A. Swiglo, Patricia J. Erwin, and Victor M. Montori*

Department of Medicine (A.A.A.), Knowledge and Encounter Research Unit (A.A.A., M.C., M.B.E., D.E., B.A.S., P.J.E., V.M.M.), Mayo Clinic Libraries (P.J.E.), and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (M.C., D.E., B.A.S., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905

* To whom correspondence should be addressed. E-mail: montori.victor@mayo.edu.

Context: Women with primary or secondary adrenal insufficiency report a decreased health-related quality of life (HRQOL) despite traditional adrenal replacement therapy. Dehydroepiandrosterone (DHEA) has been studied as an agent to improve HRQOL in these patients.

Objective: We sought to conduct a systematic review and meta-analysis of randomized controlled trials of DHEA effects on HRQOL in women with adrenal insufficiency.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, CINAHL, and PsycInfo) and reference lists of eligible studies through July 2008.

Study Selection: Eligible trials randomly assigned women with primary or secondary adrenal insufficiency to either DHEA or control and measured the effect of treatment on HRQOL.

Data Extraction: Reviewers working independently and in duplicate assessed the methodological quality of trials and collected data on patient characteristics, interventions, and outcomes.

Data Synthesis: We found 10 eligible trials that measured HRQOL and depression, anxiety, and sexual function. Random-effects meta-analysis showed a small improvement in HRQOL in women treated with DHEA compared with placebo [effect size of 0.21; 95% confidence interval, 0.08 to 0.33; inconsistency (I2) = 32%]. There was a small beneficial effect of DHEA on depression; effects on anxiety and sexual well-being were also small and not statistically significant.

Conclusions: DHEA may improve, in a small and perhaps trivial manner, HRQOL and depression in women with adrenal insufficiency. There was no significant effect of DHEA on anxiety and sexual well-being. The evidence appears insufficient to support the routine use of DHEA in women with adrenal insufficiency.

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-0672v1

Predicting Recurrence of Nonfunctioning Pituitary Adenomas

Tae-Woong Noh, Hyeong Jae Jeong, Mi-Kyung Lee, Tai Seung Kim, Sun Ho Kim*, and Eun Jig Lee*

Endocrinology (T.-W.N., E.J.L.), Pituitary Tumor Clinic and Institute of Endocrinology (T.-W.N., S.H.K., E.J.L.), and Pathology, Yong-Dong Severance Hospital (H.J.J.), Pathology Ilsan Hospital (M.-K.L.), Pathology (T.S.K.), and Neurosurgery (S.H.K.) and Yonsei Brain Research Institute, Yonsei University College of Medicine, 120-752 Seoul, Korea

* To whom correspondence should be addressed. E-mail: SUNKIM@YUHS.AC or ejlee423@yuhs.ac.

Context: Nonfunctioning pituitary adenomas are commonly diagnosed as large tumors. Most are detected incidentally during imaging studies or as a result of neurological manifestations. Depending on severity, most patients with large tumors require surgery and adjunctive therapies because of the high rate of tumor recurrence. The ability to predict the recurrence of a tumor at the time of the initial surgery would be helpful in deciding whether adjunctive therapy is necessary and decreasing morbidity. We investigated the use of several cellular markers for predicting the recurrence of nonfunctioning pituitary adenomas.

Objective: A tissue array block was made using tissue from 35 cases of nonfunctioning pituitary adenomas (16 cases with early recurrence ?4 yr after surgery, 10 cases with late recurrence >4 yr after surgery, and nine cases without recurrence). Levels of tumor tissue cellular markers associated with cell proliferation or apoptosis were analyzed, and immunohistochemical study of cellular markers was conducted using sectioned slides from the tissue array block.

Results: High Ki-67 and TUNEL labeling indexes were associated with recurrent nonfunctioning pituitary adenomas. Tumors with a high level of expression of phospho-Akt, phospho-p44/42 MAPK, and PTTG1 were associated with early recurrence. However, high levels of expression of phospho-CREB and ZAC1 were inversely associated with recurrence.

Conclusions: Tumors with high levels of expression of phospho-Akt and phospho-p44/42 MAPK and low levels of expression of phospho-CREB and ZAC1 should be followed closely and may require adjunctive therapy to prevent tumor recurrence.

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-0471v1

Pituitary disorders may affect as many as 20 percent of the population

 

Denise Dador
More: Bio, E-mail, Facebook, Home Page, News Team

LOS ANGELES (KABC) -- Researchers believe there may be millions of people with unexplained symptoms who are being misdiagnosed. Doctors say problems with the brain's pituitary gland are more common than most people think.

Many of us suffer from fatigue, headaches, infertility and weight gain. Most of us would never think those symptoms could possibly add up to a brain tumor.

Pituitary disorders may affect as many as 20 percent of the population. And the signs are often quite difficult to discern.

We all have trouble seeing as we age, but within a few months Tom Lobl's vision practically deteriorated sharply.

"I was seeing double vision. Letters were disappearing, and I was having trouble reading signs on the street when I was driving," said Lobl.

An eye doctor prescribed glasses, but it just kept getting worse. Then ...

"An MRI found the tumor," said Lobl. A non-cancerous brain tumor growing on his pituitary gland. It so big it was squishing the gland into a sliver.

"There are probably many people that are walking around that have abnormalities in the pituitary gland that we don't know about," said Dr. Daniel Kelly.

Neurosurgeon Dr. Daniel Kelly at Saint John's Health Center says Lobl probably had this tumor for 10 years. Often the symptoms are misdiagnosed.

"Many of the men we see that have low libido from low testosterone they may simply be treated with Viagra because no one bothered to test the testosterone level," said Kelly.

The pituitary gland may weigh less than a gram but doctors call it the "master gland" because it controls so many aspects of life. It's affects metabolism, reproductive function and your response to stress.

If left untreated: "They can have what's called an 'adrenal crisis.' Because the pituitary stops making the critical stress hormone," said Kelly.

A blood test can tell if something is going on with the pituitary gland. Patients can be treated with medication, but Lobl needed surgery.

Dr. Kelly enters the pituitary cavity through the nose. Using endoscopic tools he can remove the tumor without any scarring or cutting through key structures in the skull.

Within a few days, Lobl was up and about. Now, 15 months after surgery, he feels like a new person.

"I'm back to my normal activities and strength," said Lobl. "I feel a lot younger than I did. The tumor made me feel old."

Endonasal surgery to remove a pituitary tumor does have potential complications such as stroke and blood clots. But Dr. Kelly says the chances are less than 1 percent.

Kids can present with pituitary tumors, but it mostly occurs in adults. The age range is usually between 20 and 80 years old.

http://abclocal.go.com/kabc/story?section=news%2Fhealth%2Fyour_health&id=7765964

40 Days of Thankfulness: Day Twenty One

Today, I'm thankful that I got to see a friend I haven't seen for a while and we got to play several piano duets. Neither of us was quite as rusty as we thought we'd be.

40 Days of Thankfulness: Day Twenty

Today is a very special day for me.  I am thankful to so many, named and unnamed.  This is the 23rd anniversary of my pituitary surgery at the NIH in Bethesda, Maryland.

I couldn't have gotten to surgery without a myriad of books from the public library, my parents who watched my son while I was at NIH for 6 weeks pre-op, an oncologist, the endo who got me there... So many, and so many years of sickness just trying to get diagnosed.

I won't bore anyone with my "story" but if anyone is interested, it's available here.

The short version is that I knew I was sick starting about 2003.  No doctors would offer any help.  A chance description of Cushing's convinced me that this was what I had.  Even when I presented Xerox copies of medical texts to doctors, they would all say that I couldn't have it.  It was "too rare".  I was fat.  I cheated on my diet.  I was depressed.  Go away.  Take drugs.

I finally got to an endo who got me into NIH in 2006.  During six weeks away from home as an in-patient, they diagnosed me with pituitary Cushing's.

For those who don't know, here's where the pituitary gland is:

I had a 7 year old son and I was sure I was going to die during surgery, if not before. I wrote letters "just in case".  I was terrified of what could happen and also what would happen if I never had surgery.  I knew I couldn't live with the Cushing's.

A college contempory of mine wasn't so lucky.  Luckily, I didn't read this in the Alumni magazine until after my surgery. She had the same operation. She came from my home town. We  had the same major at the same college, we were the same age. We had the same surgical and medical team. I recovered. The other woman died during surgery.

So, today, on my 23rd anniverary, I am thankful that I saw my son grow up, that my husband stuck with me, that I'm still alive, that I'm able to help others beat Cushing's...

Thanks to Dr Edward Oldfield, NIH, nurses, doctors, Fairfax County Public Library and how it all worked out in the end.

 

Are Guidelines for Glucocorticoid Coverage in Adrenal Insufficiency Currently Followed?

Coralie Leblicq, MD, Diane Rottembourg, MD, Johnny Deladoëy, MD, PhD, Guy Van Vliet, MD, Cheri Deal, PhD, MD Corresponding Author

Received 11 January 2010; received in revised form 14 July 2010; accepted 17 August 2010. published online 01 November 2010.

 

Objectives

To search for evidence of acute adrenal failure linked to inappropriate use of stress management protocols.

Study design

Patients followed up for primary adrenal insufficiency (n = 102) or secondary adrenal insufficiency (n = 34) between 1973 and 2007 were included. All hospitalizations, both urgent (n = 157) and elective (n = 90), were examined. We recorded clinical evidence of acute adrenal failure, parental management before admission, and details of glucocorticoid prescription and administration in the hospital setting.

Results

For urgent hospitalizations, subgroup and time period did not influence the percentage of patients hospitalized (primary adrenal insufficiency 45%; secondary adrenal insufficiency 38%; P = .55). The use of stress glucocorticoid doses by parents increased significantly after 1997 (P < .05), although still only 47% increased glucocorticoids before hospitalization. Stress doses were more frequently administered on arrival in our emergency department after 1990 (P < .05); patients with signs or symptoms of acute adrenal failure decreased to 27% after 1997 (P < .01). Twenty-four percent of all hospitalizations were marked by suboptimal adherence to glucocorticoid stress protocols, with rare but significant clinical consequences.

Conclusions

In spite of an increased use of glucocorticoid stress dose protocols by parents and physicians, patients remain at risk of morbidity and death from acute adrenal failure. This risk may be minimized with conscientious application of stress protocols, but other patient-specific risk factors may also be implicated.

 

Keywords

21OH, 21-hydroxylase, 3?HSD, 3-?-hydroxysteroid dehydrogenase, ACTH, Adrenocorticotropic hormone, AI, Adrenal insufficiency, CAH, Congenital adrenal hyperplasia, ED, Emergency department, EH, Elective hospitalization, HPA, Hypothalamic-pituitary-adrenal, PAI, Primary adrenal insufficiency, UH, Urgent hospitalization

 

Endocrinology Service and Research Center, CHU Sainte-Justine and Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada

Reprint requests: Cheri Deal, PhD, MD, FRCPC, Endocrinology Service, CHU Sainte-Justine Hospital, Research Center, 3175 Côte Sainte-Catherine, Montréal (Québec), Canada, H3T 1C5.

Supported by scholarships from the Belgian Study Group of Pediatric Endocrinology (C.L.), the Fonds de Recherche en Santé du Québec (C.D.), and a donation from Group Cossette Communications (C.D.). The authors declare no conflicts of interest.

PII: S0022-3476(10)00690-6

doi:10.1016/j.jpeds.2010.08.021

 

From http://www.jpeds.com/article/PIIS0022347610006906/abstract?rss=yes

40 Days of Thankfulness: Day Nineteen

Today I'm thankful for my maternal grandmother.

I was thinking of her last night when we were watching an old episode of This Old House and they were remarking about how Boston used to be a lot of swamp land. I told DH that The Fens, (Fenway Park is on the outskirts), used to be a wetland for a long time and is now a beautiful park.

When I was growing up, my Nana used to live right on the outskirts of The Fens and in the summers I used to go there to play on the swings and run through the gardens.

So, I started thinking about my grandmother again and how brave she was. In the early part of the century she had been living in Scotland with her husband and they had a young son - my father. His husband was in the Black Watch during World War I, and he died in Peshawar, India.

For whatever reason, she and her sister (who she never spoke to!) decided to come to America, to Boston to live. So, when my dad was only 5 they sailed to the US. I have pictures of him coming off the boat wearing a little kilt.

Somewhere along the line Nana married again, to a hard-working man who helped provide for their little family.

Until my grandmother died, she was a waitress at a YMCA. But she managed to save a pile of money - under her mattress, in the closet, behind the sofa. It was amazing. Her American Dream, I guess.

I cannot imagine having her courage, leaving the US with a small child, and starting life anew in a completely new country.

I wish I had been able to tell Nana while she was still alive how much I admired her. I am thankful that she came here - or I wouldn't have been born.

40 Days of Thankfulness: Day Eighteen

 

This is going to sound really stupid but today I am thankful for my dropbox.  I have files all over the place and I work on them on different computers (PC and Mac), or my iPhone, iPad and other places.  If I'm away from home without anything (rarely happens!) I can still access my stuff online and do with it whatever I want.

I am really lazy and it's so nice to have my files synced everywhere.  I don't have to try to find a cable, zip drive or SD card.  Sometimes I'll find an image or a program I want to install on a different computer and I just stash it in my dropbox.  When I'm done, I delete it or move it to its permant home to save space on the dropbox.

I'm also cheap so I just have the free version and I'm always monitoring how much space is available.  I seem to be running about about a third capacity most of the time.

This really makes my life a little easier and, for that, I'm very thankful today!

 

The new diet rules

Nov 1, 2010 11:39 AM | By Nicole Sparrow, Longevity Magazine

You’ve tried every diet in the book and failed. What’s stopping you from dropping the superfluous kilos?

It seems like every time you turn around, there’s a new diet on the block. Low fat, low carbs, low GL. Baffled? We don’t blame you. As it turns out, weight loss is a complex science and there’s a lot we still don’t know. But, the good news is scientists are definitely getting better at cracking the fat riddle.

Diet traps

‘HEALTHY’ DOESN’T MEAN LOW-KJ

You think you’re a healthy eater. Your morning meal is a healthy fruit and yoghurt smoothie followed by oats and honey with wholewheat toast. So how come you’re still putting on weight? You could be falling for the “healthy food” trap. You pop into a local healthy fast-food chain. You opt for the healthy sarmie with hummus on low-GI bread, you not only eat the whole sandwich, but decide to have a smoothie, too. Unfortunately, while this is a nutritious choice it’s still a whopper when it comes to your waistline. Ultimately a kilojoule is still a kilojoule and if you eat too much, regardless of whether it’s healthy, you’ll gain weight.

THE SLOW METABOLISM MYTH

Loads of people complain that they can’t lose weight because of a slow metabolism. There’s no easy way to break this to you so we’re just going to be blunt: there’s a good chance you don’t. Dr Donald Hensrud from The Mayo Clinic in the US, says that yes, there is such a thing as a slow metabolism, but “it’s rare, and it’s usually not what’s behind being overweight”. In fact, he notes that overweight people are likely to have a higher metabolism than their thinner counterparts because bigger people burn more kilojoules, even at rest. If you are convinced you have a slow metabolism, he advises you talk to your doctor about doing medical tests to establish whether this is the case. Certain medication or rare conditions like Cushing’s syndrome and hypothyroidism can slow down your metabolic rate.

UNDERESTIMATING YOUR KILOJOULE CONSUMPTION

“Researchers have observed that overweight people underestimate how much they eat by twice as much as normal-weight people do,” say experts at Cornell University in the US. “It is because everyone consistently underestimates size as things get larger – distance, weight, height of buildings and loudness. And that applies to estimating how many calories [kilojoules] we eat.” The answer then, is to eat smaller meals. And while we hear a collective “duh” from your direction, Cornell University experts maintain that the smaller your meal, the better you become at accurately predicting its kilojoule content.

Top tips on getting the upper hand

EAT SOUP

You know how you’ve been advised to drink a glass of water before a meal, the idea being that you’ll feel fuller quicker and therefore eat less? This is only right in part. Taking in liquid with your food will make you full faster, but it won’t last for very long, unless you blend it all together. If you eat soup, your stomach stays distended for longer (i.e. you feel full) and keeps a dieter’s enemy – those frustrating hunger pangs – at bay. A great tip is to opt for low-kilojoule, veggie-based soups as these are also a good source of fibre and nutrients.

GET ENOUGH CALCIUM

For ages people watching their weight were encouraged to avoid dairy based on the fear that it would make them gain weight. However, in 2000, findings from the University of Tennessee’s Nutrition Institute suggested that eating calcium could make your body better at burning fat. In a study of overweight lab mice, the team found that those who ate dairy calcium lost more weight. Later studies have confirmed these findings in humans and have also established that while calcium supplements also work, for some reason dairy calcium is more effective.

WATCH YOUR PORTION SIZE

Remember the popcorn containers at the movies when you were a kid? They didn’t just seem smaller – they were. Over the years portion sizes have become bigger and so have our waistlines. Even food portions in Da Vinci’s masterpiece, The Last Supper, have been super-sized over the years. And when it comes to that primitive, Homer Simpsonesque “must eat food” part of our brains, we simply haven’t figured this out, so portions get bigger and we continue to eat more. To lose weight and keep it off, you need to wise up to this and opt for smaller portions or plates.

EAT PROTEIN

Advocates of diets like Atkins maintain eating protein helps you feel full for longer and we’ve now established why: it’s all down to peptide YY (PYY), a hungerfighting hormone. Protein is better than other foods at triggering the release of PYY. Eating protein at meals will help keep those gnawing hunger pangs at bay for longer. Not only that, but other research has found that if weight loss is your goal, eating protein helps you lose more weight and keep it off longer.

 

From http://www.timeslive.co.za/lifestyle/article737846.ece/The-new-diet-rules

GH Response to Oral Glucose Tolerance Test: A Comparison between Patients with Acromegaly and Other Pituitary Disorders.

Author(s)
Verrua E, Filopanti M, Ronchi CL, Olgiati L, Ferrante E, Giavoli C, Sala E, Mantovani G, Arosio M, Beck-Peccoz P, Lania AG, Spada A

Institution
Department of Medical Sciences (E.V., M.F., C.L.R., L.O., E.F., C.G., E.S., G.M., M.A., P.B.-P., A.G.L., A.S.), University of Milan, and Unit of Endocrinology and Diabetology (E.V., M.F., C.L.R., L.O., E.F., C.G., E.S., G.M., P.B.-P., A.G.L., A.S.), Fondazione Instituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, 20122 Milan, Italy; and Unit of Endocrine Diseases (M.A.), Ospedale S. Giuseppe Multimedica, 20123 Milan, Italy.

Source
J Clin Endocrinol Metab 2010 Oct 20.

Abstract
Context: The cutoff value of nadir GH after an oral glucose tolerance test (OGTT) used to define disease remission in acromegaly is higher than that observed in healthy subjects. However, it is uncertain whether the impaired GH inhibition might be related to subtle abnormalities of GH secretion or to functional and/or anatomical hypothalamic-pituitary disconnection due to tumor per se or treatments.

Objective: The objective of the study was to evaluate the impact of pituitary disorders other than acromegaly on GH response to OGTT.

 

Design, Subjects, and Methods: Thirty-three patients (24 females and nine males, aged 50.1 ± 12.3 yr, 13 operated and two irradiated) with various hypothalamic-pituitary disorders (HPDs), 45 healthy subjects (controls), and 42 cured acromegalic patients matched for sex, age. and body mass index were investigated. All subjects were studied for IGF-I levels and GH levels before and during the OGTT.

Results: In HPD patients mean postglucose nadir GH levels were 0.11 ± 0.08 μg/liter without any difference between patients treated with neurosurgery and/or radiotherapy and untreated and between patients with and without pituitary stalk alterations and/or hyperprolactinemia. Mean nadir GH values were similar in HPD patients and controls (0.11 ± 0.08 vs. 0.08 ± 0.08 μg/liter, P = 0.23) and lower than those found in cured acromegalic patients (0.18 ± 0.13 μg/liter, P = 0.02), although there was an overlapping in about half of patients.

Conclusions: Hypothalamic control of glucose-mediated GH suppression is not perturbed in patients with HPD. These data indicate that defective GH suppression to glucose that is found in acromegaly is unlikely to reflect a lack of integrity of hypothalamic function.

Language
ENG

Pub Type(s)
JOURNAL ARTICLE

PubMed ID
20962023

From http://www.unboundmedicine.com/medline/ebm/record/20962023/full_citation/GH_Response_to_Oral_Glucose_Tolerance_Test:_A_Comparison_between_Patients_with_Acromegaly_and_Other_Pituitary_Disorders_

40 Days of Thankfulness: Day Seventeen

 

Today I am thankful for my dog, Mimi.  She's a beautiful dog, sweet, loving and usually very mild-mannered, but she'll bark her head off whenever she hears someone in the driveway.

Tonight, she barked at potential trick-or-treaters and we have lots of candy left over.  :)

Thanks, Mimi!

 

Exogenous Cushing's syndrome due to topical corticosteroid application: case report and review literature

We report on an 8-month-old female infant who developed Cushing’s syndrome and adrenal insufficiency after diaper dermatitis treatment through the misuse of Clobetasol without doctor’s prescription. Physiologic dose of  hydrocortisone was prescribed to prevent an adrenal crisis for 3 months and discontinued when HPA axis recovery was confirmed by normal morning cortisol and ACTH levels.

Content Type Journal ArticleDOI 10.1007/s12020-010-9393-6

Authors
Therdpong Tempark, Division of Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330 ThailandVoraluk Phatarakijnirund, Division of Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Sor Kor Building 11th Floor, Bangkok, 10330 ThailandSusheera …

From http://www.prescriptiondrugs2go.com/popular-drug-information/c/chantix/exogenous-cushing%E2%80%99s-syndrome-due-to-topical-corticosteroid-application-case-report-and-review-literature-2.html

40 Days of Thankfulness: Day Sixteen

 

Today I am thankful that the skunk already passed by when  I took Mimi out for a walk!

It's so not fair!  I can't smell lots of flowers or perfumes but I can smell a skunk blocks away.

40 Days of Thankfulness: Day Fifteen

I hope I'm not jinxing myself but today I am thankful that I haven't had any migraines for a long time.

It's not "just" not having migraines, but the fact that, should I get one, there's nothing I can do about them anymore.

I used to get migraines quite often, a hormone thing probably.  I spent lots of hours in a completely dark room, blocking out sound, trying to keep my head from pounding.

There was a long period of time that I had a migraine 6 days out of the week for several weeks.  By accident, a friend asked me on a Monday if I had one that day and that started me thinking - why do I have them every day except Mondays?  I figured out that it wasn't a migraine at all but an allergy headache - I was allergic to the bath oil I was using Monday-Saturday.  I gave that to my Mom and those headaches went away.

I still often get allergy headaches.  Since my Cushing's transsphenoidal pituitary surgery, I can't smell things very well and I often don't know if there's a scent that is going to trigger an allergic reaction.  In church and elsewhere, my Mom will be my "Royal Sniffer" and if someone is wearing perfume or something scented, she'll let me know and we'll move to a new location.

There's a double whammy here - since my kidney cancer surgery my doctor won't let me take NSAIDs, asperin, Tylenol, any of the meds that might help a headache go away.  My only hope would be that coffee from Day Fourteen. And that's definitely not usually enough to get rid of one of these monsters.

So, I am very thankful that, for the moment, I am headache/migraine free!

Prevalence of Endocrine Diseases in Morbidly Obese Patients Scheduled for Bariatric Surgery: Beyond Diabetes

Paola Fierabracci, Aldo Pinchera, Silvia Martinelli, Giovanna Scartabelli, Guido Salvetti, Monica Giannetti, Andrea Pucci, Giulia Galli, Ilaria Ricco and Giorgia Querci, et al.

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Abstract

Background 

Bariatric surgery allows stable body weight reduction in morbidly obese patients. In presurgical evaluation, obesity-related co-morbidities must be considered, and a multidisciplinary approach is recommended. Precise guidelines concerning the endocrinological evaluation to be performed before surgery are not available. The aim of this study was to evaluate the prevalence of common endocrine diseases in a series of obese patients scheduled for bariatric surgery.

Methods 

We examined 783 consecutive obese subjects (174 males and 609 females) aged 18–65 years, who turned to the obesity centre of our department from January 2004 to December 2007 for evaluation before bariatric surgery. Thyroid, parathyroid, adrenal and pituitary function was evaluated by measurement of serum hormones. Specific imaging or supplementary diagnostic tests were performed when indicated.

Results 

The overall prevalence of endocrine diseases, not including type 2 diabetes mellitus, was 47.4%. The prevalence of primary hypothyroidism was 18.1%; pituitary disease was observed in 1.9%, Cushing syndrome in 0.8%, while other diseases were found in less than 1% of subjects. Remarkably, the prevalence of newly diagnosed endocrine disorders was 16.3%.

Conclusions 

A careful endocrinological evaluation of obese subjects scheduled for bariatric surgery may reveal undiagnosed dysfunctions that require specific therapy and/or contraindicate the surgical treatment in a substantial proportion of patients. These results may help to define the extent of the endocrinological screening to be performed in obese patients undergoing bariatric surgery.

Keywords  Bariatric surgery - Obese patients - Endocrinological evaluation

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From http://www.springerlink.com/content/nq6hj23286x3k61u/