Day Ten, Cushing’s Awareness Challenge 2015

Posted on April 10, 2015 by MaryO

In March of 1987, after the endo finally  confirmed that I had Cushing’s, I was sent to a local hospital where they repeated all those same tests for another week and decided that it was not my adrenal gland (Cushing’s Syndrome) creating the problem. The doctors and nurses had no idea what to do with me, so they put me on the brain cancer ward.

When I left this hospital after a week, we didn’t know any more than we had before.

As luck would have it, NIH (National Institutes of Health, Bethesda, Maryland) was doing a clinical trial of Cushing’s. I live in the same area as NIH so it was not too inconvenient but very scary at first to think of being tested there. At that time I only had a choice of NIH, Mayo Clinic and a place in Quebec to do this then-rare pituitary surgery called a Transsphenoidal Resection.

My husband asked my endo if it were his wife, if he would recommend this surgery.  The endo responded that he was divorcing his wife – he didn’t care what happened to her.  Oh, my!

I chose NIH – closest and free. After I was interviewed by the doctors there, I got a letter that I had been accepted into the clinical trial.

The night before I was admitted, I signed my will.  I was sure I was going to die there.  If not during testing, as a result of surgery.

The first time I was there was for 6 weeks as an inpatient. More of the same tests.

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn’t walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Several were from Greece.

My first roommate was a nurse.  She spent the entire first night screaming in pain.  I was very glad when they moved me to a new room!

Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with – either a cure or dying. While I was at NIH, I was gaining about a pound a day!

During the time I was home the weekend  before surgery, a college classmate of mine (I didn’t know her) DID die at NIH of a Cushing’s-related problem. I’m so glad I didn’t find out until reading the alumnae magazine a couple months later!  She was the same class, same major, same home-town, same disease…

We have a Scottish doctor named James Lind to thank for the clinical trial.  He  conducted the first ever clinical trial in 1747 and developed the theory that citrus fruits cured scurvy.  Lind  compared the effects of various different acidic substances, ranging from vinegar to cider, on groups of afflicted sailors, and found that the group who were given oranges and lemons had largely recovered from scurvy after 6 days.

I’d like to think that I advanced the knowledge of Cushing’s at least a little bit by being a guinea  pig in 1987-1989.

From the NIH: http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx

Hope through Research

Several components of the National Institutes of Health (NIH) conduct and support research on Cushing’s syndrome and other disorders of the endocrine system, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development (NICHD), the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the National Center for Research Resources.

NIH-supported scientists are conducting intensive research into the normal and abnormal function of the major endocrine glands and the many hormones of the endocrine system. Researchers continue to study the effects of excess cortisol, including its effect on brain structure and function. To refine the diagnostic process, studies are under way to assess the accuracy of existing screening tests and the effectiveness of new imaging techniques to evaluate patients with ectopic ACTH syndrome. Researchers are also investigating jugular vein sampling as a less invasive alternative to petrosal sinus sampling. Research into treatment options includes study of a new drug to treat the symptoms of Cushing’s syndrome caused by ectopic ACTH secretion.

Studies are under way to understand the causes of benign endocrine tumor formation, such as those that cause most cases of Cushing’s syndrome. In a few pituitary adenomas, specific gene defects have been identified and may provide important clues to understanding tumor formation. Endocrine factors may also play a role. Increasing evidence suggests that tumor formation is a multistep process. Understanding the basis of Cushing’s syndrome will yield new approaches to therapy.

The NIH supports research related to Cushing’s syndrome at medical centers throughout the United States. Scientists are also treating patients with Cushing’s syndrome at the NIH Clinical Center in Bethesda, MD. Physicians who are interested in referring an adult patient may contact Lynnette Nieman, M.D., at NICHD, 10 Center Drive, Room 1-3140, Bethesda, MD 20892-1109, or by phone at 301-496-8935. Physicians interested in referring a child or adolescent may contact Constantine Stratakis, M.D., D.Sc., at NICHD, 10 Center Drive, Room 1-3330, Bethesda, MD 20892-1103, or by phone at 301-402-1998.

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Does a normal urine free cortisol result rule out Cushing’s syndrome?

Posted on March 7, 2015 by MaryO

ENDO_2015

 

March 07, 2015

SAT 379-412-Cushing’s Syndrome

Does a normal urine free cortisol result rule out Cushing’s syndrome?

ST Sharma, LK Nieman

Summary: Researchers conducted this study to assess the diagnostic accuarcy of urine free cortisol (UFC) and 24-hour urine 17-hydroxycorticosteroids (170HCS) in patients with Cushing’s syndrome, concluding that in patients with mild CS, UFC can be falsely normal or only minimally elevated. Further, they found that to help in making a diagnosis and prevent treatment delays, clinicians may consider incorporating multiple collections and use of complimentary screening tests including 24-hour urine 17OHCS and late night salivary cortisol (LNSC) testing.

Methods:

  • For this retrospective study, researchers included all CS patients evaluated at the National Institutes of Health (NIH) from 2009 to 2014.
  • The screening tests used for CS included UFC, 17OHCS, midnight serum cortisol and low dose (1 mg overnight or 2-day 2 mg/day) dexamethasone suppression test (DST).
  • They defined abnormal as values above reference range for UFC, 17OHCS and LNSC, a midnight serum cortisol ≥7.5 mcg/dL, and post-dexamethasone cortisol values ≥1.8 mcg/dL.
  • Hourly 24-hour sampling for cortisol was performed in a few cases with a mild clinical phenotype and equivocal test results.
  • Researchers measured UFC using liquid chromatography/tandem mass spectrometry (LC-MS/MS), and 17OHCS was measured using colorimetric methodology with Porter-Silber reaction (reported as mg/g of creatinine).
  • For this study, they used the mean of the first two UFC and 17OHCS values (appropriate collection by urine volume and creatinine) obtained within 30 days of initial NIH presentation.

Results:

  • In all, 72 patients were diagnosed with CS (aged 18-77 years, 51 females), 51 of whom had CD, 10 had ectopic CS, and 2 had an adrenal source of Cushing’s based on pathology.
  • Biochemical tests such as inferior petrosal sinus sampling (IPSS) suggested ectopic CS, but no tumor was found (occult) in 6 patients.
  • In 2 patients with failed transsphenoidal surgery, IPSS was indicative of a pituitary source, and one patient did not complete evaluation for ACTH-dependent CS.
  • UFC results were available in all patients, 17OHCS in 70, LNSC in 21, midnight serum cortisol in 68, and DST results in 37 patients.
  • UFC was falsely normal in 6 patients and only minimally elevated (<2 x ULN) in 13 patients (normal renal function, no history of cyclicity, all had CD); of these 19 patients, 24-hour 17OHCS was abnormal in all, LNSC was abnormal in 12, midnight serum cortisol was abnormal in 18, and DST was abnormal in 12 patients.
  • Hourly 24-hour sampling for cortisol performed in 3 of these patients revealed abnormal nadir (>7.5 mcg/dL) and mean daily serum cortisol (>9 mcg/dL) levels.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ5BA369FDE9DE4CED82CB6A7CD5BFD1BE/42581/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2015&nonus=0

Filed under: Clinical trials, Cushing's, Meetings and Conferences, pituitary, Treatments | Tagged: , , , , , , , , , , , | Leave a comment »

Utility of measurement of dexamethasone levels in the diagnostic testing for Cushing’s syndrome

Posted on June 21, 2014 by MaryO

From Day 1 of the 16th International Congress of Endocrinology and the Endocrine Society’s 96th Annual Meeting and Expo »

Chicago, IL – June 21, 2014

ST Sharma, JA Yanovski, SB Abraham, LK Nieman

Summary: Dexamethasone (dex) suppression tests (DST) are used for screening and differential diagnosis of Cushing’s syndrome (CS). The 1 mg overnight (LD) DST is used to diagnose CS, the dex-suppressed CRH stimulation (Dex-CRH) test to differentiate CS from pseudocushings (PCS) while the 8 mg overnight (HD) DST is used to differentiate Cushing’s disease (CD) from ectopic ACTH syndrome (EAS). Researchers assessed the utility of dex levels in improving the diagnostic accuracy of these tests and they found that low dex and high CBG levels can account for false positive (FP) DST and Dex-CRH test results. Use of a higher dex dose in pts with low dex levels can help decrease FP results.

Methods:

  • This is a retrospective study of patients (pts) with CS, PCS and normal volunteers (NV) who had a dex level measured as part of LDDST, HDDST or Dex-CRH test.
  • A post-dex cortisol (F) level ≥1.8 mcg/dl in the LDDST and a 15 min post-CRH F level ≥1.4 mcg/dl in the Dex-CRH test suggested CS.
  • A ≥69% suppression of F levels in HDDST indicated CD.
  • Dex levels

Results:

  • LDDST (n=77): Post-dex F was abnormal in 44 pts, 37 of these did not have CS on follow-up.
  • Proportion of pts with low dex levels was similar in those with incorrect or correct LDDST results (P=0.7).
  • Three of 5 pts with an abnormal result and low dex levels (44-117 ng/dl) had suppressed post-dex F levels after a 2 mg overnight DST. HDDST (N=56): Results were not consistent with the final diagnosis (CD or EAS) in 13 (23%) pts.
  • Of these, 5 had low dex levels (400-1220 ng/dl).
  • Proportion of pts with low dex levels was similar between those with correct and incorrect HDDST results (P=0.5).
  • HDDST in 1 pt with ACTH-dependent CS suggested EAS (28% suppression) with low dex level.
  • IPSS indicated CD.
  • After a doubled dex dose (16 mg), F levels suppressed by 76%, changing the HDDST result to CD.
  • Dex-CRH (n=139): Results were consistent with the final diagnosis in 133 pts (74 CS, 20 NV, 39 PCS).
  • Six pts with an abnormal result had dex levels
  • Of these, repeat testing with doubled dex dose (1 mg every 6 hours) in 2 pts led to higher dex levels (610, 757 ng/dl) and normal F level in one.
  • Two pts with abnormal result were on OCPs, 1 with a known high cortisol binding globulin (CBG) level.
  • None had CS on follow-up.
  • There was no correlation between dex and post-dex F levels in LDDST, 15 min post-CRH F levels in Dex-CRH test and % suppression of F post-dex in HDDST (P=NS).

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Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis

Posted on May 21, 2013 by MaryO

Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis: Analysis of Noninvasive Coronary Angiography Using Multidetector Computerized Tomography

Journal of Clinical Endocrinology and Metabolism, 05/21/2013  Clinical Article

  1. Nicola M. Neary*,
  2. O. Julian Booker*,
  3. Brent S. Abel,
  4. Jatin R. Matta,
  5. Nancy Muldoon,
  6. Ninet Sinaii,
  7. Roderic I. Pettigrew,
  8. Lynnette K. Nieman and
  9. Ahmed M. Gharib

–Author Affiliations


  1. Program in Reproductive and Adult Endocrinology (N.M.N., L.K.N., B.S.A.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Laboratory of Cardiac Energetics (O.J.B.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; Integrative Cardiovascular Imaging Laboratory (J.R.M., R.I.P., A.M.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Critical Care Medicine (N.M.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; and Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
  1. Address all correspondence and requests for reprints to: Ahmed M. Gharib, MB, ChB, National Institutes of Health, Building 10, Room 3-5340, Mail Stop Code 1263, 10 Center Drive, Bethesda, MD 20892. E-mail: agharib@mail.nih.gov.

  1. ↵* N.M.N. and O.J.B. contributed equally to this work.

Abstract

Background: Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushing’s syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown.

Objective: To determine whether CS patients have increased coronary atherosclerosis.

Design: A prospective case-control study was performed.

Setting: Subjects were evaulated in a clinical research center.

Subjects: Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushing’s disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index.

Primary outcome variables: Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion.

Results: CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm3] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05).

Conclusions: Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.

  • Received October 29, 2012.
  • Accepted March 7, 2013.

From JCEM

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Day Eleven, Cushing’s Awareness Challenge

Posted on April 11, 2012 by MaryO

In March of 1987, after the endo finally  confirmed that I had Cushing’s, I saw sent to a local hospital where they repeated all those same tests for another week and decided that it was not my adrenal gland (Cushing’s Syndrome) creating the problem. The doctors and nurses had no idea what to do with me, so they put me on the brain cancer ward.

When I left this hospital after a week, we didn’t know any more than we had before.

As luck would have it, NIH (National Institutes of Health, Bethesda, Maryland) was doing a clinical trial of Cushing’s. I live in the same area as NIH so it was not too inconvenient but very scary at first to think of being tested there. At that time I only had a choice of NIH, Mayo Clinic and a place in Quebec to do this then-rare pituitary surgery called a Transsphenoidal Resection.

My husband asked my endo if it were his wife, if he would recommend this surgery.  The endo responded that he was divorcing his wife – he didn’t care what happened to her.  Oh, my!

I chose NIH – closest and free. After I was interviewed by the Doctors there, I got a letter that I had been accepted into the clinical trial.

The night before I was admitted, I signed my will.  I was sure I was going to die there.  If not during testing, as a result of surgery.

The first time I was there was for 6 weeks as an inpatient. More of the same tests.

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn’t walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Several were from Greece.

Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with – either a cure or dying. While I was at NIH, I was gaining about a pound a day!

During the time I was home the weekend  before surgery, a college classmate of mine (I didn’t know her) DID die at NIH of a Cushing’s-related problem. I’m so glad I didn’t find out until reading the alumnae magazine a couple months later!  She was the same class, same major, same home-town, same disease…

We have a Scottish doctor named James Lind to thank for the clinical trial.  He  conducted the first ever clinical trial in 1747 and developed the theory that citrus fruits cured scurvy.  Lind  compared the effects of various different acidic substances, ranging from vinegar to cider, on groups of afflicted sailors, and found that the group who were given oranges and lemons had largely recovered from scurvy after 6 days.

I’d like to think that I advanced the knowledge of Cushing’s at least a little bit by being a guinea  pig in 1987-1989.

From the NIH: http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx

Hope through Research

Several components of the National Institutes of Health (NIH) conduct and support research on Cushing’s syndrome and other disorders of the endocrine system, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development (NICHD), the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the National Center for Research Resources.

NIH-supported scientists are conducting intensive research into the normal and abnormal function of the major endocrine glands and the many hormones of the endocrine system. Researchers continue to study the effects of excess cortisol, including its effect on brain structure and function. To refine the diagnostic process, studies are under way to assess the accuracy of existing screening tests and the effectiveness of new imaging techniques to evaluate patients with ectopic ACTH syndrome. Researchers are also investigating jugular vein sampling as a less invasive alternative to petrosal sinus sampling. Research into treatment options includes study of a new drug to treat the symptoms of Cushing’s syndrome caused by ectopic ACTH secretion.

Studies are under way to understand the causes of benign endocrine tumor formation, such as those that cause most cases of Cushing’s syndrome. In a few pituitary adenomas, specific gene defects have been identified and may provide important clues to understanding tumor formation. Endocrine factors may also play a role. Increasing evidence suggests that tumor formation is a multistep process. Understanding the basis of Cushing’s syndrome will yield new approaches to therapy.

The NIH supports research related to Cushing’s syndrome at medical centers throughout the United States. Scientists are also treating patients with Cushing’s syndrome at the NIH Clinical Center in Bethesda, MD. Physicians who are interested in referring an adult patient may contact Lynnette Nieman, M.D., at NICHD, 10 Center Drive, Room 1-3140, Bethesda, MD 20892-1109, or by phone at 301-496-8935. Physicians interested in referring a child or adolescent may contact Constantine Stratakis, M.D., D.Sc., at NICHD, 10 Center Drive, Room 1-3330, Bethesda, MD 20892-1103, or by phone at 301-402-1998.

 

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