The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome

Posted on July 9, 2015 by MaryO

J Clin Endocrinol Metab. 2004 Mar;89(3):1222-6.

Findling JW1, Raff H, Aron DC.

Abstract

Low-dose dexamethasone suppression testing has been recommended for biochemical screening when Cushing’s syndrome is suspected. The criterion for normal suppression of cortisol after dexamethasone is controversial.

To assess diagnostic utility (sensitivity), we report the results of low-dose dexamethasone suppression testing in 103 patients with spontaneous Cushing’s syndrome. There were 80 patients with Cushing’s disease (78%), 13 with the ectopic ACTH syndrome (13%), and 10 with cortisol-producing adrenocortical adenomas (10%). Fourteen (18%) of 80 patients with Cushing’s disease suppressed serum cortisol to less than 5 micro g/dl (<135 nmol/liter) after the overnight 1-mg test, whereas six patients (8%) actually showed suppression of serum cortisol to less than 2 micro g/dl (<54 nmol/liter). In addition, the 2-d, low-dose dexamethasone suppression test yielded false-negative results in 38% of patients when urine cortisol was used and 28% when urinary 17-hydroxycorticosteroids were used. Serum cortisol after the 1-mg test correlated with baseline urinary free cortisol (r = 0.705, P < 0.001), plasma ACTH level (r = 0.322, P = 0.001), and urinary free cortisol after the 2-d test (r = 0.709, P = 0.001).

This study provides evidence that low-dose dexamethasone may suppress either plasma cortisol or urinary steroids to levels previously thought to exclude Cushing’s syndrome and that these tests should not be used as the sole criterion to exclude the diagnosis of endogenous hypercortisolism.

PMID:
15001614
[PubMed – indexed for MEDLINE]

From http://www.ncbi.nlm.nih.gov/pubmed/15001614

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Crooke’s changes common in patients with Cushing’s syndrome, high cortisol production

Posted on July 9, 2015 by MaryO
Oldfield EH, et al. J Clin Endocrinol Metab. 2015;doi:10.1210/JC.2015-2493.
July 8, 2015

 

Evidence of Crooke hyaline changes in the pituitary gland points to a higher likelihood of Cushing’s syndrome in adults, with the changes in basophil cells occurring in 75% to 80% of patients with the hormonal disorder, according to research in The Journal of Clinical Endocrinology & Metabolism.

In a retrospective review of hospital patient records from adults with Cushing’s syndrome who underwent pituitary surgery, researchers also found that a higher degree of cortisol production, as well as exposure to excess glucocorticoids, are often associated with Crooke’s changes in adults.

“The presence of Crooke’s changes is a clear indication of the presence of Cushing’s syndrome, although the absence of Crooke’s changes does not exclude it,” the researchers wrote.

Edward H. Oldfield, MD, FACS, of the department of neurological surgery at University of Virginia Health System, and colleagues analyzed electronic hospital data from 213 consecutive patients with Cushing’s syndrome who received pituitary surgery between 2008 and March 2014. Researchers reviewed analysis of the normal pituitary tissue included with the specimens obtained at surgery, as well as cortisol production measured by 24-hour urine.

Within the cohort, Crooke’s changes occurred in 74% of patients; Crooke’s changes occurred in 81% of patients with an adrenocorticotropic hormone tumor.

Researchers also found that 91% of patients with an adrenocorticotropic hormone-producing tumor and a urinary free cortisol test at least fourfold the upper limit of normal had evidence of Crooke’s changes vs. 74% of patients with a urine cortisol amount that was less than fourfold the upper limit of normal (P = .008).

“Our results clearly demonstrate a correlation between the degree of cortisol production and the presence of Crooke’s changes,” the researchers wrote. “Patients with cortisol production exceeding fourfold upper limit almost all had Crooke’s changes.”

Researchers said study results indicate that the presence of Crooke’s changes may be used to indicate that a patient has Cushing’s syndrome following a pituitary surgery in which no tumor is found.

“However, the absence of Crooke’s changes does not reliably indicate the absence of Cushing’s syndrome, as 19% of patients with a proven [adrenocorticotropic hormone-producing tumor] did not have Crooke’s changes,” the researchers wrote. – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B838a3557-f284-4fda-b93d-73dbb4823667%7D/crookes-changes-common-in-patients-with-cushings-syndrome-high-cortisol-production

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ALD403 (migraine drug) and ALD1613 (for Cushing’s disease)

Posted on July 2, 2015 by MaryO

As it moves into crucial Phase 3 drug trials for its flagship migraine treatment, Bothell-based Alder Biopharmaceuticals (Nasdaq: ALDR) is looking to raise a lot of cash.

Alder is offering up to $200 million shares of its common stock, according to SEC filings.

The company plans to use the money to develop its drugs ALD403 (its migraine drug) and ALD1613 (for Cushing’s disease), conduct clinical trials and commercialize these drugs. Funds will also go toward “general corporate purposes,” which might include the acquisition or licensing of other products, businesses or technologies, according to those filings.

From http://www.bizjournals.com/seattle/blog/health-care-inc/2015/06/alder-biopharmaceuticals-sets-out-to-raise-200m-to.html

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Multiple aberrant hormone receptors in Cushing’s Syndrome

Posted on June 26, 2015 by MaryO
Eur J Endocrinol. 2015 May 13. pii: EJE-15-0200. [Epub ahead of print]
Multiple Aberrant Hormone Receptors in Cushing’s Syndrome.
El Ghorayeb N1, Bourdeau I2, Lacroix A3.

Author information

Abstract

The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing’s syndrome include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands.

Screening for aberrant expression of GPCR in BMAH and unilateral adrenal tumors of patients with overt or subclinical CS demonstrates the frequent co-expression of several receptors. Aberrant hormone receptors can also exert their activity by regulating the paracrine secretion of ACTH or other ligands for those receptors in BMAH or unilateral tumors.

The aberrant expression of hormone receptors is not limited to adrenal Cushing’s syndrome but can be implicated in other endocrine tumors including primary aldosteronism and Cushing’s disease. Targeted therapies to block the aberrant receptors or their ligands could become useful in the future.

PMID:
25971648
[PubMed – as supplied by publisher]

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Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging

Posted on June 24, 2015 by MaryO

Objectives : MRI has proven to be the best imaging modality in the evaluation of pituitary tumors. Dynamic Imaging is technically a new tool, which has emerged with lot of promise in the evaluation of pituitary adenomas, particularly in accurate delineation of those microadenomas with no contour abnormality and in differentiating residual/recurrent adenoma from surrounding post operative tissue. Dynamic MR imaging is not only useful in the evaluation of pituitary microadenomas but has an equally important role in the assessment of macroadenoma as well. This study analyses and reviews the value of dynamic MR Imaging in pituitary adenomas and postoperative pituitary tumors.

Materials and Methods : A prospective MR Study was undertaken in twenty-five consecutive patients with suspected pituitary adenomatous lesions. These patients were subjected to dynamic MR imaging at our Department from Jan 1997 to Dec 1998. The study was performed on a 0.5T super conducting MR imaging system with Fast Spin echo technique. Gadodiamide (0.1 mmol/Kg) was administered over sixty seconds by hand injection. Dynamic coronal images were obtained simultaneously from three different portions of the gland. Fifteen images were obtained from each of the three portions at an interval of twenty to thirty seconds between the images.

Result : Dynamic MRI was performed in nineteen patients with microadenoma and six cases of macroadenoma. Dynamic MRI study was of diagnostic value in comparison with routine contrast MRI in eleven of the nineteen patients. Dynamic study did not add to the diagnosis and was merely of confirmatory value in remaining eight patients. Dynamic MRI study was used to identify the optimal time for delineation of the adenomatous tumor, by virtue view of the simultaneous differential contrast enhancement patterns between normal pituitary gland and adenoma. Further the enhancement pattern of the normal pituitary gland, the adenomatous nodule and the optimal delineation were individually assessed. This evaluation revealed the average time in seconds for onset of enhancement and the peak enhancement of normal pituitary gland were 43.1 and 111.9 seconds respectively. In comparison the pituitary adenomatous nodules exhibited an average time of 105.8 seconds for onset of enhancement and 188.1 seconds for peak enhancement. The average time in seconds for optimal tumor delineation was 93.9 seconds.

Conclusion : Dynamic MR Imaging has emerged as a technically refined tool in the evaluation of pituitary adenomas. The key questions in evaluation of pituitary adenomas include the presence or absence of a tumor, the number, the location of adenoma nodule, the invasive effects on adjacent structures and the post therapy status of adenoma. Clearly, dynamic MR Imaging is the foremost imaging modality answering these vital questions in patients with pituitary adenomas.

via Value of dynamic MRI imaging in pituitary adenomas Indrajit I K, Chidambaranathan N, Sundar K, Ahmed I – Indian J Radiol Imaging.

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