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Cushing's syndrome with no clinical stigmata - a variant of glucocorticoid resistance syndrome.

ABSTRACT: Background:Cortisol resistance syndrome is a very rare condition characterized by high cortisol levels, but without any clinical features of Cushing's syndrome. Our objective is to present such a case. Case presentation:A 41?year old female presented with mild hirsutism and elevated urinary cortisol levels. Plasma cortisol levels were elevated and were not suppressed by conventional doses of dexamethasone on multiple occasions, but decreased following administration of higher doses of dexamethasone. Adrenocorticotropic hormone (ACTH) levels were inappropriately elevated. Despite significantly elevated cortisol levels, she did not develop any clinical signs or symptoms of Cushing's syndrome. Pituitary and adrenal imaging did not reveal any abnormalities. Genetic testing for human glucocorticoid receptor did not reveal any mutations. Conclusions:Although we were not able to identify any new mutations, we believe that our patient has a variant of cortisol resistance syndrome. This syndrome should be considered in the differential diagnosis of patients who present with high levels of cortisol but have no clinical features of Cushing's syndrome.

SUBMITTER: Gossain VV

PROVIDER: S-EPMC6299537 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Cushing's syndrome with no clinical stigmata - a variant of glucocorticoid resistance syndrome.

Gossain Ved V VV El-Rifai Mohammad M Krishnan Preethi P Bhavsar Bhavini B

Clinical diabetes and endocrinology 20181218

<h4>Background</h4>Cortisol resistance syndrome is a very rare condition characterized by high cortisol levels, but without any clinical features of Cushing's syndrome. Our objective is to present such a case.<h4>Case presentation</h4>A 41 year old female presented with mild hirsutism and elevated urinary cortisol levels. Plasma cortisol levels were elevated and were not suppressed by conventional doses of dexamethasone on multiple occasions, but decreased following administration of higher dose ...[more]

PMID: 30598838

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Project description:Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing's syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing's disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing's syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing's disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing's syndrome is under control.

Project description:Abstract submitted to the Journal of clinical encodcrinology and metabolism: The molecular mechanisms responsible for the ectopic expression of the GIP receptor in the adrenal cortex of patients with GIP-dependent Cushing’s syndrome (CS) are unknown. Chronic adrenal stimulation by ACTH in Cushing’s disease (CD) or by GIP in GIP-dependent AIMAH both lead to induction of a set of genes which stimulate adrenal proliferation and steroidogenesis. The objective of this study was to compare the whole genome expression profile of adrenal glands of five cases of GIP-dependent bilateral macronodular adrenal hyperplasia with CS, one case of GIP-dependent adenoma, compared to five cases of ACTH-dependant hyperplasias (CD) and a pool of adrenals from 62 normal individuals. We used the genome-spanning Affymetrix U133 plus 2.0 microarray oligochips to identify genes differentially expressed specifically in GIP-dependent CS and which would be candidate genes implicated in the ectopic expression of the GIP receptor in the adrenal cortex. After data normalization and filtering, genes with differential expression were identified with a multi-step statistical analysis involving a student’s t-test, a filter on flags and a SAM analysis. A total of 721 probesets were thus isolated with intensity levels robustly related to the presence of a GIP-dependent hyperplasia. We performed a functional classification to further define potentially important biological processes and signaling mechanism for the formation of GIP-dependent AIMAH. Various probesets were related to metabolic processes, cell-surface and intracellular signaling, tumorigenesis, transport and transcription factors. The most relevant genes had their expression profile confirmed by real-time RT-PCR. This study reports an extensive series of potentially novel targets in the identification of the molecular mechanisms of ectopic expression of the GIP-receptor in this pathology. Keywords: Comparative genomic analysis

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Cushing's syndrome with no clinical stigmata - a variant of glucocorticoid resistance syndrome.

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Cushing's syndrome with no clinical stigmata - a variant of glucocorticoid resistance syndrome.

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