Occult Cushing’s Syndrome in Type-2 Diabetes

Abstract

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.

Measurement of late-night salivary cortisol with an automated immunoassay system

“…It is not uncommon that Cushing's syndrome is diagnosed only in advanced disease states several years after the onset of symptoms, and so the disease is typically associated with substantial morbidity and mortality (1,2). Mild forms of Cushing's syndrome, however, probably often remain undiagnosed in obese diabetic patients (3,4). Therefore, reliable and convenient screening tests for Cushing's disease are of particular clinical importance.…”

Factitious Cushing's syndrome masquerading as Cushing's disease

“…2,17 Most cases of ACTH-independent Cushing's syndrome are correctly classified by demonstrating a suppressed plasma ACTH, 18 though cases of ACTH-independent Cushing's syndrome with a plasma ACTH at the lower end of the reference interval have been reported. 19,20 This has usually been in patients with mild glucocorticoid excess, 21 not the apparently ten-fold elevation in urinary free cortisol found in our patient. A reliable ACTH assay is crucial to differentiate ACTH-dependent from ACTH-independent Cushing's syndrome.…”

Recommendations of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism for the diagnosis of Cushing’s disease in Brazil

“…However, the most studied risk condition is diabetes mellitus, which was found to have a prevalence of 0.8% (0-3.3%) in a group of 2,381 diabetic patients from 12 studies (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Striking Cushing's features have not been described in diabetic patients with an HbA1c between 8.4-12.2% associated with hypertension and overweight/obesity (BMI between 25.4-34.5 kg/m 2 ).…”