Endocrine Abstracts

The concept of subclinical hypercortisolism remains controversial in Endocrinology. Preclinical Cushing’s syndrome, subclinical Cushing’s syndrome or subclinical hypercortisolism, recently renamed in the European Society of Endocrinology Adrenal Incidentaloma Guidelines as ‘autonomous cortisol secretion’, is an example where a definition and name has not been universally agreed upon. Previous studies from Italy have used multiple tests of the hypothalamic-pituitary-adrenal (HPA) axis in patients with adrenal incidentaloma, and defined subclinical Cushing’s as patients having any two abnormal tests. Earlier in 2017, a Korean group proposed modified criteria for subclinical hypercortisolism based on their study that identified which tests were most likely to predict (1) post-operative adrenal suppression and (2) presence of metabolic complications. The most sensitive combination of tests in this study was a cortisol of >138 nmol/l after 1 mg of dexamethasone OR post-dexamethasone cortisol >61 nmol/l, plus either ACTH <2.2 pmol/l or dehydroepiandrosterone-sulphate (DHEA-S) of <2.17 μmol/l in men and <0.95 μmol/l in women. Unlike subclinical hyperthyroidism, where TSH is able to be accurately quantitated, the ACTH immunoassay is not as robust at low concentrations. The addition of DHEA-S to the model provides another marker of cortisol autonomy in cases where ACTH is not fully suppressed. Several studies have shown that subclinical autonomous hypercortisolism is associated with several major comorbidities such as obesity, type 2 diabetes, hypertension and cardiovascular events, as well as osteoporosis and vertebral fractures. Adrenal incidentaloma patients with an abnormal 1 mg dexamethasone suppression test have increased mortality. Surgical resection may improve some of the comorbidities, but to date there has not been a study which has examined any beneficial effect on mortality. A multicentre randomised controlled trial is required to answer this important question.