Cushing’s Syndrome

Cushing’s syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. Cushing’s disease, pituitary-dependent Cushing’s syndrome, is the most common cause of endogenous hypercortisolism. The recommended screening tests include the 1mg overnight dexamethasone suppression test, late-night salivary cortisol (at least 2 samples), and 24-hour urinary free cortisol (at least two 24-hour collections). If the initial test is positive on 2 occasions the patient should be evaluated by an endocrinologist for further assessment. Plasma 09:00h ACTH measurement guides imaging and further investigations. If ACTH is elevated/inappropriately normal, MRI scanning of the pituitary should be performed, but if ACTH is suppressed imaging of the adrenals should follow. The corticotrophin releasing hormone (CRH) or desmopressin tests helps distinguishing pituitary from ectopic ACTH-dependent Cushing's syndrome, while bilateral petrosal sinus sampling remains the gold standard test and should be considered, if available, with the exception of the presence of a pituitary macroadenoma. It is prudent to perform a CT of the thorax, abdomen and pelvis in all patients. Transsphenoidal surgery is the first line treatment for Cushing’s disease, followed by radiotherapy as a second-line option. Adrenalectomy is the first-choice treatment for adrenal ACTH-independent Cushing’s syndrome and resection of the ACTH source should be performed for the ectopic ACTH-dependent Cushing’s syndrome, where possible. Bilateral adrenalectomy can always be considered as an option. Steroidogenesis inhibitors remain the most effective medical agents and are useful when surgery or the effects of radiotherapy are awaited or are unsuccessful. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.