Cushings syndrome (CS) is characterized by chronic overproduction of cortisol resulting in significant morbidity and, when untreated, an increased mortality. CS is divided into adrenocorticotropin (ACTH)-dependent CS and ACTH-independent CS. ACTH-dependent CS, the majority of cases, can be caused by a corticotroph pituitary adenoma and, more rarely, by ectopic ACTH production. ACTH-independent CS is usually caused by an unilateral adrenal adenoma and less frequent by an adrenal carcinoma and bilateral adrenal hyperplasia.
The diagnosis CS is biochemically established by demonstration of increased urinary cortisol excretion, insufficient cortisol suppression by dexamethasone and absence of the cortisol diurnal rhythm. In case of ACTH-dependent CS and a negative MRI of the sellar region, bilateral inferior petrosal sinus sampling (BIPSS) is performed to differentiate between a non-visible pituitary adenoma and ectopic ACTH production. If BIPSS shows no central to peripheral ACTH gradient the ectopic cause can often be visualized with CT and somatostatin receptor scintigraphy. In patients with ACTH-independent CS, CT or MRI of the abdomen is performed to detect an adrenal neoplasia.
Surgery is the primary treatment for all causes of CS. The remission rate in patients with pituitary-dependent CS varies between 60 and 80% after transsphenoidal adenomectomy. Patients with persistent or recurrent pituitary-dependent CS can be treated with radiotherapy and/or medical therapy with neuromodulatory drugs (dopamine agonists, somatostatin analogs), adrenal blocking drugs (ketoconazole, metyrapone) or glucocorticoid receptor antagonists (mifepristone). Ectopic ACTH production is frequently accompanied by severe hypercortisolism which may necessitate bilateral adrenalectomy.