Cushing's syndrome

Abstract

Endogenous Cushing's syndrome results from prolonged, excessive concentrations of circulating cortisol. Cushing's syndrome should be considered in individuals with features unusual for their age, multiple and progressive features or adrenal incidentalomas, and children with decreasing height percentile and increasing weight. Endogenous Cushing's syndrome is more common in women than men. Adrenocorticotropic hormone (ACTH)-dependent causes account for around 80% of cases. Of the ACTH-dependent cases, 80% result from pituitary adenomas (Cushing's disease) and the remainder from ectopic ACTH secretion. Non-ACTH-dependent Cushing's syndrome is caused by benign adrenal adenomas in 60% and carcinomas in 40%. Specialist assessment and treatment warrants referral to major centres. Diagnostically, the most discriminating clinical features are thin skin, easy bruising and proximal myopathy. There should be a high index of clinical suspicion before instigating investigations. Biochemical diagnosis is by a combination of dexamethasone suppression tests, assessment for loss of circadian rhythm and measurement of urinary free cortisol. When differentiating pituitary and non-pituitary sources of ACTH, reliance should be placed on biochemical evaluation. Medical therapy is used to lower plasma cortisol, before surgery or after incomplete surgical treatment. Trans-sphenoidal surgery is the treatment of choice for Cushing's disease; laparoscopic bilateral adrenalectomy can be used in refractory cases.