CUSHING'S SYNDROME

metabolic disorder caused by overactivity of the adrenal cortex, usually secondary to other disease processes. If caused by a tumour of the pituitary gland, it is called Cushing's disease. The condition is characterized by a combination of manifestations, including obesity of the trunk; muscle wasting and generalized protein breakdown; florid complexion; high blood pressure; skin atrophy resulting in excess bruisability and the appearance of abdominal streaks (striae); osteoporosis (resulting from breakdown of the protein framework of the bone rather than from decalcification); diabetes mellitus; facial obesity (moon face); and fat in the area between the shoulders (buffalo hump). Various other pathologic changes are associated with Cushing's disease, including atherosclerosis of the large arteries, calcification or atherosclerosis of the renal blood vessels, and abnormalities in other endocrine glands. The condition is named for Harvey Cushing, the American neurosurgeon who in 1932 first described the complex of symptoms in patients with pituitary tumours. Cushing's syndrome is caused by the adrenal gland's excessive secretion of cortisol (hydrocortisone). In general, anything that increases the adrenal gland's secretion of glucocorticoid hormones will cause Cushing's syndrome, including adrenal tumours, enlargement of the outer layers of the adrenal gland, or overproduction of adrenocorticotropic hormone (ACTH), the major pituitary hormone regulating adrenal function. Excess ACTH may result from pituitary tumours (Cushing's disease), as in Cushing's first group of symptomatic patients, or from inappropriate production of the hormone by other tissues that do not ordinarily make ACTH. Treatment with corticosteroid drugs may also induce Cushingoid symptoms. Although relatively rare in all populations, Cushing's syndrome is four times as common in women as in men and may appear during or just following pregnancy. It can occur at any age but most typically appears during the third to sixth decades of life. Many of the manifestations of Cushing's syndrome disappear when the cause of the cortisol excesses is removed. If the cause is from ACTH or steroid treatment, remission occurs when treatment is discontinued. In the spontaneous types, partial or complete surgical removal of the overactive adrenal cortices or removal of the ACTH-producing tumour of the pituitary is followed by a remission of the symptoms and signs. Daily treatment with cortisol is essential if the adrenal cortices have been completely removed, but it may also be necessary after partial removal of these glands. Cushing's syndrome is also treated at times by irradiation of the pituitary with a proton beam, by implants of radioactive materials, or by administration of certain chemical agents that block cortisol production. Even when Cushing's syndrome has been eradicated, however, some of the changes produced by the disorder may continue. This is true, for example, of heart, blood vessel, and kidney changes and osteoporosis.