Cushing Syndrome

This disease, first described by Harvey Cushing in 1932, refers to any clinical entity due to excessive and prolonged secretion and action of glucocorticoids, although the cause of the disease may relate to any one of a number of origins.

Primary hypercortisolism may be due to an adrenal cortical tumor (adenoma or carcinoma). Cushing Syndrome of secondary origin may derive from a pituitary tumor secreting an excess of adrenocorticotropic hormone (ACTH), or to ectopic ACTH production, or to pituitary corticotroph hyperplasia. The simultaneous measurement of plasma ACTH and cortisol is useful in differentiating between adrenal hyperplasia (due to excess pituitary ACTH stimulation) and adrenal tumors as the cause of Cushing Syndrome.

In patients with adrenal tumors, plasma cortisol levels are high but the concentration of ACTH is low or undetectable. In contrast, both cortisol and ACTH plasma levels are elevated in bilateral adrenal hyperplasia, and both can be lowered by exogenous dexamethasone (a synthetic glucocorticoid) administration.

Some symptoms of cortisol excess are central (truncal obesity), hypertension, glucose intolerance, hirsutism, osteoporosis, polyuria, and polydipsia. The hyperglycemia resulting from excess glucocorticoids leads to so-called steroid diabetes, where prolonged elevated levels of glucose may, in time, lead to pancreatic beta-cell exhaustion (diabetes mellitus). The change in fat distribution is due to the lipolytic action of ACTH and glucocorticoids on the normal fat depots.

The redistribution of fat may not be due to the direct actions of glucocorticoids, but rather to the insulin that is secreted in response to increased hepatic glucose formation. Although the actions of insulin on the normal depots are apparently antagonized by cortisol, insulin appears able to exert a lipogenic effect in other areas of the body, such as the face, upper back, and supraclavicular fat pads.

The catabolic actions of glucocorticoids on skeletal muscle cause thinning of the extremities. Loss of protein matrix of bones causes severe osteoporosis, which may severely affect the spinal column. The excess androgens produced are the cause of hirsutism in the female. Again, the hyperpigmentation that may be present in Cushing Syndrome of secondary origin may be due to the presence of increased circulating levels of ACTH. Polyuria and polydipsia are due to the loss of large volumes of water as a result of solvent drag during the process of excessive glucose excretion by the kidneys.

A number of treatments are possible depending mostly on identifying the cause and removing it. If it is being caused by medications, it should be discontinued when feasible. In most cases of Cushing Syndrome, the treatment is to find the direct or indirect cause (e.g., adrenal gland tumor, pituitary tumor, etc.) and treat it surgically, medically, or by radiation. If the cause cannot be found, the adrenal glands can be removed surgically or suppressed with medications that reduce the glands' production of cortisol.