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Cushing's Syndrome Information

Cushing's syndrome or hypercortisolism or hyperadrenocorticism is an endocrine disorder caused by excessive levels of the endogenous corticosteroid hormone cortisol. It may also be induced iatrogenically by treatment with exogenous corticosteroids for other medical conditions. It was discovered by American physician, surgeon and endocrinologist Harvey Cushing (1869-1939) and reported by him in 1932.

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), "moon face", excess sweating, telangiectasia (dilation of capillaries), atrophy of the skin (which gets thin and bruises easily) and other mucous membranes, purple or red striae on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). A common sign is the growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump). The excess cortisol may also affect other endocrine systems and cause, for example, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to frank psychosis. Depression and anxiety, including panic attacks, are common.

Other signs include persistent hypertension (due to the aldosterone-like effects) and insulin resistance, leading to hyperglycemia (high blood sugars) which can lead to diabetes mellitus. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation of the skin, due to its ability to stimulate melanocyte receptors.

If an adrenal adenoma is identified it may be removed by surgery. Pituitary ACTH producing adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed replacement with hydrocortisone or prednisolone is imperative.

In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome (Nelson et al 1960).

In iatrogenic Cushing's, dose adjustment may be sufficient or it may be necessary to change to another type of immunosuppresive medication.

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