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Cushing's syndrome

Cushing's syndrome or hypercortisolism 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. more...

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Signs and symptoms

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); many develop frank diabetes. Untreated Cushing's syndrome can lead to heart disease and increased mortality.

Diagnosis

When Cushing's is suspected, a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH levels) and 24-hour urinary measurement for cortisol have equal detection rates (Raff & Findling 2003). A novel approach is sampling cortisol in saliva over 24 hours, which may be equally sensitive. Other pituitary hormones may need to be determined, and performing physical examination directed for any visual field defect may be necessary if a pituitary lesion is suspected (which may compress the optic chiasm causing typical bitemporal hemianopia).

When these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed. These should be performed when other tests are positive, to decrease likelihood of incidentalomas (incidental discovery of harmless lesions in both organs). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the cortisol levels in various veins in the body by venous catheterisation working towards the pituitary (petrosal sinus sampling) is necessary.

Pathophysiology

Cortisol is secreted by the adrenal glands under regulation by the pituitary gland and hypothalamus. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. Cushing's disease refers only to hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a pituitary gland adenoma.

Therapy

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.

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