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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.
Signs and symptoms
Symptoms include weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), "moon face", excess sweating, atrophy of the skin (which gets thin and bruises easily) and other mucous membranes, purple striae on the trunk and legs, proximal muscle weakness (hips, shoulders), and hirsutism (male-pattern hair growth). 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.
When Cushing's is suspected, both 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. A novel approach is sampling cortisol in saliva over 24 hours, which may be equally sensitive. Other screening blood tests commonly performed are a full blood count, electrolytes, renal function and liver enzymes. Other pituitary hormones may need to be determined, and determining the visual field may be necessary if a pituitary lesion is suspected (which may compress the optic nerve).
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 (employing catheterisation) is necessary.
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.
If an adrenal adenoma is identified it may be removed by surgery. Post-operatively most patients will require steroid replacement 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 iatrogenic Cushing's, dose adjustment may be sufficient or it may be necessary to change to another type of immunosuppresive medication.
Incidence of causes of Cushing's syndrome per million person-years: -
- Cushing's disease: 10
- Primary adrenal: 3
- Ectopic ACTH: 1.4
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