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Chapter: Biology of Disease: Disorders of the Endocrine System

Diagnosis and treatment of Cushing’s syndrome

A clinical suspicion of the syndrome is supported by hypokalemia and alkalosis, high urinary free cortisol, which is normally less than 300 nmol per 24 h, and loss of the usual diurnal rhythm of cortisol secretion.

Diagnosis and treatment of Cushing’s syndrome

A clinical suspicion of the syndrome is supported by hypokalemia and alkalosis, high urinary free cortisol, which is normally less than 300 nmol per 24 h, and loss of the usual diurnal rhythm of cortisol secretion. Initial screening criteria are followed by tests using the cortisol analog, dexamethasone, which is not detected by the usual methods of measuring cortisol. Dexamethasone, however, suppresses ACTH production and cortisol secretion in normal people. The low dose dexamethasone test involves giving 1 mg of dexamethasone at night. A blood specimen is taken for cortisol measurement the following morning. A failure of dexamethasone to suppress cortisol release is suggestive of Cushing’s syndrome or disease. To distinguish between the two, a high dose dexamethasone test may be used or the concentration of ACTH in plasma measured. The high dose dexamethasone test consists of administering 2 mg of dexamethasone every 6 h for a period of 48 h. The concentration of cortisol in the plasma is then measured at 09.00 h on the morning following the last dose. In Cushing’s syndrome, due to excessive secretion of cortisol by an adrenal tumor or in response to an ectopic source of ACTH, suppression of cortisol does not occur. In Cushing’s disease, caused by a pituitary lesion secreting ACTH, the concentration of cortisol is suppressed to less than 50% of its value prior to the test. Plasma ACTH levels are raised in patients with Cushing’s disease and ectopic ACTH production, but are low in patients who have an adrenal tumor that secretes cortisol.



The management and treatment of Cushing’s syndrome depends upon its cause. Drugs, such as metyrapone, that inhibit the synthesis of cortisol may be used. Tumors can be removed surgically.


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