Diurnal variation of plasma cortisol levels

The Correct option Answer: a, b

Diurnal variation of plasma cortisol levels is lost in hypercortisolism, caused by both adrenal tumors and pituitary lesions. Dexamethasone, by negative feedback, suppresses the hypothalamic pituitary secretion of ACTH and effects the consequent lowering of both plasma cortisol and urinary 17-hydroxycorticosteroid excretion. Administration of a single dose of 2 mg of dexamethasone suppresses plasma cortisol and urinary 17-hydroxycorticosteroids by at least half when compared to control values from untreated normal patients (low dose suppression test).

In Cushing disease, with a setpoint of ACTH secretion higher than normal, low-dose dexamethasone is insufficient to suppress ACTH. High-dose dexamethasone suppression is achieved by 2 mg of dexamethasone administered every 6 hours for 24 hours. A normal response is to lower the 17-hydroxycorticosteroid excretion by more than one half. In the case of Cushing disease, the hypothalamic steroid receptors that allow negative feedback are intact but at a higher setpoint. In this case, 17-hydroxycorticosteroid secretion does decrease significantly after high-dose dexamethasone administration. Adrenal tumors, other causes of ectopic production of ACTH, and most cases of nodular hyperplasia do not respond to dexamethasone suppression with a decrease in steroid secretion.

With an adrenal tumor, pituitary ACTH is already suppressed; therefore, dexamethasone cannot suppress it further. With ectopic ACTH secretion, the tissue producing ACTH has no receptors for steroids and thus negative feedback cannot be achieved. Therefore, high dose dexamethasone suppression will differentiate hypercortisolism of pituitary and adrenal origins.

Potentially the most helpful new test for this purpose uses the administration of recombinant CRH to release ACTH and consequently to stimulate cortisol secretion. CRH (1 mg/kg) is administered intravenously, and serial blood samples obtained for 3 hours after administration. The normal pituitary adrenal axis responds by a moderate increase in ACTH and cortisol. With Cushing disease, the ACTH and cortisol rise are accentuated. With adrenal autonomous production of cortisol and with ectopic ACTH production, there is virtually no response to CRH.

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