Secondary hypercortisolism

Overproduction of cortisol by hyperplastic adrenal cortices can result from oversecretion of ACTH (secondary hypercortisolism) due to a defect at the level of the pituitary or median eminence or to ectopic production of ACTH. The former condition is known as Cushing s disease and the latter as ectopic ACTH syndrome. In both conditions, the adrenal cortex functions normally and secretes cortisol in proportion to the level of ACTH. 

Hyperfunction of the adrenal glands occurs in Cushing s syndrome, a disorder caused by excessive secretion of cortisol by the adrenal gland (hypercortisolism). Other causes of adrenal gland hyperfunction include primary and secondary aldosteronism (not discussed in this chapter refer to textbook Chap. 79 for more information on these disorders). 

Infusion of exogenous CRF increases ACTH levels and provides a test of pituitary sensitivity. In several studies of major depression, the ACTH response to CRF was shown to be blunted, reflecting a reduced sensitivity of the pituitary to CRF (e.g., Krishnan 1993). This finding has been widely interpreted as reflecting a downregulation of pituitary CRF receptors secondary to CRF hypersecretion, but may also reflect increased cortisol inhibition of ACTH secondary to hypercortisolism (Krishnan 1993 Yehuda and Nemeroff 1994). 

An intriguing hypothesis first proposed by Schatzberg and colleagues (1985) is that the development of delusions in patients with depression is secondary to the effects of hypercortisolism on dopaminergic systems. 

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