Dissociation of cortisol and adrenal androgens (AA) in selected patients with hypopituitarism

Abstract

Dissociation of secretion of cortisol and AA, observed in several physiologic and pathologic conditions, has led to the hypothesis that secretion of AA may be controlled by another hormone in addition to ACTH. An alternate hypothesis attempts to explain all instances of such dissociation by changes in ACTH alone, wherein ACTH controls synthesis of AA by changing the intraadrenal concentration of cortisol. This hypothesis does not allow for dissociation of cortisol and AA in a subject with normal ACTH secretion and intact adrenals. To test this hypothesis, we studied cortisol secretion in 4 patients (20-26 years) with idiopathic hypopituitarism (who never received cortisol replacement therapy) and deficiency of AA as reflected by lack of adrenarche and low levels of serum DHEAS. Determination of serum cortisol and 17-OH progesterone (17 OHP) at 2 h intervals for 2 days and of cortisol and 17 OHP responses to insulin induced hypoglycemia and glucagon infusion revealed normal cortisol and 17 OHP secretion in 2 of the 4 patients. Although intraadrenal concentrations of cortisol and serum levels of ACTH were not measured, there is no reason to suspect that these levels should be abnormal in the 2 patients who had normal cortisol secretion. Low serum levels of DHEAS in these patients cannot be explained by deficiency of ACTH secretion. Our data provide further evidence that secretion of AA may be controlled by another hormone in addition to ACTH.