Testing the Axis

With the probable exception of vasopressin, which may stimulate adrenocorticotropic hormone (ACTH) release directly, all substances now in use for testing the integrity of the hypothalamus-pituitary-adrenal axis act indirectly through feedback or stress mechanisms. To the former mechanism belongs the metyrapone (Metopirone) test; to the latter, the insulin or lysine-induced hypoglycemia and the pyrogen-provoked stress. Recently these tests have been subjected to comparative studies.

Metyrapone inhibits 11-β-hydroxylase, an enzyme essential for cortisol formation. Suppression of cortisol in turn causes a feedback release of ACTH, with consequent stimulation of the adrenal cortex. Since the latter is unable to synthesize cortisol, it floods the circulation with cortisol precursors and the urine with their excreated metabolites. In the presence of normal adrenal function, these excretory products provide an indirect estimate of ACTH activity. Of the two generally measured metabolites—11-desoxy-oxogenic steroids and 17-oxogenic steroids (OGS)—the latter has been shown by Metcalf and Beaven¹