COMPARISON OF ADRENOCORTICOTROPIN AND ADRENAL-STEROID RESPONSES TO CORTICOTROPIN-RELEASING HORMONE VERSUS METYRAPONE TESTING IN PATIENTS WITH HYPOPITUITARISM

We compared the responses of ACTH and cortisol (F) to corticotropin-releasing hormone (CRH) administration (ovine 1 mu g/kg i.v. bolus) with the responses of urinary 17-OH corticosteroids (17-OHCS) and serum deoxycorticosterone (DOC) to metyrapone administration (450 mg/ m(2)/dose every 4 h x seven doses) in 16 hypopituitary patients. Glucocorticoid therapy for these patients was withheld for a minimum of 3 wk before testing. The CRH test was performed 3 d before or 3 wk after the metyrapone test was used to diagnose the ACTH reserve status. In nine ACTH-intact hypopituitary patients (postmetyrapone 17-OHCS > 12.2 mu mol/m(2)/d; DOC greater than or equal to 11.5 nmol/L), the peak F (497-773 nmol/L) and ACTH (5.2-22 pmol/L) responses to CRH stimulation were similar to those of normal subjects (F peak = 554-993 nmol/L and ACTH peak = 6-25 pmol/L at 15-60 min). In one patient with partial ACTH deficiency (postmetyrapone 17-OHCS = 10.5 mu mol/m(2)/d; DOC = 6 nmol/L), the peak F response was low and delayed (246 nmol/L at 180 min) and the peak ACTH response was normal (7 pmol/L). Six severely ACTH-deficient patients (postmetyrapone 17OHCS< 5.4 mu mol/m(2)/d; DOC less than or equal to 3.4 nmol/L) had a low F response at 15-90 min in all, with a delayed rise in three at 120-180 min in response to CRH administration, where as ACTH responses were variable: absent or low, normal, delayed, or persistently exaggerated. In conclusion, the CRH-stimulated F response pattern in hypopituitary patients was comparable to the urinary 17-OHCS and serum DOC response to metyrapone administration. Thus, F response pattern to CRH was useful in the evaluation of ACTH reserve in hypopituitary patients. ACTH response to CRH in ACTH-deficient patients was not consistently useful for ACTH reserve evaluation because of the variable response possibly resulting from a different etiology (hypothalamus versus pituitary) of ACTH deficiency.