PLASMA CORTICOTROPIN AND CORTISOL RESPONSES TO OVINE CORTICOTROPIN-RELEASING HORMONE (CRH), ARGININE-VASOPRESSIN (AVP), CRH PLUS AVP, AND CRH PLUS METYRAPONE IN PATIENTS WITH CUSHINGS-DISEASE

The CRH test may sometimes be useful in the differential diagnosis of Cushing's syndrome, because most patients with pituitary ACTH-dependen t Cushing's syndrome (Cushing's disease) respond to CRH, but those wit h other causes of Cushing's syndrome usually do not. However, about 10 % of Cushing's disease patients fail to respond to CRH. We wondered if ne could eliminate these false negative results either by exploiting the potential additive or synergistic effects of another ACTH secretag ogue or by reducing glucocorticoid inhibition of CRH's ACTH-releasing effect. We compared the effect on plasma ACTH and cortisol in 51 patie nts with Cushing's disease of administering ovine CRH (1 mu g/kg BW, i v) alone, arginine vasopressin (AVP; 10 U, im) alone, the combination of CRH and AVP, and CRH after pretreatment with metyrapone (1 g, orall y, every 4 h for three doses; CRH + MET). The rates of nonresponse (AC TH increment, <35%; cortisol increment, <20%) to AVP and CRH alone wer e 26% and 8%, respectively; all patients responded to CRH + AVP. The l ack of response was not due to improper administration or rapid metabo lism of the agonist, because plasma CRH and AVP concentrations were si milar in responders and nonresponders. A synergistic ACTH response to CRH + AVP occurred in 65% of the patients. MET pretreatment increased basal plasma ACTH levels in most patients and induced the greatest mea n peak ACTH response to CRH, but 8% of the patients did not respond to CRH + MET with an ACTH increment of 35% or more. Because all of the C ushing's disease patients tested in this study responded to the combin ation of CRH + AVP, whereas 8% failed to respond to CRH alone, we conc lude that CRH + AVP administration may provide a more reliable test fo r the differential diagnosis of ACTH-dependent Cushing's syndrome than administration of CRH alone. Whether this improved sensitivity is acc ompanied by unaltered specificity for Cushing's disease must be tested in patients with chronic ectopic ACTH syndrome.