A COMPARISON OF THE EFFECTS OF HUMAN AND OVINE CORTICOTROPIN-RELEASING HORMONE ON THE PITUITARY-ADRENAL AXIS

To compare the clinical efficacy of ovine and human sequence corticotr opin-releasing hormone (CRH), we examined the effects of both peptides on ACTH and cortisol secretion in normal human volunteers, obese subj ects, and patients with pituitary-dependent (Cushing's disease) and ad renal-dependent Gushing's syndrome. All subjects in each group were st udied twice in random order. One hundred micrograms of CRH were admini stered as an iv bolus through an in-dwelling forearm cannula at 0930 h , and thereafter, blood was drawn every 15 min for 2 h for the measure ment of ACTH and cortisol. In the normal subjects, the peak ACTH, peak incremental ACTH, and mean area under the curve after CRH treatment w ere greater with ovine CRH than human CRH, although there was no diffe rence in the cortisol response, however it was analyzed. There was no difference in the ACTH or cortisol response to the two preparations in the obese subjects, and no significant difference was found, for eith er cortisol or ACTH, between obese subjects and normal volunteers. Wit h both varieties of CRH, Gushing's disease resulted in greater respons es for ACTH and cortisol than those seen in the other 2 groups (P < 0. 001 for all comparisons), but there was no difference between the sequ ences. However, a significant cortisol response, defined as an increas e of greater than 4 times the coefficient of variation of the assay (2 4%), was seen in all 10 Gushing's patients with human CRH, but in only 8 with ovine CRH. In 3 patients with adrenal tumors, serum cortisol d id not change after the administration of either preparation, whereas plasma ACTH remained undetectable throughout the study. We suggest tha t although ovine sequence CRH causes more prolonged and greater ACTH, and possibly cortisol, secretion compared to human CRH, the discrimina tory value of the CRH test, in terms of either the diagnosis or differ ential diagnosis of Gushing's syndrome, is comparable for the two pept ide sequences.