Responsiveness of the Hypophyseal-Adrenocortical Axis to Corticotropin-Releasing Factor in Pituitary-Dependent Cushing’s Disease

Corticotropin-releasing factor [(CRF) 200 micrograms] was administered iv to five patients with classical pituitary-dependent Cushing's disease and to five normal subjects. In both groups no changes were observed in the plasma concentrations of hGH, PRL, TSH, LH, or FSH. In the normal subjects plasma ACTH levels rose from 41 +/- 9 (SEM) pg/ml to 87 +/- 28 pg/ml after 60 min (P less than 0.01) and plasma cortisol levels from 0.30 +/- 0.06 mumol/liter (8.0 +/- 0.2 micrograms/dl) to 0.53 +/- 0.07 mumol/liter (14.2 +/- 0.2 micrograms/dl) after 60 min (P less than 0.001). In the patients with classical Cushing's disease plasma ACTH levels increased from 109 +/- 23 to 281 +/- 78 pg/ml after 30 min (P less than 0.01) and plasma cortisol levels from 0.45 +/- 0.06 mumol/liter (12.0 +/- 0.2 micrograms/dl) to 1.02 +/- 0.21 mumol/liter (27.2 +/- 0.6 micrograms/dl) after 120 min (P less than 0.005). The absolute increments of ACTH and cortisol levels in the patients with Cushing's disease were significantly (P less than 0.02 and P less than 0.05, respectively) higher than in the normal subjects. In individual patients, however, CRF responses were rather variable; three of the patients had ACTH or cortisol increases within the mean +/- SD of the responses of the control subjects. In another patient with Cushing's disease due to bilateral macro- and micronodular adrenocortical hyperplasia, who had nonsuppressible circulating ACTH and cortisol levels, unresponsiveness to CRF was shown. These results indicate that testing the pituitary-adrenocortical axis of patients with Cushing's disease may reveal hyperresponsiveness, normal responsiveness, and even unresponsiveness.