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Responsivity of Adrenocorticotropin to Corticotropin-Releasing Hormone and Lack of Suppressibility by Dexamethasone Are Related Phenomena in Cushing's Disease^*

University of Nijmegen Nijmegen, The Netherlands
Department of Medicine, Division of Endocrinology, and Department of Experimental and Chemical Endocrinology Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Ad R. M. M. Hermus, M.D., Department of Medicine, Division of Endocrinology, St. Radboud Hospital, University of Nijmegen, Nijmegen 6500 HB, The Netherlands.

The ACTH and cortisol responses to 100 µg ovine corticotropin-releasing hormone (CRH) in 19 consecutive patients with Cushing's disease were compared with those in 13 normal subjects. In 2 patients with Cushing's disease, plasma ACTH and cortisol did not increase after CRH administration. Compared to the normal subjects, maximal ACTH increments [135 ± 25 (±SEM) VS. 42 ± 6 pg/ml; P < 0.001, by Wilcoxon's two-sample test] and maximal cortisol increments (17.7 ± 1.8 vs. 9.4 ± 1.1 µg/100 ml; P < 0.01 by Wilcoxon's test) after CRH were significantly higher in the 17 CRH-responsive patients with Cushing's disease. In the normal subjects, there was a significant negative correlation between the basal cortisol level and the maximal ACTH (r = –0.65; P < 0.05, by Spearman's rank correlation test) and cortisol (r = –0.95; P < 0.001, by Spearman's test) responses to CRH. In contrast, in the CRHresponsive Cushing patients, there was no significant correlation between the basal cortisol level and the maximal ACTH (r = 0.10; P > 0.10, by Spearman's test) and cortisol (r = 0.14; P > 0.10, by Spearman's test) increments after CRH treatment. In the normal subjects, there was no significant correlation between the basal ACTH level and the maximal ACTH increments after CRH administration (r = –0.24; P > 0.10, by Spearman's test). Again in contrast, in the CRH-responsive Cushing patients, maximal ACTH increments after CRH treatment correlated positively with basal ACTH levels (r = 0.69; P < 0.005, by Spearman's test). Moreover, in these patients, the maximal ACTH increments after CRH were positively correlated with the ACTH levels after suppression with higher and lower doses of dexamethasone. We conclude that in Cushing's disease, unlike in normal subjects, circulating cortisol is not the major modulator of ACTH and cortisol responses to CRH, and that in these patients, responsivity of ACTH to CRH and lack of suppressibility by dexamethasone are related phenomena.

^* Presented in part at the 67th Annual Meeting of The Endocrine Society, Baltimore, MD, June 19–21,1985 (Abstract 1004).

Received July 11, 1985.

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