Journal of Clinical Endocrinology & Metabolism, Vol 75, 1358-1361, Copyright © 1992 by Endocrine Society

ARTICLES

Pulsatile human corticotropin-releasing hormone prevents dexamethasone- induced suppression of the plasma cortisol response to hypoglycemia in normal men

PC Avgerinos, CK Kiamouris, IP Petrakos, IK Kleanthous, PA Zorzos, TN Dimitriadis, SA Raptis and GB Cutler Jr
Second Department of Internal Medicine, University of Athens Evangelismos Hospital, Greece.

Insulin-induced hypoglycemia causes a sequential stimulation of all three components of the hypothalamic-pituitary-adrenal axis. States of acute glucocorticoid excess, such as the overnight (1 mg) dexamethasone suppression test (DST), inhibit both the basal cortisol level and the response to an insulin tolerance test (ITT). However, whether this negative feedback effect is exerted primarily at the hypothalamic or the pituitary level is not clear. To explore this question further we have examined the cortisol response to insulin-induced hypoglycemia in three experimental settings, in the following order: 1) a control ITT performed at 0900 h after an overnight hospital stay (cITT); 2) an ITT at 0900 h after oral dexamethasone, 1 mg, at 2300 h on the previous evening (DST + ITT); and 3) an ITT at 0900 h after dexamethasone, 1 mg, at 2300 h and hCRH, 1 microgram/kg iv, at 90 min intervals from 0100- 0700 h (DST+hCRH + ITT). The response to ITT was defined as the peak cortisol increment (peak minus baseline). Since the study objective was to test whether overnight pulsatile hCRH could prevent dexamethasone- induced suppression of the response to a morning ITT, only subjects that demonstrated a greater than 25% decrease in the cortisol response to DST + ITT vs. cITT received the full protocol (five of nine normal men). Basal ACTH and cortisol secretion remained suppressed throughout the night during both the Dex + ITT and Dex + hCRH + ITT studies when compared to the control study (cITT, P < 0.05). However, the cortisol response to hypoglycemia during DST + hCRH + ITT was significantly greater than during DST+ITT (P < 0.05) and was similar to the cITT response. Thus, pulsatile hCRH, administered during the 10 h between dexamethasone and the subsequent hypoglycemic stimulus, prevented acute suppression by dexamethasone of the cortisol response to hypoglycemia. We conclude that the dexamethasone-induced inhibition of the cortisol response to hypoglycemia results primarily from suppression by dexamethasone of basal hypothalamic corticotropin-releasing factor and the consequent impairment of corticotroph responsiveness to exogenous and endogenous corticotropin-releasing factor.

This article has been cited by other articles:

				G. Francisco, C. Hernandez, R. Galard, and R. Simo Usefulness of Homeostasis Model Assessment for Identifying Subjects at Risk for Hypoglycemia Failure during the Insulin Hypoglycemia Test J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3408 - 3412. [Abstract] [Full Text] [PDF]

				G. Dickstein Commentary to the Article: Comparison of Low and High Dose Corticotropin Stimulation Tests in Patients with Pituitary Diseasee J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4531 - 4532. [Full Text]