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The Role of Endogenous Growth Hormone-Releasing Hormone in Acromegaly

Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (E.V.D., A.L.B., C.A.J.), Pituitary and Neuroendocrine Center and Department of Neurosurgery (W.F.C., A.L.B.), Department of Biostatistics (M.B.B.), and Department of Pediatrics (V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Veterans Affairs Medical Center (A.L.B., C.A.J.), Ann Arbor, Michigan 48105; and Department of Pharmacology (S.Y.K., R.T.), University of Texas Southwestern Medical Center, Dallas, Texas 75235

Address all correspondence and requests for reprints to: Eleni V. Dimaraki, M.D., M.S., 2650 Ridge Avenue, Suite 5111, Evanston, Illinois 60201. E-mail: e-dimaraki{at}northwestern.edu.

Context: Some indirect evidence suggests hypothalamic control of GH secretion in acromegaly.

Objective: The objective of the study is to examine whether GH secretion in acromegaly is dependent on endogenous GHRH.

Patients and Study Design: We studied eight patients with untreated acromegaly due to a GH-producing pituitary tumor. All patients received an iv infusion of normal saline for 24 h and GHRH-antagonist (GHRH-ant) at 50 µg/kg·h for 7 d. GH was measured every 10 min for 24 h during the normal saline infusion and on the last day of the GHRH-ant infusion. A group of nine different patients with untreated acromegaly served as the control group and underwent blood sampling for GH every 10 min for two 24-h periods to assess the day-to-day variability of GH secretion.

Setting: The study was set in a university referral center.

Main Outcome Measure: Twenty-four-hour mean GH was the main outcome measured.

Results: In six of eight subjects treated with GHRH-ant, 24-h mean GH decreased by 5.8–30.0% during iv GHRH-ant and, in three subjects, the change in the 24-h mean GH was greater than the upper limit of the 95% confidence interval of the spontaneous day-to-day variability of the mean GH in patients with acromegaly. Based on the binomial distribution, the probability of this magnitude of change to occur in three of eight subjects by chance alone is 0.0008.

Conclusion: In some patients with acromegaly due to a pituitary adenoma, GH secretion is under partial control by endogenous GHRH.