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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 3 956-959
Copyright © 1999 by The Endocrine Society

Original Studies

Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency1

Hiralal G. Maheshwari, Asad Rahim, Stephen M. Shalet and Gerhard Baumann

Center for Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Medical School (H.G.M., G.B.), Chicago, Illinois 60611; and the Department of Endocrinology, Christie Hospital (A.R., S.M.S.), Withington, Manchester, United Kingdom M20 4BX

Address all correspondence and requests for reprints to: G. Baumann, M.D., Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611. E-mail: gbaumann{at}nwu.edu

The mechanism of the synergistic relationship between GH-releasing peptide (GHRP) and GHRH with respect to GH secretion is poorly understood. We report the response to hexarelin, a potent GHRP, in patients affected with a homozygous mutation in the GHRH receptor gene, with consequent GHRH resistance and GH-deficient dwarfism. This newly described syndrome is the human homolog of the little (lit/lit) mouse. Intravenous administration of hexarelin (2 µg/kg) to four male adult patients (dwarfs of Sindh) resulted in a complete lack of elevation in plasma GH levels (<1 ng/mL), an at least 50- to 100-fold deviation from the normal response. In contrast, plasma PRL, ACTH, and cortisol levels rose in a normal manner in response to hexarelin. We conclude that an intact GHRH signaling system is critical for GHRPs to exert their effect on GH release, but that the GHRH system is not necessary for the effect of GHRP on PRL and ACTH secretion. Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency.




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