Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency.
The Journal of clinical endocrinology and metabolism
confidence
Key findings
Hexarelin failed to raise GH in GHRH receptor-deficient patients but normally raised PRL, ACTH, cortisol; intact GHRH signaling needed for GH effect.
View source on PubMed (PMID 10084578) ↗
- Sample size
- 4
- Population
- Male adult patients with homozygous GHRH receptor gene mutation (GHRH resistance, GH-deficient dwarfism; dwarfs of Sindh)
- Dosing
- 2 microg/kg
- Duration
- single administration
- Route
- intravenous
- Blinding
- not_reported
- Controls
- none
- Drug class
- GH secretagogue
Measured endpoints
- plasma GH response to hexarelinNo changehormonalnot_reportedeffect: <1 ng/mL; 50-100 fold deviation from normal
- plasma PRL response to hexarelinIncreasedhormonalnot_reportedeffect: normal rise
- plasma ACTH response to hexarelinIncreasedhormonalnot_reportedeffect: normal rise
- plasma cortisol response to hexarelinIncreasedhormonalnot_reportedeffect: normal rise
Full abstract
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 microg/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.