Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation of a Novel Oral Stimulation Test for the Diagnosis of Adult GH Deficiency

Abstract

Context:In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.Objective:The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.Design:This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1–29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.Main Outcome Measure:Peak GH area under the receiver operating characteristic curve after macimorelin was measured.Results:Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m2) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = −0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.Conclusion:Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.

Adult Growth Hormone Deficiency – Benefits, Side Effects, and Risks of Growth Hormone Replacement

“…With macimorelin, an orally active GH secretagogue, a recent study reported that peak GH (an optimal cut point of 2.7 ng/mL) offered 82% sensitivity, 92% specificity, and 87% accuracy (Garcia et al, 2013). In general macimorelin was well tolerated; and compared to other stimulation tests, GH responses were rapid and the test does not require parental administration of agents.…”

What is next after anamorelin?

“…It also decreases energy expenditure [21], and activates lipogenesis and decreases lipolysis and lipid oxidation [18,22]. Ghrelin also increases GH and insulin-like growth factor (IGF)-1 which has anabolic effects in muscle and may downregulate inflammation having a positive effect on muscle mass and function [9,23]. Although GRLN is the only identified receptor for ghrelin to this date, mounting evidence suggest the presence of an alternative receptor that may mediate its effect in muscle, fat and liver where the GRLN receptor is not expressed [19,24,25].…”

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: A Neuroendocrine Approach to Patients With Traumatic Brain Injury

“…Agents used to stimulate GH secretion include insulin, glucagon, growth hormone-releasing hormone (GHRH) plus arginine, arginine alone, or ghrelin mimetics (43,44). In the U.S., GHRH is currently not commercially available, and ghrelin mimetics have not been Food and Drug Administration-approved for testing.…”