Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.
Open Access
- 1 June 2013
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 98 (6), 2422-9
- https://doi.org/10.1210/jc.2013-1157
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.Keywords
This publication has 27 references indexed in Scilit:
- Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice GuidelineJournal of Clinical Endocrinology & Metabolism, 2011
- Is Lack of Recombinant Growth Hormone (GH)-Releasing Hormone in the United States a Setback or Time to Consider Glucagon Testing for Adult GH Deficiency?Journal of Clinical Endocrinology & Metabolism, 2009
- Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of AustraliaActa Endocrinologica, 2007
- Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiencyActa Endocrinologica, 2006
- Growth Hormone (GH) Replacement Therapy in Adult-Onset GH Deficiency: Effects on Body Composition in Men and Women in a Double-Blind, Randomized, Placebo-Controlled TrialJournal of Clinical Endocrinology & Metabolism, 2004
- Body Composition, IGF-I and IGFBP-3 Concentrations as Outcome Measures in Severely GH-Deficient (GHD) Patients after Childhood GH Treatment: A Comparison with Adult Onset GHD PatientsJournal of Clinical Endocrinology & Metabolism, 2002
- Sensitivity and Specificity of Six Tests for the Diagnosis of Adult GH DeficiencyJournal of Clinical Endocrinology & Metabolism, 2002
- Effects of GH replacement on endothelial function and large‐artery stiffness in GH‐deficient adults: a randomized, double‐blind, placebo‐controlled studyClinical Endocrinology, 2002
- Withdrawal of Long-Term Physiological Growth Hormone (GH) Administration: Differential Effects on Bone Density and Body Composition in Men with Adult-Onset GH Deficiency*Journal of Clinical Endocrinology & Metabolism, 2000
- Measures of Submaximal Aerobic Performance Evaluate and Predict Functional Response to Growth Hormone (GH) Treatment in GH-Deficient Adults1Journal of Clinical Endocrinology & Metabolism, 1999