PMID-29860473 – Macimorelin as Diagnostic Test for Adult GH Deficiency
Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a Diagnostic Test for Adult GH Deficiency. J Clin Endocrinol Metab. 2018;103(8):3083-3093.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29860473 |
| DOI | 10.1210/jc.2018-00665 |
| Year | 2018 |
| Journal | Journal of Clinical Endocrinology & Metabolism |
| Study Type | RCT (Diagnostic Accuracy Study) |
| Evidence Level | II |
| Sample | n=157 (106 with suspected AGHD + 51 matched healthy controls) |
| Peptide(s) Studied | Macimorelin |
Key Findings
- Pivotal Phase 3 diagnostic study comparing oral macimorelin test to the insulin tolerance test (ITT) as reference standard
- Using a GH cut-point of 2.8 ng/mL, macimorelin achieved 87% sensitivity, 96% specificity, and 9% misclassification rate
- At a cut-point of 5.1 ng/mL: 92% sensitivity, 96% specificity, 8% misclassification rate
- Concordance between macimorelin and ITT was 95% using the 2.8 ng/mL cut-point
- The test requires a single oral dose (0.5 mg/kg) with GH measured at baseline, 30, 45, 60, and 90 minutes
- Reproducibility was high with 94% agreement between two macimorelin tests performed in the same subjects
- This study provided the clinical evidence for FDA approval (December 2017)
Study Design
Multicenter, open-label, two-way crossover diagnostic study. Subjects with suspected adult GH deficiency (AGHD) and healthy matched controls each underwent both a macimorelin test and an ITT on separate days. GH was measured at defined timepoints after each stimulation test. ROC analysis determined optimal GH cut-points. Reproducibility assessed by repeat macimorelin testing in a subset.
Limitations
- Not all patients tolerate or are eligible for the ITT comparator (cardiac/seizure history exclusions)
- Moderate sample size for a diagnostic test validation
- BMI may affect GH response to macimorelin (higher BMI associated with lower GH peaks), requiring potential BMI-adjusted cut-points
- CYP3A4 interactions may affect macimorelin pharmacokinetics (avoid strong CYP3A4 inhibitors)
- Limited data in patients with recent pituitary surgery or radiation (<6 months)
Clinical Relevance
This study established macimorelin as the first oral GH stimulation test, replacing the insulin tolerance test (ITT) which carries risks of severe hypoglycemia and is contraindicated in cardiac and seizure patients. For the Ageless Pep Academy curriculum, macimorelin is important because it validates the GHS-R1a (ghrelin receptor) as a reliable target for stimulating pituitary GH release. Macimorelin is pharmacologically related to MK-677 (ibutamoren) — both are non-peptide peptidomimetic GHS-R1a agonists. While MK-677 is used off-label for chronic GH elevation, macimorelin's FDA-approved role is purely diagnostic (single-dose). This distinction is clinically important: single-dose GHS-R1a activation is diagnostic, while chronic activation raises IGF-1 and is used for body composition effects.
Related
#research #RCT #macimorelin #evidence-level-II #gh-axis