Validating Macimorelin: A Simple Oral Test for Diagnosing Adult Growth Hormone Deficiency

This was a multicenter, open-label study with 50 AGHD patients and 48 matched healthy controls. The first 43 patients and 10 controls received both oral macimorelin and IV arginine+GHRH in a crossover design. When the GHRH analog became unavailable in the US, the remaining 10 patients and 38 controls were tested with macimorelin alone. Peak GH levels were measured and ROC analysis was used to determine optimal diagnostic cutoffs.

Adult GH deficiency is underdiagnosed partly because existing tests require IV infusions in clinical settings. An oral test that patients simply drink could make diagnosis far more accessible and routine. Macimorelin (later FDA-approved as Macrilen) represented a paradigm shift in endocrine diagnostics — from invasive IV stimulation tests to a simple oral solution.

Ghrelin mimetics like macimorelin demonstrate how peptide science extends beyond therapeutics into diagnostics. This study helped pave the way for macimorelin's FDA approval in 2017 as the first oral GH stimulation test — a milestone that made GH deficiency testing accessible to more patients and clinicians. It also highlights how ghrelin pathway modulation has practical clinical applications beyond appetite regulation.

The study design changed midway when the GHRH analog became unavailable in the US, meaning only a subset of participants completed the full crossover comparison. The open-label design introduces potential bias. The high prevalence of obesity in the study population (58%) complicates interpretation, though the authors addressed this with BMI-specific cutoffs. Sample size, while adequate for a diagnostic validation study, was modest.