Oral macimorelin, a ghrelin mimetic peptide, accurately diagnosed adult growth hormone deficiency with 82% sensitivity and 92% specificity — comparable to the standard IV arginine+GHRH test but far more convenient.
0.96 AUCOral macimorelin's diagnostic accuracy was nearly perfect, making it a viable replacement for invasive IV growth hormone stimulation tests
What the researchers found
Oral macimorelin achieved an area under the ROC curve of 0.96 for diagnosing adult GH deficiency, with 82% sensitivity and 92% specificity at a GH cutoff of 2.7 ng/mL. Peak GH levels differed dramatically between patients and controls: 2.36 ± 5.69 ng/mL in AGHD patients versus 17.71 ± 19.11 ng/mL in healthy controls (P < 0.001).
Obesity (BMI > 30 kg/m²), present in 58% of subjects, significantly affected results — peak GH levels were inversely correlated with BMI in controls (r = -0.37, P = 0.01). Using separate cutoffs of 6.8 ng/mL for non-obese and 2.7 ng/mL for obese subjects reduced the overall misclassification rate to 11%. The diagnostic accuracy was comparable to the arginine+GHRH test in the crossover portion of the study.
Why it matters
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.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
This is a multicenter clinical validation study with a crossover design component, comparing a new diagnostic test against an established standard. While not a randomized controlled treatment trial, it provides strong diagnostic evidence with rigorous statistical analysis (ROC curves, sensitivity/specificity calculations).
When this study was published
Published in 2013, this validation study preceded macimorelin's FDA approval in 2017. The findings have been confirmed by subsequent larger studies and the drug is now commercially available as Macrilen for clinical diagnostic use.
The bigger picture
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.
Questions still open
- How does macimorelin's diagnostic accuracy hold up in larger, more diverse populations including different age groups and ethnicities?
- Could macimorelin-based testing be useful for monitoring GH replacement therapy effectiveness over time?
- What is the optimal approach for patients with borderline BMI values between the obese and non-obese cutoff categories?
Common questions
What is macimorelin and how does it work?
Why is an oral GH test better than the existing IV tests?
Read the original research
Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.
The Journal of clinical endocrinology and metabolism, 98(6), 2422-9
Citation
Garcia, J M; Swerdloff, R; Wang, C; Kyle, M; Kipnes, M; Biller, B M K; Cook, D; Yuen, K C J; Bonert, V; Dobs, A; Molitch, M E; Merriam, G R. (2013). Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.. The Journal of clinical endocrinology and metabolism, 98(6), 2422-9. https://doi.org/10.1210/jc.2013-1157