Macimorelin as a Diagnostic Test for Adult Growth Hormone Deficiency.
PURPOSE: Diagnosis of adult growth hormone deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the gold standard GHST but is labor-intensive, may cause severe hypoglycemia, and is contraindicated in certain patients. Macimorelin, an orally-active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose.
METHODS: This multicenter, open-label, randomized, 2-way crossover trial was designed to validate the efficacy and safety of a single-dose oral macimorelin for AGHD diagnosis compared to the ITT. Subjects with high (n=38), intermediate (n=37), and low (n=39) likelihood for AGHD and healthy, matched controls (n=25) were included in the efficacy analysis of the study.
RESULTS: After the first test, 99% of macimorelin and 82% of ITTs were evaluable. Using GH cut-off levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for the ITT, negative agreement was 95.38% (CI 87%-99%), positive agreement was 74.32% (CI 63%-84%), sensitivity was 87%, and specificity was 96%. Upon retesting, reproducibility was 97% for macimorelin (n=33). In post-hoc analyses, a GH cut-off of 5.1 ng/mL for both tests resulted in 94% (CI 85-98%) negative agreement, 82% (CI 72-90%) positive agreement, 92% sensitivity and 96% specificity. No serious adverse events were reported for macimorelin.
CONCLUSIONS: Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with comparable accuracy to the ITT. A GH cut-off of 5.1 ng/mL for the macimorelin test provides excellent balance between sensitivity and specificity.
Neurosciences (Brain & Spine)
Garcia, Jose M; Biller, Beverly M K; Korbonits, Márta; Popovic, Vera; Luger, Anton; Strasburger, Christian J; Chanson, Philippe; Medic-Stojanoska, Milica; Schopohl, Jochen; Zakrzewska, Anna; Pekic-Djurdjevic, Sandra; Bolanowski, Marek; Swerdloff, Ronald; Wang, Christina; Blevins, Thomas; Marcelli, Marco; Ammer, Nicola; Sachse, Richard; and Yuen, Kevin C J, "Macimorelin as a Diagnostic Test for Adult Growth Hormone Deficiency." (2018). Journal Articles and Abstracts. 229.