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Abstract
Adult growth hormone deficiency (AGHD) causes a reduction in lean body mass, bone mineral density, exercise tolerance and overall quality of life and treatment with growth hormone (GH) improves some of these outcomes. Because symptoms are non-specific and random GH levels are not useful in establishing its diagnosis, provocative tests are often necessary. The insulin tolerance test is the ‘gold standard’ test for diagnosis of AGHD but it is often cumbersome to perform and is contraindicated in certain patients due to the risk of hypoglycemia. Administration of the orally available ghrelin mimetic and GH secretagogue macimorelin increases GH levels acutely via the ghrelin receptor GHSR1-a and it has been shown to have good sensitivity and specificity for diagnosing AGHD. Here we review the evidence of the potential use of macimorelin for this indication.
Financial & competing interests disclosure
JM Garcia receives research support from the Department of Veterans Affairs (MERIT grants: I01-BX000507 and I01 CX000174 and the NIA T32AG000183 and AG040583). The content is solely the responsibilities of the authors and does not necessarily represent the official views of the funding agencies. JM Garcia is a consultant for and receives research support from Æterna Zentaris Inc. and Helsinn Therapeutics Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Diagnosis of adult growth hormone deficiency (AGHD) is not straightforward and often requires growth hormone-provocative tests.
Insulin tolerance test is considered the gold standard test, although it is contraindicated in certain populations due to the risk of hypoglycemia. Hence, there is a need for safer and more convenient provocative testing in the appropriate clinical context to diagnose AGHD.
Use of novel growth hormone secretagogues for provocative testing is being studied.
Macimorelin, a synthetic ghrelin analog and growth hormone secretagogues, has emerged as a safe and convenient alternative to the insulin tolerance test, with sensitivity and specificity comparable to that of other provocative tests.
If approved, macimorelin-stimulated growth hormone test may become a useful provocative test in the diagnosis of AGHD.