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Neuroendocrine and Pituitary
Tumor Clinical Center (NEPTCC) Bulletin

Winter 2018/2019 | Volume 24, Issue 2

Macimorelin as a Diagnostic Test for Adult GH Deficiency


The evaluation for growth hormone deficiency (GHD) is an important step in the management of adults with known or suspected pituitary disorders. Growth hormone (GH) replacement has been shown to have positive effects on body composition, muscle mass, bone density, liver health and quality of life (1). However, GH replacement is an expensive therapy and carries the burden of daily injections for patients. Thus, accurate diagnostic testing is critical to identifying patients with true GHD who may benefit from GH replacement.

The insulin tolerance test (ITT) is considered the gold standard test for the diagnosis of adult GHD. However, this test requires induction of hypoglycemia and is thus contraindicated in the elderly, those with seizure disorders or cardiovascular disease. Growth hormone releasing hormone (GHRH)-arginine testing was previously available in the United States for testing of GHD, which offered an alternative testing procedure with established cut-offs stratified by body mass index (2). However, GHRH was withdrawn from the U.S. market in 2008, although it is still available in other markets. Glucagon stimulation testing has remained as a viable alternative to the ITT in the U.S., however, it requires an IM injection, 3-4 hours of testing time and can cause nausea and vomiting (1,3-5).

Macimorelin, a ghrelin analog, is a GH secretagogue that can be administered as an oral solution. Piccoli et al. established that oral administration of macimorelin led to rapid absorption and a substantial peak in GH levels in 36 healthy male volunteers between 50-75 minutes later with no adverse events (6). A subsequent study by Garcia et al. established that a GH cutoff of 2.7 ng/mL on oral macimorelin testing had 82% sensitivity and 92% specificity for the diagnosis of GHD in a population of 50 individuals with adult onset GHD versus controls matched for age, BMI, sex and estrogen status. This study was initially designed to compare the efficacy of macimorelin versus GHRH-arginine, however, the full protocol could not be completed once GHRH was withdrawal from the U.S. market (7).

More recently, Garcia et al. performed a randomized, open-label, two-way crossover trial to compare macimorelin with the standard ITT for diagnosis of adult GHD (8). They studied 139 adults age 18-65 years, including adults at risk for GHD as well as controls. The individuals at risk for GHD were subdivided into three categories based on their pituitary disease and other hormone deficits, including (A) high likelihood (n=38), (B) moderate likelihood (n=37) and (C) low likelihood of GHD (n=39).? A fourth group (D) of controls (n=25) with no pituitary disorders were studied and matched to group A (high likelihood of GHD) for sex, age, BMI and estrogen status. Notable exclusions for all groups included age >65 years old, uncontrolled diabetes mellitus (hemoglobin A1C >8.0%) and extreme obesity (BMI >40 kg/m2).

These individuals were randomized with regards to the order of the ITT and macimorelin testing. The ITT was performed per standard protocol with serum sampling for GH and glucose at 15, 30, 45, 60, 90 and 120 minutes after the administration of insulin. Macimorelin testing involved a dose of 0.5 mg/kg administered as an oral solution within a 30-minute window with serum sampling for GH at 30, 45, 60 and 90 minutes after administration.

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