Sensitivity and specificity of the macimorelin test for diagnosis of AGHD

Abstract

Objective: The macimorelin test is approved for the diagnosis of adult growth hormone deficiency (AGHD) based on its efficacy vs the insulin tolerance t est (ITT). Macimorelin has a significant advantage over ITT in avoiding hypoglycemia. A nalyses were conducted to determine whether macimorelin performance is affected by age, BMI, or sex, and evaluate its performance vs ITT over a range of GH cutpoints. Design: Post hoc analyses of data from a previous randomized phase 3 study included participants aged 18–66 years with BMI <37 kg/m2 and high (Group A), intermediate (Group B), or low (Group C) likelihood for AGHD based on pituit ary history, and matched controls (Group D). Methods: Probability of AGHD was estimated using unadjusted, age-adjusted, BMI-adjusted, and sex-adjusted logistic models. Area under the curv e (AUC) of the estimated receiver operating characteristic (ROC) curve (range, 0–1; 1 = perfect) was compared for adjusted vs unadjusted models. Separate analyses evaluated agreement, sensitivity, and specificity for macimorelin and ITT using cutpoints of 2.8, 4.0, 5.1, and 6.5 ng/mL. Results: For participants in Group A (n = 41) and Group D (n = 29), unadjusted, age-adjusted, BMI-adjusted, and sex-adjusted models had ROC AUCs (9 5% CIs) of 0.9924 (0.9807–1), 0.9924 (0.9807–1), 0.9916 (0.9786–1), and 0.9950 (0 .9861–1), respectively. Conclusions: Macimorelin performance was not meaningfully affected by age, B MI, or sex, indicating robustness for AGHD diagnosis. Of the 4 GH cutpoints evaluated, the cutpoint of 5.1 ng/mL provided maximal specificity (96%) and high sensiti vity (92%) and was in good overall agreement with the ITT at the same cutpoint (87%).

Keywords

• macimorelin
• adult growth hormone deficiency
• diagnosis
• insulin tolerance test