Comparative Validation of the Growth Hormone-Releasing Hormone and Arginine Test for the Diagnosis of Adult Growth Hormone Deficiency Using a Growth Hormone Assay Conforming to Recent International Recommendations

Context: The GHRH plus arginine (GHRH + Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). Objectives: The objectives of the study were to validate the GHRH + Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests. Design: This was a multicenter, randomized, open-label, phase III study. Setting: The study was conducted at 10 French university hospitals. Subjects: Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH + Arg-GHRH + Arg-ITT test sequence and 34 to the ITT-ITT-GHRH + Arg test sequence. Interventions: Each subject underwent three tests of GH secretion separated by 24 h or more. Main Outcome Measures: The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. Results: Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 mu g/liter for GHRH + Arg corresponding to 3 mu g/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH + Arg test was measured at about 3.67 mu g/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH + Arg test was expressed by 74% of subjects. Conclusions: The GHRH + Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH + Arg test represents a good alternative to the ITT for the diagnosis of AGHD. (J Clin Endocrinol Metab 95: 3684-3692, 2010)