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.

Abstract

The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). 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. This was a multicenter, randomized, open-label, phase III study. The study was conducted at 10 French university hospitals. 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. Each subject underwent three tests of GH secretion separated by 24 h or more. The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 microg/liter for GHRH+Arg corresponding to 3 microg/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 microg/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. 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.