Reproducibility and variability of the arginine test in normal adults - Comparison between sexes

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) rem ains controversial, mainly as regards stimulation tests and suggested cut-o ff lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual rep roducibility has been reported. Given the safety of the arginine test (AST) , we decided to evaluate the incidence of false negatives (non responder no rmal subjects), its reproducibility and variability. Twenty five healthy no n-obese volunteers (16 males, 9 females) with a chronological age range bet ween 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g /kg IV infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 an d 90 minutes, and it was repeated in the same subject 7 to 30 days later; i n females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) mu g/L; maximal resp onse (Mx Resp) 10.00 (0.48-48.80) mu g/L. 2nd test B: 0.50 (0.38-27.0) mu g /L; Mx Resp 11.00 (0.50-47.70) mu g/L. The statistical evaluation (Wilcoxon signed rank test) showed no differences between B vs. B and Mx Resp vs Mx Resp. Separated by sex, males showed: Ist test: B 0.45 (0.35-4.30) mu g/L; Mr Resp 6.30 (0.48-48.80) mu g/L. 2nd test B 0.46 (0.38-8.80) mu g/L; Mx Re sp 10.90 (0.50-47.70) mu g/L, while females showed 1st test: B 5.20 (0.50-2 2.60) mu g/L; mx Resp 14.00 (3.50-36.70) mu g/L. 2nd test B 3.60 (0.75-27.0 0) mu g/L; Mx Resp 13.00 (3.70-28.10) mu g/L. The statistical comparison (M ann Whitney test) showed significant differences between both sexes in basa l values of the first and second test (p < 0.001), and in the maximal respo nse of the first test (p < 0.03). The statistical analysis did not show sig nificant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values greater than or equal to 3 mu g/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results betwee n tests 1 and 2. All females evaluated produced responses above 3 mu g/L in both tests. The results of the present study demonstrate that, particularl y in men, AST has no clear limit of normality while it shows good intra-ind ividual reproducibility. In conclusion, at present the biochemical diagnosi s of AGHD requires a clear and precise standardization which includes all v ariables that can modify the GH response to the stimulus used.