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

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) remains controversial, mainly as regards stimulation tests and suggested cut-off lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual reproducibility has been reported. Given the safety of the arginine test (AST), we decided to evaluate the incidence of false negatives (non responder normal subjects), its reproducibility and variability. Twenty five healthy non-obese volunteers (16 males, 9 females) with a chronological age range between 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g/kg i.v. infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 and 90 minutes, and it was repeated in the same subject 7 to 30 days later; in females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) micrograms/L; maximal response (Mx Resp) 10.00 (0.48-48.80) micrograms/L. 2nd test B: 0.50 (0.38-27.0) micrograms/L; Mx Resp 11.00 (0.50-47.70) micrograms/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: 1st test: B 0.45 (0.35-4.30) micrograms/L; Mx Resp 6.30 (0.48-48.80) micrograms/L. 2nd test B 0.46 (0.38-8.80) micrograms/L; Mx Resp 10.90 (0.50-47.70) micrograms/L, while females showed 1st test: B 5.20 (0.50-22.60) micrograms/L; mx Resp 14.00 (3.50-36.70) micrograms/L. 2nd test B 3.60 (0.75-27.00) micrograms/L; Mx Resp 13.00 (3.70-28.10) micrograms/L. The statistical comparison (Mann Whitney test) showed significant differences between both sexes in basal values of the first and second test (p < 0.001), and in the maximal response of the first test (p < 0.03). The statistical analysis did not show significant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values > or = 3 micrograms/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results between tests 1 and 2. All females evaluated produced responses above 3 micrograms/L in both tests. The results of the present study demonstrate that, particularly in men, AST has no clear limit of normality while it shows good intra-individual reproducibility. In conclusion, at present the biochemical diagnosis of AGHD requires a clear and precise standardization which includes all variables that can modify the GH response to the stimulus used.