Endocrine Abstracts

Background: Adult GH deficiency (GHD) is diagnosed by provocative testing of GH secretion. To improve diagnostic accuracy of GHRH plus arginine (GARG) testing, we evaluated the influence of age, BMI, and sex. Furthermore, we aimed to established normative data for an automatic immunoassay specifically measuring 22kD human GH.

Methods: Eighty-seven patients with hypothalamic-pituitary disease and 200 healthy controls were enrolled. Controls were prospectively stratified for sex, age (18–30, 31–50, ≥51 years), and BMI (<25 {lean}, 25-29.9 {overweight}, ≥30 kg/m² {obese}), with at least ten subjects in each subgroup. All participants received GHRH (1 μg/kg i.v.) and L-arginine (30 g via 30 min infusion), with blood sampling over 120 min. GH was measured by immunoassay (iSYS, IDS). ROC analysis identified cutoffs with ≥95% specificity for GHD.

Results: In controls, multiple stepwise regression analysis revealed that BMI (21%, P<0.0001), sex (20%, P<0.0001), and age (5%, P<0.001), accounted for 46% of GH peak level variability during GARG. Fifty-one patients with ≥2 additional pituitary hormone deficiencies were considered GHD, the remaining 36 patients were GH sufficient (GHS). Comparison of peak GH during GARG (GHD vs GHS+controls) revealed an overall cutoff of 3.9 ng/ml (sensitivity 86%, specificity 95%). BMI-adjusted cutoffs were established for males and females (lean: 6.5 vs 9.7 ng/ml; overweight: 3.5 vs 8.5 ng/ml; obese: 2.2 vs 4.4 ng/ml).

Conclusion: BMI and sex account for most of the variability of peak GH levels during GARG. Consequently, the diagnostic accuracy of the GARG test is significantly improved by use of adjusted cutoffs. Especially gender differences during GH stimulation testing may require more attention for the correct diagnosis of GHD.