Gender has to be taken into account in diagnosing adult growth hormone deficiency by the GHRH plus arginine test

Objective: Data on the effect of gender on the interpretation of the GHRH plus arginine stimulation test (GHRH + ARG test) is controversial. We validated the GHRH + ARG stimulation test in control subjects and patients with organic or idiopathic pituitary disease and a suspicion of adult growth hormone deficiency (AGHD) using the Immulite 2000 XPi GH assay. Design: We studied 126 apparently healthy adults (median age 38.8 years) and 34 patients with a suspicion of AGHD (median age 42.2 years). Identification of AGHD with the GHRH + ARG test was investigated with commonly accepted BMI-related consensus cut-off limits for peak GH concentrations. Serum samples collected during the GHRH + ARG test were analysed for GH in 2014-2015. Serum IGF-1 concentrations were studied as a reference. Results: In 14 of 65 (22%) control males the GH peak value was below the BMI-related cut-off limits for GH sufficiency indicating a false diagnosis of AGHD. All control females had a normal GHRH + ARG response. Median peak GH response was significantly (p < 0.001) higher in female (39.3 mu g/L) than in male controls (21 mu g/L). According to consensus cut-offs all but one young female patient had a deficient response compatible with a diagnosis of AGHD. Conclusions: The GH response to stimulation by GHRH + ARG is gender-dependent, being lower in healthy males than in females. Gender should be considered when defining cut-off limits for peak GH concentrations in the GHRH + ARG test. The presently used BMI-related cut-off levels will lead to a significant misclassification of males as GH deficient.