Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: results from a prospective randomized multicenter study.

Abstract

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST. To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5mg in patients >90kg) with weight-based dosing (WB: 0.03mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3ng/ml and ≥18µg/dL, respectively. 28 Patients with hypothalamic-pituitary disease and 1-2 (n=14) or ≥3 (n=14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order. Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92% sensitivity, 100% specificity) and 2.0ng/mL (96% sensitivity and 100% specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r=-0.32, P=0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8µg/dL (92% sensitivity, 100% specificity) and 11.2µg/dL (92% sensitivity and 100% specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST. The GST correctly classified GHD using GH cut-points of 1ng/ml for FD-GST and 2ng/ml for WB-GST, hence using 3ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9µg/dL for FD-GST and 11µg/dL for WB-GST.