SAT-431 Parameters of Glucose Metabolism Independently Predict Post Glucose Load Growth Hormone Concentrations in Patients with Acromegaly

Abstract

Background: In healthy subjects, growth hormone (GH) concentrations following an oral glucose suppression test (OGTT) are known to be under the impact of gender, age, BMI an estrogen use. To date, very few data exist on factors influencing nadir GH in patients with acromegaly. Methods: In the present study, we evaluated factors related to nadir GH concentrations during a 2h-75g-OGTT analysing data from 410 OGTTs performed in 134 patients with acromegaly in a tertiary care center. All patients were not receiving any acromegaly-specific medical therapy, 119 OGTTs were performed at the initial disease diagnosis, 281 were performed after at least one pituitary surgery. The relationship between GH supression and IGF-1, morphological data and parameters of lipid and glucose metabolism was tested using uni- and multivariate regression analysis. Results: In the whole cohort (43% males), nadir GH concentrations were neither related to gender, nor to BMI, but positively correlated to fasting GH (P=0.000), IGF-1 (P=0.000), tumour size (P<0.001), plasma glucose (P=0.000), insulin (P=0.000), C-peptide (P=0.000), fasting and OGTT-based indices of insulin secretion and sensitivity, and also to the gonadotropic activity with gonadotropic insufficiency observed in male and female patients with higher disease activity (P=0.000). In addition, nadir GH negatively correlated to age (P=0.001) and HDL-cholesterol concentrations (P=0.003). Only parameters of glucose metabolism (prehepatic beta-cell function, HOMA-insulin resistance index, OGIS-insulin sensitivity index) independently predicted nadir GH concentrations in the whole cohort, as well as in the group of patients with high IGF-1 levels (pre- and postoperative), and also when OGTTs performed in men and women were separately analysed. In OGTTs performed after normalisation of IGF-1 postoperatively, nadir GH remained in a positive relationship to fasting GH and IGF-1, but negatively correlated to all parameters of glucose metabolism, and positively correlated to HDL-cholesterol. Conclusion: In a large single center series, we find that parameters of glucose metabolism are the main direct predictors of nadir GH concentrations in patients with active acromegaly. The relationship between nadir GH and glucose metabolism reflects the diabetogenic effects of GH, and might also impact the cutt off value of nadir GH during OGTT used for the biochemical definition of acromegaly.