The natural history of partial growth hormone deficiency in adults: A prospective study on the cardiovascular risk and atherosclerosis

Background: Partial GH deficiency (GHD) in adults is poorly studied. Objective: The objective of the study was to investigate the natural history and clinical implications of partial GHD. Study Design: This was an analytical, observational, prospective, case-control study. Patients: Twenty-seven hypopituitary patients (15 women, ages 20-60 yr) and 27 controls participated in the study. Main Outcome Measures: Measures included GH peak after GHRH plus arginine [(GHRH+ARG), measured by immunoradiometric assay]; IGF-I (measured after ethanol extraction) z-SD score (SDS); glucose, insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels; and common carotid arteries intima-media thickness (IMT) measured periodically. Results: At study entry, partial GHD patients had significantly lower IGF-I and HDL-cholesterol levels and homeostasis model assessment index than controls. During the 60 months of median follow-up, 11 patients had severe GHD (40.7%), seven normalized their GH response (25.9%), and nine showed persistently partial GHD (33.3%). Patients with developed severe GHD at baseline had similar age and body mass index and lower GH peak (11.5 ± 1.8 vs. 14.3 ± 1.5 and 12.8 ± 1.1 μg/liter, P = 0.008) and IGF-I SDS (-0.88 ± 0.48 vs. 0.15 ± 0.58 and -0.42 ± 0.78; P = 0.01) than the patients with normal GH secretion or partial GHD. Severe GHD was accompanied by decreased IGF-I SDS and increased total to HDL cholesterol ratio, triglycerides, homeostasis model assessment index, and carotid intima-media thickness; normalization of GH secretion was accompanied by increased IGF-I SDS. By receiving-operator characteristic analysis, predictors of severe GHD were a baseline GH peak after GHRH+ARG of 11.5 μg/liter (sensitivity 64%, specificity 94%) and a baseline IGF-I SDS of -0.28 (sensitivity 91%, specificity 63%). Conclusions: Of 27 patients with partial GHD after pituitary surgery, 40.7% developed severe GHD and 25.9% normalized their GH response. With the assay used, changes in the GH peak response to GHRH+ARG were accompanied by changes in the IGF-I SDS, metabolic profile, and carotid IMT. A peak GH of 11.5 μg/liter or less and IGF-I SDS -0.28 or less were highly predictive of delayed deterioration of GH secretion.