Circulating ADMA concentrations are elevated in hypopituitary adults with and without growth hormone deficiency

Abstract

Cardiovascular mortality is increased in patients with hypopituitarism. Elevated concentrations of the endogenous NO synthase antagonist asymmetrical dimethylarginine (ADMA) may be related to the development of atherosclerosis and are associated with cardiovascular risk. We studied the concentrations of ADMA in hypopituitary patients with and without growth hormone deficiency (GHD) and in healthy subjects. Plasma from 44 patients with hypopituitarism with (n = 30) and without GHD (n = 14) and from 25 age- and sex-matched healthy controls was taken for analysis of L-arginine, ADMA, symmetrical dimethylarginine (SDMA) and clinical parameters. Further plasma from 10 hypopituitary patients was examined before and after treatment with 9 g of oral L-arginine for 14 days. Asymmetrical dimethylarginine was significantly higher in the hypopituitary patients than in the controls (0.63 +/- 0.12 vs. 0.51 +/- 0.15 micromol L(-1); P < 0.005). L-arginine and the L-arginine/ADMA ratios were lower in the subjects with hypopituitarism (53 +/- 18 vs. 90 +/- 29 micromol L(-1) and 87 +/- 31 vs. 185 +/- 59; both P < 0.0001). Symmetrical dimethylarginine was comparable between the patients and the controls. L-arginine and dimethylarginines were associated with 2-h stimulated glucose levels in a glucose tolerance test (r = 0.33; P < 0.05), but not other cardiovascular risk factors. Oral L-arginine supplementation normalized the reduced L-arginine/ADMA ratio in the hypopituitary patients. Asymmetrical dimethylarginine is elevated in patients with hypopituitarism independent of GHD and traditional risk factors. This might contribute to the increased cardiovascular morbidity in hypopituitary patients.