Growth hormone (GH) deficiency is associated with insulin insensitivity, abnormalities of endothelial function and increased cardiovascular mortality. Hyperhomocysteinaemia is also associated with impaired endothelial function, and it has been established as a risk factor for cardiovascular disease. GH treatment improves lipid profile and endothelial function, but it is not known whether it can affect homocysteine levels.
Material & Methods: Twenty-three patients aged 39.9+/-16.9 (mean+/-SD), with childhood (n=9) and adult-onset (n=14) GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. Fasting insulin, IGF-1, total homocysteine (Hcy), free T4 and creatinine were measured at baseline (V1), at 3 months (V2) and then at 6 months (V3) on GH treatment. Plasma vitamin B12 & folate were measured at baseline (V1) and at 6 months (V3). The data were analysed by paired t-test, univariate correlation and multilinear regression models. Results: There was a significant negative correlation between Hcy and B12 & folate both at V1 and V3 (B12: r=-0.55 & -0.61, p=007 & 0.02; folate: r=-0.66 & -0.45, p=0.001 & 0.03 at V1 and V3 respectively). At V1 there was also a positive correlation between Hcy and creatinine (r=0.48, p=0.02). GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001, V1 to V2, and V2 to V3 respectively), and insulin (p=0.068, p<0.001). There was no significant change in B12, folate, free T4 or creatinine levels (p=ns). Though Hcy levels increased from V1 to V2 (from 7.7+/-0.53 to 9.15+/-0.45 (mean+/-SEM in mmol/l), p=0.002), this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3 was no longer significant (p=0.45). In multilinear regression only B12 & folate were consistently associated with Hcy levels.Conclusions: Growth hormone treatment causes a transient, but non-sustained increase in total homocysteine. Contrary to our expectations, normalisation of IGF-1 levels in GH-deficient individuals is not associated with a fall in total homocysteine. Improvement in cardiovascular risk profile following GH treatment is thus unlikely to be related to a decrease in homocysteine concentrations
08 - 11 Apr 2002
British Endocrine Societies