Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH-deficiency: a double-blind placebo-controlled study

OBJECTIVES Patients with adult GH-deficiency are thought to have an increas ed risk of cardiovascular disease. Sialic acid (SA) concentrations have bee n proposed as a marker of atherosclerotic disease probably related to an in flammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated. PATIENTS We performed a randomised, double-blind placebo-controlled study i n 18 patients with adult GH-deficiency before and after 3 months GH replace ment therapy (0.036 U/kg/d; GH-treated group: 6 females, 3 males; age: 47.3 +/- 5.4 years., mean +/- SEM; placebo-group: 5 females, 4 males; mean age 50.2 +/- 4.7). In addition, SA concentrations were measured in 18 sex and a ge matched healthy control subjects. METHODS Blood samples were obtained after an overnight fast. Serum SA, trig lycerides and cholesterol were measured using enzymatic methods. Lipoprotei n classes were separated by ultracentrifugation. Insulin and IGF-I were det ermined by radioimmunoassay, HbA(1C) was measured by anion exchange liquid chromatography. RESULTS SA concentrations of the patients with adult GH-deficiency were not significantly different compared to the control group (GH-deficient group: 2.29 +/- 0.02 mmol/l, mean +/- SEM vs. control group: 2.09 +/- 0.13 mmol/l , P = 0.25). Before GH replacement therapy SA concentrations correlated pos itively with the patients age (r = 0.45; P < 0.04) and fasting insulin conc entrations (r = 0.5; P <0.03) but not with fasting lipid profile. GH replac ement therapy significantly increased IGF-I (GH: + 27 +/- 2.6 vs, placebo: + 1.0 +/- 0.8 nmol/l, P<0.001) and fasting insulin concentrations (GH: + 71 .9 +/- 8.0 vs. placebo: +19.6 +/- 22.6 pmol/l, P< 0.04) compared to placebo therapy. SA concentrations (GH: -0.41 +/- 0.15 vs. placebo: -0.01 +/- 0.12 mmol/l, P<0.05), total cholesterol (GH: - 0.71 +/- 0.16 vs, placebo: 0.23 +/- 0.21 mmol/l, P<0.003) and LDL-cholesterol (- 0.71 +/- 0.14 vs, placebo: - 0.12 +/- 0.21 mmol/l P<0.04) significantly decreased after GH replacemen t therapy compared to placebo therapy. No significant correlation between c hanges in SA concentrations and changes in lipid profile were observed foll owing GH replacement therapy. CONCLUSION These results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistan ce, secondly, the proposed beneficial effect of GH on the atherosclerotic p rocess is likely to be multifactorial and cannot only be explained by chang es in lipid profile and finally, SA might be a useful marker for the proces s of atherosclerotic disease in interventional studies.