LONG-TERM TREATMENT WITH GROWTH-HORMONE DECREASES PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND TISSUE-PLASMINOGEN ACTIVATOR IN GROWTH HORMONE-DEFICIENT ADULTS

The syndrome of growth hormone deficiency (GHD) in adults is associate d with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition, We have p reviously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. T he aim of the present investigation was to study coagulation and fibri nolysis in 17 patients with adult-onset GHD during two years of treatm ent with recombinant human GH (12 mu g/kg body weight/day). The impact of the contemporary changes in metabolic variables and body compositi on on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-I activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased daring the GB treatment period (p < 0.05). T he decrease was more pronounced in patients with high pre-treatment le vels of the different variables. alpha(2)-antiplasmin decreased (p < 0 .05), while plasminogen was unchanged during two years of GH treatment . Fibrinogen concentrations tended to decrease after two years of GN t reatment (p = 0.06), while the coagulation factors VII and VIII were u nchanged. von Willebrand factor demonstrated a transient decrease afte r 18 months of GH treatment. The coagulation inhibitor, protein C, dec reased (p < 0.05), while antithrombin was unchanged. Fasting plasma in sulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, to tal cholesterol and triglycerides were unaltered. Body hi decreased du ring the initial GH treatment but: was unaltered after two years, whil e lean body mass increased (p < 0.001) and the waist over hip circumfe rence ratio tended to decrease (p = 0.06). In conclusion PAI-1 activit y, PAI-1 antigen and t-PA antigen decreased during long-term GH treatm ent, These changes may be a direct effect of GH itself or may be secon dary to the favourable chan,aes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treat ment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysi s.