Summary
The syndrome of growth hormone deficiency (GHD) in adults is associated with premature
atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns
and abnormal body composition. We have previously shown that GH-deficient adults have
increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1)
activity.
The aim of the present investigation was to study coagulation and fibrinolysis in
17 patients with adult-onset GHD during two years of treatment with recombinant human
GH (12 μg/kg body weight/day). The impact of the contemporary changes in metabolic
variables and body composition on coagulation and fibrinolysis was studied. The patients
received conventional thyroid, adrenal and gonadal hormone replacement therapy.
PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels
decreased during the GH treatment period (p <0.05). The decrease was more pronounced
in patients with high pre-treatment levels of the different variables. a2-antiplasmin
decreased (p <0.05), while plasminogen was unchanged during two years of GH treatment.
Fibrinogen concentrations tended to decrease after two years of GH treatment (p =
0.06), while the coagulation factors VII and VIII were unchanged, von Willebrand factor
demonstrated a transient decrease after 18 months of GH treatment. The coagulation
inhibitor, protein C, decreased (p <0.05), while antithrombin was unchanged.
Fasting plasma insulin increased (p <0.01), but blood glucose did not differ after
two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol
and triglycerides were unaltered. Body fat decreased during the initial GH treatment
but was unaltered after two years, while lean body mass increased (p <0.001) and the
waist over hip circumference ratio tended to decrease (p = 0.06).
In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term
GH treatment. These changes may be a direct effect of GH itself or may be secondary
to the favourable changes in body composition. It remains to be seen whether changes
in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk
in patients with GHD. The present results suggest that GH plays a role in the regulation
of fibrinolysis.
