Context: Adults with growth hormone deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1): the major inhibitor of plasminogen activation in the circulation.

Objective: To determine the fibrinolytic profile of adults with GHD in comparison to controls.

Study Design and Participants: A prospective, observational study including 12 adults with GHD. Twelve gender, age, and BMI-matched adults served as controls.

Main Outcome Measures: The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibinolytic potential by venous occlusion test.

Results: Adults with GHD exhibited an unfavorable 24-hour fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/mL after adjustment for baseline PAI-1; P=0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/mL after adjustment for baseline tPA; P=0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity >4 IU/mL following venous occlusion (7.2 IU/mL [IQR 0.8-17.4]; P=0.018). Endothelial function was impaired in GHD, as quantified by % flow-mediated vasodilation over 120 seconds (AUC 3.8 [IQR -2.4-7.9] vs. 12.8 [IQR 2.1-19.4]; P=0.043).

Conclusions: Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.