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Endothelial Function and Coagulant Factors in Growth Hormone-Treated Hypopituitary Adults Receiving Desmopressin

Departments of Medicine (J.C.S., H.A.L., J.L., S.D., L.M.E., M.F.S., J.S.D.), Cardiology (J.G.), and Haematology (P.C.), University Hospital of Wales, Cardiff CF14 4XN, United Kingdom

Address all correspondence and requests for reprints to: Dr. Jamie C. Smith, Department of Diabetes and Endocrinology, Old Building, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom. E-mail: jamie.smith{at}virgin.net.

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. L-Deamino-8-D-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 ± 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 ± 16 yr). Fifteen healthy controls (group C) (mean age, 48 ± 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean ± SD) (A, 3.3 ± 1.0 g/liter vs. B, 3.5 ± 0.9 vs. C, 2.6 ± 0.8, P < 0.05), factor VIII (A, 130% ± 30% vs. B, 128% ± 30% vs. C, 104% ± 35%, P < 0.05) and von Willebrand factor antigen (A, 124% ± 35% vs. B, 134% ± 45% vs. C, 93% ± 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% ± 2.0% vs. B, 4.7% ± 1.6%) and was similar to that in the control group (C, 5.7% ± 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.

Abbreviations: DDAVP, L-Deamino-8-D-arginine; FMD, flow-mediated dilatation; vWF, von Willebrand factor; VWF:Ag, vWF antigen.