Effect of Thyroxine Replacement on Creatinine, Insulin-Like Growth Factor 1, Acid-Labile Subunit, and Vascular Endothelial Growth Factor

Abstract

Hypothyroidism is associated with endothelial dysfunction, arterial hypertension, and impaired kidney function (1)(2)(3). An increased serum creatinine and decreased glomerular filtration rate and renal blood flow have been described (2)(4)(5). These deleterious consequences may result from several mechanisms, including direct and indirect effects of thyroid hormones on blood vessels. Insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF), growth factors with both local and systemic effects, may be involved as potential mediators. Hypothyroidism causes low concentrations of IGF-1, which can be normalized by thyroxine replacement therapy (6). IGF-1 is known to increase forearm blood flow and creatinine clearance in humans (7)(8)(9). VEGF increases endothelial nitric oxide synthase activity, contributing to the relaxing capacity of the renal vasculature (10)(11)(12)(13). Thus, both IGF-1 and VEGF may improve endothelial function and renal blood flow. The purpose of this study was to test the effect of thyroxine therapy on serum creatinine, IGF-1, and VEGF in hypothyroid patients. Patients with newly diagnosed primary hypothyroidism who had been referred to the Division of Endocrinology and Diabetes at the University Hospital in Zurich between February 1998 and July 2002 were included in this prospective case series. Oral informed consent was obtained from all patients. Patients with neoplastic disease, secondary hypothyroidism, and thyroid cancer were excluded from the study because VEGF is often increased in patients with tumors, including tumors of the pituitary gland and the thyroid (14)(15). All laboratory values were measured in the hypothyroid and the euthyroid …