Effects of 18 months of l-T4 replacement in women with subclinical hypothyroidism

P>Context Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term l-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of l-T4 replacement in SCH are poorly understood. Objectives To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of l-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. Design Fifty-six women with SCH before and after l-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after l-T4 in a subgroup of women with SCH. Results Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0 center dot 05), and following l-T4 replacement decreased (P < 0 center dot 05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0 center dot 05) in SCH. These variables also normalized following l-T4. Following l-T4 replacement the carotid artery baseline diameter increased by 7 center dot 1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12 center dot 5% and following endothelium-dependent vasodilatation by 17 center dot 5% (P < 0 center dot 05). However, the increment following reactive hyperaemia did not differ before or following l-T4 replacement. Conclusion Normalization of cardiovascular risk factors following l-T4 replacement in SCH potentially explains reduced CIMT. Increased carotid and brachial artery diameters and normalized eGFR indicates a haemodynamic effect of l-T4 replacement, the importance of which requires further investigation.