Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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 < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement.


CONCLUSIONS
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.
Adrees
M
M
Department of Clinical Chemistry, Adelaide and Meath Hospital incorporating the National Children's Hospital, Dublin 24, Ireland.
Gibney
J
J
El-Saeity
N
N
Boran
G
G
D000328:Adult; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008875:Middle Aged; D013974:Thyroxine / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D002784:Cholesterol; D013974:Thyroxine