The effect of levothyroxine replacement therapy at alteration of serum paraoxonase-1 and carotis intima media thickness in subclinical hypothyroidism and clinical hypothyroidism

The influence of hypothyroidism on atherosclerosis is still not very well understood. There is substantial evidence that hypothyroidism alters several traditional risk factors such as increase in circulating levels of low-density lipoprotein (LDL) cholesterol, hs-CRP levels, induction of diastolic hypertension, altered coagulability, direct effects on vascular endothelium, however we have not yet well known the mechanism of risk factor for cardiovascular diseases. Human and animal studies support the hypothesis that oxidative modification of LDL plays a crucial role in the pathogenesis of atherosclerosis. HDL associated paraoxonase-1(PON-1) defence barrier against lipid peroxides from oxidized LDL. There is an obvious need to know whether PON-1 activity levels can influence atherosclerosis in subclinical and hypothyroid patients. Carotis Intima- media thickness (CIMT) is a close marker of early atherosclerotic changes and a widely accepted surrogate end point for cardiovascular events. The aim of our study was to determine serum paraoxonase-1 (PON-1) activity levels which can be play a crucial role in oxidative stress and assess carotis intima media thickness (CIMT) in overt and subclinical hypothyroidism and to investigate the effect of levothyroxine treatment on paraoxonase-1 activity level and CIMT. The study was performed in age- and sex- matched 8 overt hypothyroid (mean age: 47, 63 ± 12,88), 25 subclinical hypothyroid patients (mean age:48,96 ± 8,42) and 24 healthy controls (mean age : 42,79 ± 8,12). Blood samples were obtained from patients with hypothyroidism before levothyroxine replacement and, since four months at beginning, after two months achieving a euthyroid state with levothyroxine. Lipid parameters and antropometric findings were also recorded. PON-1 activity was determined from initial velocity of p- nitrofenol production at 37º C and recorded at 405 nm by a Hitachi DP Modular System. Both of overt, subclinical hypothyroid control and groups had similar PON-1 activity levels, hs- CRP and CIMT at the time of diagnosis. PON-1 activity levels were not correlated with the degree of thyroid failure or CIMT. After achieving euthyroid state with levothyroxine replacement, PON-1 activity and hs- CRP levels were not significantly decreased in patients with overt and subclinical hypothyroidism (p> 0,05). PON-1 activity levels of overt and subclinical hypothyroid patients after levothyroxine replacement were similar to the healthy controls (p> 0,05). Two months of stable euthyrodism induced a significant decrease of mean-CIMT in subclinical hypothyroid state. After restoration of euthyroidism, mean CIMT was not statical significant decreased in clinical hypothyroid state. Subclinic and clinic hypothyroid patients were compare with which have similiar traditional risk factors control group, there is not meningful difference was observed in aterosclerotic events. Like other researchs levotiroksin replacement therapy influenced positively CIMT and aterosclerotic events. Both of overt, subclinical hypothyroid control and groups had similar PON-1 activity levels, hs- CRP and CIMT at beginning and after levotiroksin replacement therapy.