The Effects of Thyroxin Replacement Therapy on the Levels of Serum Soluble Cd40 Ligand and other Biochemical Cardiovascular Risk Markers in Patients with Hypothyroidism

Objective: Hypothyroidism is believed to implicate in-creased risk for cardiovascular disease. However, the results of prospective studies conducted in patients with hypothyroidism are controversial. Moreover the effect of levothyroxin on the cardiovascular risk profile is also unclear. Soluble CD40 ligand (sCD40L) is a protein expressed mainly by activated platelets which have been found to be associated with cardio-vascular events. The Aim of our Study: Was to investigate serum sCD40L levels and the effect of levothyroxin replacement on sCD40L levels in overt and subclinical hypothyroidism (SCH). Design: We assessed lipid profile, serum sCD40L and high sensitive C-reactive proteins (hsCRP) levels in 20 sub-clinical and 20 overt hypothyroid age-matched patients with hypothyroidism at baseline and one month after achieving euthyroidism by levothyroxin replacement, and compared them with the data from 20, age-matched, healthy controls. Results: Overt and subclinical hypothyroid patients had increased sCD40L levels compared to age-matched controls. Also, hsCRP levels were significantly increased in both hypothyroid groups but both parameters were not found to be correlated with each other. Change in lipid profiles was observed before and after thyroxin treatment in overt hypothy-roid patients. After levothyroxin replacement, serum sCD40L levels decreased significantly in the patients with both sub-clinical and overt hypothyroidism. Levothyroxin replacement also significantly reduced hsCRP levels in both groups of patients. Soluble CD40L showed significant negative corre-lations with Free 3.5.3’- triiodothyronine (FT3), Free thyroxin (FT4) and a significant positive correlation with TSH in both hypothyroid patients while no correlation of hsCRP levels with thyroid functions were detected. No correlation was found between sCD40 and hsCRP in this study. Conclusion: The values of sCD40L and hsCRP in our study suggest that inflammatory pathways are complex and may be affected by different factors in hypothyroidism. As high sCD40L was shown to predict cardiovascular disease and myocardial infarction in several prospective studies, the observed marked lowering of sCD40L after levothyroxin might be of clinical relevance in hypothyroid patients. It is possible that the initiation of adequate treatment in subclinical hypothyroidism may reduce the cardiovascular risk.