Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients

Merve Arici, Ezgi Oztas, Fatih Yanar, Nihat Aksakal, Beyza Ozcinar, Gul Ozhan
2018 Endocrine journal  
Thyroid hormones play a vital role in the human body for growth and differentiation, regulation of energy metabolism, and physiological function. Hypothyroidism is a common endocrine disorder, which generally results from diminished normal circulating concentrations of serum thyroxine (fT4) and triiodothyronine (fT3). The primary choice in hypothyroidism treatment is oral administration of levothyroxine (L-T4), a synthetic T4 hormone, as approximately 100-125 μg/day. Generally, dose adjustment
more » ... s made by trial and error approach. However, there are several factors which might influence bioavailability of L-T4 treatment. Genetic background could be an important factor in hypothyroid patients as well as age, gender, concurrent medications and patient compliance. The concentration of thyroid hormones in tissue is regulated by both deiodinases enzyme and thyroid hormone transporters. In the present study, it was aimed to evaluate the effects of genetic differences in the proteins and enzymes (DIO1, DIO2, TSHR, THR and UGT) which are efficient in thyroid hormone metabolism and bioavailability of L-T4 in Turkish population. According to our findings, rs225014 and rs225015 variants in DIO2, which catalyses the conversion of thyroxine (pro-hormone) to the active thyroid hormone, were associated with TSH levels. It should be given lower dose to the patients with rs225014 TT and rs225015 GG genotypes in order to provide proper treatment with higher effectivity and lower toxicity. are mainly skin manifestations, atherosclerosis, bone mineral density, heart rate, obesity, hyperlipidaemia, bradycardia, fatigue and depression, which all have serious impact on life quality [1, 2] . Hypothyroidism, one of the most common endocrine disorders, is caused by lack of action of thyroid hormones that play a vital role in the human body for growth and differentiation, and regulation of energy metabolism, and physiological function. Hypothyroidism generally results from diminished normal circulating concentrations of fT3 and fT4 [3, 4] . The production of thyroid hormones is regulated by hypothalamuspituitary-thyroid axis through a negative feedback system. The secretion of T3 and T4 is controlled by both hypo-
doi:10.1507/endocrj.ej17-0162 pmid:29321381 fatcat:ostj7263ovhtjcaelmfyvuizjq