Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis

SUMMARY Objective: The type 2 deiodinase (D2)-Thr92Ala polymorphism has been associated with decreased D2 activity in some in vitro experiments but not in others. So far no association between the D2-Thr92Ala polymorphism and serum thyroid hormone levels has been observed in humans, but in a recent study in athyroid patients, it was suggested that patients homozygous for the Ala(92) allele needed higher thyroxine doses to achieve TSH suppression. We studied the association between the D2-Thr92Ala polymorphism with thyroid hormone levels and thyroxine dosage, in patients treated for differentiated thyroid carcinoma (DTC) and in a group of patients treated for Hashimoto thyroiditis. Design: Cross sectional study Patients: We studied 156 patients with DTC treated with TSH suppressive thyroid hormone replacement therapy for longer than 3 years and 141 patients with Hashimoto thyroiditis treated for at least 6 months with thyroxine. Measurements: In all patients, serum levels of TSH, free thyroxine, triiodothyronine and reverse T3 were measured and genotypes of the D2-Thr92Ala polymorphism were determined by Taqman assay. Univariate regression analysis was performed to determine the relation between thyroxine dosages and the D2-Thr92Ala polymorphism corrected for age, gender, BMI and serum TSH levels. Results: Both in DTC patients and Hashimoto patients, no association was observed between serum thyroid hormone levels or thyroxine dosages in presence of the D2-Thr92Ala polymorphism. Categorization of DTC patients according to degree of TSH suppression did not change these results. Conclusion: The D2-Thr92Ala polymorphism is not associated with thyroid hormone levels or thyroxine dose in patients treated for DTC or Hashimoto thyroiditis