Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3′-triiodothyronine therapy

Introduction: Some patients on levothyroxine replacement display significant impairment in psychological well- being, compared with sex- and age- matched controls. Levothyroxine- treated patients can be assumed to derive T-3 exclusively from deiodination of T-4, which, in the central nervous system, is regulated by type II deiodinase (DII). Objective: We investigated whether two recently identified polymorphisms in the DII gene (DII- ORFa- Gly3Asp and DII- Thr92Ala) are determinants of well- being and neurocognitive functioning and associated with a preference for replacement with a combination of T3 and T4. Methods: Genotypes for both polymorphisms were determined in 141 patients with primary autoimmune hypothyroidism, adequately treated with levothyroxine monotherapy and participating in a randomized clinical trial comparing T-4 therapy with T-4/T-3 combination therapy. Questionnaires on well- being and neurocognitive tests were performed at baseline. Results: Allele frequencies in patients with primary hypothyroidism were similar to those of healthy blood bank donors ( 32.0 vs. 33.9% for DII- ORFa- Gly3Asp and 40.4 vs. 38.8% for DII- Thr92Ala). DII polymorphisms were not associated with measures of well- being, neurocognitive functioning, or preference for combined T-4/T-3 therapy. Conclusion: The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well- being, neurocognitive functioning, or appreciation of T-4/T-3 combination therapy in patients treated for hypothyroidism.