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Polymorphisms in Type 2 Deiodinase Are Not Associated with Well-Being, Neurocognitive Functioning, and Preference for Combined Thyroxine/3,5,3'-Triiodothyronine Therapy

Departments of Endocrinology and Metabolism (B.C.A., W.M.W., E.F.), Psychiatry (E.M.W., J.H., A.H.S.), and Cardiology (J.G.P.T.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; Department of Internal Medicine (R.P.P., T.J.V.), Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands; and Department of Psychiatry (W.J.G.H.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Wilmar M. Wiersinga, M.D., Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, F5-171, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: w.m.wiersinga{at}amc.uva.nl.

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 T₃ exclusively from deiodination of T₄, 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 T₄ therapy with T₄/T₃ 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 T₄/T₃ therapy.

Conclusion: The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well-being, neurocognitive functioning, or appreciation of T₄/T₃ combination therapy in patients treated for hypothyroidism.

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