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This version published online on September 6, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0451
A more recent version of this article appeared on November 1, 2005
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Submitted on March 2, 2005
Accepted on August 26, 2005

Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning and preference for combined T4/T3 therapy

Bente C. Appelhof, Robin P. Peeters, Wilmar M. Wiersinga*, Theo J. Visser, Ellie M. Wekking, Jochanan Huyser, Aart H. Schene, Jan G.P. Tijssen, Witte J.G. Hoogendijk MD, PhD, and Eric Fliers

Departments of Endocrinology and Metabolism, Psychiatry, Cardiology, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands and Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

* To whom correspondence should be addressed. 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).

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 (JCEM 2005; 90: 2666). 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.
Key words: hypothyroidism • autoimmunity • thyroid hormone • drug therapy • combination • type 2 deiodinase • polymorphisms • well-being • psychiatric status rating scales • neuropsychological tests




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