title: Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, F5-171, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Bente C
authors.initials: BC
authors.lastname: Appelhof
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Ellie M
authors.initials: EM
authors.lastname: Wekking
authors.forename: Jochanan
authors.initials: J
authors.lastname: Huyser
authors.forename: Aart H
authors.initials: AH
authors.lastname: Schene
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013974:Thyroxine / Q000008:administration & dosage*; D014284:Triiodothyronine / Q000008:administration & dosage*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II