Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy.
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.
Appelhof
Bente C
BC
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, F5-171, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Peeters
Robin P
RP
Wiersinga
Wilmar M
WM
Visser
Theo J
TJ
Wekking
Ellie M
EM
Huyser
Jochanan
J
Schene
Aart H
AH
Tijssen
Jan G P
JG
Hoogendijk
Witte J G
WJ
Fliers
Eric
E
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
D007453:Iodide Peroxidase; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II