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Endocrine Abstracts (2023) 92 OP04-01 | DOI: 10.1530/endoabs.92.OP-04-01

ETA2023 45th Annual Meeting of the European Thyroid Association ETA 2023 Oral Session 4: Young Investigators / Clinical and Translational (6 abstracts)

Interaction between DIO2 polymorphisms and LT4 treatment on psychological well-being outcomes and cardiovascular risk factors: a population-based cross-sectional study in uk biobank

Christian Zinck Jensen 1 , Jonas Lynggaard Isaksen 2 , Gustav Ahlberg 3 , Morten Salling Olesen 3 , Birte Nygaard 1 , Christina Ellervik 4 & Jørgen Kim Kanters 2


1Copenhagen University Hospital – Herlev and Gentofte, Center for Endocrinology and Metabolism, Herlev, Denmark; 2University of Copenhagen, Laboratory of Experimental Cardiology, Department of Biomedical Sciences, Copenhagen, Denmark; 3Copenhagen University Hospital - Rigshospitalet, Laboratory for Molecular Cardiology, The Heart Centre, Department of Cardiology, Copenhagen, Denmark; 4Boston Children’s Hospital, Department of Laboratory Medicine, Boston, United States


Objectives: Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment. We investigated, as previously hypothesized, if single nucleotide polymorphisms (SNPs) in rs225014 (Thr92Ala), rs225015, or rs12885300 (ORFa-Gly3Asp) in the Deiodinase 2 gene (DIO2), or rs17606253 in the Monocarboxylate Transporter 10 gene (MCT10) were associated with outcomes indicative of local tissue hypothyroidism in LT4-treated patients and controls.

Methods: We included 18,761 LT4-treated patients and 360,534 controls in a population-based cross-sectional study in UK Biobank. LT4 treatment was defined as a diagnosis of hypothyroidism and self-reported use of LT4 without use of T3. Outcomes were psychological well-being, cognitive function, and cardiac risk factors. Associations were evaluated by linear, logistic, or ordinal logistic multiple regression. Adjustments included sex, age, sex-age interaction, and genetic principal components 1-10.

Results: Compared to controls, LT4 treatment was adversely associated with almost all outcomes, most noteworthy: Increased frequency of tiredness (P < 0.001), decreased well-being factor score (P < 0.001), increased reaction-time (P < 0.001), and increased BMI (P < 0.001). Except for a significant association between the minor rs225015 A allele and financial dissatisfaction, there was no association of rs225014, rs225015, rs12885300, or rs17606253 with any outcomes in LT4-treated patients. For all outcomes, carrying the risk allele at these four SNPs did not amplify symptoms associated with LT4 treatment compared to controls.

Conclusions: rs225014, rs225015, rs12885300, and rs17606253 could not explain changed psychological well-being, cognitive function, or cardiac risk factors in LT4-treated patients. Our findings do not support a gene-treatment interaction between these SNPs and LT4 treatment.

Volume 92

45th Annual Meeting of the European Thyroid Association (ETA) 2023

European Thyroid Association 

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