Endocrine Abstracts

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.