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Endocrine Abstracts (2022) 86 EC1.3 | DOI: 10.1530/endoabs.86.EC1.3

SFEBES2022 Early Career and Plenary Orals Clinical Endocrinology Trust Best Abstract Clinical (1 abstracts)

Individuals on levothyroxine have higher HADS anxiety and depression scores than the general population and this is exacerbated by the Thr92Ala substitution in DIO2

Peter Taylor 1 , Eirin Haug 2 , Adrian Heald 3 , Lakdasa Premawardhana 1 , Onyebuchi Okosieme 1 , Michael Stedman 4 , Bjørn Asvold 2 & Colin Dayan 1

1Cardiff University, Cardiff, United Kingdom. 2NTNU, Trondheim, Norway. 3University of Manchester, Manchester, United Kingdom. 4Res Consortium, Andover, United Kingdom

Introduction: Around 15% of people diagnosed with primary hypothyroidism remain significantly symptomatic despite TSH normalisation with levothyroxine (LT4). The Thr92Ala substitution (rs225014) in a key deiodinase that activates T4 to T3, DIO2 may influence tissue levels of T3 but previous studies have been inconsistent regarding symptoms on LT4 and the presence of this polymorphism.

Methods: We assessed HADS anxiety and depression scores in the HUNT2 study in 52, 609 individuals (6, 906 with the Thr92Ala substitution) of whom 1, 569 had a history of LT4 use (194 with the Thr92Ala substitution). Anxiety and depression scores were assessed by comparing patients on LT4 to the general population, initially overall and then by Thr92Ala status, with adjustment for age, sex and educational attainment.

Results: The Thr92Ala substitution was present in 13% of the population and was not associated with increased HADS scores in individuals not on LT4. Compared to individuals not on LT4, after adjustment HADS total score was 0.71 points higher (0.39, 1.02, p < 0.001) in subjects on LT4 overall, 0.56 points higher (0.22, 0.89, p< 0.001) in individuals on LT4 but not homozygous for Thr92Ala, and 1.83 points higher (0.93, 2.73 p< 0.001) in individuals on LT4 who were homozygous for Thr92Ala. Thr92Ala non-homozygous individuals on LT4 were 22% more likely than those not on LT4 to reach the threshold for HADS anxiety caseness, while homozygous individuals were 208% more likely.

Conclusion: Individuals homozygous for DIO2 Thr92Ala on LT4 have significantly reduced quality of life compared to those non-homozygous, but there is no effect in the absence of LT4. Since individuals are not aware of their genotype, this provides strong objective evidence for a biological basis to persistence of symptoms in some individuals on LT4. Previous inconsistent results on the effect of Thr92Ala are likely to have been due to low statistical power.

Volume 86

Society for Endocrinology BES 2022

Harrogate, United Kingdom
14 Nov 2022 - 16 Nov 2022

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