ETA2023 45th Annual Meeting of the European Thyroid Association ETA 2023 Oral Session 8: Hypothyrodism / Nodules (5 abstracts)
1Cardiff University, School of Medicine, Cardiff University School of Medicine, Cardiff, United Kingdom; 2Ntnu; 3Cardiff University; 4Salford Royal Hospital, Endocrinology, Salford, United Kingdom; 5Res Consortium, United Kingdom; 6Yyf Hospital, University Hospital of Wales, Aneurin Bevan University Health Board, Cardiff, United Kingdom; 7Cardiff University, Prince Charles Hospital, Cardiff, United Kingdom; 8Hunt Research Centre, Øya, Norway; 9Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom
Context: Approximately 15% of people with hypothyroidism remain symptomatic despite treatment. The Thr92Ala substitution in DIO2, may influence T3 tissue levels.
Methods: We assessed HADS anxiety and depression scores in HUNT2 in 50,901 individuals (6,687 homozygous for Thr92Ala) of whom 1,480 had a history of levothyroxine use (180 homozygous for Thr92Ala). Anxiety and depression caseness (score>=8) by levothyroxine and Thr92Ala status was assessed using logistic regression, adjusting 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 levothyroxine. Compared to individuals not on levothyroxine, HADS total score was 0.71 points higher (0.39-1.02, P < 0.001) in subjects on levothyroxine overall, and 1.83 points higher (0.93-2.73 P < 0.001) in individuals on levothyroxine who were also homozygous for Thr92Ala. Thr92Ala non-homozygous individuals on levothyroxine were 22% more likely than those not on levothyroxine to reach the threshold for HADS anxiety caseness, whilst homozygous individuals were 208% more likely. In GENTHYR individuals on higher doses of levothyroxine (≥100mg) with Thr92Ala had higher HADS caseness OR=1.86 (95%CI 1.10-3.14) P = 0.02, but this was not seen in individuals on lower doses.
Conclusion: Individuals homozygous for Thr92Ala in DIO2 on levothyroxine have significantly reduced quality of life compared to those non-homozygous, in a dose-dependent manner 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.