• Christina Lyko, Manuel R Blum, Nazanin Abolhassani, Mirah J Stuber, Cinzia Del Giovane, Martin Feller, Elisavet Moutzouri, Jolanda Oberle, Katharina T Jungo, Tinh-Hai Collet, den ElzenWendy P JWPJAtalmedial Diagnostics Centre, Amsterdam, The Netherlands.Amsterdam UMC, Department of Clinical Chemistry, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands., PoortvlietRosalinde K ERKEDepartment of Public Health and Primary Care, Leiden University Medical Center UMC, Leiden, The Netherlands., Robert S Du Puy, Olaf M Dekkers, Stella Trompet, J Wouter Jukema, Drahomir Aujesky, Terry Quinn, Rudi Westendorp, Patricia M Kearney, Jacobijn Gussekloo, Diana Van Heemst, Simon P Mooijaart, Douglas C Bauer, and Nicolas Rodondi.
• Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
• J. Intern. Med. 2022 Dec 1; 292 (6): 892903892-903.

BackgroundAntithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4).ObjectiveTo determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies.MethodsWe pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire.ResultsAmong 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment.ConclusionsAmong older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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