TY - JOUR

T1 - Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism

T2 - A pooled analysis of two randomized controlled trials

AU - Lyko, Christina

AU - Blum, Manuel R.

AU - Abolhassani, Nazanin

AU - Stuber, Mirah J.

AU - Del Giovane, Cinzia

AU - Feller, Martin

AU - Moutzouri, Elisavet

AU - Oberle, Jolanda

AU - Jungo, Katharina T.

AU - Collet, Tinh-Hai

AU - den Elzen, Wendy P. J.

AU - Poortvliet, Rosalinde K. E.

AU - Du Puy, Robert S.

AU - Dekkers, Olaf M.

AU - Trompet, Stella

AU - Jukema, J. Wouter

AU - Aujesky, Drahomir

AU - Quinn, Terry

AU - Westendorp, Rudi

AU - Kearney, Patricia M.

AU - Gussekloo, Jacobijn

AU - Van Heemst, Diana

AU - Mooijaart, Simon P.

AU - Bauer, Douglas C.

AU - Rodondi, Nicolas

PY - 2022

Y1 - 2022

N2 - Background Antithyroid 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). Objective To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. Methods We 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. Results Among 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. Conclusions Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

AB - Background Antithyroid 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). Objective To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. Methods We 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. Results Among 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. Conclusions Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

KW - autoimmune thyroid disease

KW - levothyroxine treatment

KW - subclinical hypothyroidism

KW - QUALITY-OF-LIFE

KW - PEROXIDASE ANTIBODIES

KW - CARDIOVASCULAR RISK

KW - L-THYROXINE

KW - HEALTH

KW - THYROTROPIN

KW - COMMUNITY

KW - SYMPTOMS

KW - DISEASE

KW - ASSOCIATION

U2 - 10.1111/joim.13544

DO - 10.1111/joim.13544

M3 - Journal article

C2 - 35894851

VL - 292

SP - 892

EP - 903

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0955-7873

IS - 6

ER -