• Manuel R Blum, Baris Gencer, Luise Adam, Martin Feller, Tinh-Hai Collet, Bruno R da Costa, Elisavet Moutzouri, Jörn Dopheide, Michèle Depairon, Gerasimos P Sykiotis, Patricia Kearney, Jacobijn Gussekloo, Rudi Westendorp, David J Stott, Douglas C Bauer, and Nicolas Rodondi.
• Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
• J. Clin. Endocrinol. Metab. 2018 Aug 1; 103 (8): 2988-2997.

ContextSubclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist.ObjectiveTo assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis.Design And SettingRandomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial.ParticipantsParticipants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range].InterventionLevothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations.Main Outcome MeasuresCarotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound.ResultsOne hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, -0.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference -0.03; 95% CI, -0.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14).ConclusionNormalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.

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