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  • Title: Impact of Thyroid Hormone Therapy on Atherosclerosis in the Elderly With Subclinical Hypothyroidism: A Randomized Trial.
    Author: Blum MR, Gencer B, Adam L, Feller M, Collet TH, da Costa BR, Moutzouri E, Dopheide J, Depairon M, Sykiotis GP, Kearney P, Gussekloo J, Westendorp R, Stott DJ, Bauer DC, Rodondi N.
    Journal: J Clin Endocrinol Metab; 2018 Aug 01; 103(8):2988-2997. PubMed ID: 29846630.
    Abstract:
    CONTEXT: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. OBJECTIVE: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. PARTICIPANTS: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. INTERVENTION: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. MAIN OUTCOME MEASURES: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. RESULTS: One 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). CONCLUSION: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.
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