Impact of thyroid hormone therapy on atherosclerosis in the elderly with subclinical hypothyroidism: a randomized trial

Blum, M. R. et al. (2018) Impact of thyroid hormone therapy on atherosclerosis in the elderly with subclinical hypothyroidism: a randomized trial. Journal of Clinical Endocrinology and Metabolism, 103(8), pp. 2988-2997. (doi: 10.1210/jc.2018-00279) (PMID: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/Setting: Randomized, double-blind, placebo-controlled trial nested within the TRUST trial. Participants: Participants aged ≥65 years with SHypo (thyroid-stimulating hormone, TSH, 4.60-19.99 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: 185 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, as compared to 5.29±2.21 mIU/L with placebo (p<0.001). After a median treatment of 18.4 months (interquartile range 12.2-30.0 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% confidence interval (CI)-0.01 to 0.06, p=0.30). 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 4.6-6.9, 7.0-9.9, and ≥10mmol/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.

• Item Type: Articles
• Additional Information: This study was supported by a grant of the Swiss National Science Foundation to Dr. Rodondi (SNSF 320030-150025 and 320030-172676), and an investigator-driven grant of the Velux Stiftung (974a, to Dr. Rodondi). The TRUST Trial was supported by a research grant (grant agreement number 278148) from the European Union FP7-HEALTH-2011 program and by grants from the Swiss National Science Foundation (SNSF 320030-150025, to Dr. Rodondi), the Swiss Heart Foundation (to Dr. Rodondi) and Velux Stiftung (974a, to Dr. Rodondi). Dr. Blum’s work was supported by an intramural personal grant by the Clinical Trials Unit of the Bern University Hospital at the University of Bern, Switzerland (grant number 84801053) and by a grant from the Swiss National Science Foundation (P2BEP3_175289). Dr. Collet’s research is supported by grants from the Swiss National Science Foundation (PZ00P3- 167826).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David
• Authors: Blum, M. R., Gencer, B., Adam, L., Feller, M., Collet, T.-H., da Costa, B. R., Moutzouri, E., Dopheide, J., Depairon, M., Sykiotis, G. P., Kearney, P., Gussekloo, J., Westendorp, R., Stott, D. J., Bauer, D. C., and Rodondi, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Clinical Endocrinology and Metabolism
• Publisher: Oxford University Press
• ISSN: 0021-972X
• ISSN (Online): 1945-7197
• Published Online: 28 May 2018
• Copyright Holders: Copyright © 2018 Endocrine Society
• First Published: First published in Journal of Clinical Endocrinology and Metabolism 103(8): 2988-2997
• Publisher Policy: Reproduced in accordance with the publisher copyright policy