Carotid Intima Media Thickness Not Reduced With Levothyroxine in Subclinical Hypothyroidism

Carotid artery
Carotid artery
Treatment with levothyroxine to normalize thyroid-stimulating hormone did not significantly reduce carotid intima media thickness in elderly patients with subclinical hypothyroidism.

In elderly patients with subclinical hypothyroidism, treatment with levothyroxine to normalize thyroid-stimulating hormone (TSH) conferred no significant reduction in carotid intima media thickness (CIMT) or carotid atherosclerosis, according to study findings published in the Journal of Clinical Endocrinology and Metabolism.

Patients with untreated subclinical hypothyroidism (mean age, 74.1 years) who participated in the TRUST (Thyroid Hormone Replacement for Subclinical Hypothyroidism; Identifier: NCT01660126) trial were included in this substudy analysis ( Identifier: NCT02832934; n=185). The TSH levels in participants ranged from 4.60 to 19.99 mIU/L.

An international team of researchers treated patients with levothyroxine at a starting dose of 50 µg per day, which was dose-titrated to normalize TSH levels within a standard reference range. Participants in the placebo group underwent mock titrations to determine comparative outcomes. The final mean CIMT represented the primary outcome, and secondary end points included plaque presence, maximum CIMT, and maximum carotid plaque thickness.

A total of 96 patients were randomly assigned to receive levothyroxine and 89 patients were randomly assigned to receive placebo. Levothyroxine was associated with a greater decrease in the overall mean TSH±SD from baseline to the median 18.4-month (interquartile range, 12.2-30.0 months) follow-up (6.35±1.95 mIU/L to 3.55±2.14 mIU/L vs 5.29±2.21 mIU/L, respectively; P <.001). There was no significant difference, however, between the treatment and placebo groups with regard to the change in CIMT at the median follow-up (0.85±0.14 mm vs 0.82±0.13 mm, respectively; between-group difference 0.02 mm; 95% CI, −0.01 to 0.06; P =.30).

In addition, there was no significant difference between the levothyroxine and placebo groups with regard to the presence of carotid plaque (70.8% vs 75.3%, respectively; P =.46). The maximum carotid plaque thickness was also similar in both the treatment and control participants (2.38±0.92 mm vs 2.37±0.91 mm, respectively; between-group difference −0.03, 95% CI, −0.34 to 0.29; P =.86). According to the investigators, no significant interactions were found between levothyroxine and mean CIMT based on baseline TSH (categories: 4.6-6.9, 7.0-9.9, and ≥10 mmol/L) or cardiovascular disease (P ≥.14 for all).

Limitations of this analysis included its predominantly older patient population and the lack of robust patient groups with TST >10 mIU/L, which may have reduced generalizability.

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Overall, the findings from this study suggest “no evidence in favor of using levothyroxine to treat older adults with mild subclinical hypothyroidism with the goal of lowering [cardiovascular] risk” in elderly patients.


Blum MR, Gencer B, Adam L, et al. Impact of thyroid hormone therapy on atherosclerosis in the elderly with subclinical hypothyroidism: a randomized trial [published online May 28, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-00279