Impact of thyroid disorders on flow-mediated dilation: a systematic review and meta-analysis

Background: Endothelial dysfunction may contribute to the increased cardiovascular risk associated with thyroid diseases. This systematic review and meta-analysis aimed to assess endothelial function, evaluated by flow-mediated dilation (FMD), in both hypo and hyperthyroidism, and its response to treatment. Methods: We searched Embase and PubMed (until April 2025) for studies on FMD in hypo- and hyperthyroidism (PROSPERO registration number: CRD42024629806). Risk of bias was assessed using Cochrane criteria. Mean differences (MD) with 95% confidence intervals (CI) were calculated using random-effects models. Statistical heterogeneity was assessed with I² statistics. Analyses were conducted using Review Manager 5.4.1. Results: Forty-two studies (1,663 subjects with hypothyroidism, 247 with thyrotoxicosis/endogenous hyperthyroidism, and 1520 euthyroid controls) were included. FMD was significantly reduced in subjects with untreated hypothyroidism compared to euthyroid controls (MD -2.99, 95% CI, -3.83, -2.14; I2 = 99%), improved with levothyroxine treatment (MD 3.06, 95% CI: 1.94, 4.19; I2 = 91%) and reached values similar to controls upon restoration of euthyroidism (MD 0.22, 95% CI: -0.75, 1.18; I2 = 75%). A non-statistically significant difference emerged comparing untreated hyperthyroid subjects with controls (MD - 2.55; 95% CI: -5.38, 0.28; I² = 98%), and low risk of bias studies showed reduced FMD in this subset (MD - 6.57; 95% CI: -7.53, - 5.60; I² = 45%). Subclinical hyperthyroidism was associated with FMD impairment (MD - 4.21; 95% CI: -7.07, - 1.35; I² = 97%). Conclusion: Hypothyroidism is associated with endothelial impairment, reversible after restoration of euthyroidism, highlighting the importance of appropriate management. Hyperthyroidism, especially subclinical, seems associated with FMD reduction, but larger, well-designed studies are needed.