Endothelial progenitor cells in subclinical hypothyroidism: the effect of thyroid hormone replacement therapy.

CONTEXT: Subclinical hypothyroidism (SCH) is associated with cardiovascular (CV) risk factors, and possibly CV disease. However, its management remains controversial. Endothelial progenitor cells (EPC), expressing both endothelial and stem cell markers, are known to offer a novel CV risk marker.

OBJECTIVE

The aim of the study was to ascertain whether EPC count or function is reduced in SCH and whether it improves with T(4) therapy.

DESIGN AND INTERVENTION: EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T(4) together with CV risk factors in 20 SCH and healthy controls (HC).

MAIN OUTCOME MEASURE: EPC count was measured at baseline and after T(4) replacement in SCH.

RESULTS

EPC count was significantly reduced in SCH compared to HC: median (range)-CD133+/VEGFR-2+, 0.09 (0.02-0.44) vs. 0.47 (0.17-2.12), P < 0.001; CD34+/VEGFR-2+, 0.10 (0.04-0.46) vs. 0.39 (0.11-2.13), P < 0.001; whereas EPC function was similar. There was a significant positive correlation between CD133+/VEGFR-2+ with free T(4) levels (r = 0.38; P = 0.02); high-density lipoprotein cholesterol levels (r = 0.51; P = 0.001); and negative correlation with TSH concentrations (r = -0.64; P < 0.001). After adjustment for conventional CV risk factors, SCH predicted lower EPC count, beta coefficient/P value: CD133+/VEGFR-2+ (-0.77/<0.001), and CD34+/VEGFR-2+ (-0.71/<0.001). In SCH participants, EPC count increased and was similar to HC after T(4); CD133+/VEGFR-2+, 0.32 (0.03-0.94) vs. 0.09 (0.02-0.44), P < 0.001; and CD34+/VEGFR-2+, 0.26 (0.06-0.88) vs. 0.10 (0.04-0.46), P < 0.001.

CONCLUSION

SCH predicted lower EPC count, which improved with T(4) treatment, independent of other CV risk factors, providing additional evidence that T(4) replacement may improve CV risk in SCH.