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This version published online on November 6, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1421
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Submitted on July 6, 2009
Accepted on October 20, 2009

Endothelial Progenitor Cells in Subclinical Hypothyroidism: The Effect of Thyroid Hormone Replacement Therapy

S. K. Abdul Shakoor, Ali Aldibbiat, Lorna E. Ingoe, Susan C. Campbell, Latika Sibal, James Shaw, Philip D. Home, Salman Razvi, and Jolanta U. Weaver*

Department of Endocrinology (S.K.A.S., L.E.I., S.R., J.U.W.), Queen Elizabeth Hospital, Gateshead NE9 6SX, United Kingdom; and Institute of Cellular Medicine (S.K.A.S., A.A., S.C.C., L.S., J.S., P.D.H., J.U.W.), Newcastle University, Newcastle NE2 4HH, United Kingdom

* To whom correspondence should be addressed. E-mail: J.U.Weaver{at}ncl.ac.uk.

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 T4 therapy.

Design and Intervention: EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T4 together with CV risk factors in 20 SCH and healthy controls (HC).

Main Outcome Measure: EPC count was measured at baseline and after T4 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 T4 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 T4; 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 T4 treatment, independent of other CV risk factors, providing additional evidence that T4 replacement may improve CV risk in SCH.






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