Objective: To evaluate the effect of recombinant human TSH (rhTSH) on biomarkers of vascular endothelial cell and platelet activation in patients monitored for thyroid carcinoma remnant.
Methods: Circulating levels of soluble(s) intercellular adhesion molecule (sICAM)-1 and sE-selectin, as indices of vascular endothelial cell activation, of sP-selectin and sCD40 ligand (sCD40L), as indices of platelet activation, and of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), as an index of lipid peroxidation, were evaluated in 20 patients (16 females, 48.0 +/- 13.6 years) at baseline and after intramuscular rhTSH injection (0.9 mg/day on two consecutive days).
Results: At baseline, serum TSH values were below normal whereas free T3 and free T4 were within the normal range. After rhTSH injection, serum TSH increased significantly but free T3 and free T4 remained unchanged. Concomitantly, plasma sICAM-1 concentrations increased significantly (from 155.9 +/- 39.1 to 183.6 +/- 38.1 ng/ml, P < 0.03), as did those of sE-selectin (from 74.8 +/- 15.4 to 91.4 +/- 12.2 ng/ml, P < 0.0006), sP-selectin (from 56.4 +/- 13.7 to 72.2 +/- 14.9 ng/ml, P < 0.002), sCD40L (from 2.1 +/- 0.9 to 2.8 +/- 1.1 ng/ml, P < 0.03) and total 8-iso-PGF(2alpha)(from 238.5 +/- 47.0 to 307.8 +/- 41.2 pg/l, P < 0.0001). Changes in circulating levels of sCD40L were directly correlated with changes in levels of plasma total 8-iso-PGF(2alpha) (r = 0.523, P < 0.02) and sP-selectin (r = 0.480, P < 0.03).
Conclusions: Supraphysiological concentrations of rhTSH might exert proatherogenic effects by promoting activation of vascular endothelial cells and platelets probably through enhanced oxidative stress.