Objectives. To assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism and autoimmune thyroiditis (sHT).

Background. sHT patients are characterized by peripheral endothelial dysfunction and low grade inflammation.

Methods. In 53 sHT and 45 healthy subjects we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (0.15-15 µg·min-1.dL-1) with and without local vascular COX inhibition by intrabrachial indomethacin (50 µg·min-1.dL-1), or nitric oxide synthase blockade by L-NMMA (100 µg·min-1.dL-1), or the antioxidant vitamin C (8 mg·min-1.dL-1). The protocol was repeated 2 h after systemic non-selective COX inhibition (indomethacin, 100 mg) or selective COX-2 blockade (celecoxib, 200 mg) oral administrations.

Results. sHT patients showed higher CRP and IL-6 values. In controls, vasodilation to acetylcholine was blunted by L-NMMA and unchanged by vitamin C. In contrast, in sHT the response to acetylcholine, reduced in comparison to controls, was resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to acetylcholine and the inhibition of L-NMMA on acetylcholine. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to acetylcholine in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib.

Conclusions. In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2 dependent pathway leading to increased production of oxidative stress.