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Low-Grade Systemic Inflammation Causes Endothelial Dysfunction in Patients with Hashimoto’s Thyroiditis

Department of Internal Medicine, University of Pisa, 67-56100 Pisa, Italy

Address all correspondence and requests for reprints to: Stefano Taddei, M.D., Department of Internal Medicine, University of Pisa, Via Roma, 67-56100 Pisa, Italy. E-mail: s.taddei{at}med.unipi.it.

Objective: The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis.

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 (Ach) (0.15–15 µg/min·dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 µg/min·dl) or nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100 µg/min·dl) or the antioxidant vitamin C (8 mg/min·dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations.

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

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