Decreased serum vascular endothelial growth factor-D levels in metastatic patients with differentiated thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor-D (VEGF-D) has been identified as one of the lymphangiogenic growth factors involved in metastatic diffusion. The aim of this study is to evaluate the serum VEGF-D levels in patients with differentiated thyroid cancer at different conditions of disease. DESIGN AND PATIENTS: We studied prospectively the VEGF-D plasma levels in 96 subjects affected by differentiated thyroid cancer. The patients were divided into three groups according to the clinical and biochemical findings: patients with no evidence of disease (Cured), patients with pathological (>1 ng/ml) stimulated thyroglobulin (Tg) (Path-Tg/rhTSH) levels only after rhTSH and patients with elevated basal Tg levels (Path-Tg/LT4). RESULTS: The serum VEGF-D concentrations in patients of group Cured were not different from the controls, while group Path-Tg/rhTSH showed baseline serum VEGF-D levels significantly lower than group Cured and controls (P < 0·001 and P < 0·01, respectively). Moreover, the patients of group Path-Tg/LT4 showed median serum cytokine concentrations at baseline not significantly different from the patients of group Path-Tg/rhTSH. The rhTSH stimulation did not modify the difference in serum VEGF-D levels in patients of group Cured and group Path-Tg/rhTSH. CONCLUSIONS: Our data demonstrate that the VEGF-D serum levels are reduced in patients with metastases of differentiated thyroid cancer, regardless of the degree of metastatic spread. It is possible that some other molecule produced by the tumoral tissue could affect the VEGF-D physiologically produced of from different tissues, thus conducting to a decrease in the VEGF-D found in blood of patients with evidence of metastatic differentiated thyroid cancer.

Innate immune activity in plaque of patients with untreated and L-thyroxine-treated subclinical hypothyroidism.

CONTEXT: A strong association between subclinical hypothyroidism (SCH) and atherosclerotic diseases, independent of the traditional risk factors, was noted. OBJECTIVE: The objective of the study was to evaluate the association between SCH and the inflammatory potential of atherosclerotic plaques as well as the role of L-T(4) replacement therapy (LTR) on regulation of plaque inflammation. EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES: We examined the differences in macrophage content, proinflammatory cytokine infiltration, and oxidative stress between asymptomatic carotid plaques of patients with and without SCH and LTR. SETTING AND PARTICIPANTS: Plaques were obtained from 23 SCH patients with LTR (treated), 34 untreated SCH patients, and 30 control patients without SCH enlisted to undergo carotid endarterectomy for extracranial high-grade (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T lymphocytes, human leukocyte antigen (HLA)-DR(+) cells, nuclear factor-κB (NF-κB), inhibitory-κBß (IκBß), TNF-α, nitrotyrosine, matrix metalloproteinase-9 (MMP-9), and collagen content (immunohistochemistry and ELISA). RESULTS: Compared with control plaques, SCH plaques had more macrophages, T lymphocytes, and HLA-DR(+) cells, TNF-α, NF-κB, markers of oxidative stress (nitrotyrosine and O(2-) production), and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBß levels (P < 0.001). Compared with plaques from treated patients, plaques from untreated patients had more macrophages, T lymphocytes, HLA-DR(+) cells, TNF-α, NF-κB (P < 0.001), nitrotyrosine, O(2-) production, and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBß levels (P<0.001). CONCLUSIONS: These data suggest a potential interplay between SCH and inflammatory activity in atherosclerotic plaque progression toward instability. Moreover, LTR might contribute to plaque stabilization by inhibiting the innate immunity-dependent plaque rupture in patients with SCH.