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Clinical Investigations |
1 Department of Nuclear Medicine, Commissariat à l’Energie Atomique, Institut Gustave Roussy, Villejuif, France
2 Department of Physics, Commissariat à l’Energie Atomique, Institut Gustave Roussy, Villejuif, France
3 Department of Statistics, Commissariat à l’Energie Atomique, Institut Gustave Roussy, Villejuif, France
4 Department of Pathology, Commissariat à l’Energie Atomique, Institut Gustave Roussy, Villejuif, France
5 Department of Clinical Biology, Commissariat à l’Energie Atomique, Institut Gustave Roussy, Villejuif, France
The high sensitivity of the thyroid gland to the carcinogenic effects of radiation during childhood contrasts with the absence of demonstrable carcinogenic effects of radiation in adults. To better understand these age-related variations, we studied follicular morphometry, functional status, and proliferative activity in 31 thyroid glands removed from relatives of medullary thyroid carcinoma patients, with ages ranging from 3 to 39 y. Methods: The mean follicular diameter (MFD) was estimated, and immunohistochemistry was performed with antibodies directed to molecules involved in iodide transport (Na+/I- symporter [NIS], pendrin, and apical iodide transporter), in organification (thyroperoxidase [TPO] and Duox), in cell cycle and growth (Ki-67, cyclin A and D1, and galectin-3), and in angiogenesis (vascular endothelial growth factor and nitric oxide synthase III [NOSIII]). Results: Compared with older patients, patients who were 
12 y old had a smaller MFD (P < 0.001) and more frequently positive NIS, pendrin, and Duox (P < 0.01). Proliferation rate as indicated by cyclin A expression was also higher in patients < 12 y (P < 0.01) but peaked at the time of puberty. Staining for NIS, pendrin, TPO, Duox, and NOSIII was stronger in thyroid glands with a smaller MFD (P < 0.001). On multiple tests adjusted for age and thyroid mass, TPO, Duox, and NOSIII remained significantly correlated to MFD (P < 0.001), whereas staining for NIS and pendrin did not. This finding suggests that NIS and pendrin expression is related mainly to the age of the patient. Conclusion: Smaller follicles with a higher expression of proteins involved in iodide metabolism were found in younger children. In cases of radioiodine contamination in children, the result will be a higher radioactive concentration and, hence, higher radiation doses. This event may induce the development of thyroid cancer under conditions of accelerated proliferation, as evidenced at puberty.
Key Words: thyroid follicles • iodine pathway • radioiodine • proliferation rate
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