After Radiation

The Natural Thyroid Diet

The Natural Thyroid Diet

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Figure 3. Histological data of the thyroids after 15, 35, 55 and 110 weeks under normal iodine conditions (In; black bars I), iodine deficiency (I-; gray bars G ) and iodine supplement (I+; dark-grey bars D ) with or without irradiation (n = 10; meanĀ±SEM).

(* = statistical significance In vs. I- or I+, p < 0.05; # = statistical significance 1+ vs. I-, p < 0.05)

Figure 3. Histological data of the thyroids after 15, 35, 55 and 110 weeks under normal iodine conditions (In; black bars I), iodine deficiency (I-; gray bars G ) and iodine supplement (I+; dark-grey bars D ) with or without irradiation (n = 10; meanĀ±SEM).

(* = statistical significance In vs. I- or I+, p < 0.05; # = statistical significance 1+ vs. I-, p < 0.05)

Figure 4. Histological examples of tumors induced after 4Gy radiation of the thyroid region under normal nutrition iodine conditions (A and B), iodine deficiency (C and D) and iodine supplementation (E and F; magnification x100). A, Metaplasia of squamous epithelium with dermoid cysts (55 weeks). B, Squamous cell carcinoma of the cervical soft tissue beside the thyroid gland (55 weeks). C, Adenocarcinoma of a salivary gland (glandula submandibularis; 55 weeks). D, Follicular thyroid carcinoma with a bizarre pattern (110 weeks). E, Follicular thyroid carcinoma, small follicular/insular type (110 weeks). F, Papillary thyroid carcinoma, predominant follicular pattern, sporadic papillae (110 weeks).

Figure 4. Histological examples of tumors induced after 4Gy radiation of the thyroid region under normal nutrition iodine conditions (A and B), iodine deficiency (C and D) and iodine supplementation (E and F; magnification x100). A, Metaplasia of squamous epithelium with dermoid cysts (55 weeks). B, Squamous cell carcinoma of the cervical soft tissue beside the thyroid gland (55 weeks). C, Adenocarcinoma of a salivary gland (glandula submandibularis; 55 weeks). D, Follicular thyroid carcinoma with a bizarre pattern (110 weeks). E, Follicular thyroid carcinoma, small follicular/insular type (110 weeks). F, Papillary thyroid carcinoma, predominant follicular pattern, sporadic papillae (110 weeks).

rates. At week 55 and 110, all non-irradiated animal groups were free of malignant tumors, and benign tumors were not detected until week 55.

Iodine-dependent changes after radiation:

After radiation, there were increases in T3 and T4, and a significant decrease in TSH in the group with iodine deficiency. The hormone concentrations of the normal iodine and high iodine groups were not significantly altered. In all groups, thyroid weight was not significantly influenced by radiation. Histologically, the most important finding in irradiated low iodine diet thyroids was the total destruction of follicles observed at week 15. After this destruction, a short-term increase in T3 (7th week) was measured. After the 55th week, a complete restitution of the follicle structure was seen. In contrast to the sole manipulation of iodine intake, radiation treatment led to a higher number of benign tumors, starting 55 weeks after having changed nutritional iodine supply, and to malignant tumors after 110 weeks. Parathyroid carcinomas were also induced: squamous cell carcinomas of the cervical soft tissue and adenocarcinomas of the salivary glands. The thyroid carcinomas were solitary tumors, their size ranged between 0.1 and 1.5mm. Neither local lymph node metastasis nor distant metastasis was found.

Conclusions

This animal model clearly supports the concept that in thyroid carcinogenesis, there is a very long latency period between the mutational event and the developement of malignant changes. This contradicts previous studies using a higher stimulation of thyrocyte proliferation by iodine deficiency, where malignancies were detected after much shorter time intervals (Axelrad & Leblond 1955). Large doses of iodine may induce thyroid carcinomas (Correa & Welsh 1960). We showed that mild iodine excess is not necessarily associated with the formation of thyroid malignant neoplasms, but when combined with a mutagen, carcinomas arise with high frequency. These data on mild forms of high iodine intake thus put a note of caution to a long term-use of high iodine. It was shown that euthyreosis is best protection against thyroid cancer before environmental hazards are effective.

The well-defined setting in these experiments clearly demonstrates that mutational lesions acquired by radiation are clinically silent over a long period oftime. It is tempting to use such a model to search for candidate genes altered by mutagens, but which are not changed in thyroid adenomas found under control conditions. The definition of such changes may then have important implications for the characterization of the malignant potential of a given adenoma well before cytological or histological changes occur.

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