1.Iodine and thyroid cancer
Iodine is an essential trace element, and it is generally believed that iodine deficiency is endemic goiter. Iodine deficiency leads to reduced synthesis of thyroid hormones and increased levels of thyroid stimulating thyroid follicular hyperplasia and hypertrophy, resulting in goiter and the appearance of thyroid hormones, which increases the incidence of thyroid cancer. There is no consensus on the opinion, but it is mostly follicular thyroid cancer, which is not the most common type of thyroid cancer There is no significant change in the incidence of thyroid cancer before and after iodized salt prophylaxis, and the proportion of papillary thyroid cancer increases after the implementation of effective iodized salt prophylaxis, with more intake of foods containing very high iodine and a high iodine diet may increase the incidence of thyroid The incidence of papillary thyroid cancer may be increased by high iodine diet.
2.Radiation and thyroid cancer
Irradiation of thyroid gland of laboratory rats with X-rays can promote the development of thyroid cancer in animals, which can lead to the deformation of cell nucleus and a great reduction of thyroxine synthesis, resulting in carcinogenesis; on the other hand, it can destroy the thyroid gland and cannot produce endocrine hormone, and the resulting large secretion of thyroid stimulating hormone (TSH) can also promote thyroid cell carcinogenesis.
In clinical practice, many facts show that thyroid gland development is related to the effect of radiation. Children who have received radiation therapy to the upper mediastinum or neck during infancy due to thymus enlargement or lymphadenopathy are especially prone to thyroid cancer because the cells of children and adolescents are proliferating vigorously and radiation is an additional stimulus to promote the formation of tumors. In adults, thyroid cancer is less likely to occur after neck radiation therapy.
3. Chronic stimulation of thyroid stimulating hormone and thyroid cancer
Thyroid follicles are highly differentiated and have the function of polyiodine and synthesis of thyroglobulin. TSH also regulates the growth of thyroid follicular cells through cAMP-mediated signaling pathway, and thyroid cancer may occur. Increased serum TSH level induces nodular goiter, and thyroid follicular carcinoma can be induced after administration of mutagens and TSH stimulation, and clinical studies have shown that TSH inhibitory therapy in differentiated thyroid cancer plays an important role in the treatment process after surgery, but whether TSH stimulation is a causative factor for the development of thyroid cancer remains to be confirmed.
4. Role of sex hormones and thyroid cancer
The relationship between sex hormones and thyroid cancer has been emphasized because there are significantly more women than men with well-differentiated thyroid cancer. Clinical comparison of the tumor sizes of well-differentiated thyroid cancer reveals that the tumors of young people are usually larger than those of adults, and the cervical lymph node metastasis or distant metastasis of thyroid cancer occurs earlier in young people than in adults, but the prognosis is better than that of adults. It is possible that the increased secretion of estrogen is related to the occurrence of thyroid cancer in young people, so some people study the sex hormone receptors in thyroid cancer tissues and found that there are sex hormone receptors in thyroid tissues: estrogen receptor (ER) and progesterone receptor (PR), and ER in thyroid cancer tissues. but the effect of sex hormones on thyroid cancer is still inconclusive.
5. Goitre-producing substances and thyroid cancer
Animal experiments have confirmed that prolonged use of goitre-producing substances can induce thyroid cancer and also hinder the synthesis of thyroid hormones, increase TSH secretion, stimulate thyroid follicular hyperplasia, and may produce neoplastic thyroid gland with diffuse enlargement of thyroid gland, and cause thyroid tumor.
6.Other: Thyroid disease and thyroid cancer
(1) Nodular goiter: The occurrence of thyroid cancer in nodular goiter has always been valued as a risk factor associated with the development of thyroid cancer, and the incidence of thyroid cancer in nodular goiter can be as high as 4% to 17%.
The reasons for the current belief that there is no necessary association between thyroid cancer and nodular goiter are.
(1) Comparing the cytohistologic changes of nodular goiter and thyroid cancer, nodular goiter is a lesion of the thyroid follicles that manifests as highly dilated follicles with flattened follicular wall cells, dilated follicles converging into nodules of variable size filled with large amounts of colloid, and incomplete fibrous envelope around the nodules. However, the most common type of thyroid cancer is not follicular thyroid cancer but papillary thyroid cancer.
②Comparing the age of onset of nodular goiter and thyroid cancer, we found that the age of onset of thyroid cancer was significantly lower than that of nodular goiter, which does not seem to support that thyroid cancer is secondary to nodular goiter.
(iii) Comparing the incidence of nodular goiter and thyroid cancer, the incidence of nodular goiter in the population was 40,000 per 1 million, while thyroid cancer was only 40 per 1 million, much lower than the 4% to 17% incidence of thyroid cancer in nodular goiter; the high incidence of thyroid cancer in nodular goiter was related to the cases selected for surgical treatment, some of which were even suspected clinically to have malignant thyroid lesions, and thus is not universally relevant.
Nevertheless, the presence of thyroid cancer in nodular goiter remains indisputable. Nodular goiter is TSH-induced follicular epithelial hyperplasia in different parts of the thyroid gland, which results in papillary hyperplasia and vascular regeneration, and papillary hyperplasia has the potential to develop papillary thyroid cancer. After feeding rats or mice with drinking water and grain from iodine deficiency disease areas, increased serum TSH levels not only induce nodular goiter, but also the occurrence of thyroid cancer in nodular goiter, including papillary thyroid cancer and follicular thyroid cancer, the incidence of which is as high as 15.6% and is a risk factor for the development of thyroid cancer.
(2) Thyroid hyperplasia: The relationship between thyroid hyperplasia and thyroid cancer is still unclear, but some reports found that congenital hyperplastic goiter without proper treatment for a long time eventually develops thyroid cancer.
(3) Thyroid adenoma: Most people believe that thyroid cancer occurs with solitary thyroid adenoma, and if thyroid cancer is secondary to thyroid adenoma, the type of thyroid cancer should be mainly follicular carcinoma, but the fact is that papillary thyroid carcinoma accounts for the majority of cases, and patients with follicular thyroid carcinoma often have a history of previous adenoma, but it is quite difficult to confirm the relationship between the two, even with histological observation. Even with histological observation, it is difficult to confirm the relationship between them.
(4) Chronic lymphocytic thyroiditis (Hashimoto
The actual incidence of HT and thyroid cancer can be two unrelated diseases that coexist in the thyroid gland. On the other hand, focal HT may also be an immune response of the body to thyroid cancer. It is possible that HT leads to destruction of thyroid follicular cells, hypothyroidism, and decreased thyroid hormone secretion, which feedback causes increased TSH, which continuously stimulates thyroid follicular cells, and thyroid follicular cells overproliferate and become cancerous; it is also possible that TSH acts as a promoting factor and becomes cancerous while thyroid oncogenes are overexpressed; it is also believed that HT and thyroid cancer share a common background of autoimmune abnormalities.
(5) Hyperthyroidism: Because of the low level of serum TSH in hyperthyroid patients, it was previously believed that thyroid cancer does not occur in hyperthyroid patients, or the incidence of thyroid cancer is consistent between hyperthyroid patients and the general population (0.6% to 1.6%), and the incidence of thyroid cancer is 2.5% to 9.6
The actual incidence of thyroid cancer in patients with surgical treatment of hyperthyroidism is unclear either because of the large thyroid gland or because thyroid nodules are already present, and most of them are treated with medication. Therefore, the clinical situation of hyperthyroidism combined with thyroid cancer should be taken seriously, and we should be more alert to the presence of thyroid cancer.
Thyroid cancer can be seen in various causes of hyperthyroidism, including Graves’ disease, but is rarely caused by the tumor itself, which secretes thyroid hormone (LATS), which is not inhibited by thyroid hormone feedback and stimulates thyroid follicles, and TSAb, which is a TSH receptor antibody (TSH
Receptor
TSAb) is one of the TSH Receptor Antibodies (TSH Receptor Antibodies, TRAb), which may induce thyroid cell malignancy and thyroid cancer, but it has not been confirmed, but it is still controversial. Whether it is Graves’ disease or toxic nodular goiter, the tumor lesions are mostly small or insidious, with low incidence of metastasis and better prognosis, also similar to non-hyperthyroid patients with thyroid cancer.
7.Family factors and thyroid cancerThyroid cancer is rarely an independent familial syndrome.
Thyroid cancer is associated with familial polyposis of the colon (e.g. Gardner syndrome), including adenomatous polyps of the colon combined with soft tissue, most often with fibromatosis, combined with fibrosarcoma, which is an autosomal dominant disease, caused by mutations in the APC gene located on chromosome 5q21 to q22. The latter is a signaling protein involved in the regulation of cell proliferation and can become cancerous in a minority of individuals under TSH stimulation.