Thyroid tumors

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

ACTH-secreting non-pituitary tumors (ectopic ACTH syndrome)—15% of cases of endogenous Cushing s syndrome usually from small cell lung carcinoma, bronchial carcinoids, pheochromocytoma, or thymus, pancreatic, ovarian, or thyroid tumor. The tumor is usually disseminated (difficult to localize). 

Plasma cell disorders Plasma cell disorders Inflammation-associated, familial Mediterranean fever Familial amyloidotic neuropathy, systemic senile amyloidosis Dialysis-associated amyloidosis Familial amyloidotic neuropathy, aortic amyloidosis Familial systemic amyloidosis Familial systemic amyloidosis Familial systemic amyloidosis Familial cerebral hemorrhage with amyloidosis Sporadic and familial Alzheimer s disease, familial cerebral hemorrhage with amyloidosis Spongiform encephalopathies C-cell thyroid tumors Insulinoma, type II diabetes Atrial amyloidosis Prolactinomas pituitary amyloidosis Iatrogenic amyloidosis Corneal amyloidosis ... 

Gonsky R et al. Identification of rapid turnover transcripts overexpressed in thyroid tumors and thyroid cancer cell lines use of a targeted differential RNA display method to select for mRNA subsets. Nucleic Acids Res 1997 25 3823-3831. 

Pyrethrins (I) Pyrethrins induce the formation of liver and thyroid tumors by mechanisms that appear to be similar to those of other non-genotoxic, mitogenic substances, e.g., phenobarbital, which produce tumors in rodents, and these tumors are not predictive of hazard in humans at relevant exposures [99]... 

Case Study 2 An evaluation of the human relevance of the liver and thyroid tumors in rats induced by pyrethrins based on mode of action [118, 128-130]... 

To understand the MOA by which the thyroid tumors are produced, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels, and hepatic thyroxine UDP-glucuronosyltransferase activity was also investigated [128]. The treatment of male rats with 8,000 ppm pyrethrins, female rats with 3,000 and 8,000 ppm pyrethrins, and both sexes with phenobarbital resulted in increased thyroid gland... 

Heart/myocardium Tumor cellsh Tumor cellsh Tumor cellsh Thyroid Tumor cellsh Normal bone ... 

The most important and extensively studied pesticides of this group (Fig. 10, Table 3) are Amitrole and several members of the family of s-triazines [89,151, 153,155,156]. Amitrole had been widely used as a herbicide,but its uses as a registered product for application on food crops were canceled starting in 1971 because it was suspected of inducing thyroid tumors in rats [157 -162]. Amitrole is soluble in water, with a weak basic character (PKb = 10) and behaves chemically as a typical aromatic amine. 

Chlorate is mutagenic in Salmonella and induces chromosome aberrations and micronuclei in mammalian cells [78]. It has also been shown to induce thyroid tumors in laboratory animals [79]. The U.S. LFA has placed chlorate on the current CCL-3 [54], as well as its Umegulated Contaminant Monitoring Rule-3 (UCMR-3) [80] to collect further national data, and is currently considering it for regulation. 

It has been demonstrated that At is embryotoxic in pregnant mice, and there also exists a dose-related occurrence of associated fetal malformations (29, 30). Long-term studies in female rats that had received 0.5 /tCi g At systemically indicated a significant incidence of radiation-induced mammary carcinomata (39/45 44%) and endometrial polyps (43/55 76.4%) at 14 months after treatment. No thyroid tumors were found (50). Detailed macroscopic radiation dosimetric studies related to the biodistribution of At in animal models have been reported (29, 33, 39). 

Spontaneous thyroid tumors derived from the thyroid follicular cell occur in l%-3% of laboratory rats (adenomas and carcinomas combined in a variety of strains of rats aged 2 or more years). 

The lARC has determined that there is sufficient evidence for the carcinogenicity of amitrole to experimental animals and inadequate evidence for carcinogenicity to humans. It was noted that amitrole produces thyroid tumors in rodents by a nongenotoxic mechanism that involves interference with the functioning of the thyroid peroxidase, resulting in a reduction in circulating thyroid hormone concentration and an increase secretion of thyroid-stimulating hormone. Amitrole would not be expected to produce thyroid cancer in humans exposed to concentrations that do not alter thyroid hormone homeostasis. 

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

Hiasa Y, Kitahori Y, Enoki N, et al 4,4 -Diaminediphenylmethane Promoting effect on the development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl) nitrosamine. J Natl Cancer Inst 72 471-476, 1984... 

Carcinogenesis There has been evidence of oncogenic activity in studies with oxytetracycline (adrenal and pituitary tumors) in rats and minocycline (thyroid tumors) in rats and dogs. 

Holm, L.E., Eklund, G., and Limdell, G. (1980a). Incidence of malignant thyroid tumors in humans after exposure to diagnostic doses of iodine-131 II. Estimation of thyroid gland size, thyroid radiation dose, and predicted versus observed number of malignant thyroid tumors, J. Natl. Cancer Inst. 65,1221. 

Holm, LJl, Daahlquist, L, Israelsson, A., and Lundell, G. (1980b). Malignant thyroid tumors after iodine-131 therapy, N. Engl. Med. J. 303,188. 

Shore, R.E., Woodard, E., Hildreth, N., Dvoretsky, R, hemplemann, L. and Pasternack, P. (1985). Thyroid tumors following thymus irradiation, J. Natl. Cancer Inst. 74,1177. 

This response is absolute nonsense. Sweden had banned the herbicide amitrole and several bis-dithiocarbamate fungicides because of flawed scientific evaluations that misinterpreted thyroid tumors in rodents, known to lack relevance for humans, as indicators of a human risk associated with normal usage. In contrast to Sweden s action, IARC and the U.S. Environmental Protection Agency cleared all of them of suspicions of causing cancer at current exposure levels,45 and the EU has approved amitrole for general use. Sweden s Minister of the Environment, Kj ell Lars-son, has declared that Sweden will fight all the way to the European Court of Justice to stop reintroduction of these horribly dangerous pesticides. 

The function of the target molecule may be critical or mncritical. Thus, if the target molecule is an enzyme, this could be involved in a crucial metabolic pathway, such as mitochondrial oxidative phosphorylation. In this case, an adverse interaction with the ultimate toxicant is likely to lead to cell dysfunction and possibly death (e.g., as with cyanide or salicylate). Chemicals such as methimazole and resorcinol, which are activated to free radical intermediates by thyroperoxidase, cause destruction of the enzyme. This then disturbs thyroid hormone synthesis and thyroid function with pathological consequences such as thyroid tumors. 

Holm LE, Dahlqvist I, Israelsson A, Lundell G. Malignant thyroid tumors after iodine-131 therapy a retrospective cohort study. N Engl J Med 1980 303(4) 188-91. 

Braga M, Ringel MD, Cooper DS. Sudden enlargement of local recurrent thyroid tumor after recombinant human TSH administration. J Clin Endocrinol Metab 2001 86(11) 5148-51. 

Hyperthyroidism (thyrotoxicosis) results in the increased secretion of thyroid hormones. This condition may occur secondary to a number of conditions, including thyroid tumors and problems in the... 

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