ethylenethiourea and Hyperthyroidism

The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.. We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.. The literature research (1999-March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946-1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78-10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21-0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.. There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.

Topics: Antithyroid Agents; Case-Control Studies; Ethylenethiourea; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Neoplasms

A literature review of individual pregnancies and recent surveys involving large cohorts reveal an association between congenital malformation and maternal hyperthyroidism, suggesting that some aspect of hyperthyroidism or its treatment might compromise the development of the fetus. Experiments have shown that the thyroid antagonist, ethylenethiourea (ETU), causes fetal malformations when administered to pregnant rats, but it is not known whether it is ETU or the imbalance in maternal thyroid hormone which it causes which is the teratogenic agent. Here we employ in vitro culture to determine the possible direct effects on rat embryos of two thyroid antagonists, ETU and methimazole (MMI), the latter being one which is used for treatment of thyrotoxicosis in humans. It was found that ETU can compromise the development of rat embryos in vitro, confirming that ETU has a direct effect on the rat embryo. It was also found that MMI can cause abnormal development of rat embryos in vitro, although the concentration at which MMI disturbs rat embryogenesis is higher than that which is reached in hyperthyroid patients treated with clinical doses of MMI or carbimazole.

Topics: Abnormalities, Drug-Induced; Animals; Embryo, Mammalian; Ethylenethiourea; Hyperthyroidism; Imidazoles; In Vitro Techniques; Methimazole; Rats; Rats, Inbred Strains

Ethylenethiourea (ETU) was given by gavage at a dose of 40 mg/kg/day from Days 7 through 15 of gestation to hypothyroid and euthyroid rats, and to rats given exogenous thyroxine, to determine whether ETU teratogenicity occurs through alteration of maternal thyroid function. At sacrifice on Day 20 of gestation 84-100% of the fetuses in all groups given ETU were malformed regardless of the thyroid status of the dams. Ten percent of the fetuses of dams thyroparathyroidectomized at 75 days of age that were not given ETU were malformed; no malformations were noted among the fetuses of the other groups not given ETU. Hence, ETU was found to induce teratogenicity in rats but not through alteration of maternal thyroid status. In addition, it was determined that ETU lowered serum thyroxine concentration, that hypothyroidism itself increased the background level of malformations in the rat, and that hypothyroidism qualitatively and quantitatively increased the incidence of specific malformations after ETU administration.

Topics: Animals; Body Weight; Ethylenethiourea; Female; Fertility; Hyperthyroidism; Hypothyroidism; Imidazoles; Organ Size; Pregnancy; Rats; Teratogens; Thyroid Gland

Topics: Antithyroid Agents; Ethylenethiourea; Hyperthyroidism

Topics: Ethylenethiourea; Humans; Hyperthyroidism; Imidazoles; Thyrotoxicosis