title: Thiocyanate induces cell necrosis and fibrosis in selenium- and iodine-deficient rat thyroids: a potential experimental model for myxedematous endemic cretinism in central Africa.
abstract: Thyroid destruction leading to endemic myxoedematous cretinism is highly prevalent in central Africa, where iodine (I) and selenium (SE) deficiencies as well as thiocyanate (SCN) overload are combined. All three factors have been studied experimentally in the etiology of the disease, but they have never been studied in combination. In a model using rats, we have previously shown that combining I and SE deficiencies increases the sensitivity of the thyroid to necrosis after iodide overload, an event unlikely to occur in the African situation. To develop a model that would more closely fit with the epidemiological findings, we have determined whether an SCN overload would also result in thyroid necrosis as does the I overload. The combination of the three factors increased by 3.5 times the amount of necrotic cells, from 5.5 +/- 0.3% in the I-SE+ thyroids to 18.9 +/- 1.6% in the I-SE-SCN-overloaded ones. Methimazole administration prevented the SCN-induced necrosis. SE- thyroids evolved to fibrosis, whereas SE+ thyroids did not. TGFbeta was prominent in macrophages present in SE- glands. Thyroid destruction in central Africa might therefore originate from the interaction of three factors: I and SE deficiencies by increasing H(2)O(2) accumulation, SE deficiency by decreasing cell defense and promoting fibrosis, and SCN overload by triggering follicular cell necrosis.
mesh_terms: D000350:Africa, Central; D000818:Animals; D013956:Antithyroid Agents / Q000008:administration & dosage; D003409:Congenital Hypothyroidism; D004195:Disease Models, Animal; D019353:Endemic Diseases; D005260:Female; D005355:Fibrosis; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007455:Iodine / Q000172:deficiency*; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D008713:Methimazole / Q000008:administration & dosage; D009230:Myxedema; D009336:Necrosis; D010472:Perchlorates / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000172:deficiency*; D017670:Sodium Compounds / Q000008:administration & dosage; D013861:Thiocyanates / Q000633:toxicity*; D013961:Thyroid Gland / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D013956:Antithyroid Agents; D010472:Perchlorates; D017670:Sodium Compounds; D013861:Thiocyanates; D016212:Transforming Growth Factor beta; D008713:Methimazole; D007455:Iodine; C031068:sodium perchlorate; D006861:Hydrogen Peroxide; D012643:Selenium; C031760:thiocyanate