MedGen

Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). The most prevalent cause of thyroid dyshormonogenesis is TPO deficiency (Park and Chatterjee, 2005). Defects in TPO cause a severe form of congenital hypothyroidism characterized by a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration (Bakker et al., 2000). This release of radioiodide represents total iodine organification defect (TIOD), a disruption of the process by which iodide present in the thyroid is oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin (TG; 188450) to form iodotyrosine. [from OMIM]

Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). Dyshormonogenesis can be caused by recessive defects at any of the steps required for normal thyroid hormone synthesis. In untreated patients thyroid dyshormonogenesis is typically associated with goitrous enlargement of the thyroid secondary to long-term thyrotropin (TSH; see 188540) stimulation. Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder. Genetic Heterogeneity of Thyroid Dyshormonogenesis Other forms of thyroid hormone dysgenesis include TDH2A (274500), caused by mutation in the thyroid peroxidase gene (TPO; 606765) on 2p25; Pendred syndrome, a form of thyroid hormone dysgenesis associated with deafness (TDH2B; 274600) and caused by mutation in the SLC26A4 gene (605646) on 7q31; TDH3 (274700), caused by mutation in the thyroglobulin gene (TG; 188450) on 8q24; TDH4 (274800), caused by mutation in the iodotyrosine deiodinase gene (IYD; 612025) on 6q25; TDH5 (274900), caused by mutation in the DUOXA2 gene (612772) on 15q21; and TDH6 (607200), caused by mutation in the DUOX2 gene (606759) on 15q21. [from OMIM]

An abnormal result of the perchlorate discharge test. In this test, first radioactive iodine is administered, sufficient time is allowed to pass so that the radioactive iodine is captured by the thyroid,and then, perchlorate is administered orally. The perchlorate displaces non-organified iodide from the thyroid. The perchlorate discharge test is considered positive (abnormal) if there is an abnormally rapid loss of radioactive iodine from the thyroid. [from HPO]