Table 1.
Timeline of Advances That Have Contributed to Our Understanding of Thyroid Hormone Metabolism and Its Physiological Importance
| Year | Report | Reference |
|---|---|---|
| 1820 | Iodine is shown to be important for normal function of the thyroid gland | (1) |
| 1878 | The syndrome called myxedema is noted to be associated with thyroid atrophy | (3) |
| 1883 | Thyroidectomy is shown to result in cachexia strumipriva, which resembled myxedema | (6) |
| 1890 | Symptoms of myxedema are shown to be alleviated by a graft of sheep thyroid | (8) |
| 1896 | Symptoms of myxedema ameliorated with an iodinated substance isolated from the thyroid | (10,11) |
| 1914 | An active compound, thyroxin, containing 65% iodine is purified from the thyroid | (12) |
| 1926 | The active compound is synthesized, its structure is determined, and it is renamed thyroxine | (13) |
| 1947 | [131I] iodide derived by deiodination of injected [131I]T4 is found in rat urine | (16) |
| 1947 | Significant radioactivity is found in the liver, bile, and GI tract after injection of [131I]T4 | (16) |
| 1948 | The main circulating iodinated compound is demonstrated to be T4 | (14) |
| 1952 | Conjugate of T4 with GA is detected in bile | (17) |
| 1952 | The enterohepatic circulation of T4 is demonstrated | (19) |
| 1952 | T3 is identified in thyroid and plasma | (25) |
| 1956 | TH shown to undergo oxidative deamination to form acetic acid analogs in vivo | (22) |
| 1960 | Conjugate of T4 with sulfate is detected in plasma | (18) |
| 1970 | 5′D of T4 to T3 is demonstrated in athyreotic humans | (31,32) |
| 1972 | TH nuclear receptors that have a higher affinity for T3 than T4 are discovered | (34) |
| 1977 | 5D of TH is demonstrated in cultured monkey hepatocarcinoma cells | (41) |
| 1979 | First report indicating that 5′D of T4 is critical for its physiological action | (43) |
| 1982 | Evidence suggesting that there are two mechanisms for 5′D of TH is reported | (40) |
| 1991 | A cDNA for D1 is cloned, and the enzyme is shown to contain selenocysteine at its active site that is necessary for full enzyme activity | (51,52) |
| 1994 | A cDNA for D3 is cloned and the deiodinase shown to be a selenoprotein | (54) |
| 1995 | A cDNA for D2 is cloned and the deiodinase shown to be a selenoprotein | (55) |
| 2001 | A mouse completely deficient in D2 is created by targeted disruption of its gene | (56) |
| 2002 | Identification of human DIO2 SNP associated with impaired glucose metabolism | (71) |
| 2004 | 3-Iodothyronamine is shown to be an endogenous active derivative of the thyroid hormone | (70) |
| 2006 | Mice completely deficient in D1 or D3 are created by targeted disruption of their genes | (57,59) |
| 2021 | Mutations in the human DIO1 gene associated with abnormal TH metabolism are reported | (66) |
5′D, 5′-deiodination; 5D, 5-deiodination; D1, type 1 deiodinase; D2, type 2 deiodinase; D3, type 3 deiodinase; GA, glucuronic acid; GI, gastrointestinal; SNP, single-nucleotide polymorphism; T3, 3,5,3′-triiodothyronine; T4, thyroxine; TH, thyroid hormone.