{"id":8674,"date":"2025-02-18T21:44:21","date_gmt":"2025-02-18T13:44:21","guid":{"rendered":"https:\/\/www.seenda.cn\/?p=8674"},"modified":"2025-03-17T14:02:48","modified_gmt":"2025-03-17T06:02:48","slug":"therapeutic-use-of-levothyroxine-a-historical","status":"publish","type":"post","link":"https:\/\/www.seenda.cn\/therapeutic-use-of-levothyroxine-a-historical.html","title":{"rendered":"Therapeutic Use of Levothyroxine: A Historical Perspective 70 Years of Levothyroxine NCBI Bookshelf"},"content":{"rendered":"

Therapeutic Use of Levothyroxine: A Historical Perspective 70 Years of Levothyroxine NCBI Bookshelf<\/h1>\n

T4 is converted to T3 within cells by specific deiodinases, which also deactivate thyroid hormones, by converting T4 into reverse T3, and T3 into diiodothyronine. A complex of T3, its intracellular thyroid hormone receptor, and the thyroid hormone-responsive element alters the transcription of a large number of genes to mediate the pleiotropic physiological actions of thyroid hormones. LT4 was introduced into the therapeutic armamentarium in the USA in the 1950s without a requirement for regulatory oversight. This situation is very different today, with increasingly close regulatory attention paid to the standards of manufacture of LT4 products. This has led to the development of new formulations of LT4, with more accurate and reproducible dosing, designed to improve the accuracy and reproducibility of exposure to LT4 for a patient taking this medication. The first attempts at iodine supplementation, either using a tincture of iodine, or with iodised salt, followed during the following decade 4.<\/p>\n

T3 hormone medication<\/h2>\n

The substance that would come to be known as thyroxine (T4) was isolated in the USA in 1915 and fully chemically characterised in 1926 (and published the following year 18). It was also established that LT4 had greater biological activity than a racemic mixture. The discovery of triiodothyronine (T3) as a \u201cnormal constituent of the organic iodine fraction of the plasma\u201d of subjects with normal thyroid function or hyperthyroidism followed in 1952 19. The likely reason for this dismissive outburst lay at the feet of that medical colossus, Charles \u00c9douard Brown-S\u00e9quard, the French neurologist and physiologist. A kind of scientific Ulysses, he had held university chairs in Richmond, Virginia and in Harvard, Paris, Geneva and Paris again.2 He declined the chair of physiology in Glasgow because of the weather! The story goes that he once refused a colossal fee of \u00a310,000 to see a wealthy American patient in Italy because he did not think he was the best person to advise and, besides, private practice interfered with research!<\/p>\n

Figure. Events influencing the evolution of treatment trends in hypothyroidism.<\/h3>\n

L-Thyroxine monotherapy, the novel and physiologically savvy method for treatment of hypothyroidism, contrasted with the traditional approach of natural thyroid preparations that was marred by potency concerns. In less than a decade, there was a major shift in treatment of hypothyroidism such that normalization of TSH with l-thyroxine monotherapy became the new standard of care (Appendix Table) (52). Many clinicians advocated for this to be first-line therapy and for patients previously treated with desiccated thyroid to be transitioned to l-thyroxine monotherapy (50). The development of TSH radioimmunoassay (43) provided the first sensitive and specific marker of systemic thyroid hormone status (Figure). Clinicians could now titrate therapy to achieve a serum TSH within the normal range as a specific marker of replacement adequacy (44). For patients who were once treated with doses that normalized their symptoms, BMR, or serum PBI, the use of serum TSH revealed such doses to be typically supratherapeutic (45, 46).<\/p>\n

This was partly due to limitations of chemically synthesised LT4, which was produced as an acid and had limited bioavailability before the synthesis of a sodium salt of in 1949 21. This preparation entered clinical use in that year in the USA, and entered clinical use in Europe some years later. The early attempts at thyroid replacement via \u201corgan therapy\u201d (as the practice of administration of extracts of animal organs became known), described briefly in the previous section, were taking place at a time when this practice was becoming widespread in the management of other conditions 20. For example, a report by a leading physician in France on the allegedly rejuvenating effects of self-injection with animal testicular extracts led to great enthusiasm for this practice among other physicians. Eventually, a growing association with widespread quackery in the hands of other practitioners led to a general discrediting of the principle of \u201corganotherapy\u201d 20, 21.<\/p>\n

3. Technological Advances: Better Assays of Thyroid Function<\/h3>\n