Some snippets which include "important dates" in the history of thyroid medicines in the UK.
Thyroid and its Constituents
In 1873 the English physician Sir William Withey Gull, who was at that time the Resident Physician at Guy's Hospital, published a paper entitled 'On a cretinoid state supervening in adult life in women'. The paper described the symptoms and changed appearance of a Miss B who had a thyroid deficiency.
In 1888 W.M. Ord renamed this condition myxoedema — hypothyroidism. In 1891 the physician George Redmayne Murray evaluated the treatment of myxoedema with subcutaneous injections prepared from an extract of fresh sheep thyroid which he injected into a 46-year-old woman with myxoedema. After three months the patient was dramatically better. He followed up with further cases. Other physicians evaluated treatment with whole sheep thyroid or an oral thyroid extract, and this latter became the treatment route of choice. Dry Thyroid was first introduced as a medicinal substance in the 1898 BP. It was described as a powder prepared from fresh and healthy thyroid gland of the sheep. The healthy glands were minced and dried at a temperature of 32.2°C to 37.8°C. The fat was removed by treatment with petroleum spirit, and the powder was then dried. The specification in the monograph merely describes it as 'a light dull-brown powder, with a very faint meat-like odour and taste'. The clinical indication for the product was treatment of hypothyroidism. In December 1914 thyroxine, the principal hormone in thyroid, was isolated by the American chemist Edward Kendall working at the Mayo Clinic. Its structure was determined by Harington in 1926. The 1932 BP included both Thyroid — Dry Thyroid, and Thyroxine Sodium. Thyroid by then could be prepared from oxen, sheep or pigs and had a specification of 0.1 per cent of iodine in combination as thyroxine and not more than 10 per cent of the content of total iodine. Curiously the 1948 BP omitted Thyroxine Sodium but retained Thyroid and Thyroid Tablets, again defined the Thyroid as containing 0.1 per cent thyroxine. This was presumably because thyroxine was much more expensive than Thyroid as it took 3 tons of pigs' thyroid to isolate just 33 grams of thyroxine.39 A team of Glaxo chemists synthesised it in 1949. In the 1958 BP Thyroxine Sodium reappeared.
In 1952 a trace contaminant in thyroxine was identified by Gross and Pitt-Rivers as liothyronine. It was more potent than thyroxine and it was a metabolite of thyroxine. Liothyronine Sodium and Liothyronine Tablets were added in the 1960 Addendum to the 1958 BP. Until recently it was mainly used in the management of myxoedema coma, but has now been advocated for routine management of myxoedema. The introduction to the 1963 BP stated that the use of thyroxine had by then become widely established. However Thyroid and Thyroid Tablets were still widely used by the more conservative physicians. The BP Commission expressed concern that the then current analytical methods were not always adequate to measure the activity of samples. The 1963 BP introduced an assay based on determination of total iodine in thyroid in combination with a limit test for inorganic iodide, but reservations were expressed about the adequacy of these tests. They were regarded as an interim measure whilst a biological assay was being developed.
[Here follows the letter I have already posted as:
The British Pharmacopoeia, 1864 to 2014: Medicines, International Standards ...
By Anthony C. Cartwright