Notes on Some Remedies

investigate its toxicity to the rat. They noted that animals dying after sulphaguanidine showed goitres which on microscopical section were found to be due to hyperplasia and were practically free from colloid. The same effect was produced more or less by other sulpha drugs such as sulphadiazine and sulphapyridine, and Richter and Clisby (1942) showed that other sulphur compounds, notably thiourea and its derivative, thiouracil, had a well-marked goitrogenic effect. Kennedy (1942) and his colleagues who were investigating the action of rape seed in rat thyroid found the causative agent in allylthiourea. These discoveries led to a study of the mode of action of these thio compounds, and the investigations that followed revealed that they inhibit the physiological activity of the thyroid gland and produce the somewhat odd combination of hypothyroidism and thyroid hyperplasia. This is interpreted as meaning that the thyroid gland is not producing sufficient hormone, thyroxine, for the needs of the body and is being stimulated to hyperplasia to remedy this deficiency. The cause of the hypothyroidism was at first obscure, it could not be due to any neutralizing action of thiourea on the hormone for it is abolished by the coincident administration of thyroxine. It was eventually thought, and this was supported by experimental evidence, that the action of thiourea is to prevent the synthesis of the thyroid hormone and that the lack of this hormone is the cause of hypothyroidism. In response to this condition the pituitary gland is stimulated to increase its thyrotropic activity and in turn the thyroid gland becomes hyperplastic, but is unable to relieve the hypothyroid condition owing to blocking of the thyroxine elaborating mechanismIt was Astwood (1943) who suggested and introduced with beneficial results the clinical use of thiourea and thiouracil in hyperthyroidism, a toxsemic state caused by excessive secretion of thyroxine, and since then many confirmatory reports have been published in England and America.