The idea of thyroid replacement therapy
At a meeting of the Clinical Society of London in November 1883, Felix Semon drew attention to Kocher’s presentation at the German Surgical Society the previous April, and proposed that myxoedema, cachexia strumipriva and cretinism were all due to the same cause, namely, absence or degeneration of the thyroid (Semon 1883). At the time, Semon was a 34-year-old assistant physician for Diseases of the Throat at St Thomas’s Hospital, London (he would later be knighted as the doyen of British laryngology). According to Rolleston (1936) and Medvei (1993) his remarks ‘excited ridicule’. There is no suggestion of this in the British Medical Journal’s detailed transcription of the proceedings, nor in the exceedingly brief original written minutes of the meeting (an extended account must have been written up at some later point for the BMJ). Ridicule may not, of course, have been minuted. Semon in his autobiography says only that his ‘extremely bold assertion was received with polite scepticism’ (Semon and McIntyre 1926),though he writes of antagonism towards him in his early career. Nonetheless, his very astute idea of the commonality of these conditions caught on, one senior member at the meeting suggesting that British surgeons be canvassed for their experience of thyroidectomy. The following month the Society set up a committee, which included Semon, to investigate the whole matter. He had already advised Ord to write to Kocher, as mentioned above. Indeed, Semon’s role in the unfolding thyroid story deserves much better recognition.
The Society’s survey was a remarkable project, enlisting Europe-wide – including Russian – surgical evidence. One hundred and fifteen surgeons were contacted, including two in Australia. Sixty nine replies were received, 64 of which were usable though to a variable extent. The Committee’s very detailed findings and influential conclusions were published five years later, in 1888, as a supplement volume to the Society’s Transactions (Clinical Society of London 1888). The report fully endorsed Semon’s view, drawing particularly on animal work carried out by Victor Horsley, one of the committee’s members. Horsley had separately reported the effects of total thyroidectomy on monkeys, concluding that myxoedema was almost certainly due to loss of thyroid function and not to ‘chronic asphyxia’, as the Clinical Society’s report summarised Kocher’s explanation (Horsley 1885). He also observed initial tetanic manifestations post-operatively, no doubt due to unwitting removal or operative ischaemia of the parathyroid glands, whose separate identity and function were still unrecognised. The report’s section on treatment, however, had very little to say, surprisingly making no mention of the possibility of any kind of thyroid replacement therapy despite acknowledging that, four years earlier, Moritz Schiff in Geneva had reported some success in transplanting canine thyroid in thyroidectomised dogs (Schiff 1884). Kocher, too, had by then tried thyroid transplantation in one of his patients and would continue experimenting with this till the end of his life (Tröhler 2010b; 2010c).
Horsley went on to advocate a trial of grafting, specifically sheep’s, thyroid to treat myxoedema and cretinism (Horsley 1890). In June 1890, Bettencourt and Serrano of Lisbon did the experiment, inserting half of a sheep’s thyroid subcutaneously into the infra-mammary region on each side of one of their patients (Bettencourt and Serrano 1890; 1891). They found that the graft worked immediately, before it could have vascularised, and concluded that its effect was likely to have been due to simple absorption of juice from the grafted gland, a conclusion of extraordinary importance. They had observed a rise in temperature within 24 hours – not associated with any features suggesting a postoperative febrile reaction – and, over the course of the one month’s follow-up, the patient’s bloating and weight had decreased, bodily movement and speech had improved, sweating had resumed and there was an almost complete resolution of a preoperative anaemia. These findings, and others describing the benefits, albeit transient, of intravenous injection of thyroid extract in thyroidectomised dogs (Gley 1891; Vessale 1891), added to the growing recognition of the thyroid’s endocrine function (although the word ‘endocrine’ was not used until 1904 (Medvei 1993))
In Britain, at a meeting of the Northumberland and Durham Medical Society on 12 February 1891, George Murray, 3 years qualified, having taken advice from Horsley, who had been one of his undergraduate teachers (Paget 1919), presented his idea to treat a case of myxoedema with an extract of sheep’s thyroid given subcutaneously (Murray 1891b). He, too, Medvei (1993) tells us, was ridiculed. While the typed minutes of the meeting contain no trace of ridicule; indeed, to the contrary, what could be interpreted as cautious support, Medvei has sourced a reliable account of one senior member of the Society saying: ‘It would be just as sensible to treat a case of locomotor ataxia with an emulsion of spinal cord’. The medical college at Newcastle refused to help.