When was thyroid disease discovered

This event occurs in all cretins whereas the second postnatal period of thyroid hormone deficit takes place in a subgroup only. It is the length and severity of this second event that will decide the extent of clinical hypothyroid symptoms present. Though the exact cause of myxedematous cretinism is still unclear, a wealth of skillful research has demonstrated the importance of iodine. Zimmermann has recently published a superb review of the early iodine prophylaxis [ 56 ].

In a detailed report pages delivered in by a committee set up by the Clinical Society in London on the relationship between cretinism, myxedema, and struma thyropriva, the clinical symptoms are described in detail but treatment is hardly mentioned [ 57 ].

However, a few other investigators were toiling with the possibility of therapy and clarifying thyroid function. Thus, the eminent German physician and physiologist Moritz Schiff — while working in Berne performed important experiments. Similar grafting was performed by von Eiselberg who at the same time transplanted thyroid and parathyroid tissue and thus became the first to perform parathyroid grafting [ 59 ], though obviously he was unaware of the function of parathyroid glands.

They were discovered in [ 5 ], but it would last almost until the end of the century before their function was recognized [ 60 ]. Thyroid transplantation in man was soon taken up by Bettencourt and Serrano in Lisbon [ 61 ]. The effect was remarkably swift and—in fact, so swift that the authors wisely suggested that it might be due to the absorption of the juice from healthy thyroid gland by the tissues of the patient.

In a letter in June [ 62 ], Horsley informed George Redmayne Murray — about the progress made in various European countries as to finding treatment for hypothyroidism. Murray at that time was a pathologist at the Hospital for Sick Children in Newcastle. A few months later, Murray published the first account of a human patient with hypothyroidism given substitution with thyroid extract injected subcutaneously [ 63 ].

Clinically, the effect was beyond doubt. The patient lived almost 30 years on thyroid substitution—eventually to die of cardiac failure in [ 64 ]. Within months, it was discovered that oral administration of thyroid extract was effective [ 65 — 67 ]. Fenwick [ 68 ] noted a marked increase in diuresis after commencement of thyroid substitution therapy. Naturally, the central question as far as thyroid extract was concerned, was which substance was responsible.

Magnus-Levy demonstrated the important fact that desiccated thyroid and iodothyrin increase oxygen consumption and output of carbon dioxide [ 70 ]. A vivid description has been given of what a physician might encounter at that time [ 71 ].

Around , an Irish general practitioner was asked to see a lady who obviously was dying, her family being aware no treatment was possible. The diagnosis was clinically obvious. The GP had just read in the British Medical Journal about the proposed treatment of myxedema and straight away got hold of thyroid glands from sheep. Following the instructions in the papers, he prepared a substance which was administered to the patient who stunned everybody by a swift and complete, almost biblical, recovery.

Incidentally, the physician later gained further fame by operating on an old and destitute woman on his kitchen table, curing her cataract.

In , Murray—not without a little pride—summed up the present state of treatment of hypothyroidism [ 72 ]. In the idiopathic form it is a symptom of chronic interstitial thyroiditis, just as anasarca may be a symptom of renal disease or ascites of hepatic disease. Thus the myxedema can be cured, although the chronic interstitial thyroiditis still remains.

In on Christmas day, at the Mayo Clinic, Edward Calvin Kendall — crystallized a substance—later to be named thyroxine—containing When he repeated the procedure, he failed to isolate any crystals.

It would take 15 frustrating months finally to get the procedure right. This allowed studies on its physiological properties. Perhaps because of the war, thyroxine was not chemically identified until [ 75 ]. About 25 years later, Gross and Pitt-Rivers [ 76 ] detected the second thyroid hormone—triiodothyronine, which at the same time also was demonstrated by French investigators [ 77 , 78 ]. Almost as if they were introducing a completely new drug, Hart and Maclagan in [ 79 ] reviewed the use of thyroxine and particularly L-thyroxine.

Actually, it had been available since the s but had not gained wide acceptance maybe because of its high cost —despite its obvious advantages. Desiccated thyroid was much used for many years and as late as leading British endocrinologists felt compelled to warn against its use [ 80 ].

It is still being marketed and hence probably used in some countries—for example, USA. He had advocated the use of extracts from ovaries and testes—many of his theses were based on excellent results in experiments he had performed on himself [ 82 , 83 ]. In some respects, his theories would lead medicine into an abyss of eeriness and utter bewilderment, but in other instances it would precipitate important progress in endocrine therapy.

There can be little doubt that the benefit of thyroid substitution was a major support for the soundness of organotherapy. A veritable industry grew up and extracts from a variety of organs including brain and spinal cord were marketed and widely used Figures 3 a — 3 c. Organotherapy could claim some other successes.

Around Vassale in Italy [ 84 ] and Gley [ 85 ] in France had injected thyroidectomized dogs with extract of thyroid glands from sheep. There was an excellent effect on postoperative tetany which they ascribed to thyroid insufficiency. In , two reports, one from Germany [ 87 ] and one from Italy [ 88 ], demonstrated the swift and unquestionable effect of extract of the posterior lobe of the hypophysis on polyuria in diabetes insipidus.

Patients were made devour a whole pancreatic gland per day. The results, however, were dismal. Pancreatic transplantation was attempted, first in [ 90 ], but proved an utter disaster. As an illustration of the belief in organotherapy though not necessarily involving the thyroid , an interesting piece of evidence is provided by a short novel The Creeping Man [ 91 ] written by Sir Conan Doyle — —a physician by education.

Briefly, the story deals with a professor who at a somewhat advanced age plans to marry a much younger and pretty woman. To some consternation of his family members and associates, his behavior undergoes a distinct change. He starts to climb walls, walk on all four and in general behave like an animal.

His faithful dog begins to attack him. Sherlock Holmes solves the puzzle by demonstrating that the professor had begun treating himself with extract from testicular? Today, this plot will appear queer, almost meaningless. Tam [ 92 ] has given an excellent account of thyroid organotherapy in Britain.

The status of enzymes and hormones in therapy. Careful study of the history of hypothyroidism reveals that investigators not widely known have in fact played a crucial role in the development of our knowledge of thyroid insufficiency. Thus, today probably only few are acquainted with Felix Platter who gave the first description of cretinism, with Curling who described patients with myxedema in , and perhaps even with Chatin who was the first to suggest the significance of iodine in thyroid pathology.

On the other hand, the immense importance of Kocher and Horsley in the last half of the 19th century is well known. At this time, Murray successfully introduced treatment with thyroid extract in hypothyroidism.

In France, an apparently adequate prophylaxis for one of mankind's major scourges; cretinism was launched at an early time. This policy was soon discontinued. The reason why this practice was terminated is not entirely clear. For more than a century, the safety of iodine prophylaxis was heatedly discussed until it was realized that the purpose of iodine prophylaxis ideally should be to ensure a sufficient iodine intake [ 93 ].

Problems would appear if iodine was given in supraphysiological amounts [ 94 ]. So within less than 50 years, hypothyroidism was recognized, and effective treatment was made available.

Prevention of the most frequent type of hypothyroidism was documented, and preventive intervention had in fact been instituted. However, partly because the medical establishment and health authorities showed little concern, early initiatives were abandoned causing much misery to generations in large parts of the world.

The authors are thankful to Mr. Lindholm and P. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles.

Journal overview. Special Issues. Lindholm 1 and P. Academic Editor: Marian Ludgate. Received 15 Jan Accepted 17 Mar Published 08 Jun Abstract The last part of the 19th century was a period of great achievements in medicine and endocrinology. Introduction During the 50 years preceding World War I, medicine saw a wealth of new ideas and novel procedures, not in the least within the field of endocrinology.

Early Observations on Myxedema In , a potentially important paper was published by Thomas Blizard Curling — , surgeon at the London Hospital [ 18 ]. Figure 1. First photo of a patient with myxedema. From Ord This is not the usual celebratory image before and after successful treatment.

It is a picture of the woman, aged 21 in , and then seven years later, unrecognisably aged by the effects of undiagnosed and untreated thyroid deficiency. It is poignant because she probably dies of the disease, the introduction in of effective treatment with subcutaneous injections of thyroid extract by George Murray of Newcastle-upon-Tyne coming too late Murray a.

A number of steps led to the discovery of thyroid replacement therapy: the slow understanding that this debilitating disease, myxoedema, was in some way linked to the thyroid; the acceptance of the notion that the thyroid elaborated some important factor with an endocrinefunction; the emergence of the principle of replacement therapy: and the introduction of replacement therapy in practice. But, contrary to general belief, Murray was not the first to treat myxoedema effectively.

The history of the thyroid gland goes back millennia. Its long history is inseparable from that of goitre — Latin guttur , neck or throat — for there must always have been people with goitrous swollen necks.

August Hirsch in his monumental three-volume work, Handbook of Geographical and Historical Pathology , provides many past references worldwide to endemic goitre and endemic cretinism, notably prevalent in mountain valley regions but absent in coastal regions Hirsch Amongst these — and suggestive evidence of a general public awareness of goitre — is Juvenal in the early 2 nd century CE asking rhetorically: Quis tumidum guttur miratur in Alpibus [ Who wonders at a swollen neck in the Alps].

Rolleston quotes a source in describing an incident involving an English traveller in the Tyrol of whom it was remarked that he would have been quite handsome if only he had had a goitre, such was the almost universal presence of goitre in that region Rolleston , presumably a long-standing feature.

Faith, sir, you need not fear. He also, astutely, in light of things to come, recommended it preoperatively to diminish goitre size and vascularity. Zimmerman Coindet is regarded as the first to try iodine but, in fact, William Prout in London had done so earlier in , five years after iodine was discovered Prout Further historical detail on this aspect is provided by Rolleston and more recently by Medvei in their extensive monographs Rolleston ; Medvei and by Zimmerman One of the grounds for earlier antagonism was that a goitre exempted young men from military service in the French army!

Yet, challenges in the delivery and uptake of iodine prophylaxis remain Miles Missing, because China was then largely a closed book to the West, otherwise it is likely there would have been earlier progress on the thyroid and in several other scientific and technical matters. For the Chinese were not just well aware of an environmental influence on goitre, they looked on it as an anomaly and were treating it.

There is reference to treating goitre with burnt sponge and seaweed in BCE Iason But any possibility of the use of algae dating from around BCE, as has been hinted at Morse ; Rolleston — many traditional Chinese medicines being attributed to the cultural hero and divine, Shen Nong, who is supposed to have lived then — is based on mythology.

Powdered shells of molluscs are reported to have been used in the 5 th century CE from the Goitre Prescriptions of the Abbot Shen Needham This is presumably insofar as they distinguished cretinism — by whatever name they called it — from other forms of childhood mal-development. It is also most likely to have been in the context of goitrous cretinism, for there is reference to this as well as to the treatment of goitre per se with sheep or deer thyroid in the wonderfully titled Thousand Gold Remedies or Thousand Golden Ducats Prescriptions Wong and Lien-The ; Maciocia The Chinese also recognised then that there were different kinds of goitre: solid neck swellings — malignant tumours — that could not be cured, and movable ones that could Needham The extent to which they distinguished and how they managed thyrotoxic goitres is not clear.

Remarks in a recent paper on traditional Chinese medicine suggest they may have been aware of a difference and a difficulty in treatment with seaweed Xixiao One of these recommended taking thyroid glands from gelded rams, washing them in warm water, removing the fat, then drying them and chopping them up and mixing with jujubes Chinese dates — no doubt to try to disguise the taste — to make into pills.

Another advised a single thyroid gland be removed from a sheep, the fat taken off, and the raw gland sucked by the patient until all the juice had been extracted and swallowed and the gland itself then eaten.

Yet another involved air-drying various animal thyroids to powder, to be taken every night in cold wine. It seemed not to matter which animal was used, whether pigs, sheep, water buffalo or deer; all seem to have been judged effective. One seaweed prescription may have consisted of baking seaweed and sea grass to dryness, then grinding the mixture into a powder that was to be taken in warm water daily Lu It seems improbable that these apparently routine therapeutic interventions of long ago were not the result of astute observation and experience.

While their origin may have lain in serendipity or in some instinctive idea of treating like with like, a diseased thyroid with a healthy one — the Chinese thung lei identity of categories principle Needham — their firm incorporation into Chinese pharmacopoeic texts is most likely to have been because they were seen to work. China might not have been the only ancient civilisation to use seaweed for goitre.

For in a paper on the role of algae as a food in antiquity in Central and South America, evidence is presented that dried seaweed was imported into the Andean highlands, an endemic goitrous area Aaronson The discovery of iodine in , millennia after the Chinese and perhaps other ancient civilisations were using seaweed empirically, was serendipitous and the circumstances are interesting.

A French chemist, Bernard Courtois, noticed violet fumes while washing seaweed ash with sulphuric acid in the manufacture of saltpetre. Davy, assisted by Michael Faraday, worked on it in Paris, visiting the city in under special permission from Napoleon, having gone there to collect a prize and medal Napoleon had awarded him in for his electro-chemical work Williams ; Knight ; Lamont-Brown Indeed, French chemists calling on Davy for help in identifying a new substance connected with saltpetre potassium nitrate , a key component of gunpowder, is also remarkable for it might have proven of military importance.

Up to the middle of the 19 th century there appears to have been no knowledge of thyroid biology but much speculation. That the thyroid must have some important function was suggested by its very generous blood supply. Some wondered whether it functioned as a vascular shunt to prevent sudden rushes of blood to the brain — a neat idea!

Others thought it was involved in voice production by some facilitating, perhaps lubricating, action on the larynx.

Indeed, the two thyroid lobes had originally been called the laryngeal glands. The 19 th century thus began with thyroidology at best in embryo; but during that century endocrinology was born and the thyroid was its standard bearer.

This language is almost identical to that of Ruysch and Haller more than a century earlier. In this case, the peculiarities of the individual were fully sufficient to indicate the importance of the defective part. It is not even cited in any of the following seminal papers — no joined-up thinking for King.

In , at a meeting of the Royal Medical and Chirurgical Society of London, chaired by Thomas Addison,Thomas Blizzard Curling, surgeon at the London Hospital, provided a clear clinico-pathological correlate in a paper entitled: Two cases of absence of the thyroid body and symmetrical swellings of fat tissue at the sides of the neck, connected with defective cerebral development Curling Post mortem examination in each revealed no trace of thyroid tissue and that the swellings consisted only of fat.

He described four living cases, aged from 8 to 20 years. He noted particularly that none of them had a goitre and that one had been well up to the age of eight and, although now physically cretinous, aged 16, she remained very intelligent. Gull was an interesting personality with apparently a remarkable presence, resembling Napoleon in face, form and manner Figure 2 Rolleston Gull is credited with the first description of hypothyroidism in adults and his paper was important in defining a recognisable clinical syndrome.

Yet many doctors must have come across such patients. The Edinburgh physician, Sir Byrom Bramwell, later in , recounted his general practitioner father showing him a typical case in , and a colleague encountering one in and recognising it did not conform to any known condition Bramwell Others realised in retrospect they had seen similar cases Duckworth This was possibly due to carpal tunnel syndrome, a potential complication of hypothyroidism, but then an unknown entity.

He reached the same conclusion: that destruction of the thyroid might relate in some way to the condition of his patients, although he opined there could be some more ultimate cause.

He also presented an engaging theory to explain the lethargy, inertia and slow responses associated with the disease.

It is sobering to read his descriptions of the increasingly wretched life endured by these patients, culminating in death in coma or from almost certain cardiac failure. It was a memorable, snappy for the times, single-word label which — notwithstanding some controversy over its appropriateness Rolleston — must have helped to focus attention on a condition which, despite its frequency and unifying features, had long gone unidentified.

Six years later, he chaired the committee set up by the Clinical Society of London to investigate the whole matter. He also later undertook some of the earliest metabolic studies of the effects of treating myxoedema with thyroid extract, showing the rapid weight loss and rise in temperature and in urinary volume and nitrogen excretion that occurred Ord and White How fitting it is that it should be two Swiss doctors whose practices unlocked an understanding of the importance of the thyroid.

For they each identified the late effects of total ablation extirpation of goitres. Reverdin first presented his findings briefly at a meeting of the Medical Society of Geneva on 13 September Reverdin and then in an extended paper co-authored with his cousin Auguste Reverdin in June Reverdin and Reverdin a. In light of his findings in , Reverdin thereafter sought to conserve a part of the gland during thyroidectomy for goitre, speculating that its complete removal may have been responsible for these late effects.

He had noticed that no such problems followed removal of only one lobe of the gland. Kocher, on the other hand, surprisingly appears to have been either unaware of the reports by Gull and Ord, or omitted to refer to them. He first reported his findings to the Congress of the German Surgical Society on 4 April and they were published later that year Kocher Reverdin had remarked in that paper that he wondered when Kocher would publish his findings.

In support of his denigration of Reverdin, Kocher fastens on a paper Reverdin had published in April Reverdin and Reverdin a. The transcription of his presentation is brief and there is no mention at that point of any awareness of Gull or Ord, and it may be he had not yet made the connection.

Kocher was present at that meeting. Indeed, he and Reverdin had had a conversation a few days beforehand — on a steamboat! A full analysis of them is provided by Michler and Benedum That Reverdin was the prime mover is the understanding of some latter-day reviewers of the history of thyroid surgery Zimmerman and Veith ; Welbourn ; DuBose et al.

It is also obvious that Kocher, like many surgeons of the time, cannot have engaged in routine postoperative outpatient follow-up, for otherwise the ensuing problems in his goitre-operated patients would have been detected years earlier.

None of these observations about Kocher should detract from his contributions. They serve rather to show that Reverdin should be recognised more widely. In respect of this key moment in the history of the thyroid, Reverdin could be said to hold the intellectual property. The thought has been expressed that perhaps he should have shared the Nobel Prize with Kocher Ellis ; Rowley Reverdin, in , three days short of his 85 th birthday and two years before his death, received a telegram from the International Conference on Goitre in Bern, paying tribute to his pioneering role in myxoedema Reverdin It was a nice touch.

Kocher, who was from Bern, had died there 10 years earlier, age Ridicule may not, of course, have been minuted. 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. 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.

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. 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.

He, too, Medvei tells us, was ridiculed. The medical college at Newcastle refused to help. He declined the chair of physiology in Glasgow because of the weather! Rolleston ; Olmsted Beginning on 13 April , he injected a year-old woman with most of the characteristic features of myxoedema, with 1. This led Murray to consider that injections every weeks would suffice to maintain improvement.

It included photographs before and after treatment and a temperature chart showing an increase in temperature within days of starting treatment. This was a telling early alert for the need for caution. Other cases were presented at that BMA meeting, including two who failed to respond to thyroid injections British Medical Journal Years later, Murray learned that the lack of success in these two cases had been because thymus, not thyroid, had been supplied by the butcher! Murray But Murray, contrary to general understanding, was not the first to try subcutaneous injections of thyroid extract in myxoedema.

Portuguese researchers had already done so. Murray had been aware of this and referred to their results in detail in his first BMJ paper. Indeed, he spoke about them when he originally presented his plan of treatment in February, , and it seems very likely they had informed his thinking. In it, they intimated their intention to try hypodermic injections of thyroid juice in another myxoedematous patient under their care.

And on 15th November, , three months before Murray presented his identical plan to the Northumberland and Durham Medical Society, and almost a year before his first paper in the BMJ , Antonio-Maria Bettencourt-Rodrigues reported beneficial effects from thyroid injections at a meeting of the Lisbon Society of Medical Sciences Bettencourt It has a disgusting taste, so attempts were made to disguise this in a sandwich or lightly fried with anchovy paste on toast or taken with current jelly.

How reminiscent of the Chinese, centuries earlier — steeping the gland in wine or taking it in jujubes sounds better! One early report is worth quoting in extenso because of the modernity of its language, the appreciation of the importance of controlled conditions, and the finding of a direct correlation between whole thyroid dose and pulse and temperature rise. First, it requires the most scrupulous care in the preparation of the extract, the demand for which is never likely to be so great as to enable it to be supplied when manufactured under the ideal conditions at less than an almost prohibitive price, and few medical men have the time to devote to its preparation themselves.

His monograph, titled Notes of lymphomatous in the thyroid gland struma lymphomatosa , was 30 pages long with five figures. This article was his only publication on the thyroid gland. He was only Soon after the monograph was published, Hashimoto went to Germany to further pursue his research. After a short time working at Kyusyu, Hashimoto returned to his hometown to work at the family practice.

Although it was a modest hospital — its grounds totaling less than one acre — Hashimoto had more patients that he could handle. At age 52, he was infected with typhoid fever on one of his house calls. Hashimoto died on Jan. Hashimoto identified lymphocytic thyroiditis by examining tissue samples and goiters of four middle-aged women.

The goiters caught his attention because unlike the colloid goiter, which was commonly found, these goiters had a preponderance of lymphoid cells. Two of the women also had hypothyroidism. He was confident that this was a newly discovered disease. He named it struma lymphomatosa and emphasized infiltration of lymphoid cells and formation of lymphoid follicles with a germinal center.

Neither of these had been reported previously. Hashimoto did thorough research for his monograph and defended his classification with numerous comparisons to existing diseases of the thyroid.