Cachexia Strumipriva Research Articles

The discovery of thyroid replacement therapy. Part 3: A complete transformation

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. 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 and Medvei 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’, 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 in Part 2 of this paper. 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. 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 summarized Kocher’s explanation. He also observed initial tetanic manifestations postoperatively, no doubt due to unwitting removal or operative ischaemia of the parathyroid glands, whose separate identity and function were still unrecognized. 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. 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. Horsley went on to advocate a trial of grafting, specifically sheep’s, thyroid to treat myxoedema and cretinism. In June 1890, Bettencourt and Serrano of Lisbon did the experiment, inserting half of a sheep’s thyroid subcutaneously into the inframammary region on each side of one of their patients. They found that the graft worked immediately, before it could have vascularized, and concluded that its effect was likely to have been due to simple absorption of juice from the grafted gland, a conclusion of extraordinary DECLARATIONS

Theodor Kocher (1841-1917) Nobel Prize Centenary 2009

One hundred years ago, in 1909, Theodor Kocher was awarded the Nobel Prize in Physiology and Medicine for his work on the physiology, pathology, and surgery of the thyroid gland. In the late 19th century, the resection of the thyroid was feared because of its high mortality rate. Kocher's innovative techniques resulted in safe outcomes. His observations that radical resection of the thyroid results in 'cachexia strumipriva' contributed to the recognition that the thyroid is essential for normal growth, development and metabolism. He made many other seminal contributions to the field of surgery and medicine, and his expertise was internationally recognized. Kocher served as the chairman of surgery at the University of Bern in Switzerland, his alma mater, until his death in 1917.

Editorial comment

It is fitting that this commentary begins by citing the work of Emil Theodor Kocher. Fitting, not because Kocher was a surgeon and this is a surgical journal, but because he is known as much, if not more, for his contributions to pathophysiology than to surgery. Not that Kocher’s surgical achievements were trivial. He did receive the 1909 Noble Prize in Medicine and Physiology “for his work on the physiology, pathology and surgery of the thyroid gland” [ [1] Noble Prize Citation. The Noble Foundation. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1909/. Accessed October 11, 2007. Google Scholar ]. As noted by Kazi and Rhys-Evans [ [2] Kazi R. Rhys-Evans P. Theodor E. Kocher (1841–1917): Nobel surgeon of the last century. J Otorhinolaryngol. 2004; 3 (Available from: http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijorl/vol3n1/kocher.xml. Accessed October 11, 2007.) Google Scholar ], Kocher, along with Lister and Hallsted, “did more to improve operative mortality than any other surgeons of their time.” Nonetheless Kocher’s legacy is to be the first to definitively associate the removal of the thyroid gland with a syndrome identical to acquired myxedema. Kocher’s 1909 Nobel Prize lecture [ [3] Kocher TE. Noble prize lecture. The Noble Foundation. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1909/kocher-lecture.pdf. Accessed October 11, 2007. Google Scholar ] is a classic description of severe hypothyroidism. He called the disorder that occurred after complete thyroidectomy “cachexia strumipriva.” The name is paradoxical, because Kocher used “fat” or “fatty” ≥20 times when describing patients with cachexia strumipriva. Influence of obesity and surgical weight loss on thyroid hormone levelsSurgery for Obesity and Related DiseasesVol. 3Issue 6PreviewThe pathophysiologic relationship between morbid obesity and thyroid hormones is not well understood. The goal of this study was to evaluate the influence of obesity and weight reduction after bariatric surgery on thyroid hormone levels. Full-Text PDF

The emergence of endocrinology

Endocrinology was recognized as a new branch of biological science mainly as a result of events which took place between about 1890 and 1905, but ideas and discoveries dating from antiquity contributed to it also. Experiments supporting the concept of internal secretions by the testicles were described by Aristotle (4th c. B.C.) and by Hunter (18th c.) and Berthold (19th c.). In 1855 Bernard described glucose as an internal secretion of the liver and Addison reported the effects of adrenal disease in man. Adrenalectomy was fatal in animals. Goitre was known in antiquity and cretinism had been described by Paracelsus. Myxoedema was reported by Gull in 1873, and Kocher described cachexia strumipriva in 1883. In 1888 cretinism, myxoedema and cachexia strumipriva were attributed to thyroid insufficiency. In the 1890s Gley found that tetany after thyroidectomy was due to removal of the parathyroids. In 1884 Rehn proposed that toxic goitre was due to thyroid excess. In 1889 Brown-Séquard claimed that injections of testicular extract rejuvenated the elderly, and in 1893 he introduced organotherapy. In 1891 Murray treated myxoedema successfully with thyroid extract. In 1893 Oliver and Schäfer found that an adrenal extract raised the blood pressure, and soon adrenaline was extracted from the adrenal medulla. Adrenocortical deficiency was proposed as the cause of Addison's disease, and in 1896 Osler prepared an extract which relieved one patient. Diabetes mellitus, described in the first century, was usually fatal. Thirst and polyuria followed experimental pancreatectomy, and pancreatic lesions were found in some human diabetics. In the 19th century workers in France and Germany found that diabetes resulted from absence of an internal secretion by the islets of Langerhans and, in 1893, Laguesse described the function of the islets as "endocrine". In 1895 Beatson treated advanced breast cancer successfully by oöphorectomy. In 1895 Schäfer commended study of the internal secretions to physiologists. In 1902 Bayliss and Starling discovered secretin, a chemical messenger secreted by the intestinal mucosa. In 1905 Starling proposed the name "hormone" for this class of internal secretions. By then endocrinology had been launched as a new branch of science. The crucial events which led to the recognition of endocrinology as a new branch of biological science took place between about 1890 and 1905. Many ideas and discoveries dating from antiquity and apparently unrelated at first had, however, contributed to it. Most of the organs and tissues that form the endocrine system were recognized over 100 years ago.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathologic changes in adult myxedema: survey of 10 necropsies.

THE pathology of adult myxedema as recorded in the literature is based upon the findings of relatively few autopsies. The opportunity has seldom been presented to study at necropsy either untreated or inadequately treated cases. The present study was initiated because of the availability of 10 such cases at the Wayne County General Hospital in a 15-year period. Typical clinical features of the myxedematous state were present in all. The first clinical recognition of myxedema has been attributed to Sir William Gull (1) in 1873. The first autopsy in a case of myxedema was reported in 1877 by Sir William Ord (2). The term “myxedema” was proposed by Ord, because the chief feature appeared to be a mucin-yielding edema involving chiefly the connective tissue. Subsequent authors described the similarity of spontaneous myxedema, cachexia strumipriva (post-thyroidectomy myxedema) and cretinism. Loss of thyroid function later became recognized as the common denominator of these states. The Report of a Committee of the Clinical Society of London (3) published in 1888 included the data on 20 autopsies of cases of myxedema. This publication is the classic source of reference for the pathology of myxedema. Since that time, 10 autopsies have been reported by Bastenie (4), and 9 by Means (5). A few single case reports have appeared (6–14). Two cases were studied by histochemical methods (6, 7).

CHILDHOOD MYXEDEMA OBSERVATIONS THROUGH INFANCY, CHILDHOOD AND EARLY ADULT LIFE

The cerm cretinism implies a congenital disease characterized by physical and mental retardation due to an absence or deficiency of the normal thyroid secretion. The degree of physical and mental infirmity is dependent entirely upon the supply of the thyroid gland product. The disease was described by Paracelsus1 early in the 17th century. He was the first to point out the connection between cretinism of the offspring and goitre of the parents. Wolfgang Hoefer,2 an Austrian physician, published in 1675 his observations on cretinism in the Styrian Mountains. Until the middle of the 19th century, however, the disease was only imperfectly differentiated. Fagge described the sporadic form in 1871 and, in 1873 Gull emphasized the similarity of the disease to adult myxedema. Some years later, following the experiments conducted by Victor Horsley, a Commission appointed by the Clinical Society of London reported that myxedema and cachexia strumipriva were identical, that sporadic cretinism was myxedema occurring...

TOTAL ABLATION OF THE THYROID

ABSTRACT To the Editor:— Permit me to express my delight in Dr. Christian's communication concerning total ablation of the thyroid (The Journal, January 5, p. 64). Doubtless, this letter create a stop movement in regard to this operation. Dr. Christian's authoritative voice must have a sobering effect on the enthusiasts.It seems that my paper Is Total Thyroidectomy Rational as a Method of Treatment? (Canad. M. A. J., November 1934), pursuing the same purpose, has appeared timely.I differ with Dr. Christian on his assumption that the disturbing factors of cachexia strumipriva will limit the applicability and the effectiveness of this new method of treating cardiac disease to a relatively small group of patients. When one speaks of selection of cases in a general way, it does not mean much. As I pointed out in my paper, so far there is no scientific way of defining such a group of

THE OCCURRENCE OF PARATHYROIDS ON THE ANTERIOR SURFACE OF THE THYROID GLAND

One of the great problems in thyroid surgery has always been the avoidance of injury to the parathyroids. Early surgeons soon found that total thyroidectomy frequently led to fatal tetany. Such postoperative tetany was first described in 1881 by Weiss in Billroth's clinic. Tetany at first was confused with the symptoms of hypothyroidism following total thyroidectomy, and the two were regarded as different expressions of the same condition. Attempts to solve this problem by animal experimentation led at first to contradictory and confusing results. Schiff, in 1884, showed that total thyroidectomy in cats and dogs led almost invariably to tetany and death. On the other hand, total thyroidectomy in rabbits and other herbivorararely produced tetany but was followed by the development of cachexia strumipriva. For a time an explanation was not offered for these diverse results. In 1891, Gley published a series of papers describing the effect of experimental total

A CASE OF MYXEDEMATOUS PSYCHOSIS

INTRODUCTION In 1873, Gull described five cases of a peculiar disease under the title On a Cretinoid State, Supervening in Adult Women, and explained the similarity to sporadic cretinism, which was described by Hilton Fagge. In 1877, Orth reported five similar cases, and noticed especially the condition of the skin, in which he found an excess of mucin. He, accordingly, named the disease myxedema. He found also, in a case that came to necropsy, atrophy of the thyroid gland, which was previously noticed by Curling in a case of sporadic cretinism. An exact understanding of this condition, however, is dated from the time when Reverdin and Kocher recognized cachexia strumipriva, and when the same condition was brought out experimentally by removing the thyroid. Semon is the first one who claimed definitely that myxedema, cachexia strumipriva, sporadic and endemic cretinism, are in the same disease group, and are characterized by the failure

THE BASAL METABOLISM IN HYPOTHYROIDISM

In connection with an extended study of the basal metabolism in exophthalmic goiter, which has been in progress since 1914 and on which a preliminary report was published in the spring of 1917, 1 opportunities arose to study several cases of hypothyroidism. The present series comprises observations on six patients and includes practically every condition clinically associated with hypothyroidism, namely, myxedema, cretinism, cachexia strumipriva, and cancer of the thyroid gland. The effect of thyroid administration on the basal metabolism has been studied over a long period of time in the case of a cretin and in one patient with myxedema; also in a patient with cachexia strumipriva, before, during and after the appearance of hypothyroid symptoms. The methods employed have been fully described in earlier papers, 2 and consisted briefly in the determination of the gas exchange of the recumbent subject while in the postabsorptive condition by means of the small Benedict

Transplantation of the thyroid and parathyroid glands into various organs and tissues

M.G. and M.G. The question of a thyroid gland transplant arose soon after the discoveries of Ord (1880), replacing the absence of a thyroid gland in myxedemic patients at autopsy, a neuropathologist Weiss (1880), who indicated that after total extirpation of the thyroid gland, convulsions appear, called by him tetany, Reverdin (1882) and Kocher (1883), who firmly established that complete removal of the thyroid gland leads to sharp changes in both the mental and the physical organism. He called this disease Renegdin myxedema postoperatorie, and Kocher cachexia strumipriva. They also pointed out that cretinism depends on the absence of a thyroid gland.

THE HYPOPHYSIS CEREBRI CLINICAL ASPECTS OF HYPERPITUITARISM AND OF HYPOPITUITARISM

Few chapters in the history of medicine tell a more creditable story than that which relates our progress toward a better understanding of the thyroid and parathyroid glands. A combination of clinical, experimental and surgical experiences during the past twenty years has served to unveil many of the mysteries which formerly surrounded the function of these structures, whose normal activities prove to be so essential to the maintenance of physiologic equilibrium. Myxedema, cretinisn, exophthalmic goiter, surgical myxedema (cachexia strumipriva) and tetany have come to be understandable maladies, definitely amenable to rational methods of treatment—and organotherapy, when glandular activity is subnormal, or partial surgical removal to correct functional over-activity, is a triumph of the experimental method in medicine, at the hands of Horsley, Kocher, Halsted, Gley, Vassale and Generale, MacCallum and a host of others. Not the least memorable incident of the entire story was the recognition, first by the Italian

A REPORT OF TWO CASES OF MYXEDEMA WITH REMARKS ON AN ANOMALOUS TYPE.

Myxedema is a general disorder of metabolism, dependent upon diminished or lost thyroid function. Among various morbid processes affecting the gland and which have been observed to give rise to myxedema are the following: atrophy, atrophy associated with calcareous degeneration, atrophy with enlargement of the pituitary body, actinomycosis, syphilitic degeneration of the organ, and the presence of neoplasms. It is to be recollected, however, that disease of the thyroid is not followed by cachexia strumipriva, provided even a small portion of the gland remains functional. The truth of this dictum was shown by the postmortem findings in the case contributed by Sieveking, 1 in which sarcoma had invaded the thyroid. This fact is also fully confirmed by the results of experimental extirpation of the thyroid in animals; total removal of the gland is regularly followed by myxedema (except functional accessory thyroids be present), while if even one-tenth of it is

Note on a Possible Means of Arresting the Progress of Myx dema, Cachexia Strumipriva, and Allied Diseases

Note on a Possible Means of Arresting the Progress of Myx dema, Cachexia Strumipriva, and Allied Diseases