Exophthalmic Goiter Research Articles

Iodine in the Therapy of Graves' Disease: A Century After Henry S. Plummer.

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Robert James Graves (1796-1853), The Irish School of Medicine, and Graves' Disease.

Robert James Graves, a native of Dublin, Ireland, was a physician rather than a surgeon; however, his name is well-known to all general and endocrine surgeons. He was born in Dublin, Ireland, and received his BA and MB degrees from Trinity College (formerly, Dublin University). After further studies throughout Europe, he received his "licentiate" from the Royal College of Physicians of Ireland in 1820 and was appointed Physician to the Meath Hospital in Dublin in 1821. Graves received many honors during his career including the following: King's Professor in the Institute of Medicine (1824); President of the Royal College of Physicians of Ireland (1843-44); and a Fellow of the Royal Society (FRS, 1849). In addition, he was a prominent member of the Irish School of Medicine which also included William Stokes (1804-1878) (Cheyne-Stokes breathing, Stokes-Adams attacks) and Dominic Corrigan (1802-1880) (Corrigan's pulse). Graves' description of exophthalmic goiter was in 1835, some 49 years after that of Caleb Hillier Parry (1755-1822) of Bath, England; however, Bath's report was not published till 1825 or 3 years after his death. Graves' disease is still the eponym applied to this form of hyperthyroidism in the United States.

Parry and Parry’s Disease

THE MANIn 1778 the Charter of Incorporation was granted by George Ill to the presidents and associates of the Medical Society of Edinburgh, confirming Robert Freer, James Melliar, Andrew Wardrop and Caleb Parry in their office as Presidents. Caleb Parry, whose name appears here, became a highly esteemed practitioner at Bath and like Heberden acquired a lifelong habit of taking notes. He described the first recorded case of facial hemiatrophy in 1814, of congenital idiopathic dilatation of the colon in 1825, and in 1786 he left an account of exophthalmic goitre so complete and original that it more justly entitles him to the honour of its discovery than either Flajani in 1800, Graves in 1835, or von Basedow in 1840.Caleb Hillier Parry was born on October 21st 1755, at Cirencester, near Gloucester, where his father Joshua was a non-conformist minister. His early education was at the grammar school in Cirencester, where he met Edward Jenner: and the latter dedicated his epochal Inquiry in the Causes and Effects of the Variolae Vaccinae" to "C. H. Parry, M.D., at Bath, My Dear Friend." At the age of 18, Parry became a student of medicine at Edinburgh, in the days when William Cullen dominated the scene. Parry spent two of his undergraduate years in London, but when he returned in 1777, he was elected a president of the Medical Society of Edinburgh. And it was during his term of office that the Royal Charter was achieved, an honour which remains unique for an undergraduate society.

Professor Thoma Ionescu (1860-1926) founder of the modern Romanian school of surgery.

Professor Thoma Ionescu (1860-1926) founder of the modern Romanian school of surgery.

A tale of two celts.

The eponym "Graves' disease" is usually applied to the condition of immunogenic hyperthyroidism, in no small part due to the promotion and influence of the French physician Armand Trousseau who wrote in 1862, "Du Goître Exophthalmique, ou Maladie de Graves." However, the distinguished Bath physician Caleb Hillier Parry, a friend of both Edward Jenner and John Hunter, first described the clinical picture of thyrotoxicosis associated with exophthalmos and cardiac dysfunction in a paper published posthumously in 1825, some 10 years before Robert Graves' initial report. Graves was unaware of Parry's earlier description and considered that the thyroid condition in the four female cases that he studied might be secondary to functional cardiac disorders and palpitations. The many outstanding contributions to medicine and science of Parry and Graves, two truly remarkable nineteenth century Celtic physicians, are compared and discussed. A case is made for considering the renaming of immunogenic hyperthyroidism as Parry's disease, a proposal made by Sir William Osler, who was the first to recognise Parry's claim for priority for the recognition of exophthalmic goitre.

History of sympathetic surgery.

The first reported operation on the upper sympathetic system was performed by Alexander in 1889. The initial indications (epilepsy, exophthalmic goiter, idiocy, glaucoma) are obsolete. For some subsequent indications (angina pectoris, vasospastic disorders, and painful conditions) sympathectomy has still a limited application. The main indications today are hyperhidrosis (since 1920) and blushing. Renewed attempts to perform the operation for psychological conditions have been reported. The technique of sympathectomy has been modified over the century, with a trend to minimize the extent of surgery: from open to endoscopic approaches; from resection of ganglia to thermoablation, thermotransection, and clipping. The sequelae of the operation (mainly compensatory hyperhidrosis) present a major problem in a small percentage of operated patients. Techniques of reversal (by nerve grafting and unclipping) have been proposed. Meticulous follow-up studies are required to evaluate the merits of these techniques. Improved knowledge of the functions and interrelations of the autonomic nervous system is required to understand the mechanism of these sequelae and learn how to avoid or treat them.

Thomas Peel Dunhill: pioneer thyroid surgeon.

Thomas Peel Dunhill, a name by now almost completely forgotten in his native Australia, was born in 1876 near Kerang in the State of Victoria. Although he qualified as a pharmacist in 1898, Dunhill had already decided to study medicine and graduated in 1903 from the Clinical School of the Melbourne Hospital. He was regarded as an outstanding student. In 1905 Dunhill was invited to join the Senior Medical Staff at St Vincent's Hospital by Mother Berchmans Daly, the then Mother Rectress. In 1906 Dunhill was awarded the MD and in 1907 he performed his first thyroid lobectomy under local anaesthesia for toxic goitre. As early as 1908, Dunhill understood the essentials for successful surgery in thyrotoxicosis--enough thyroid had to be removed to cure the condition. To this end, he advocated a bilateral attack on the thyroid and advocated thyroidectomy in the thyrocardiac patient. He did this before Theodor Kocher, Charles Mayo, William Halsted or George Crile. In 1911 Dunhill visited the USA and England and communicated his results to the thyroid surgeons in both countries (230 cases of exophthalmic goitre operated on with four deaths). The English could not, or would not, believe his results as the mortality of surgery for exophthalmic goitre at St Thomas's Hospital, London in 1910 was 33%. Dunhill served with distinction in the Great War and his abilities favourably impressed George Gask, who was to become the Professor of Surgery at St Bartholomew's Hospital, London. Gask eventually invited Dunhill to join his Unit and Dunhill left St Vincent's Hospital in 1920. Between 1920 and Dunhill's retirement at the age of 60 in 1935, he became the outstanding general surgeon at St Bartholomew's Hospital. Dunhill and Cecil Joll, were regarded as the leading thyroid surgeons in the UK. Knighted in 1933, Dunhill was appointed surgeon to the Royal Household, serving four British monarchs. In addition to his brilliant surgical career, Dunhill maintained a love for the land. He was an expert fly fisherman. Dunhill retired from surgical practice in 1949 and died at the age of 80 in 1957 at his London home. Many eulogies were delivered, especially by Sir James Paterson Ross and Sir Geoffrey Keynes, his former pupils. Dunhill's exploits as a thyroid surgeon in the development of a safe and effective treatment for thyrotoxicosis and in operating on the thyrocardiac enables this modest, courteous and loyal Australian to be included with Theodor Kocher, Charles Mayo, William Halsted and George Crile in the pantheon of pioneer thyroid surgeons.

Ophthalmic Eponyms From the Mayo Clinic

Ophthalmic Eponyms From the Mayo Clinic

OPP 4001 The Ultrasound Image of tissues inside orbita of the exophthalmic goiter

OPP 4001 The Ultrasound Image of tissues inside orbita of the exophthalmic goiter

Surgery for exophthalmic goitre in Australia, 1907

Thomas Dunhill 1876-1957, Australian born surgeon (Melbourne 1907-1914 and London 1920-1941) performed partial thyroidectomy for exophthalmic goitre using Th. Kocher's method of local anaesthesia on seven consecutive severely toxic patients in 1907 with a successful outcome in all seven. A brief outline of the life and achievements of Thomas Dunhill is appended.

An endocrinologic approach to a medicine disease.6.An advance of endocrine therapy.4.Medical treatment of exophthalmic goiter and chronic thyroiditis.

An endocrinologic approach to a medicine disease.6.An advance of endocrine therapy.4.Medical treatment of exophthalmic goiter and chronic thyroiditis.

The pathogenesis of Graves' disease and Hashimoto's thyroiditis.

It is about 150 years since the publication of the original descriptions of the disorder now termed Graves' disease (toxic diffuse goitre, exophthalmic goitre, Von Basedow's disease) (Parry, 1825; Graves, 1835; Von Basedow, 1840) and over 60 years since Hashimoto's thyroiditis (struma lymphomatosa) was first described (Hashimoto, 1912). However, until the past 15 years, there was little understanding of possible pathogenic mechanisms in these disorders. At the present time, notwithstanding several persistent points of contention and gaps in our knowledge, it appears that Grave's disease and Hashimoto's thyroiditis are most probably closely related primary immunological disorders.

Studies of exophthalmic goiter—VI. Morbidity and mortality in The Netherlands, Switzerland, Norway and Sweden

Studies of exophthalmic goiter—VI. Morbidity and mortality in The Netherlands, Switzerland, Norway and Sweden

THE NONOPERATIVE TREATMENT OF SURGICAL CONDITIONS IN CHILDREN

As the derivation of the word surgeon from its Greek roots indicates–however much to the dismay of today's cerebral practitioners of the craft–the surgeon is a manual worker. The operative act is so central to surgery and to the life of the surgeon that it has come almost to be equated with surgery and, although I decry it, the word surgery frequently replaces the word operation. The fact is, nevertheless, that operation, being the application of a mechanical technique to disease, is properly employed in the solution of mechanical problems. It is true that, in the past and in the present, some of the most brilliant achievements of surgery have been in the cure or correction of dangerous diseases certainly not mechanically caused, for which there was no nonoperative treatment. This was certainly true until recently for exophthalmic goiter and for that matter, while all would agree that ultimately some nonoperative method will prevail, there are many patients still–and children specifically–in whom I, among others, think hyperthyroidism is still best treated by operation. Nothing else is quite so successful as operation in the treatment of duodenal ulcer or most forms of cancer, yet all of us will accept the fact that in the end, since these are, except in their late stages, not mechanical diseases, specific and nonoperative treatments will be devised which will aim at directly reversing the causative mechanisms. It is precisely in this sort of a search that surgeons are constantly engaged. True enough, as surgeons, we believe that operations are unequivocally good for people.

Pretibial Myxedema and Nonthyrotoxic Thyroid Disease

Four patients had a distinct variant of exophthalmic goiter (Graves' disease) characterized by pretibial myxedema and nonthyrotoxic thyroid disease. A review of literature revealed 19 cases with similar findings. All were adults and two thirds were women. Exophthalmos and acropachy were present. One third were hypothyroid and the rest were euthyroid at the time the pretibial myxedema, exophthalmos, and acropachy developed. None had ever had signs or symptoms of hyperthyroidism. Long-acting thyroid stimulator (LATS) was present in all cases in which it was sought. Even though a hypermetabolic state was not present in these patients, the occurrence of dermopathy, opthalmopathy, and LATS furnished three of the four components of Graves' disease. Present evidence suggests that the thyroid disease in the patients, whether it be primary hypothyroidism or thyroiditis, is etiologically closely related to the diffuse toxic goiter of Graves' disease.

Thyroid Suppressibility and Long-Acting Thyroid Stimulator in Thyrotoxicosis

We examined the relationship of thyroid suppressibility to long-acting thyroid stimulator (LATS) levels in 14 thyrotoxic patients on long-term treatment with antithyroid drugs (mean duration of treatment, 11.9 months). Twenty-minute¹³¹I thyroid uptake and LATS levels before and after liothyronine sodium administration were measured before and at one- to three-month intervals during antithyroid drug treatment. Eight patients developed thyroid suppressibility during therapy; of these, three had detectable LATS levels prior to treatment and there was no decline in LATS levels with treatment and restoration of suppressibility. Of six patients whose thyroid uptake remained nonsuppressible during long-term treatment (mean, 11.1 months), LATS was undetectable in both the serum and concentrated immunoglobulin G (IgG) fraction of four. These studies suggest that in exophthalmic goiter (Graves' disease), thyroid nonsuppressibility may reflect an intrinsic thyroid abnormality rather than the presence of circulating LATS.

Hyperpigmentation in Thyrotoxicosis

To the Editor:— The signs of thyrotoxicosis have been memorized by medical students for decades; however, changes in skin pigmentation seem to be frequently overlooked. In our experience, alterations in pigmentation have been a useful and interesting physical finding. Increases in pigmentation are often seen in exophthalmic goiter (Graves' disease) and may be either diffuse or chloasmal in nature. These skin changes can be seen in either exposed or unexposed areas but are rarely seen on the buccal mucosa, nipples, or genitals. The cause of the pigmentary changes is still speculative; however, it is known that the pigment is melanin. Tyrosine is an amino acid common to both melanin and thyroxine; and it is well established that patients with thyrotoxicosis have tyrosine intolerance with elevated serum tyrosine levels. 1 Many theories have been advanced to explain the phenomenon of hyperpigmentation such as elevated levels of adrenocorticotropic hormone (ACTH) or tyrosine,

Endocrine disease and anaesthesia. A review of anaesthetic management in pituitary, adrenal and thyroid diseases.

Endocrine disease and anaesthesia. A review of anaesthetic management in pituitary, adrenal and thyroid diseases.

Studies of exophthalmic goitre—V: The course of mortality in Canada, 1921–1965 and its significance

The course of mortality from exophthalmic goitre in 6 provinces of Canada has been reviewed. There was a marked increase in each province in 1924 or shortly thereafter. This continued for twenty or thirty years and was accompanied by a steady shift to greater and greater age of death. The order of mortality in cohorts of 5 or 10 yr difference in age continued the same from the period of the first marked increase in mortality for 30 or 40 yr or until the age of 70–79. The ages at which the women died are consistent with the view that nearly all had acquired the disease between 1924 and 1929, or earlier. It is believed that these facts support the view expressed by Meulengracht in 1949 that exophthalmic goitre might be caused by a “specific infectious agent of unknown nature” [13]. This agent might have been brought to Canada by military personnel in returning from Europe in 1919 or it might be related to the pandemic of influenza in 1917–1918, or it might not be related to either occurrence. It is proposed to obtain statistics from countries not directly involved in the war of 1914–1918 in order to test the first of these hypotheses.

Cause of increased plasma concentration of iodotyrosines in Graves' disease.

SUMMARY In most cases of Graves' disease the level of iodotyrosines in the plasma is above normal. With a view to ascertaining the cause of this phenomenon simultaneous determinations were made of the iodotyrosine and long-acting thyroid stimulator (LATS) levels in the plasma and of the titre of thyroid antibodies. It was found that high plasma concentrations of iodotyrosines in exophthalmic goitre were mainly due to auto-immune thyroiditis, but that LATS may also contribute to the phenomenon.