Historical Aspects

The striking clinical malady of exophthalmic goiter, with its distinctive protruding eyes, tachycardia, nervousness, and enlarged thyroid, has been known for more than 150 years. Thyrotoxicosis was first described in 1786 by Parry, a physician in England, but was not reported until after his death in 1825. It was also noted by von Basedow and a handful of others.1 To this day, on the continent of Europe, it is known as Basedow's disease. In the English-speaking world it is named for Robert James Graves because of a lucid monograph he wrote on the subject. As with many medical eponyms, however, he was not the first to describe the condition.2 It was during the next century that Dr. Henry Plummer first described toxic nodular goiter, which came to be known as Plummer's disease. Both of these physicians made everlasting contributions to the field of endocrinology.

Robert James Graves (1796-1853)

Robert James Graves (Fig. 7-1) was a descendant of a colonel in Cromwell's army. He was described as a brilliant student, highly cultured, handsome, and charming. In Dublin, Ireland, where he was born and trained in medicine, he received the highest educational award, the Golden Medal, for organizing medical education.3 He introduced "clinical teaching," which has evolved into bedside teaching today, encouraging students to actually examine patients, present them to the professor, and write clinical histories—a novel idea at the time.14 He insisted that his students attend autopsies to correlate findings there with the patient's state prior to death.3 This was met with great opposition by the then current tradition that students have extensive book knowledge and little practical experience.1

Dr. Graves' clinical lectures were the talk of the town, where he introduced many novel concepts including the pinhole pupil after pontine hemorrhage, timing the pulse by watch, and abandoning the practice of bleeding and starving patients with pyrexia.1'3 5 His book, Clinical Lectures on the Practice of Medicine, is regarded as a medical masterpiece.4 He was a pioneer in proper nutritional therapy for the sick and requested that his epitaph read: "He Fed the Fevers."1 In 1835, he published his famous monograph, "A Newly Observed Affection of the Thyroid Gland in Females."

Three cases of violent and long continued palpitations ... in each of which the same peculiarity presented itself... (with) enlargement of the thyroid gland... the eyes assumed a singular appearance for the eye balls were apparently enlarged, so that when she slept or tried to shut her eyes, the lids were incapable of closing. When the eyes were open, the white sclerotic could be seen, to a breadth of several lines, all around the cornea. ...The enlargement of the thyroid ... seems ... essentially different from goiter, in not attaining a size at all equal to that observed in the latter disease.6

Henry Plummer (1874-1937)

The death rate in the United States from hyperthyroidism around 1908 was 25%. The extremely high mortality in goiter surgery was underscored by Samuel Gross, who stated the following:

Can the thyroid gland, when in a state of enlargement, be removed with a reasonable hope of saving the patient? Experience emphatically answers no ... no sensible man will. ... Every stroke of a knife will be followed by a torrent of blood, and lucky will it be for him if his victim lives long enough to enable him to finish his horrid butchery.7

By 1918, Charlie Mayo had performed his 5000th thyroidectomy. He had a personal death rate of 3%, a number touched by no one on the continent, in part due to Dr. Henry Plummer (Fig. 7-2).2 From Minnesota, Dr. Plummer was first consultant to Drs. Will and Charlie Mayo.7 He developed a

FIGURE 7-1. Dr. Robert James Graves. (From Jay V. Dr. Robert James Graves. Arch Pathol Lab Med 1999; 123:284.)

special interest in the thyroid gland through his neighbor, Mr. Strain, the first goiter patient to be operated on by the Mayo brothers.2 In 1913, Dr. Plummer first distinguished toxic adenomatous goiter from exophthalmic goiter. Until the availability of radioactive iodine, which made scintigraphy possible in the mid-1940s, this disease was an entirely

FIGURE 7-2. Dr. Henry Plummer. (From Clapesattle H. The Doctors Mayo. Rochester, MN, Mayo Foundation for Medical Education and Research, 1990.)

clinical one. He was a pioneer in the development of radiographic diagnosis and therapy.8 His other achievements include designing the tube system for transporting patient records and the complex medical record system still in use at Mayo today.9 He later developed the first intercom system and irrigation system in the United States.2

By 1922, Dr. Plummer was elaborating a theory about goiter disease. He led weekly "goiter lunches" to share his expertise.2 When thyroxine (T4) proved to be 65% iodine, he posed the hypothesis that the extra toxic substance he postulated to be the cause of crises in exophthalmic goiter was a noniodinated molecule of T4, a compound discovered at the Mayo Clinic by Dr. Edward Kendall.29 He reasoned that a (then unknown) stimulus causes the thyroid gland to work too fast and if not enough iodine was readily available in the blood, the gland would turn out a half-finished product, a molecule of T4 with the essential iodine missing. At once, he believed that iodine should be tried on his goiter service at St. Mary's Hospital, and the results were miraculous.2

Against all tradition, every professor of medicine, every textbook ... following his own understanding of the function of the thyroid, [he] saved the life of a woman by injecting 5.0 mg of thyroxine intravenously.8

At the Association of American Physicians in May 1923, he presented his results that administration of iodine preoper-atively and postoperatively would prevent the crises that caused death after symptomatic treatment of exophthalmic goiter. He found that iodine in both nonoperative cases and as preoperative treatment significantly reduced mortality.7 His work turned the most treacherous operation known to surgery into one of the safest in the hands of any competent operator. It was hailed as one of medicine's greatest gifts to surgery and the Germans coined the fitting word for it—Plummerung?

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