The Thyroid Gland: A Brief Historical Perspective

Ronald C. Hamdy, MD, FRCP, FACP

Disclosures

South Med J. 2002;95(5) 

Introduction

One of the first references to the thyroid gland in Western medicine is in 1656, when it was thought that the main function of the thyroid gland was to lubricate the trachea.[1] It was also believed to have a cosmetic function in women. Paintings going back to ancient Egypt often emphasize the size of the thyroid gland in women. In the early 1800s, the thyroid was thought to be a vascular shunt to divert the blood flow from the brain. In 1811, cancer of the thyroid was the first disease of the thyroid to be described.[2]

Rush[3] reported in 1820 that the thyroid gland is larger in women because it is "necessary to guard the female system from the influence of the more numerous causes of irritation and vexation of mind to which they are exposed than the male sex." Also in 1820, Hofrichter[4] stated: "If it were indeed true that the thyroid contains more blood at some times than at others, this effect would be visible to the naked eye; in this case women would certainly have long ceased to go about with bare necks, for husbands would have learned to recognize the swelling of this gland as a danger signal of threatening trouble from their better halves."

It is remarkable that the association between an enlarged thyroid gland and the characteristic clinical features of hyperthyroidism was not recognized until 1786, when Parry noted them,[5] but did not publish them until almost 40 years later, in 1825. This publication was followed by the classic descriptions of Graves[6] and von Basedow[7] in 1835 and 1840, respectively. Cretinism was described in 1871.[8] In 1874, Gull noted the clinical changes associated with atrophy of the thyroid gland,[9] and 4 years later, Ord coined the term myxedema because he felt that excessive mucus formation and deposition under the skin were responsible for the characteristic thickening of the subcutaneous tissue.[10]

In 1884, thyroidectomies were successfully performed for the treatment of toxic goiter.[11] In Europe, Theodore Kocher (1841-1917), a Swiss surgeon, performed over 2,000 thyroidectomies with a reported mortality rate of 5%, while in the United States, Charles Horace Mayo became an authority on thyroid surgery.[12] In 1891, Murray obtained a good clinical response in patients with hypothyroidism by injecting them with thyroid extracts.[13] Shortly afterward, Howitz, Mackenzie, and Fox independently found that thyroid extracts were effective when administered orally.[1]

The results of experimental thyroidectomies to elucidate the exact functions of the thyroid gland were misinterpreted because investigators also inadvertently removed the parathyroid glands.[1] Gley, in 1891, was able to differentiate the functions of the thyroid from those of the parathyroid glands.[14] In 1895, Magnus-Levy established the effect of the thyroid on the metabolic rate, the low metabolic rate in patients with hypothyroidism, and the fact that the administration of thyroid extracts to these patients and to individuals with normal thyroid function increased their oxygen consumption.[15] Hashimoto's disease was described in 1912.[16]

Edward Kendall, professor of physiological chemistry at the Mayo Clinic, isolated thyroxine in crystalline form in 1915, and established that the crystalline form had the same effects as the thyroid extract from which it was obtained.[17] A decade later, in 1926, Harington defined the chemical formula of thyroxine, and a year later synthesized the hormone.[18,19] Meticulous studies, however, revealed that the calorigenic effect of synthetic thyroxine was less than that of thyroid extracts. The enigma was not resolved until 25 years later, when triiodothyronine (T3) was isolated and synthesized in the early 1950s.[20,21]

The presence of thyroid-stimulating antibodies in Graves' disease was determined in 1956,[22] and that of thyroid antibodies in Hashimoto's disease in 1957.[23] Medullary thyroid carcinoma was recognized as a distinct entity in 1959.[24] The definition of the exact role of the thyroid gland in calcium metabolism had to wait for the discovery of calcitonin in 1961.

The first description of resistance to thyroid hormone was not made until 1967, when two young deaf-mute patients with features of juvenile hypothyroidism were found to have significantly elevated levels of circulating thyroid hormones.[25] Evidence that circulating T3 is derived largely from peripheral monodeiodination of thyroxine was not available until 1970.[26] Reports of cases of postpartum thyroiditis with hypothyroidism or thyrotoxicosis were not made until the mid-1970s.[27] The T3-binding receptors were identified in 1972,[28] and their homology to the viral oncogene erbA was recognized in 1986.[29,30] The fact that point mutations in the thyroid-hormone receptor accounted for hormone resistance was established in 1989 and 1990.[31]

The gene for the ß-subunit of thyroid-stimulating hormone (TSH) was cloned in 1988,[32] and that of TSH receptor in 1989.[33] It was then determined that both loss-of-function and gain-of-function mutations in that receptor accounted for specific types of hypothyroidism and hyperthyroidism.[34] The development of human recombinant TSH further enhanced the diagnosis and treatment of thyroid cancer.[35,36]

Thyroid dysfunction is not uncommon. The diagnosis of many of these conditions is relatively simple, and the prognosis is excellent if managed in a timely manner. Neonatal screening programs for hypothyroidism are now the standard of care, and have shown an incidence of 1 in 3,500 to 4,500 births.[37] A large number of tests, procedures, and algorithms are available to guide the clinician's efforts to diagnose thyroid dysfunction.[38,39] It is hoped that this Featured CME Topic on thyroid dysfunction/disease will be of help.

It gives me great pleasure to introduce Dr. Alan Peiris as the guest editor of this month's Special CME Feature on thyroid dysfunction.

Alan Peiris, MD, PhD, MRCP (UK), is Professor of Medicine, Department of Internal Medicine, East Tennessee State University; Staff Physician, Mountain Home Veterans Administration Medical Center; and Medical Director at the Diabetes Center, Johnson City Medical Center, Johnson City, Tenn.

The print version of this article was originally certified for CME credit. For accreditation details, contact the publisher. (link to publisher contact information: Southern Medical Assocation, 35 Lakeshore Dr, Birmingham Alabama 35209, telephone: (205)945-1840.

In publishing this section in Southern Medical Journal, the Southern Medical Association recognizes educational needs of physicians in all specialties, especially those in primary care, for current information regarding thyroid disorders. In this section, authors may have included discussions about drug interventions, whether Food and Drug Administration approved or unapproved. Therefore, it is incumbent on physicians reading this section to be aware of these factors in interpreting the contents and evaluating recommendations. Moreover, views of authors do not necessarily reflect the opinions of the Southern Medical Association. Every effort has been made to encourage the author to disclose any commercial relationships or personal benefit that may be associated with this section. If the author disclosed a relationship, it is indicated below. This disclosure in no way implies that the information presented is biased or of lesser quality, but allows participants to make informed judgments regarding program content.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....