The history of the thyroid dates from 2697 BCE when the “Yellow Emperor” Hung Ti described the use of seaweed to treat goiter. The English name “thyroid” was coined by Thomas Wharton in 1656 from the Greek word for a shield. Bernard Courtois discovered iodine in 1811 when he noted a residual purplish ash while burning seaweed. Robert Graves is known for his classic 1835 report of “palpitations, goiter, and exophthalmos” in three women, but Caleb Parry observed the same clinical features in 1786. The clinical syndrome we now recognize as hypothyroidism was characterized as “myxoedema” in 1878 by William Ord at St. Thomas Hospital. In 1891, George Murray reported that injection of thyroid extract from sheep led to improvement in symptoms in a woman with myxedema. Thomas Kocher, who reported that patients with goiter who underwent complete thyroidectomy developed cachexia strumipriva, was awarded the Nobel Prize in Physiology and Medicine in 1909. Edward Kendall discovered “thyroxin” on Christmas day in 1914. Studies by David Marine that iodine treatment prevented endemic goiter led to salt iodination, which has largely eradicated endemic cretinism. In 1973, Jean Dussault reported detection of congenital hypothyroidism by screening newborn populations.

According to Chinese legend, in 2697 BCE, the “Yellow Emperor” Hung Ti compiled “The Yellow Emperor’s Classic of International Medicine,” a pharmacopeia consisting of 162 chapters in 18 volumes [1], including the use of seaweed, and in 1596, Li Shizen’s pharmacopeia included iodine as a treatment for goiter [2]. Iodine-deficient, endemic goiter was well-known in the ancient world, is seen in the ancient art of many countries, and a connection between oceanic plants and goiter has been known since antiquity in both Western and Chinese cultures. In 1811, Bernard Courtois, a French chemist involved in the manufacture of saltpeter (potassium nitrate, which is essential for gunpowder), noticed violet fumes while washing seaweed ash (sodium carbonate) with sulfuric acid. When encountering cold surfaces, the fumes crystalized as purple crystals: the discovery of iodine [3]. Courtois’ work was confirmed, imprecisely described, but extended by Joseph Gay-Lussac, who recognized he was dealing with a newly discovered element; he named it iodine, from the Greek Ιώδης “violet-colored” [4].

The term “thyroid” apparently derives from the classic Greek word “thyra” (θύρα), meaning “door” or from the word thyreos (θυρεός), referring to a stone placed against a door to keep it closed, or a large oblong shield shaped like a door [5]. The thyroid cartilage was described by Galen and others in antiquity [5], and the gland itself was described by Leonardo Da Vinci, Vesalius, Realdus Columbus, Michelangelo, and Bartolomeo Eustachio (who also described the adrenals) during the Renaissance [6]. The English name “thyroid,” based on the Greek (above), was apparently coined by Thomas Wharton (also known for Wharton’s jelly) in his “Adenographia” (1656) [7].

Jean-Francois Coindet (1774–1834) reported the efficacy of treating goiter with various iodine preparations (rather than preparations of seaweed or sponges), settling on a tincture (alcoholic solution) whose successful use he detailed in 1821 [8]. It was long known that goiter was more common among residents of the mountains than those living by the sea. The Roman satirical poet Juvenal (2nd century AD) said “Quis tumidum guttur miratur in Alpibus?” [“Who is surprised to see a swollen goitre in the Alps?”] (Juvenal, xiii. 162) [9]. The presence of a goiter, physical deformities, and intellectual disability in individuals in the Alpine regions of Europe provided the first connection of goiter to the function of the thyroid. The term cretinism was first used in the medical literature in 1754 to describe those afflicted, apparently derived from the Latin “Christianus,” as afflicted individuals were thought unable to commit a sin [10] (Fig. 1).

Fig. 1.

Representation of two people suffering from congenital iodine deficiency syndrome, also known as cretinism. (Source: Wikimedia Commons. Copper engraving by Franz Sartori (1819) Oesterreichs Tibur, oder Natur-und Kunstgemählde aus dem oesterreichischen Kaiserthume, Vienna: A. Doll OCLC: 78745948.).

Fig. 1.

Representation of two people suffering from congenital iodine deficiency syndrome, also known as cretinism. (Source: Wikimedia Commons. Copper engraving by Franz Sartori (1819) Oesterreichs Tibur, oder Natur-und Kunstgemählde aus dem oesterreichischen Kaiserthume, Vienna: A. Doll OCLC: 78745948.).

Close modal

The clinical syndrome we now recognize as hypothyroidism was characterized as “myxoedema” in 1878 by William Ord, a physician at St. Thomas’ Hospital [11] (Fig. 2). The concept of an organ (gland) secreting a chemical substance (hormone) is attributed to the French physician Brown-Séquard, who in 1889 injected himself with testicular extracts from several animals and reported improvement in strength and stamina [12]. With recognition of this principle, in 1891, George Murray, a British physician, reported that injection of thyroid extract from sheep led to improvement in symptoms in a woman with myxedema [13]. Orally administered fresh sheep thyroid gland was first reported by Mackenzie in 1892 [14] Soon thereafter, another case with “before and after” pictures was reported by Shapland (Fig. 3) [15]. Oral thyroid was cheaper, easier to use, and lacked the attendant risk of “tonic spasms” (Mackenzie’s term) apparently from co-injecting PTH, which would have been contained in Murray’s thyroid extracts.

Fig. 2.

William Ord publishes first image of myxedema [11]. Patient who developed physical signs of hypothyroidism over a period of 11 years. (Drawings from: Lindholm J, Laurberg P. Hypothyroidism and thyroid substitution: Historical aspects. J Thyroid Res. 2011;2011:809341).

Fig. 2.

William Ord publishes first image of myxedema [11]. Patient who developed physical signs of hypothyroidism over a period of 11 years. (Drawings from: Lindholm J, Laurberg P. Hypothyroidism and thyroid substitution: Historical aspects. J Thyroid Res. 2011;2011:809341).

Close modal
Fig. 3.

Shapland’s 52-year-old patient who had had myxedema for about 10 years [15]. Left, November 12, 1882, before treatment. Right, January 20, 1883, after receiving “half an underdone thyroid gland the first thing every morning taken with ordinary food, from November 12th to January 12th.”

Fig. 3.

Shapland’s 52-year-old patient who had had myxedema for about 10 years [15]. Left, November 12, 1882, before treatment. Right, January 20, 1883, after receiving “half an underdone thyroid gland the first thing every morning taken with ordinary food, from November 12th to January 12th.”

Close modal

Robert Graves is known for his classic 1835 report of “palpitations, goiter, and exophthalmos” in three women [16], but Caleb Parry observed the same clinical features in 1786 (published posthumously by his son in 1825) [17] – yet the name Graves’ disease, coined by Armand Trousseau in 1861, persists [18]. In 1840, Adolph von Basedow completed the picture of toxic goiter [19]. He noted exophthalmos, and as he practiced in Merseburg, Germany, the triad of goiter, exophthalmos, and palpitation was frequently called Merseburg’s triad. In 1867, Adolph von Graefe described lid lag in thyrotoxicosis and coined it Basedow’s disease [20]. Up until the 1800s, the pathophysiology of Graves’ disease was unclear; cardiac and nervous system disorders were thought to be the cause [21].

Not until 1884, with the first report of thyroidectomy for a patient with Graves’ disease by Ludwig Rehn, was the thyroid suspected to be the etiology [22]. After improvement in symptoms and signs in his patients, Rehn proposed the disease was due to hyperactivity of the thyroid gland. In 1887, neurologist Paul Julius Möbius referred to Rehn’s work and suggested the cause was disordered function of the thyroid gland poisoning the body [23]. With the description of X-rays, external radiation was tried for all manner of disease, posing risks to both patient and physician: after 60 years as a practitioner, Dr. Emil H. Grubbe, who built his own X-ray machine in 1896, underwent 90 surgeries for “cancerous burns” and died of cancer [24].

“Cretinism,” a term that has mostly been replaced in the medical literature by “congenital hypothyroidism,” refers to severe thyroid hormone deficiency early in life. Until the mid-19th century, there was little to link the thyroid to cretinism. Severe hypothyroidism may be congenital or, rarely, acquired during infancy or early childhood. In 1850, Thomas Curling described two children, aged 6 months and 10 years, with the absence of goiter (noted at autopsy) and defective cerebral development [25]. More than 20 years later, C. Hilton Fagge noted similar patients and postulated “…the healthy thyroid body is capable of exerting a counteracting influence [on cretinism]” [26]. In 1883, Felix Semon tried to unify myxedema, cretinism, and cachexia strumipriva (signs and symptoms of hypothyroidism, with or without myxedema resulting from the loss of thyroid tissue) by proposing that all were manifestations of the absence or degeneration of the thyroid [27]. Horsley noted the amelioration of severe, induced hypothyroidism in animals by transplanting parts of the thyroid gland into the peritoneum of the hypothyroid animals [28]. In 1895, Bramswell showed the remarkable transformation of a child with severe hypothyroidism with marked linear growth, greater mental awareness, as well as the loss of subcutaneous edema [29]. Thus, by the end of the 19th century, endemic severe hypothyroidism was established as a condition due to the lack of thyroid hormone function. The commonality of myxedema in adults and severe hypothyroidism in children presaged the more widespread use of thyroid replacement therapy. The link between iodine deficiency and cretinism was confirmed in 1966 following a trial in Papua New Guinea which led to the discovery that administration of iodized oil to the population reduced the incidence of goiter and cretinism [30].

Theodore Emil Kocher, a Swiss surgeon, is credited with discovery of the finding that patients with goiter who underwent complete thyroidectomy developed what he termed cachexia strumipriva, a “bad condition due to removal of a struma (goiter).” Kocher (among others) proposed that surgeons conserve part of the gland to prevent this outcome. He was awarded the Nobel Prize in Physiology and Medicine in 1909 for his work on the physiology, pathology, and surgery of the thyroid gland [31].

Shortly thereafter, Edward Kendall, PhD, working at the Mayo Clinic, a center performing a lot of thyroid surgery, was isolating thyroid hormone. On Christmas day, 1914, Kendall finally succeeded in isolating thyroid hormone crystals, which he named “thyroxin” (“e” later added) [32-35] (Fig. 4). However, it was another decade until Charles Harington and George Barger determined its chemical structure (1926) and then synthesized thyroxine (T4) in 1927 [36, 37]. With this advance, the significance of iodine as a component of “tetraidothyronine” became clear. Synthesis of T4 allowed studies of its physiology; for example, in 1931, DM Lyon demonstrated the impact of T4 on body metabolism and weight homeostasis [38]. Gross and Pitt-Rivers reported biologic activity of tri-iodothyronine (T3) in 1952–1953 [39].

Fig. 4.

The modern endocrine laboratory in 1919. The three tanks in which Kendall extracted 6,550 pounds of hog thyroid glands to isolate thyroxine [34].

Fig. 4.

The modern endocrine laboratory in 1919. The three tanks in which Kendall extracted 6,550 pounds of hog thyroid glands to isolate thyroxine [34].

Close modal

Studies in the 1930s–1940s began to work out regulation of the thyroid gland by a substance produced in the pituitary. In 1931, Loeb and Bassett extracted and purified thyrotrophic substance (TSH) from bovine pituitary glands [40]. Then in 1949, RG Hoskins advanced the concept of the pituitary-thyroid axis function in a paper entitled “The thyroid-pituitary apparatus as a servo (feed-back) mechanism” [41]. Thyrotropin-releasing hormone (TRH) was isolated independently by Andrew Schally and Roger Guillemin in 1970 [42, 43], defining the hypothalamic-pituitary-thyroid axis. Schally and Guillemin shared the Nobel Prize in Medicine for their discovery in 1979.

Starting in the 1950s, an understanding of the various steps involved in the synthesis of thyroid hormone began to emerge. In 1950, John Stanbury reported two brothers described as “goitrous cretins” (Fig. 5) [44]. Radioactive iodine uptake by the thyroid was increased, though protein-bound iodine content was decreased, pointing toward a defect beyond trapping, such as a defect in oxidation/organification of iodide. Thyroid peroxidase was cloned and sequenced in 1987 [45]. The role of DUOX2 as a co-factor providing hydrogen peroxide for thyroid peroxidase activity was reported in 1999 [46]. Cloning and characterization of the Na+/I- symporter was reported in 1996 [47]. The etiology of Pendred syndrome, named after British physician Virginia Pendred, who reported deafness and goiter in an Irish family in 1896 [48], was discovered a century later (1997) to be caused by a mutation in SLC26A4, a gene coding for a chloride-iodine protein that transports iodide from the follicular cell into the colloid [49]. Characterization of iodotyrosine deiodinase (IYD or DEHAL1) was reported by Rosenberg et al. [50]. Taken together, these studies confirmed the concept that there is a gene encoding a protein controlling each step in the biosynthesis of thyroid hormone, information used to identify specific defects in subjects with dyshormonogenesis.

Fig. 5.

Twenty-five-year-old patient with “cretinism” recognized at 3 months of age, one of two brothers with congenital hypothyroidism. The thyroid gland weighted 497 g when excised [44].

Fig. 5.

Twenty-five-year-old patient with “cretinism” recognized at 3 months of age, one of two brothers with congenital hypothyroidism. The thyroid gland weighted 497 g when excised [44].

Close modal

The next step was to determine the mechanism of thyroid hormone action. The first clue came from Jack Oppenheimer’s group in 1972, who reported T3 binding to a nuclear receptor [51]. Two groups, Sap et al. [52] and Weinberger et al. [53], reported that the c-erb-A oncogene encodes a thyroid hormone receptor (published back-to-back in Nature in 1986). Thyroid hormone action was further clarified with the report in 1987 that there are two classes of T3 nuclear receptors: TRα and TRβ [54].

The remaining piece of the puzzle was to determine how thyroid hormone enters the cell. Friesema et al. [55] reported discovery of monocarboxylase transporter 8 (MCT8), the first of several thyroid hormone transporters. This discovery came full circle when MCT8 mutations were shown to be the cause of Allen-Herndon-Dudley syndrome, a disorder first reported in 1944 and characterized by severe intellectual disability [56]. This X-linked disorder is seen in boys only; the tipoff on thyroid function testing was an elevated serum T3 level, with low–normal T4 and TSH concentrations.

In the early 19th century, iodine was added to food and water after it was suggested as prophylaxis for goiter. However, this practice was abandoned until Dr. David Marine’s landmark experiment in 1916–1920 where iodide administration to 5,000 schoolgirls in Akron, Ohio, prevented development of endemic goiter [57]. Several subsequent studies produced similar results, and in 1924, iodized salt became commercially available in Michigan, followed by the remainder of the USA. Iodine deficiency remained a significant public health issue throughout the 20th century. UNICEF has called iodine deficiency the greatest preventable cause of cognitive deficits. Through public health efforts, the number of iodine-deficient regions around the world has been declining. In 2021, nearly 90% of the global population were consuming iodized salt, a significant rise from 25% in 1990.

In 1948, Drs. Jan Wolff and Israel Lyon Chaikoff discovered that excess intrathyroidal iodine levels inhibit thyroid peroxidase, leading to inhibition of organification and subsequently causing a transient decrease in thyroid hormone production. This phenomenon, now known as the acute Wolff-Chaikoff effect, protects against overproduction of thyroid hormone due to iodine excess [58-60]. Wolff and Chaikoff went on to describe that in adults, an escape from downregulation usually occurs after a few days of exposure to excess iodine, leading to resumption of normal thyroid hormone production [61, 62]. However, the immature neonatal thyroid gland is unable to escape from the acute Wolff-Chaikoff effect, making infants and children more susceptible to iodine-induced hypothyroidism [63, 64]. Further work has led to the important discovery that excess iodine exposure in utero and in the postnatal period, in the form of iodine-containing antiseptics, contrast agents, medications, and supplements, can lead to transient or permanent neonatal hypothyroidism [63, 65, 66].

In 1963, Robert Guthrie developed a test to detect phenylketonuria on blood spotted on a filter paper card [67]. The “Guthrie test” led to the novel concept of screening newborn populations, with the premise that early detection and treatment of selected disorders would prevent death or intellectual disability. In 1973, Jean Dussault developed a radioimmunoassay to measure T4 in dried blood filter paper specimens, then applied to screening newborns for congenital hypothyroidism [68]. In 1975, Dussault reported the results of screening 47,000 newborns in Quebec, with detection of 7 cases of congenital hypothyroidism (∼1:7,000) [69].

In 1978, Delbert A. Fisher and collaborators reported detection of 277 patients with congenital hypothyroidism in 1 million infants screened in North America, an incidence of 1:3,684 [70]. The success of newborn screening (NBS) was confirmed 1985 when the New England Congenital Hypothyroidism Collaborative reported similar cognitive outcome at age 6 years in children detected by NBS versus sibling controls [71]. A year later, in 1986, Cheryl Hanna and colleagues were the first to report children with congenital central hypothyroidism detected by the Northwest Regional NBS Program, made possible by collection of two routine specimens and follow-up of cases with persistently low T4 – nonelevated TSH levels. Most infants had congenital hypopituitarism, with an estimated incidence of 1:29,000 [72]. The most common etiology for congenital hypothyroidism is thyroid dysgenesis, resulting in permanent hypothyroidism. In 1995, Pacaud et al. [73] reported 3 siblings detected by NBS with transient congenital hypothyroidism caused by transplacental passage of maternal TSH receptor blocking antibody.

Four decades’ experience with NBS programs led to discoveries that challenged previous knowledge about congenital hypothyroidism. In 2000, collaborators from the New England NBS Program were the first to report “delayed TSH elevation” in preterm infants [74]. This discovery led many NBS programs to change their protocol and routinely collect 2nd or even 3rd specimens in preterm infants. In 2000, another study by Fisher and colleagues reported that up to 30 percent of infants with congenital hypothyroidism treated with thyroid hormone had a pattern similar to that of patients with thyroid hormone resistance; this “resistance” appeared to decrease over time [75]. While thyroid dysgenesis resulted in permanent hypothyroidism, other milder forms of thyroid dysfunction were found to be transient [76]. As NBS programs expanded, a reported increase in incidence was noted compared to the prescreening era [77].

Hashimoto’s thyroiditis, the most common autoimmune disease in humans and the most frequent cause of hypothyroidism [78, 79], was first reported by Hakaru Hashimoto, who in 1912 described a thyroid disorder discovered in 4 women who had undergone thyroidectomy [80]. The common pathologic findings among the thyroid glands of these patients were diffuse lymphocytic infiltration of follicles with prominent germinal centers, destruction of follicular epithelial cells, and fibrosis of the gland. This constellation of pathologic findings was coined by Hashimoto as struma lymphomatosa. At the time, many etiologies of this thyroid disorder were postulated, including infection, premalignancy, or goiter from stress [80].

In the early 1930s, Graham and McCullagh [81] used the term “Hashimoto” when distinguishing between struma lymphomatosa and Riedel’s thyroiditis; the term Hashimoto disease was later coined by Cecil Joll [82]. Riedel’s thyroiditis, initially described in 1896 [83], is characterized by inflammatory fibrosis which may extend into adjacent tissues and is now considered exceptionally rare, with an estimated incidence of 0.06% and occurring primarily in adults [84]. This was separate from the third variety of thyroiditis, subacute thyroiditis, described in 1936 by De Quervain and Giordandengo [85].

The association of Hashimoto’s thyroiditis with autoimmunity was first made in 1956, when Noel Rose and Ernest Witebsky reported lymphocytic infiltration in the thyroids of rabbits injected with rabbit thyroid extracts [86, 87]. This concept was developed further by RobertBlizzard et al. [88] who in 1960 demonstrated the association of autoimmunity with thyroid gland destruction [89]. However, it was not until the 1980s that thyroperoxidase was identified as the dominant antigen targeted by the immune system, leading to the finding that circulating antithyroid peroxidase antibody is the most sensitive and specific test for autoimmune thyroid disease [90].

Genetic links to autoimmunity were first reported in the 1970s; however, initial reports of hypothyroidism linked to gene mutations dated back to reports by J.B. Stanbury in 1950 [44]. The pathogenesis of Hashimoto’s thyroiditis is now understood to be a complex interplay of genetic susceptibility and various endogenous and environmental factors [91, 92]. Several immune-regulatory genes, including HLA, CTLA-4, and PTPN22, have been identified as playing a role in the development of autoimmune thyroiditis [45, 92]. While it is most common for autoimmune thyroiditis to occur in isolation, associations between multiple autoimmune conditions have been made, now known as autoimmune polyglandular syndromes. The constellation of autoimmune adrenal insufficiency and chronic lymphocytic thyroiditis, now recognized as Schmidt syndrome, was first reported in 1926 [93].

While hyperthyroidism was not clearly delineated until 1907 by American surgeon Charles H. Mayo, who introduced the term “hyperthyroidism,” exophthalmic goiters were commonly studied [94]. In 1905, American surgeon Robert Abbe treated exophthalmic goiter with implantation of radium into the enlarged thyroid gland [95]. In 1907, David Marine proved iodine is necessary for thyroid function and recommended iodine in the treatment of Graves’ disease in 1911, but this was not widely accepted [96]. In 1916, Bennet Allen and Philip Smith proved a TSH existed and was present in the anterior pituitary [97, 98]. X-rays were widely used to treat exophthalmic goiter, hyperplastic toxic goiter, and toxic adenoma until the 1930s [99]. In 1922, Henry Plummer, Walter Boothby, and Lewis Wilson at Mayo Clinic advanced the view that the exophthalmic goiter was caused by intensive stimulation of unknown source acting on the entire gland [100]. Plummer extensively studied the effect of iodine in exophthalmic goiter. This Mayo group used iodine therapy in preoperative management of exophthalmic goiter [101]; this decreased mortality and became widely accepted as treatment of hyperthyroidism in the 1930s. In 1933, Frederic Joliot and Irene Curie created novel “artificial” radionuclides, leading to development of useful radioactive elements by others, including radioactive iodine [102].

From 1937, several physicians and physicists used radioactive iodine to study thyroid physiology and treat hyperthyroidism. In 1941, Saul Hertz and Arthur Roberts [103] were the first to use radioiodine with the intention to treat hyperthyroidism. In 1943, Edwin B. Astwood [104] published his landmark paper on treatment of hyperthyroidism with the antithyroid drugs thiourea and thiouracil. He continued to study goitrogenic substances and introduced the more potent 6-n-propylthiouracil in 1945 [105] which was approved by the FDA in 1947. Methimazole was discovered to be an even more potent and less toxic thiourea analog in 1949 [106]. In 1951, carbimazole was introduced with the hope that the prodrug would have less toxicity than methimazole [107]. Also in the 1950s, with improvements in ion exchange chromatography, purer preparations of TSH are isolated. While studying TSH, another substance was discovered that stimulated the thyroid gland but differently from TSH. Duncan Adams and H.D. Purves first reported in 1956 the detection of this long-acting thyroid stimulator in patients with thyrotoxicosis [108]. In 1964, Kriss et al. [109] identified long-acting thyroid stimulator as an immunoglobulin that binds to and activates the thyrotropin receptor on thyroid cells as the etiology of Graves’ hyperthyroidism.

Pediatric thyroid cancer has features that distinguish it from the adult form; however, the history of thyroid neoplasia is indistinguishable. The first documentation of thyroidectomy was in 952 AD by Moorish physician Albucasis for large goiters [110, 111]. Thereafter, several surgeons attempted surgical treatments of goiters, but prior to the mid-19th century, it was difficult, bloody, rarely successful, and largely avoided even by skillful surgeons [112, 113]. In 1791, French surgeon Pierre-Joseph Desault performed the first successful partial thyroidectomy; however, surgery continued to have a high mortality, and the French Academy of Medicine even banned all thyroid operations in 1850 [114, 115]. Wilhelm Röntgen discovered X-rays in 1896 [116] followed by Marie and Pierre Curie discovering radium in 1898 [117]. The Curies suggested using X-rays to treat tumors in 1899 [118]. Roentgen rays were used in cases of inoperable thyroid carcinomas and postoperatively in the early 1910s [119-121]. Radioactive iodine use in endocrine research started in the late 1930s, with Samuel Siedlin being the first to use 131I to treat thyroid cancer in 1946 [122]. In 1948, Polish physicians Tempka et al. [123] published a preliminary report using thyroid smears of fine needle punctures. This is regarded as the first publication of using fine-needle biopsy or aspiration (FNA) as a diagnostic method [124].

In 1950, Benedict Duffy and Patrick Fitzgerald reported the connection of irradiation of an enlarged thymus and thyroid cancer when they found 10 out of 28 patients who had been subjected to chest irradiation between 4 and 16 months of life had thyroid cancer [125]. In 1955, Dwight Clark reported the increasing incidence of thyroid carcinoma since 1900 in children and adolescents, correlating with greater use of radiation of benign conditions of head, neck, and upper thorax [126]. Many large studies since have confirmed the greatest risk factor is radiation. This curbed the use of irradiation for nonmalignant conditions in pediatrics after its peak in mid 1950s.

In 1959, with progressive improvements in methods of histology, Hazard et al. [127] identified medullary carcinoma as a distinct entity. This opened the door for identification of multiple endocrine neoplasia syndromes. In 1961, a medical resident, John Sipple, published on the association of pheochromocytoma and medullary thyroid carcinoma and later earned the eponym of Sipple syndrome for MEN2A in 1968 [128].

Ultrasonography became an integral part of the clinical evaluation of the thyroid. Application of ultrasound for diagnostic thyroid imaging began in the late 1960s [129]. Although thyroid biopsies were routinely obtained in thyroiditis, it was not until 1971 that thyroid biopsies were used routinely in thyroid nodules [130]. In 1977, Paul Walfish recommended combining FNA with ultrasound to improve the accuracy of biopsy specimens, which has now become standard of care [131]. In 1985, the rearranged during transfection (RET) proto-oncogene was identified [132]. The analysis of RET mutation became clinically relevant with its role in diagnosis, prognosis, and therapeutic decision-making for childhood MTC and PTCs. In 1990s, the RET gene was found to be associated with MEN2 [133].

The expansion of knowledge regarding genetic alterations furthered the use of molecular markers on biopsies and targeted cellular therapy. Initially, while surgical resection was the only treatment option, in the early 2000s, tyrosine kinase inhibitors were initially studied as treatment for thyroid carcinomas [134]. In 2009, Steven Waguespack et al. [135] reported the first successful use of multi-kinase inhibitor to treat pediatric PTC in a 14-year-old girl.

While the use of cytopathology from FNA was a major advance in diagnosis, there was inconsistency in interpretation of results. The Bethesda System for Reporting Thyroid Cytopathology was initially proposed to address terminology and clarity of communication of FNA results in 2007. Published in 2010 and revised in 2018, it has since been adopted worldwide [136]. In 2014, The Cancer Genome Atlas project, originally launched by NIH in 2005 to comprehend the genomic alterations underlying all major cancers, published a paper on the genomic landscape of PTCs [137]. The use of molecular profile testing has increased in pediatrics, and oncogene panels are shown to have clinical utility to predict increased risk of malignancy in patients less than 19 years old [138]. In 2015, the American Thyroid Association published its inaugural guidelines on pediatric thyroid cancer. This acknowledged the difference in pathophysiology, clinical presentations, and long-term outcomes in children and need for unique guidelines [139]. In 2018, the American College of Radiology published TI-RADS, a new risk stratification system for thyroid nodules on basis of ultrasonography [140]. TI-RADS has not been validated in children, but studies on pediatric adaptations have been published.

Not applicable (no research in article).

The authors declare no conflicts of interest. Kara J. Connelly and Stephen H. LaFranchi: UpToDate author with financial relationship.

No funding was provided for this review.

All three authors Kara J. Connelly, Julie J. Park, and Stephen H. LaFranchi, equally made substantial contributions to the design, acquisition of pertinent references, development of the initial draft, and critical revision of the article.

There were no data generated for this report.

1.
Veith I (translator)
I
.
Huang Di nei jing su wen. The Yellow Emperor’s classic of internal medicine
. New edition.
Berkeley
:
University of California Press
;
1966
.
2.
Li
S
,
Luo
X
.
Compendium of Materia Medica: Bencao Gangmu
. 1st ed.
Beijing
:
Foreign Languages Press
;
2003
.
3.
Courtois
MB
.
Decouverte d’une substance nouvelle dans le Vareck
.
Ann Chim
.
1813
;
88
:
304
29
.
4.
Gay-Lussac
J
.
Sur un nouvel acide formé avec la substance découverite par M. Courtois [On a new acid formed by the substance discovered by Mr. Courtois]
.
Ann Chim
.
1813
;
88
:
311
8
.
5.
Laios
K
,
Lagiou
E
,
Konofaou
V
,
Piagkou
M
,
Karamanou
M
.
From thyroid cartilage to thyroid gland
.
Folia Morphol
.
2019
;
78
(
1
):
171
3
. .
6.
Lydiatt
DD
,
Bucher
GS
.
Historical vignettes of the thyroid gland
.
Clin Anat
.
2011
;
24
(
1
):
1
9
. .
7.
Wharton
T
.
Adenographia, sive Glandularum totius corporis descriptio
.
London
:
Typis J. G. impensis Authoris
.
1656
.
8.
Coindet
JC
.
Découverte d’un nouveau remède contre le goître
.
Ann Chim Physique
.
1820
;
15
:
49
59
.
9.
Slater
S
.
The discovery of thyroid replacement therapy. Part 1: In the beginning
.
J R Soc Med
.
2011
;
104
(
1
):
15
8
. .
10.
Brockett
L
.
Idiots and institutions for their training
.
Amer J Educ
.
1856
;
1
(
4
):
593
608
.
11.
Ord
WM
.
On Myxœdema, a term proposed to be applied to an essential condition in the “Cretinoid” affection occasionally observed in middle-aged women
.
Med Chir Trans
.
1878
;
61
:
57
78 5
. .
12.
Brown-Séquard
C-É
.
Du role physiologique et thérapeutique d’un suc extrait de testicules d’animaux d’après nombre de faits observés chez l’homme
.
Archiv Physiol Normale Patholog
.
1889
:
739
46
.
13.
Murray
GR
.
Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep
.
Br Med J
.
1891 Oct 10
;
2
(
1606
):
796
7
. .
14.
Mackenzie
HWG
.
A case of myxoedema treated with great benefit by feeding with fresh thyroid glands
.
Brit Med J
.
1892 Oct 29
;
2
(
1661
):
940
1
. .
15.
Shapland
BJD
.
The treatment of myxoedema by feeding with the thyroid gland of the sheep
.
Brit Med J
.
1893 April 8
;
1
(
1684
):
738
9
.
16.
Graves
RJ
.
Palpitation of the heart with enlargement of the thyroid gland
.
Lond Med Sur J
.
1835
;
7
:
516
7
.
17.
Parry
CH
.
Collections from the unpublished medical writings of the late Caleb Hillier Parry
.
Edinburgh Med Surg J
.
1826
;
25
(
87
):
366
92
.
18.
Trousseau
A
.
Clinique médicale de l’Hôtel-Dieu de Paris
.
J.-B. Baillière et fils
;
1861
.
19.
Von Basedow
C
.
Exophthalmos durch Hypertrophie des Zellgewebes in der Augenhohle
.
Wochens Ges Heilkd
.
1840
;
13
:
197
.
20.
Von Graefe
A
.
Über Basedow’sche Krankheit
.
Deutsche Klinik
.
1864
;
16
:
158
9
.
21.
Ahmed
AM
,
Ahmed
NH
.
History of disorders of thyroid dysfunction
.
East Mediterr Health J
.
2005 May
;
11
(
3
):
459
69
. .
22.
Rehn
L
.
Über die Exstirpation des Kropfs bei morbus Basedowii
.
Berl Klin Wochenschr
.
1884
;
21
:
163
66
.
23.
Möbius
PJ
.
Über das Wesen der Basedow’schen Krankheit
.
Centrabl Nervenheilkd Psychiatr
.
1887
;
10
:
225
9
.
24.
News of Science (Anonymous)
.
Pioneer in X-ray therapy
.
Science
.
1957 Jan 4
;
125
:
18
9
.
25.
Curling
TB
.
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
.
Med Chir Trans
.
1850
;
33
:
303
6
. .
26.
Fagge
CH
.
On sporadic cretinism, occurring in England
.
Med Chir Trans
.
1871
;
54
:
155
70.1
. .
27.
Semon
F
.
In discussion of “a typical case of myxoedema” by FD Dewitt in the proceedings of the clinical society of London
.
BMJ
.
1883
:
1072
4
.
28.
Horsley
V
.
On the function of the thyroid gland
.
Proc Roy Soc London
.
1885
;
38
:
5
7
.
29.
Bramswell
B
.
The thyroid treatment of myxedema and sporadic cretinism, with notes of twenty-three cases of myxedema and five cases of sporadic cretinism, treated with thyroid extract
.
Edinburgh Hosp Rep
.
1895
;
3
:
116
249
.
30.
Buttfield
IH
,
Hetzel
BS
.
Endemic goitre in eastern New Guinea, with special reference to the use of iodized oil in prophylaxis and treatment
.
Bull World Health Organ
.
1967
;
36
(
2
):
243
62
.
31.
Kocher
T
.
Concerning pathological manifestations in low-grade thyroid diseases
.
Nobel Lectures, Physiol or Med
.
1901–1921
;
1967
:
330
83
.
32.
Kendall
EC
.
The determination of iodine in connection with studies in thyroid activity
.
J Biol Chem
.
1914
;
19
(
2
):
251
6
. .
33.
Kendall
EC
.
The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid: Its chemical nature and physiologic activity
.
JAMA
.
1915
;
64
(
25
):
2042
3
. .
34.
Kendall
EC
.
Isolation of the iodine compound which occurs in the thyroid: First paper
.
J Biol Chem
.
1919
;
39
(
1
):
125
47
. .
35.
Kendall
EC
,
Osterberg
A
.
The chemical identification of thyroxin: Second paper
.
J Biol Chem
.
1919
;
40
(
2
):
265
334
. .
36.
Harrington
CR
.
Chemistry of thyroxine. II. Constitution and synthesis of desiodo-thyroxine
.
Biochem J
.
1926
;
20
:
293
313
.
37.
Harrington
CR
,
Barger
G
.
Chemistry of thyroxine. III. Constitution and synthesis of thyroxine
.
Biochem J
.
1927
;
21
:
169
83
.
38.
Lyon
DM
.
The problem of obesity
.
Edinb Med J
.
1931 May
;
38
(
5
):
T73
90
.
39.
Gross
J
,
Pitt-Rivers
R
.
Physiological activity of 3:5:3’-L-triiodothyronine
.
Lancet
.
1952 Mar 22
;
1
(
6708
):
593
4
. .
40.
Loeb
L
,
Bassett
RB
.
Comparison of effects of various preparations of anterior pituitary gland on thyroid of Guinea pig
.
Proc Soc Exp Biol Med
.
1930
;
27
(
6
):
490
2
. .
41.
Hoskins
R
.
The thyroid-pituitary apparatus as a servo (feed-back) mechanism
.
J Clin Endocrinol
.
1949
;
9
(
12
):
1429
31
.
42.
Burgus
R
,
Dunn
TF
,
Desiderio
D
,
Ward
DN
,
Vale
W
,
Guillemin
R
.
Characterization of ovine hypothalamic hypophysiotropic TSH-releasing factor
.
Nature
.
1970 Apr 25
;
226
(
5243
):
321
5
. .
43.
Schally
AV
,
Arimura
A
,
Bowers
CY
,
Wakabayashi
I
,
Kastin
AJ
,
Redding
TW
,
Purification of hypothalamic releasing hormones of human origin
.
J Clin Endocrinol Metab
.
1970
;
31
(
3
):
291
300
. .
44.
Stanbury
JB
,
Hedge
AN
.
A study of a family of goitrous cretins
.
J Clin Endocrinol Metab
.
1950 Nov
;
10
(
11
):
1471
84
. .
45.
Magnusson
RP
,
Chazenbalk
GD
,
Gestautas
J
,
Seto
P
,
Filetti
S
,
DeGroot
LJ
,
Molecular cloning of the complementary deoxyribonucleic acid for human thyroid peroxidase
.
Mol Endocrinol
.
1987 Nov
;
1
(
11
):
856
61
. .
46.
Dupuy
C
,
Ohayon
R
,
Valent
A
,
Noel-Hudson
MS
,
Deme
D
,
Virion
A
.
Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs
.
J Biol Chem
.
1999 Dec 24
;
274
(
52
):
37265
9
. .
47.
Dai
G
,
Levy
O
,
Carrasco
N
.
Cloning and characterization of the thyroid iodide transporter
.
Nature
.
1996 Feb 1
;
379
(
6564
):
458
60
. .
48.
Pendred
V
.
Deaf-mutism and goitre
.
The Lancet
.
1896
;
148
(
3808
):
532
. .
49.
Everett
LA
,
Glaser
B
,
Beck
JC
,
Idol
JR
,
Buchs
A
,
Heyman
M
,
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS)
.
Nat Genet
.
1997 Dec
;
17
(
4
):
411
22
. .
50.
Rosenberg
IN
,
Goswami
A
.
Purification and characterization of a flavoprotein from bovine thyroid with iodotyrosine deiodinase activity
.
J Biol Chem
.
1979 Dec 25
;
254
(
24
):
12318
25
. .
51.
Oppenheimer
JH
,
Koerner
D
,
Schwartz
HL
,
Surks
MI
.
Specific nuclear triiodothyronine binding sites in rat liver and kidney
.
J Clin Endocrinol Metab
.
1972 Aug
;
35
(
2
):
330
3
. .
52.
Sap
J
,
Munoz
A
,
Damm
K
,
Goldberg
Y
,
Ghysdael
J
,
Leutz
A
,
The c-erb-A protein is a high-affinity receptor for thyroid hormone
.
Nature
.
1986 Dec 18-31
;
324
(
6098
):
635
40
. .
53.
Weinberger
C
,
Thompson
CC
,
Ong
ES
,
Lebo
R
,
Gruol
DJ
,
Evans
RM
.
The c-erb-A gene encodes a thyroid hormone receptor
.
Nature
.
1986 Dec 18-31
;
324
(
6098
):
641
6
. .
54.
Thompson
CC
,
Weinberger
C
,
Lebo
R
,
Evans
RM
.
Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system
.
Science
.
1987 Sep 25
;
237
(
4822
):
1610
4
. .
55.
Friesema
ECH
,
Ganguly
S
,
Abdalla
A
,
Manning Fox
JE
,
Halestrap
AP
,
Visser
TJ
.
Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter
.
J Biol Chem
.
2003 Oct 10
;
278
(
41
):
40128
35
. .
56.
Allan
W
,
Herndon
CN
,
Dudley
FC
.
Some examples of the inheritance of mental deficiency: Apparent sex-linked idiocy and microcephaly
.
Am J Ment Defic
.
1944
;
48
:
325
34
.
57.
Marine
D
,
Kimball
OP
.
The prevention of simple goiter in man. Fourth paper
.
Arch Int Med
.
1920
;
25
(
6
):
661
72
. .
58.
Wolff
J
,
Chaikoff
IL
.
The inhibitory action of excessive iodide upon the synthesis of diiodotyrosine and of thyroxine in the thyroid gland of the normal rat
.
Endocrinology
.
1948
;
43
(
3
):
174
9
. .
59.
Wolff
J
,
Chaikoff
IL
.
Plasma inorganic iodide as a homeostatic regulator of thyroid function
.
J Biol Chem
.
1948
;
174
(
2
):
555
64
. .
60.
Markou
K
,
Georgopoulos
N
,
Kyriazopoulou
V
,
Vagenakis
AG
.
Iodine-induced hypothyroidism
.
Thyroid
.
2001
;
11
(
5
):
501
10
. .
61.
Wolff
J
,
Chaikoff
IL
.
The temporary nature of the inhibitory action of excess iodine on organic iodine synthesis in the normal thyroid
.
Endocrinology
.
1949 Nov
;
45
(
5
):
504
13
. .
62.
Eng
PH
,
Cardona
GR
,
Fang
SL
,
Previti
M
,
Alex
S
,
Carrasco
N
,
Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein
.
Endocrinology
.
1999 Aug
;
140
(
8
):
3404
10
. .
63.
Theodoropoulos
T
,
Braverman
LE
,
Vagenakis
AG
.
Iodide-induced hypothyroidism: A potential hazard during perinatal life
.
Science
.
1979 Aug 3
;
205
(
4405
):
502
3
. .
64.
Robuschi
G
,
Montermini
M
,
Alboni
A
,
Borciani
E
,
Cersosimo
G
,
Negrotti
L
,
Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester
.
J Endocrinol Invest
.
1987 Apr
;
10
(
2
):
183
6
. .
65.
Chung
HR
,
Shin
CH
,
Yang
SW
,
Choi
CW
,
Kim
BI
.
Subclinical hypothyroidism in Korean preterm infants associated with high levels of iodine in breast milk
.
J Clin Endocrinol Metab
.
2009 Nov
;
94
(
11
):
4444
7
. .
66.
Stagi
S
,
Manoni
C
,
Chiarelli
F
,
de Martino
M
.
Congenital hypothyroidism due to unexpected iodine sources
.
Horm Res Paediatr
.
2010
;
74
(
1
):
76
. .
67.
Guthrie
R
,
Susi
A
.
A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants
.
Pediatrics
.
1963 Sep
;
32
(
3
):
338
43
. .
68.
Dussault
JH
,
Laberge
C
.
Dosage de la thyroxine (T4) par méthode radioimmunologique dans l’éluat de sang séché: Nouvelle méthode de dépistage de l’hypothyroïdie néonatale? [Thyroxine (T4) determination by radioimmunological methods in dried blood dried blood eluate: New diagnostic method of neonatal hypothyroidism?]
.
Union Med Can
.
1973
;
102
(
10
):
2062
64
.
69.
Dussault
JH
,
Coulombe
P
,
Laberge
C
,
Letarte
J
,
Guyda
H
,
Khoury
K
.
Preliminary report on a mass screening program for neonatal hypothyroidism
.
J Pediatr
.
1975 May
;
86
(
5
):
670
4
. .
70.
Fisher
DA
,
Dussault
JH
,
Foley
TP
 Jr
,
Klein
AH
,
LaFranchi
S
,
Larsen
PR
,
Screening for congenital hypothyroidism: Results of screening one million North American infants
.
J Pediatr
.
1979 May
;
94
(
5
):
700
5
. .
71.
NECH Collaborative
.
Neonatal hypothyroidism screening: Status of patients at 6 years of age
.
J Pediatr
.
1985
;
107
(
6
):
915
9
.
72.
Hanna
CE
,
Krainz
PL
,
Skeels
MR
,
Miyahira
RS
,
Sesser
DE
,
LaFranchi
SH
.
Detection of congenital hypopituitary hypothyroidism: Ten-year experience in the Northwest Regional Screening Program
.
J Pediatr
.
1986 Dec
;
109
(
6
):
959
64
. .
73.
Pacaud
D
,
Huot
C
,
Gattereau
A
,
Brown
RS
,
Glorieux
J
,
Dussault
JH
,
Outcome in three siblings with antibody-mediated transient congenital hypothyroidism
.
J Pediatr
.
1995 Aug
;
127
(
2
):
275
7
. .
74.
Mandel
SJ
,
Hermos
RJ
,
Larson
CA
,
Prigozhin
AB
,
Rojas
DA
,
Mitchell
ML
.
Atypical hypothyroidism and the very low birthweight infant
.
Thyroid
.
2000 Aug
;
10
(
8
):
693
5
. .
75.
Fisher
DA
,
Schoen
EJ
,
La Franchi
S
,
Mandel
SH
,
Nelson
JC
,
Carlton
EI
,
The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism
.
J Clin Endocrinol Metab
.
2000 Aug
;
85
(
8
):
2722
7
. .
76.
Ford
GA
,
Denniston
S
,
Sesser
D
,
Skeels
MR
,
LaFranchi
SH
.
Transient versus permanent congenital hypothyroidism after the age of 3 years in infants detected on the first versus second newborn screening test in Oregon, USA
.
Horm Res Paediatr
.
2016
;
86
(
3
):
169
77
. .
77.
Harris
KB
,
Pass
KA
.
Increase in congenital hypothyroidism in New York State and in the United States
.
Mol Genet Metab
.
2007 Jul
;
91
(
3
):
268
77
. .
78.
Cooper
GS
,
Stroehla
BC
.
The epidemiology of autoimmune diseases
.
Autoimmun Rev
.
2003 May
;
2
(
3
):
119
25
. .
79.
Vanderpump
MPJ
.
The epidemiology of thyroid disease
.
Br Med Bull
.
2011
;
99
:
39
51
. .
80.
Hashimoto
H
.
Zur Kenntniss der lymphoatosen Veranderung der Schilddrüse (Struma lymphomatoa)
.
Langenbecks Arch Klin Chir
.
1912
;
97
:
219
48
.
81.
Graham
A
,
McCullagh
E
.
Atrophy and fibrosis associated with lymphoid tissue in the thyroid. Struma lymphomatosa (Hashimoto)
.
Arch Surg
.
1931
;
22
(
4
):
548
67
. .
82.
Joll
CA
.
The pathology, diagnosis, and treatment of Hashimoto’s disease (struma lymphomatosa)
.
Brit J Surg
.
2005
;
27
(
106
):
351
89
. .
83.
Riedel
BMCL
.
Die chronische, zur Bildung eisenharter Tumoren führende Entzündung der Schilddrüse
.
Verh Deutsch Ges Chir
.
1896
;
25
:
101
5
.
84.
Hennessey
JV
.
Clinical review. Riedel’s thyroiditis: a clinical review
.
J Clin Endocrinol Metab
.
2011 Oct
;
96
(
10
):
3031
41
. .
85.
De Quervain
F
,
Giordandengo
G
.
Die akute und subakute nicht eiterige Thyroiditis
.
Mitt Grenzgebieten Med Chir
.
1936
;
44
:
538
90
.
86.
Rose
NR
,
Witebsky
E
.
Studies on organ specificity. V. Changes in the thyroid glands of rabbits following active immunization with rabbit thyroid extracts
.
J Immunol
.
1956 Jun
;
76
(
6
):
417
27
.
87.
Caturegli
P
,
DeRemigis
A
,
Chuang
K
,
Dembele
M
,
Iwama
A
,
Iwama
S
.
Hashimoto’s thyroiditis: Celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records
.
Thyroid
.
2013
;
23
(
2
):
142
50
. .
88.
Blizzard
R
,
Hamwi
G
,
Skillman
T
,
Wheeler
W
.
Thyroglobulin antibodies in multiple thyroid diseases
.
N Engl J Med
.
1959 Jan 15
;
260
(
3
):
112
6
. .
89.
Blizzard
RM
,
Chandler
RW
.
The history and present concepts of autoimmunization in thyroid disease
.
J Pediatr
.
1960
;
57
(
3
):
399
409
. .
90.
McLachlan
SM
,
Rapoport
B
.
Thyroid peroxidase as an autoantigen
.
Thyroid
.
2007 Oct
;
17
(
10
):
939
48
. .
91.
Vladutiu
AO
,
Rose
NR
.
Autoimmune murine thyroiditis relation to histocompatibility (H-2) type
.
Science
.
1971 Dec 10
;
174
(
4014
):
1137
9
. .
92.
Zaletel
K
.
Determinants of thyroid autoantibody production in Hashimoto’s thyroiditis
.
Expert Rev Clin Immunol
.
2007 Mar
;
3
(
2
):
217
23
. .
93.
Schmidt
MB
.
Eine biglandulare Erkrankung (Nebennieren und Schilddrüse) bei Morbus Addisonii
.
Verh Dtsch Ges Pathol
.
1926
;
21
:
212
21
.
94.
Mayo
CH
.
Goiter. With preliminary report of three hundred operations on the thyroid
.
JAMA
.
1907
;
48
(
4
):
273
7
. .
95.
Abbé
R
.
Medical Radiology: Exophthalmic goitre reduced by radium
.
Archiv Roentgen Ray
.
1905
;
9
(
10
):
214
8
. .
96.
Marine
D
.
On the occurrence and physiological nature of glandular hyperplasia of the thyroid (dog and sheep), together with remarks on important clinical (human) problems
.
Bull Johns Hopkins Hosp
.
1907
;
18
:
359
64
.
97.
Allen
BM
.
The results of extirpation of the anterior lobe of the hypophysis and thyroid of Rana pipiens larvae
.
Science
.
1916
;
44
(
1143
):
755
8
. .
98.
Smith
PE
.
The effect of hypophysectomy in the early embryo upon the growth and development of the frog
.
Anat Record
.
1916 Nov 24
;
11
(
3
):
57
64
. .
99.
Engelbach
W
.
Endocrine Medicine. Vol III. The adolescent endocrinopathies: the adult endocrinopathies
.
Springfield IL
:
Charles C. Thomas
. p.
427
9
.
100.
Boothby
WM
,
Plummer
HS
,
Wilson
LB
.
Diseases of the parathyroid and thyroid glands
.
New York
:
Oxford University Press
;
1923
.
101.
Plummer
HS
.
The value of iodine in exophthalmic goiter
.
J Iowa Med Soc
.
1924
;
14
:
66
73
.
102.
Joliot
F
,
Curie
I
.
Artificial production of a new kind of radio-element
.
Nature
.
1934 Feb 10
;
133
(
3354
):
201
2
. .
103.
Hertz
S
,
Roberts
A
.
Radioactive iodine in the study of thyroid physiology: VII. The use of radioactive iodine therapy in hyperthyroidism
.
JAMA
.
1946
;
131
(
2
):
81
6
. .
104.
Astwood
EB
.
The chemical nature of compounds which inhibit the function of the thyroid gland
.
J Pharmacol Exp Therap
.
1943
;
78
(
1
):
79
89
.
105.
Astwood
EB
,
Vanderlaan
WP
.
Thiouracil derivatives of greater activity for the treatment of hyperthyroidism
.
J Clin Endocrinol Metab
.
1945
;
5
(
10
):
424
30
. .
106.
Stanley
MM
,
Astwood
EB
.
1-Methyl-2-mercaptoimidazole: An antithyroid compound highly active in man
.
Endocrinology
.
1949
;
44
(
6
):
588
9
. .
107.
Lawson
A
,
Rimington
C
,
Searle
CE
.
Antithyroid activity of 2-carbethoxythio-1-methylglyoxaline
.
Lancet
.
1951 Oct 6
;
2
(
6684
):
619
21
. .
108.
Adams
DD
,
Purves
HD
.
Abnormal responses in the assay of thyrotropin
.
Proc Univ Otago Med Sch
.
1956
;
34
:
11
2
.
109.
Kriss
JP
,
Pleshakov
V
,
Chien
JR
.
Isolation and identification of the long-acting thyroid stimulator and its relation to hyperthyroidism and circumscribed pretibial myxedema1
.
J Clin Endocrinol Metab
.
1964 Oct
;
24
(
10
):
1005
28
. .
110.
Al-Zahrawi
AA-QKA.
Albucasis de chirurgia. Arabice et Latine
.
(J. Channing, translator). Oxford
:
Clarendon Press
;
1778
.
111.
Khalaf ibn ʻAbbās
A-Q
.
La chirurgie d’Abulcasis
.
Baillière
;
1861
.
112.
Rogers-Stevane
J
,
Kauffman
GL
 Jr
.
A historical perspective on surgery of the thyroid and parathyroid glands
.
Otolaryngol Clin North Am
.
2008 Dec
;
41
(
6
):
1059
67, vii
. .
113.
Sarkar
S
,
Banerjee
S
,
Sarkar
R
,
Sikder
B
.
A review on the history of ‘thyroid surgery'
.
Indian J Surg
.
2016
;
78
(
1
):
32
6
. .
114.
Giraud
M
.
Observation sur l’extirpation d’une partie considerable de la gland thyroïde
.
J Chir
.
1792
;
2
(
3
):
3
8
.
115.
Desault
P-J
.
Parisian Chirurgical journal
. Translated by: R. Gosling:
London
;
1794
. p.
292
6
.
116.
Röntgen
WC
.
On a new kind of rays
.
Science
.
1896
;
3
(
59
):
227
31
. .
117.
Curie
M
,
Lippmann
G
.
Rayons émis par les composés de l’uranium et du thorium
.
Gauthier-Villars
;
1898
.
118.
Curie
P
,
Curie
M
.
Sur la radioactivité provoquée par les rayons de Becquerel
.
Gauthier-Villars
;
1899
.
119.
Pfahler
GE
.
The Röntgen-rays in the treatment of deep-seated malignant disease
.
Am J Med Sci
.
1909
;
137
(
4
):
515
25
. .
120.
Pfahler
GE,
Zulick JD.
The treatment of exophthalmic goiter (Basedow's or Graves' disease), by means of the Roentgen rays
.
Am J Roentgenol
.
1916
;
3
(
2
):63-72.
121.
Craver
LF
.
Cancer of the thyroid and its present-day treatment: Embodying the experience of the Memorial Hospital of New York
.
Ann Surg
.
1925 Dec
;
82
(
6
):
833
53
. .
122.
Seidlin
SM
,
Marinelli
LD
,
Oshry
E
.
Radioactive iodine therapy: Effect on functioning metastases of adenocarcinoma of the thyroid
.
JAMA
.
1946
;
132
(
14
):
838
47
. .
123.
Tempka
T
,
Aleksandrowicz
J
,
Till
M
.
Le thyrodogramme
.
Sang Thrombose Vaisseaux
.
1948
;
19
:
336
40
.
124.
Soderstrom
N
.
Puncture of goiters for aspiration biopsy
.
Acta Med Scand
.
2009
;
144
(
3
):
237
44
. .
125.
Duffy
BJ
, Jr
,
Fitzgerald
PJ
.
Thyroid cancer in childhood and adolescence; a report on 28 cases
.
Cancer
.
1950 Nov
;
3
(
6
):
1018
32
. .
126.
Clark
DE
.
Association of irradiation with cancer of the thyroid in children and adolescents
.
JAMA
.
1955
;
159
(
10
):
1007
9
. .
127.
Hazard
JB
,
Hawk
WA
,
Crile
G
 Jr
.
Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity
.
J Clin Endocrinol Metab
.
1959 Jan
;
19
(
1
):
152
61
. .
128.
Sipple
JH
.
Multiple endocrine neoplasia type 2 syndromes: historical perspectives
.
Henry Ford Hosp Med J
.
1984
;
32
(
4
):
219
21
.
129.
Fujimoto
Y
,
Oka
A
,
Omoto
R
,
Hirose
M
.
Ultrasound scanning of the thyroid gland as a new diagnostic approach
.
Ultrasonics
.
1967 Jul
;
5
:
177
80
. .
130.
Crile
G
, Jr
,
Esselstyn
CB
 Jr
,
Hawk
WA
.
Needle biopsy in the diagnosis of thyroid nodules appearing after radiation
.
N Engl J Med
.
1979 Nov 1
;
301
(
18
):
997
9
. .
131.
Walfish
PG
,
Hazani
E
,
Strawbridge
HT
,
Miskin
M
,
Rosen
IB
.
Combined ultrasound and needle aspiration cytology in the assessment and management of hypofunctioning thyroid nodule
.
Ann Intern Med
.
1977 Sep
;
87
(
3
):
270
4
. .
132.
Takahashi
M
,
Ritz
J
,
Cooper
GM
.
Activation of a novel human transforming gene, RET, by DNA rearrangement
.
Cell
.
1985 Sep
;
42
(
2
):
581
8
. .
133.
Romei
C
,
Ciampi
R
,
Elisei
R
.
A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma
.
Nature Rev Endocrinol
.
2016
;
12
(
4
):
192
202
. .
134.
Klein Hesselink
EN
,
Steenvoorden
D
,
Kapiteijn
E
,
Corssmit
EP
,
van der Horst-Schrivers
ANA
,
Lefrandt
JD
,
Therapy of endocrine disease: Response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis
.
Euro J Endocrinol
.
2015
;
172
(
5
):
R215
25
. .
135.
Waguespack
SG
,
Sherman
SI
,
Williams
MD
,
Clayman
GL
,
Herzog
CE
.
The successful use of sorafenib to treat pediatric papillary thyroid carcinoma
.
Thyroid
.
2009 Apr
;
19
(
4
):
407
12
. .
136.
Cibas
ES
,
Ali
SZ
.
The Bethesda system for reporting thyroid cytopathology
.
Am J Clin Pathol
.
2009
;
132
:
658
65
. .
137.
Cancer Genome Atlas Research Network
,
Akbani
R
,
Aksoy
BA
,
Ally
A
,
Arachchi
H
,
Asa Sylvia
L
,
Integrated genomic characterization of papillary thyroid carcinoma
.
Cell
.
2014
;
159
(
3
):
676
90
. .
138.
Bauer
AJ
.
Pediatric thyroid cancer: Genetics, therapeutics and outcome
.
Endocrinol Metab Clin North Am
.
2020 Dec
;
49
(
4
):
589
611
. .
139.
Francis
GL
,
Waguespack
SG
,
Bauer
AJ
,
Angelos
P
,
Benvenga
S
,
Cerutti
JM
,
Management guidelines for children with thyroid nodules and differentiated thyroid cancer
.
Thyroid
.
2015
;
25
(
7
):
716
59
. .
140.
Tessler
FN
,
Middleton
WD
,
Grant
EG
.
Thyroid imaging reporting and data system (TI-RADS): a user’s guide
.
Radiology
.
2018
;
287
(
1
):
29
36
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.