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Goiters were often associated with iodine deficiency in European mountain areas, with some goiters being quite disfiguring. However, some goiters seem not to be related to iodine deficiency. One of the types of goiter that are unrelated to iodine deficiency is the disease described by Hakaru Hashimoto in 1912. Hashimoto described it as a special characteristic of a new type of lymphomatous thyroid tumor in Japan, and this entity was recognized as an autoimmune disease of the thyroid many years later. Hashimoto published his article in a German journal because that was the scientific language of the time, and he thought that writing in German would make the work more widely available around the world. Patients with Hashimoto’s thyroiditis are usually asymptomatic, and some patients develop goiters with or without hypothyroidism. The goiters and hypothyroidism usually respond to treatment with thyroid hormone. The dose of thyroid hormone must be carefully titrated because there may be autonomous thyroid function resulting from thyroid-stimulating antibodies despite the hypothyroid state.
Although Professor Miyake made a great contribution to the idea of this study and the materials presented in the article, the reason for publication under a single name appears to be that Dr. Hashimoto continued the supervisory method practiced by Professor Miyake’s teacher Mikulicz and, in turn, by Dr. Mikulicz’s teacher Billroth.
The leading Japanese figures in world medicine at that time included Shibasaburo Kitasato, Hideyo Noguchi, Umetaro Suzuki, Jokichi Takamine, and Katsusaburo Yamagiwa, all of whose distinguished achievements were recognized internationally while they were alive. Hashimoto alone died without receiving any recognition, and for that reason not much is known about him, the discoverer of Hashimoto’s disease, even in Japan.
After his paper was published in the German medical jounal in 1912, Hashimoto left Japan by ship to study in Germany. However, the timing was unfortunate because of the outbreak of World War I in 1914, and Hashimoto returned to Japan in 1916 without having been able to achieve his goal.
After his returned to Japan, Hashimoto took over his family’s private practice at 34 years of age. However, he later developed intestinal typhus and died unexpectedly in 1934 at just 52 years of age.
At that time it was rare for the work of Japanese persons to be recognized abroad, and similar cases were reported in 1913 (Hashimoto’s article was published in 1912). An article by the German pathologist Simmonds entitled “Lymphatic changes in the thyroid gland” appeared ; a careful reading of the paper reveals that the pathologic findings of Hashimoto’s disease are described. In 1914, there was a similar description in an article by Heineke , and in 1922 chronic thyroiditis was reviewed by Reist . Although Reist quoted Hashimoto’s report, the German school did not consider the condition described in Hashimoto’s article to be an independent disease. Presumably they viewed it as likely to represent an early picture of the so-called Riedel’s thyroiditis that had been reported by Riedel in 1896 . The German reports were followed by others similar to that of Hashimoto in Great Britain as well, but there was hardly any quoting of the German-language articles, and there were no citations of Hashimoto’s paper. In Britain, it was reported as a new thyroid tumor under the diagnostic name “lymphadenoid goiter.”
In 1931, however, the surgeon Graham and colleagues at the Cleveland Clinic in the United States clearly stated that the struma lymphomatosa reported by Hashimoto was an independent disease that differed from Riedel’s thyroiditis. It was at this point that Hashimoto’s struma lymphomatosa article reemerged on the scene . In 1939, the name Hashimoto’s disease (struma lymphomatosa) was used in the title of an article for the first time by the London surgeon Joll , and since then the terms Hashimoto’s disease and Hashimoto’s thyroiditis have come into general use in Western countries.
Foreign books began to be imported into Japan, and the name “Hashimoto’s disease” was imported back into the country from abroad. Thus, the diagnosis “Hashimoto’s disease” was conferred on the disease by non-Japanese. It later came into widespread use in Western countries and traveled a unique path that led to its late arrival in Japan. Paying tribute to Hakaru Hashimoto was begun during the early 1950s by Hachinen Akita, a graduate of the Department of Surgery of Kyushu University and a junior graduate of the same institution as was attended by Hakaru Hashimoto.
Initially, the pathomorphologic diagnosis of Hashimoto’s disease that was discovered in this way became mainstream, but later interest was focused on Hashimoto’s disease as an organ-specific autoimmune disease. After Hashimoto’s disease was established as an autoimmune disease, its diagnosis advanced from being based on the pathomorphologic findings to autoantibody measurements. The discovery of Hashimoto’s disease was a significant step in the history of the discovery of abnormal autoimmunity and endocrine disorders, and today many diseases are known to have an autoimmune etiology. However, the root cause of Hashimoto’s disease has yet to be clarified. Finding answers in this area is among the most important current goals in modern medicine.
The major factor for the name “Hashimoto’s disease” having persisted appears to be that Hashimoto carefully reviewed earlier papers and then gave it a Latin name, “struma lymphomatosa,” which was understood everywhere in the world as a new, independent disease. At the time, he was aware of the difficulty of Japanese persons being recognized on the world stage, and he realized once again the importance of valuing every single case.
Hashimoto’s thyroiditis: at present
Today, Hashimoto’s thyroiditis is more common in women than men (9:1) and occurs most commonly during the fifth decade of life. A genetic association with haplotypes HLA-DR3, HLA-DR4, and HLA-DR5 has been found, and many other autoimmune diseases are associated with Hashimoto’s thyroiditis. The clinical manifestations of Hashimoto’s thyroiditis are often nonspecific, and many patients have no characteristic symptoms or signs. Some patients have a diffusely enlarged thyroid, and in some patients the symptoms of hypothyroidism progress insidiously.
The thyroid in Hashimoto’s disease has been as described grossly as symmetrically enlarged and firm. Microscopically, the follicular epithelium ranges from hyperplastic to atrophic. The nuclei are enlarged and contain prominent nucleoli. There may also be considerable nuclear pleomorphism and hyperchromasia. Occasional intrafollicular multinucleated giant cells may be present . There is usually slight fibrous thickening of the interlobular septa. The follicles were dilated or atrophic, and the gland is infiltrated by lymphocytes, both within the lobules and in the interstitium. Germinal centers are present and fibrotic, with the fibrosis ranging from mild to severe. Hashimoto’s original description emphasized two striking features: eosinophilic change in the follicular epithelium and shrinkage of the colloid . Ultrastructurally, the cells contain large numbers of mitochondria . Serial biopsy specimens do not show significant progression of the histologic changes with time .
The differential diagnosis of Hashimoto’s thyroiditis includes nontoxic multinodular goiter and thyroid lymphoma. Most patients with thyroid lymphoma have underlying Hashimoto’s thyroiditis and a short history of a rapidly enlarging gland. About 30% of patients with malignant lymphoma present with significant compressive symptoms.
The surgical strategy for malignant lymphoma of the thyroid gland is completely different from the surgical strategy for Hashimoto’s thyroiditis. The differential diagnosis of a prominent lymphocytic infiltrate of the thyroid should include malignant lymphoma . The lymphoid population in thyroiditis is heterogeneous, whereas in malignant lymphoma it consists of a monomorphic population of abnormal lymphocytes. If there is no follicular epithelium but a population of lymphocytes is seen, two other nonthyroidal lesions should be considered: reactive lymph node and thymoma with extension to the neck. The differential diagnosis of Hashimoto’s thyroiditis from malignant lymphoma is essential, and immunohistochemistry (IHC) studies help. IHC studies have shown that the lymphocytic infiltrate in Hashimoto’s thyroiditis is composed of both B and T lymphocytes, with T cells predominating. The lymphatic follicles contain mainly B lymphocytes, whereas the cells between the follicles are mainly T lymphocytes .
There is no etiologic treatment for Hashimoto’s thyroiditis. Hashimoto’s thyroiditis is the most common cause of primary hypothyroidism, but only about 20% of patients become hypothyroid. Hypothyroid patients with a low serum free thyroxine (T4) level and an elevated serum TSH level require treatment with thyroid hormone. The management of patients with subclinical hypothyroidism is controversial. Because their disease does not progress to overt disease, treatment is recommended . Hypothyroid patients require lifelong replacement therapy. The goal of replacement therapy is to restore and maintain the euthyroid state. Treatment of euthyroid patients is indicated to shrink large goiters . Surgery is occasionally indicated when malignancy is suspected and for goiters that cause compressive symptoms or cosmetic deformity.
The authors thank Dr. Kazuo Hashimoto, Professor Emeritus, Kanazawa University, the son of Dr. Hakaru Hashimoto, for offering valuable materials.
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