At the time of his discovery, Hashimoto was finishing his surgical training at the Kyusyu Imperial University . During this time, the primary treatment modality for a thyroid goiter was surgery and thyroidectomies were commonplace. As a result, Hashimoto had the opportunity to study the histology of many resected thyroid specimens. Over the span of 7 years, he came across the thyroid glands of four women who underwent partial thyroidectomy for the indication of goiter. The description of the histology of these glands constituted his most famous piece of work entitled “Zur Kenntniss der lymphomatosen Veranderung der Schilddruse (struma lymphomatosa)” [6]. He decided to publish this article in the German journal Archiv für Klinishe Chirurgie because German was the primary scientific language of the time. Ironically enough, he thought that the information in his article would disseminate most quickly this way .

The article itself was 30 pages long with five sections consisting of the introduction, clinical case presentations, histological description, review of previous reports, and discussion [1, 6]. The bulk of the article involved a very thorough histologic description of the thyroid goiters in the four patients. He explained the extensive lymphocytic infiltration and lymphoid follicles that had not been reported prior. Additionally, he described eosinophilic changes to follicular cells and interstitial fibrosis along with round cell infiltration [1, 6, 7].

The remainder of the article reviewed the reports available at the time differentiating this entity from other known etiologies of thyroid goiter. In meticulous detail, he explained the histological differences of struma lymphomatosa from Riedel’s thyroiditis and the clinical differences of struma lymphomatosa from Graves’ disease [6, 7]. He was confident that this was a new histologic finding within thyroid goiters [6]. Additionally, he made efforts to point out the histological similarities of struma lymphomatosa and Mikulicz’s disease, thought to be Sjögren’s syndrome today. He recognized that histologically this was similar to a modern-day autoimmune disease . He understood that a still unrecognized stimulus was responsible for the histologic changes to these thyroid glands stating, “we can assume that…the lymphocytic elements are stimulated by a certain factor” but that “at present we cannot say anything definite about the cause” [2, 6] .

After publication in 1912, Hashimoto’s work received some recognition in Germany. The next year, in 1913, a German pathologist by the name of Simmonds mentioned Hashimoto’s work, but was unsure whether it was a distinct pathologic entity of the thyroid [8]. Then, in 1914, a German surgeon thought it was a form of chronic thyroiditis [9]. However, during this time, major texts in the British and American literature failed to make mention of Hashimoto or his work when discussing inflammatory disorders of the thyroid gland [2]. Today, many believe the reasons for this relative obscurity were because it was a rare disease compared to endemic goiter; it was harder to access given the need for translation from German, and also because after World War I broke out, the perception of German scientific work on the world stage had changed [2] .

In the 1920s, there continued to be more citations of his discovery limited to German journals. They were also limited to pathology journals [2]. North American and European clinicians continued to fail to recognize his contribution. In 1925, a British pathologist independently described what he thought was a new disease terming it “lymphadenoid goiter.” In his literature review, he failed to identify that it had been described previously [10]. The Western world continued to neglect Hashimoto’s contribution .

It was not until the 1930s when Allen Graham, a surgeon from the Cleveland Clinic, pointed out that lymphomatous goiter was a distinct histologic type. He confirmed that it was different from other inflammatory conditions of the thyroid, namely Riedel’s thyroiditis [11]. He made a clear connection between Hashimoto’s description and what he had encountered, giving proper credit to him [11, 12]. After these articles were published, surgeons in the USA who had once failed to mention him a decade earlier now included Hashimoto’s work in their textbooks [13]. Hashimoto’s name became attached with the disease process. The British also followed suit, and a surgeon by the name of Cecil Joll admitted his error of not recognizing Hashimoto’s description. He later wrote a paper explicitly describing Hashimoto’s disease and crediting him with its discovery [14] .

By the end of the 1930s, Hashimoto’s thyroiditis had now become a distinct disease within the spectrum of chronic thyroiditis. In fact, the Third International Thyroid Conference in 1938 held in Washington, DC, had an entire session devoted to Hashimoto’s disease. Despite all of these new advancements, Hashimoto’s disease was still considered to be a rare thyroid disorder. Also, the connection between the disease and hypothyroidism still had not been made. Surgical intervention was still the treatment of choice during this time [2] .

Though the scientific community had embraced Hashimoto’s disease as a distinct histopathology of the thyroid gland, physicians still had not recognized its association with hypothyroidism or its etiology. There was speculation that the insulting agent might be a mysterious chemical, but no investigation into why there was lymphocytic infiltration into the thyroid gland had been conducted primarily due to World War II [2]. During the 1940s and early 1950s, this disease remained a strange histology encountered rarely among patients with thyroid goiter [2].

The first inclination that Hashimoto’s disease was an immunologic abnormality was when Fromm and associates detected an elevation of plasma gamma globulin fraction in patients with chronic thyroiditis [15]. This was followed by identification of abnormalities in serum flocculation tests in these patients [16]. Taken together, these preliminary experiments indicated that the disease might be related to a complex autoimmune reaction [17] .

In 1956, the work of two independent groups changed the way physicians understood Hashimoto’s disease. Noel Rose and Ernst Witebsky were immunologists in Buffalo, New York, who showed that when rabbits were immunized with thyroid cells, they would form antibodies to thyroglobulin. When they analyzed the thyroid glands of these animals under the microscope, they found the same lymphocytic infiltration observed by Hashimoto 40 years earlier [18]. They were also able to demonstrate the presence of these autoantibodies in the serum of patients with chronic thyroiditis and published this in a landmark paper [19]. Also in 1956, Ivan Roitt, Deborah Doniach, and colleagues from England were able to demonstrate the presence of antibodies to thyroglobulin in the serum of patients with Hashimoto’s disease [20].

Up until this time, the idea of autoimmunity had existed but was never taken seriously. Now, with these new findings, this concept was a valid theory. This work allowed for a connection to be established between the histology of the thyroid glands that Hashimoto observed and the physiologic underpinnings [2, 3]. Even more impressively, the identification of close to 80 autoimmune diseases affectin g almost every organ of the body began from this work (Fig. 3) .

Early epidemiologic studies investigating the prevalence of this disease in large populations elucidated that Hashimoto’s disease was more common than initially thought with close to 2 % of subjects having overt hypothyroidism, 10–26 % of subjects with evidence of anti-thyroid peroxidase (TPO) antibodies present in their serum, and 7.5–30 % of subjects with elevated serum thyroid-stimulating hormone (TSH) [21–24] . Today, Hashimoto’s disease is considered the most common autoimmune disease, most common endocrine disorder, and the most common cause of hypothyroidism [25]. It exists in populations at a much higher rate than what is diagnosed clinically [17]. The current estimated incidence is approximately 1 case per 1000 persons, and the prevalence is 8 cases per 1000 persons. The prevalence is 46 cases per 1000 when subjects have biochemical evidence of hypothyroidism and thyroid autoantibodies [25].