Hashimoto's Struma Research Articles

Quantified 123I-Thyroid Scan based classification of hyperthyroidism

The original thyroid scan (TS) was widely used to identify typical imaging patterns, suggesting the widely accepted main following clinical diagnoses: Grave's disease, Toxic adenoma, [hetero]-nodular goiters and thyroiditis. With the diffusion of sensitive TSH assays, considerable advances in the comprehension of the molecular mechanisms of hormonosynthesis, and new quantification possibilities especially using 123I, the TS is a textbook of molecular imaging. The image can be finely quantified with, not only as regards the Uptake (123IUp) and related parameters but also, the quantification of the spatial targeting leading to a Spatial Target Index (STI). Using this new molecular 123I-TS, TSH values, and when required, correlation to Multiparametric Ultrasounds (MPUS), we generated a basic classification system of hyperthyroidism, with well-defined indexed criteria (C11-1 to C17-3), that allows reporting 24 distinct etiologies. Selected criteria involve TS and contrast patterns, precocious 123IUp (p123IUp), maximal TSH-dependent physiological Uptake, lobar concentration, Uptake and concentration ratios, STI, 99mTc-MIBI TS and correlative MPUS. This approach allows to identify 4 subtypes of Graves’ disease, including hyperplastic, nodular and common GD variants entangled with Hashimoto's struma, 4 subtypes of Thyroid Functional Autonomy, including Disseminated Functional Autonomy, that cannot be diagnosed with other conventional procedures. Criteria C14-1 to C17-3 report on hyperthyroidism and iodine overload, factitia, main thyroiditis presentations and rare central or tumoral etiologies of hyperthyroidism. This classification, based on 123I-TS molecular imaging, leads to unprecedented diagnostic finesse and paves the way for a personalized theranostic approach in thyroid pathology. Further development towards artificial intelligence networks is under study.

The life and work of dr. Hakaru Hashimoto

Hashimoto's thyroiditis (HT), a common thyroid disease, is now recognized as an autoimmune thyroid disorder. However, little is known about its discoverer, the man who first described this disease. He presented four patients with a chronic thyroid disorder, which he termed as struma lymphomatosa, characterized by diffuse lymphocytic infiltration with germinal centers, parenchymal atrophy and eosinophilic changes in some thyroid follicular cells. Dr. Hakaru Hashimoto was born in 1881 in Japan. Once he finished his studies, he started his training at the Surgery Department of Fukuoka Medical College. Professor Miyake, the head of the department, trained Dr. Hashimoto in the technique of assessing excised thyroid glands microscopically. In 1912, he published a paper, Zur Kenntnis der lymphomatösen Veränderung der Schilddrüse (Struma lymphomatosa) in 'Archiv für klinische Chirurgie', Berlin, 1912:97:219-248. Some years later, he studied pathology under the instruction of prof. Eduard Kaufmann in Göttingen. Hashimoto's struma lymphomatosa was then ignored and forgotten until 1931, when Mr. Allen Graham of Cleveland reported struma lymphomatosa and insisted that Mr. Hashimoto had first discovered the disease and wanted to name it after him - Hashimoto's thyroiditis (HT).

The role of interleukin 2 in the development of autoimmune thyroiditis.

Interleukin 2 (IL-2) is a lymphokine that may disrupt immunological self-tolerance. While being incapable of interfering with intrathymic or peripheral clonal deletion, IL-2 may overcome functional antigen unresponsiveness in anergic T lymphocytes. Anergy of T helper cells of the inflammatory phenotype implies selective silencing of the transcription of the IL-2 gene and thus precludes autocrine IL-2/IL-2 receptor (IL-2R) mediated growth, as well as delivery of help to other T cells or B lymphocytes. Thus, IL-2 serves as a servomodulator regulating post-deletional self-tolerance. IL-2-producing and IL-2-receptive cells are present in a variety of autoimmune lesions, including spontaneous autoimmune thyroiditis developing in the Obese strain (OS) of chickens, in Hashimoto's struma lymphomatosa, and in Graves' disease. Whereas the OS is characterized by a hyperinducibility of the IL-2/IL-2R system that predisposes to the development of severe thyroid infiltration, the state of the IL-2/IL-R system in circulating lymphocytes of patients developing thyroid autoimmunity, or at risk of doing so, remains to be defined. The most frequent autoimmune side-effect of IL-2 treatment concerns the thyroid gland. IL-2 induces a lymphoid thyroiditis leading to primary hypothyroidism, especially in those patients that have pre-treatment antithyroid autoantibodies. The hypothesis is extrapolated that IL-2 induces autoimmune disease in those patients that bear undeleted thyroid-specific T cells, and in which the lack of manifest thyroiditis relies upon peripheral, post-deletional tolerance.

The treatment of hyperthyroidism with iodine-131

Uncertainty about the use of radioiodine in the treatment of thyrotoxicosis has been raised by recent publicity on irradiation thyroid carcinogenesis. Data are reviewed from the publications of the Cooperative Thyrotoxicosis Follow-up Study of 22,000 patients treated with 131 I and 14,000 patients treated surgically or solely with antithyroid drugs or surgery. No increased incidence of leukemia has occurred in 30 years of therapy. Although large tracer doses of 131 I may prove to be carcinogenic, the therapeutic doses used to treat hyperthyroidism appear to decrease the incidence of carcinoma by preventing thyroid cell replication. These is considerable evidence from the Atom Bomb Casualty Commission and from recent data on the treatment of hyperthyroidism and thyroid cancer with 131 I in children that treatment doses of 131 I have not produced abnormal fertility or birth histories. The yearly cumulative incidence of hypothyroidism after the first year of treatment with 131 I of 2.7%, as compared to 1.8% after surgery, is not decisive in affecting the choice of treatment. The published considerably higher morbidity and mortality from surgical thyroidectomy in children as compared to adults has not been generally recognized or discussed with parents. There is growing belief, therefore, that 131 I is the current treatment of choice for thyrotoxicosis in children and adolescents. The persistence of goiter after cure usually signals the presence of coexisting Hashimoto's struma. Radioiodine uptakes tests are being performed more commonly after the diagnosis of thyrotoxicosis and are confirmed with in vitro tests because of the more common presence of self-limited thyrotoxicosis and thyrotoxicosis with normal or subnormal 131 I uptake.

VITILIGO, ACHLORHYDRIA, AND PERNICIOUS ANÆMIA

The gastric acid secretion was assessed in 102 consecutive vitiligo patients by means of the augmented histamine test. Achlorhydria was found in 20 patients. 8 of these 20 patients had pernicious anæmia, only 3 of the cases being known before the study. 19 of the 20 patients with achlorhydria and all 8 with pernicious anæmia were women. The frequency of achlorhydria in men with vitiligo was normal. Serum-vitamin-B12 was abnormally low in the patients with pernicious anæmia, low to normal in those with achlorhydria without pernicious anæmia, and normal in acid secretors. Antibody to gastric parietal cells was found in 80% of vitiligo patients with achlorhydria, compared to 6% of a normal group. Antibody to intrinsic factor was found in 3 patients, all of whom had pernicious anæmia. Insulin-dependent diabetes mellitus was found in 4 of the 102 vitiligo patients, and 6 had thyroid disease (including 2 women with Hashimoto's struma).

The relationship of juvenile hypothyroidism to chronic lymphocytic thyroiditis

Eighteen cases of acquired juvenile hypothyroidism are described. Significant titers of antithyroid antibodies in sixteen of them suggest an underlying autoimmune thyroiditis. Comparison of these patients with 33 children who have Hashimoto's struma indicates that chronic lymphocytic thyroiditis may produce a spectrum of disease in childhood ranging from euthyroid goiter to nongoitrous myxedema.

Chromosome abnormalities in human thyroid disease.

An analysis was made of chromosomal abnormalities in surgical specimens of human thyroid glands. Three histologically proved normal control thyroid glands were obtained at laryngectomy. Eight histologically proved colloid-nodular goiters, 5 goiters of Graves' disease, 3 goiters of Hashimoto's struma 2 adenomas and 2 carcinomas were studied. The thyroid glands from patients with each of the 5 thyroid disease categories were demonstrated to have a greater percentage of aneuploid cells than the normal mean of 1.7% ±se of 1.20. The thyroid tissue from each disease state had a higher degree of tetraploidy and hypertetraploidy than normal controls. Graves' disease, colloid nodular goiter and Hashimoto's specimens showed a significantly greater degree of tetraploidy and octaploidy than adenoma and carcinoma specimens. Chromosomes were missing only in the colloid-nodular group. Additional chromosomes were seen in colloid-nodular goiter and in carcinoma. Marker chromosomes were found only in Graves' disease (2 pat...

Genetic Factors in Hashimoto's Struma

It has previously been established that there is a significant history of thyroid disorders in families of patients with Hashimoto's struma or chronic thyroiditis. In the present study, 99 relatives of 20 patients with Hashimoto's struma or chronic thyroiditis were studied with regard to the incidence of circulating thyroid autoantibodies; 42 of these 99 relatives were found to have such antibodies. Twenty of the 99 relatives were shown to have thyroid abnormalities (chiefly goitre); of this group of 20, antibodies were found in 12. In the remaining 79 persons (who had no clinical evidence of thyroid disease), 30 were found to have circulating antithyroid antibodies. The incidence of such antibodies among these relatives is very significantly greater than in the general population.From these and other similar studies, there is strong evidence favouring a genetic predisposition for Hashimoto's struma and chronic thyroiditis. The mode of inheritance is not yet established, and the pathogenesis of the disease has not yet been elucidated.

Genetic studies in a family with "simple" goiter.

Twenty-three goiterous individuals were identified in a large North Carolina pedigree. There was no single clinical feature that distinguished these individuals from many other patients in this area with “simple” goiter. Most were euthyroid and had a normal PBI, BEI and I131 uptake. There was no significant excess of affected individuals with taste blindness to phenylthiocarbamide. In 3 patients myxedema was provoked by the administration of Lugol's solution. Hashimoto's struma and antithyroid antibodies were found in some. Genetic analysis of a large segment of this pedigree indicated that the trait probably was inherited as a dominant character. There was a marked sex predilection for females and, in general, goiter was more severe in females during their productive years. Although sex linkage cannot be excluded with certainty, it is postulated that the abnormal gene is located on an autosome and that nongenetic factors play an important role in determining the degree of expression. Ovarian hormones may be responsible for the high degree of penetrance among females. The results of biochemical studies are reported in a companion paper, which follows this one. These studies suggest that the inherited defect is responsible for the production of an abnormal thyroglobulin that is more resistant to hydrolysis by proteolytic enzymes than normal thyroglobulin is.

Defective iodination of tyrosine a cause of nodular goiter?

Twenty patients with colloid nodular goiter, 7 patients with Hashimoto's struma, and 15 patients without thyroid disease (all non-deaf) were tested with radioactive iodine and potassium thiocyanate for a thyroidal defect in iodination of tyrosine. In the cases of colloid nodular goiter with a family history of goiter there was a higher incidence and more severe degree of defective iodination of tyrosine than in the cases of colloid nodular goiter without a family history of goiter. Defective iodination of tyrosine was demonstrated in 1 sibling with proved colloid nodular goiter and in 1 with Hashimoto's struma. Iodination of tyrosine was impaired in 1 patient with her fourth recurrence of colloid nodular goiter. These data suggest that defective iodination of tyrosine is not uncommon in euthyroid non-deaf subjects with colloid nodular goiter, and may occur on a familial basis. ATRACER dose of radioactive iodine (I131) is normally incorporated into the tyrosine molecule shortly after entering the thyroid gland (1). If an oral dose of potassium thiocyanate (KSCN) is given to a person with a normal thyroid gland two hours after the administration of a tracer dose of I131, the resultant decrease in concentration differential for ionic iodide across the follicular cell membrane does not result in an exodus of I131 from the thyroid gland because the I131 already incorporated into the tyrosine molecule does not leave the follicular cell. If the process of iodination of tyrosine is impaired, however, nonorganified I131 leaves the thyroid gland after the administration of KSCN. Defects in the organification of iodine have been noted during administration of thiouracil (2), and in goitrous cretins (3), congenitally nerve-deaf siblings in whom goiter later developed (4), and patients with Hashimoto's struma (5).

Activity of iodotyrosine deshalogenase in "normal" and diseased human thyroids.

ABSTRACT Iodotyrosine deshalogenase assays were performed on 40 surgical specimens from 39 human thyroid glands. Histologically normal thyroid tissue from 8 patients with thyroid cancer served as “normal” controls. The iodotyrosine deshalogenase activity of thyroid tissue from 10 patients with colloid adenomatous goiter and 5 patients with Hashimoto's struma was within the range of activity found in “normal” thyroid tissue. Iodotyrosine deshalogenase activity was significantly lower (P <0.02) than “normal” in the thyroid glands of 2 patients with nonspecific thyroiditis. A clearcut difference from “normal” activity (was not found in the thyroid glands of 8 thyrotoxic patients rendered euthyroid with propjdthiouracil and Lugol's solution. The Michaelis-Menten constant for iodotyrosine deshalogenase in the thyroids of these thyrotoxic patients did not differ significantly from “normal” (2.3×10−5 Mand 1.8×10−5 M, respectively). The mean iodotyrosine deshalogenase activity in carcinomatous tissue from the thy...

Hashimoto's disease in childhood.

Hashimoto's struma, or struma lymphomatosa, is considered to be a disease of the fifth and sixth decades, but it nevertheless can occur over a wide range of age. In their excellent review of the material from the Massachusetts General Hospital, Statland, Wasserman, and Vickery1reported 51 cases between the ages of 10 and 74 years. All were females. Two of their cases occurred at the age of 10 years, one at the age of 14 years; a fourth patient, who had a goiter since the age of 12, was diagnosed as having Hashimoto's struma at the age of 21. Gribetz, Talbot, and Crawford added three additional adolescent cases in 1954 and collected 11 others from the literature.2Standard textbooks rarely refer to the possibility of this disease in childhood. It is probable, however, that the incidence in the pediatric age group is higher than generally conceded. REPORT OF

Goiter due to lymphocytic thyroiditis (Hashimoto's struma); its occurrence in preadolescent and adolescent girls.

IT has long been thought that in preadolescent children most nontoxic goiters not due to carcinoma were of the simple colloid variety. The present report describes observations made on 6 children with goiters that on histologic examination exhibited changes consistent with chronic lymphocytic thyroiditis of the Hashimoto type. The frequency with which this diagnosis has been made in this clinic may be of interest in view of the supposed rarity of this condition in patients under twenty years of age. Only 11 cases occurring in children could be found in the literature.1 2 3 4 5 6 7 8 9 ¶Clinical, laboratory and pathological findings are presented below . . .

Struma lymphomatosa (Hashimoto's struma); review of fifty-one cases with a discussion of the endocrinologic aspects.

SINCE the original description of struma lymphomatosa by Hashimoto in 1912, much confusion has arisen in the literature concerning the diagnosis, pathology, and therapy of this clinicopathologic entity. The present study is a review of 51 cases of struma lymphomatosa seen at the Massachusetts General Hospital. Since the literature is lacking in reports of some of the newer laboratory methods of studying thyroid function in struma lymphomatosa, it is one of the purposes of this paper to describe such observations. Serum protein-bound-iodine determinations, radioactive-iodine (I 131 ) tracer studies, and radioautographs were obtained on several of the patients in the present series. These help to throw additional light on a number of current problems. The etiological basis of struma lymphomatosa is unknown. Various theories have been advanced to explain the picture of this entity. These hypotheses will be mentioned later in the section under Comment. METHODS AND CLASSIFICATION OF MATERIAL There

WEEKLY clinicopathological exercises: Hashimoto's struma.

WEEKLY clinicopathological exercises: Hashimoto's struma.

Chronic thyroiditis

1. 1. Reidel's struma and Hashimoto's struma are different clinical and pathologic features of a chronic degenerative disease of the thyroid gland. 2. 2. Conservative surgery is the procedure of choice in such cases. 3. 3. A period of postoperative hypothyroidism that probably varies with the individual case ensues. Symptoms during this phase can be controlled medically. This period is undoubtedly a very important one and the patients should be followed carefully. 4. 4. Following a period of four years, the two patients in this study reverted to a normal thyroid balance.