Subacute thyroiditis

Twenty-one cases of thyroiditis, generally considered a rare disease, were observed in the Los Angeles area in a period of less than two years. Eight of them were observed at one clinic in the course of six months.Although diagnosis of the disease usually is made hesitantly or apologetically, and misdiagnosis is not uncommon, the clinical pattern is fairly characteristic. Subacute thyroiditis may cause pronounced disability. Treatment with propylthiouracil or roentgen radiation appeared to be the most effective.     

Echographic findings and histological feature of the thyroid: a reverse relationship between the level of echo-amplitude and lymphocytic infiltration

In 43 patients with Graves' disease, 5 patients with painless thyroiditis and 30 patients with Hashimoto-thyroiditis ultrasonographical observations and histological examinations by needle biopsy of the thyroid were carried out simultaneously. In all cases the level of echo-amplitude was well correlated with the rate of lymphocytic infiltrations and fibrosis. In cases which exhibited marked lymphocytic infiltrations in the thyroidal biopsy specimen, no apparent echoes or very low amplitude echoes were observed in the whole thyroid and in cases in which replacement with lymphocytic infiltration was observed in almost a half part of the thyroid, several sonolucent regions were observed in the thyroid and in cases in which lymphocytic infiltration or fibrosis was observed sporadically, low-amplitude and uniform echoes were observed in the whole or several regions of the thyroid. In cases with no lymphocytic infiltration in the histological specimen, diffuse high-amplitude and uniform echoes were observed throughout the whole lobe of the thyroid. In patients with painless thyroiditis, the amplitude of echo was low when the level of lymphocytic infiltration was high and the echo-amplitude showed a tendency to increase along with the decrease in the rate of lymphocytic infiltration. From these observations it is concluded that echo-amplitude is well correlated with lymphocytic infiltration and fibrosis in patients with Hashimoto-thyroiditis, Hashitoxicosis and painless thyroiditis.     

Differential effect of cold agglutinins on lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis

Peripheral leucocytes from healthy controls, patients with Hashimoto's thyroiditis or patients with Graves' disease were assayed for susceptibility to the cytotoxic activity of cold agglutinins. Lymphocytes from patients with thyroiditis were killed as readily as control cells, however, lymphocytes of patients with Graves' disease were clearly less susceptible to lysis by cold agglutinins. Lymphocytes from patients with Graves' disease cultured for 3 days in the presence or absence of PHA, were as susceptible to cold agglutinins as were control lymphocytes and lymphocytes from patients with thyroiditis. We suggest that the amounts of Ii antigens on the surface of Graves' lymphocytes may be modulated by autoantibodies which are present in many of these patients.     

Post-partum transient thyrotoxicosis: report of two cases

Two patients with post-partum transient thyrotoxicosis associated with painless thyroiditis and low radioactive iodine uptake were described. The surreptitious use of thyroid hormones or iodine was excluded. Although the clinical course was compatible with that of subacute thyroiditis, passing through the hyperthyroid, euthyroid, hypothyroid and recovery phase, the patients showed a sustained elevation of serum anti-thyroglobulin antibody titer during the entire phase of the disease. Moreover, the histological findings obtained by the thyroid biopsy performed in a case were characteristic of chronic lymphocytic thyroiditis. Furthermore, it was of interest that the disease recurred following every delivery in 2 cases, suggesting the possible role of immunological changes induced by pregnancy and delivery in the etiology of this disease.     

Association of different pathologic processes of the thyroid gland in fine needle aspiration samples

OBJECTIVE: To evaluate the possible significant association between different pathologic processes of the thyroid gland. STUDY DESIGN: From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, a total of 1,330 cases were aspirated involving two or more palpable nodules. In 103 (1%) cases, two different pathologic processes were cytologically diagnosed. Statistical analysis was performed through four two-tailed chi 2 tests to evaluate the following events: (1) mononodularity and multinodularity vs. neoplasms, (2) colloid goiter and neoplasms, and (3) all neoplasms vs. colloid goiter and lymphocytic thyroiditis. All tests were performed using < .05 as the probability level. RESULTS: Simultaneous pathologic processes observed were: goiter and chronic lymphocytic thyroiditis (32), goiter and Hashimoto's thyroiditis (21), goiter and subacute granulomatous thyroiditis (8), goiter and follicular neoplasm (9), and goiter and papillary carcinoma (14). In 12 cases we found goiter and Hürthle cell tumor, goiter and medullary thyroid carcinoma (2), papillary thyroid carcinoma and Hashimoto's thyroiditis (2), Graves' disease and lymphocytic thyroiditis (2), and follicular neoplasm and lymphocytic thyroiditis (1). Statistical analysis showed significant association between multinodularity and neoplasms (P < .001), while the association between goiter and any type of neoplasia was not statistically significant. All the neoplasms taken together were associated with lymphocytic thyroiditis and goiter (P < .005). CONCLUSION: While there may be no statistically significant associations between the individual pathologies, it seems that having one pathology increases the risk of developing another. All the palpable nodules in the same gland should be investigated by fine needle aspiration in order to improve diagnostic sensitivity and to identify occult neoplasms.     

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.     

Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis

OBJECTIVE: To elucidate 3-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of subacute thyroiditis. STUDY DESIGN: Ultrasound-guided FNAB was performed on the inflamed area of the thyroid from 4 patients with subacute thyroiditis. The aspirates were stained and observed under a light microscope (LM). The aspirates were also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). For transmission electron microscopy (TEM), the specimen was fixed, dehydrated, embedded in an Epon mixture, cut with an ultramicrotome, mounted on copper grids, electron doubly stained with uranium acetate and lead citrate, and observed with TEM. Findings with SEM were correlated with those with LM and TEM. RESULTS: Under SEM, 3-D cytomorphology of subacute thyroiditis displayed loss of a uniform, honeycomb cellular arrangement; variation in size; and decrease or shortening of microvilli in follicular cells, which corresponded to varying degrees of cellular degeneration under TEM. Giant cells that were round or ovoid were also noted with SEM. CONCLUSION: Loss of a uniform, honeycomb cellular arrangement; variation in size and decrease or shortening of microvilli in follicular cells; and appearance of round or ovoid giant cells were characteristic 3-D cytomorphology findings in FNAB of subacute thyroiditis.     

Postpartum thyroiditis: current views on unappreciated disease

Postpartum thyroiditis is a form of autoimmune thyroiditis developing during the first 12 months postpartum as a consequence of the immunologic flare following the immune suppression of pregnancy. This disease, found in 5-10% of women in a general population and even more frequently in patients suffering from other autoimmune disorders, may re-occur in about 70% of women after a subsequent pregnancy. Postpartum thyroiditis is strongly associated with antithyroid peroxidase antibodies. Patients may present with symptoms of either thyrotoxicosis or hypothyroidism which may be transient or, in some (20-30%) cases of hypothyroidism, permanent in nature. A thyrotoxic phase of postpartum thyroiditis is usually brief and often unnoticed before a more long-lasting hypothyroid phase occurs. The diagnosis of postpartum thyroiditis is based on the observation of abnormal thyroid function tests in a postpartum antithyroid peroxidase- positive woman. In this paper, we discuss the etiopathogenesis, clinical picture, diagnosis, prognosis and treatment of postpartum thyroiditis and provide the reader with some practical guidance concerning dealing with a patient suffering from this disorder.     

Preoperative and Postoperative Evaluation of Thyroid Disease in Patients Undergoing Surgical Treatment of Primary Hyperparathyroidism

ObjectiveTo evaluate the occurrence of thyroid disease in patients undergoing parathyroidectomy for primary hyperparathyroidism.MethodsIn this case series, records of all patients with a diagnosis of primary hyperparathyroidism who underwent parathyroidectomy between January 2005 and December 2008 in our clinic were analyzed retrospectively. Preoperatively, all patients were evaluated with ultrasonography and parathyroid scintigraphy; when needed, thyroid scintigraphy and ultrasound-guided fine-needle aspiration biopsy (FNAB) were used. All patients underwent standard neck exploration. Postoperative histopathologic findings of thyroid tissue were classified as nodular/ multinodular hyperplasia, Hashimoto thyroiditis, papillary thyroid carcinoma, or normal.ResultsFifty-one women and 9 men were included. In the 60 patients, preoperative ultrasonography revealed thyroiditis (without nodules) in 13 (22%), a solitary nodule in 9 (15%) (coexistent with thyroiditis in 7 patients), multinodular goiter in 24 (40%) (coexistent with thyroiditis in 5 patients), and normal findings in 14 (23%). Rates of thyroiditis and nodular goiter were 42% and 55%, respectively. Collectively, prevalence of thyroid disease was 77%. Total thyroidectomy was performed in 27 patients, and hemithyroidectomy was performed in 15 patients. Indications for total thyroidectomy were nondiagnostic or suspicious FNAB results in 5 patients, hyperthyroidism in 4 patients, ultrasonography findings in 11 patients, and intraoperatively recognized suspicious nodularity in 7 patients. Postoperatively, thyroid carcinoma was diagnosed in 9 patients (15%).ConclusionsThyroid disease, particularly thyroid carcinoma, is common in patients with primary hyperparathyroidism. This association should be considered when selecting the surgical procedure. Intraoperative evaluation of the thyroid is as important as preoperative evaluation with ultrasonography and FNAB in patients with thyroid disease and primary hyperparathyroidism. (Endocr Pract. 2010;16:7-13)     

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in patients with Graves' disease, subacute thyroiditis, and silent thyroiditis: a longitudinal study.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was measured longitudinally in 12 patients with Graves' disease, 5 patients with subacute thyroiditis, and 1 patient with silent thyroiditis, and compared with that of 36 normal controls. The patients with Graves' disease and subacute thyroiditis were treated with anti-thyroid drug (methimazole or propylthiouracil) and prednisolone, respectively. On the other hand, no treatment was given to the patient with silent thyroiditis. Since two patients with Graves' disease clearly showed transient deterioration of the thyroid function during the treatment period, data from these two patients were separately investigated. Urinary levels of NAG in the remaining ten patients with Graves' disease before, 1, 3, 6 and 12 months after the treatment were 15.59 +/- 7.93 (SD), 8.96 +/- 6.82, 4.39 +/- 2.33, 3.46 +/- 2.24, and 3.63 +/- 2.38 U/g.creatinine (g.Cr.), respectively. Those obtained before, 1 and 3 months after the treatment were significantly higher than those of the controls (2.85 +/- 1.12 U/g.Cr.). Free thyroid hormone levels became normal or low 3 months after the treatment. The two Graves' patients mentioned above showed a transient increase in urinary NAG with concomitant changes in free thyroid hormone levels. Urinary NAG levels in the patients with subacute thyroiditis before, 2, 4, and 6 weeks after the treatment were 16.56 +/- 10.97, 6.76 +/- 2.79, 3.14 +/- 0.48 and 3.70 +/- 1.44 U/g.Cr., respectively. Those obtained before and 2 weeks after the treatment were significantly higher than those of the controls. Free thyroid hormones were normal 2 weeks after therapy. Urinary NAG in the patient with silent thyroiditis was 9.60 U/g.Cr. on the first visit and gradually decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease

We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23. There was also a notable increase in the number of CD23(+)cells in PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.     

Inhibition of experimental autoimmune thyroiditis in mice by anti-I-A antibodies

Experimental autoimmune thyroiditis is induced in mice by immunization with thyroglobulin emulsified in Freund's complete adjuvant. The disease is characterized both by thyroid infiltration with mononuclear cells and by circulating thyroglobulin antibodies. The magnitude of the thyroid infiltration and the titer of thyroglobulin antibodies are controlled by genes in the I-A subregion of the major histocompatibility complex (H-2). We investigated the in vivo effect of monoclonal anti-Ia antibodies on experimental autoimmune thyroiditis in susceptible mice. Antibodies were given around the time of immunization, later after immunization, and to mice with established disease. Monoclonal antibody produced by the hybridoma line 10-3.6 (anti-I-Ak, s, u, v, z, f) completely prevented both production of thyroglobulin antibodies and thyroid infiltrates, when given shortly before or at the time of antigen administration. This effect was dose-dependent and this monoclonal antibody decreased the severity of the disease when given after the antigen challenge but did not fully suppress established thyroiditis. The same antibody markedly decreased the number of B lymphocytes in the spleen and decreased the thyroglobulin-induced spleen cell proliferation when either given in vivo or added in vitro to cell cultures. Antibodies produced by the hybridoma line 11.2.12 (anti-I-Ak) did not show an inhibitory effect on the disease. These experiments suggest that in this model of murine thyroiditis anti-Ia antibodies act on antigen-presenting cells. Furthermore, only one monoclonal antibody, anti-Ia, suppressed the immune response to thyroglobulin, suggesting a possible role for the isotype and specificity of anti-Ia antibody.     

Materno-embryonally transferred antibodies precipitate autoimmune thyroiditis in obese strain (OS) chickens

In Obese strain (OS) chickens the role of maternal antibodies, passively transferred through the egg to the developing chick, was evaluated as a causative factor in the early development of spontaneous autoimmune thyroiditis (SAT). In the egg, passive antibody titers were highest in the yolk and lower in the allantoic fluid and sera of developing embryos. This passage of antibodies was documented by use of radiolabeled antibodies. In dams with high antibody titers, antibodies could be found in the sera of chicks at the time of hatch. Thyroglobulin was absent in the yolk of OS eggs during embryonal life, as compared with its detection in normal eggs. Immune complexes (thyroglobulin-autoantibody) detected in the thyroids of OS, but not CS, chicks at the time of hatch, or earlier, appear to reflect the presence of the maternally transferred antibodies. A pair of crosses between OS chickens, with thyroiditis, and the C strain (CS), without thyroiditis, was made to evaluate the role of transferred antibodies in the pathogenesis of autoimmune disease. When an OS chicken was the dam, maternal antibodies could be passively transferred; when a CS chicken was the dam, no maternal antibodies were present to be transferred. Nevertheless, both hybrids developed full-blown thyroiditis, demonstrating that binding of transferred maternal antibody to thyroglobulin is not a prerequisite for the induction of SAT. However, presence of maternal antibodies precipitated the onset of disease. Immune complexes formed in the embryonic thyroid are likely to participate in early autoimmune disease, although the development of full-blown thyroiditis may await the competency of the chick's immune system to provide the characteristic cellular infiltrate.     

A difficult diagnosis: a case report of combined Riedel's disease and fibrosing Hashimoto's thyroiditis

Riedel's disease (RD) is a rare form of chronic thyroiditis, predominantly characterised by fibrosis which may involve neighbouring tissues and organs. Hashimoto's disease (HD), on the other hand, is fairly common. Clinical differentiation between these diseases is often difficult, and the results of diagnostic imaging, laboratory tests and cytology studies are often similar. We report the case of a female patient with Riedel's thyroiditis displaying clinical, laboratory and radiological traits of both diseases. A 44 year-old Caucasian female was diagnosed with hypothyroidism. A fine-needle aspiration biopsy was performed; the findings were suggestive of an exacerbated chronic inflammatory process. However, a small lymphocyte-derived malignancy could not be ruled out with certainty, and so the patient was referred for elective thyroidectomy. The microscopic features of both specimens did not meet the criteria of Hashimoto's thyroiditis. The immunohistochemical studies revealed few scattered B lymphocytes (CD20 positive) and numerous scattered T lymphocytes (CD3 positive). Finally, Riedel's thyroiditis with an intense inflammatory infiltrate composed of lymphocytes was diagnosed. Reaching a diagnosis was particularly difficult in this patient, since Riedel's thyroiditis, the fibrosing form of Hashimoto's disease and malignant tumours of the thyroid can show similar traits upon physical and histopathological examination. As the clinical data was indicative of Hashimoto's thyroiditis and there were partial histological criteria of two forms of thyroiditis, namely Hashimoto's and Riedel's, the very rare diagnosis of a combined disease was made. Dense B and T lymphocytes and some plasma cell infiltrates, as well as the destruction of thyroid follicles by fibrosis extending into surrounding tissues, were supportive of the eventual diagnosis. Differentiating between the histopathological and clinical presentation of both diseases in one patient is difficult, primarily due to the partial overlapping of their histopathological traits. In order to avoid a diagnostic error, close cooperation between the endocrinologist and pathologist is mandatory. It is our opinion that in our patient the two diseases existed separately, and their coexistence was most likely coincidental.     

CTLA4 gene polymorphisms in children and adolescents with autoimmune thyroid diseases

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318)T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318)T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.     

Subacute thyroiditis associated with systemic multi-organ disorders

Subacute thyroiditis is generally thought to be a self-limited inflammatory disease of the thyroid gland. This paper describes serial observations on the clinical course of a typical patient with subacute thyroiditis. This patient showed specific features of destructive thyrotoxicosis with increases in the serum levels of acute phase reactants and in the erythrocyte sedimentation rate. She also showed signs of liver dysfunction [slightly increased alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP), and leucine aminopeptidase (LAP)], slight anemia, glucose intolerance, increased pancreatic enzymes, splenomegaly, and an increase in peripheral Leu 7 positive (NK/K) cells. These abnormalities all improved with recovery from disease. These findings indicate that in this patient with subacute thyroiditis inflammation is not limited to the thyroid gland but also involves the liver, pancreas and spleen. Thus the subacute thyroiditis in this patient may be a systemic multi-organ disease.     

Clinical studies on thyroidal autoantibodies.

In an attempt to clarify autoimmune nature of Grave's disease and Hashimoto's thyroiditis, thyroidal autoantibodies have been studied on 86 cases of Grave's disease, 54 cases of Hashimoto's thyroiditis, 31 cases of simple goiter, 11 cases of primary hypothyroidism a-d 22 cases of thyroid neoplasia as well as on 364 healthy subjects. Two kinds of tanned red cell hemagglutination tests were carreid out on each case. One method using refined human thyroglobulin for sensitization of sheep red cells has been found to be specifice for anti-thyroglobulin antibody and to be frequently positive in Hashimoto patients. However, in another method using human thyroidal microsomes (purified by ultracentrifugation) as sensitizing antigen, some heterogenous antibodies including anti-thyroglobulin antibody might be detected together with the antibody against the antigen proper to thyroidal micorsome (HF antigen)which is derived from hyperfunctioning thyroidal follicular cells of Grave's patients. hAnti-HF antibody is frequently detected both in Hashimoto and Grave's patients. In other thyroid diseases the titers of both thyroidal autoantibodies were generally low, though higher than in healthy subjects. The effect of aging on thyroidal autoantibodies in healthy subjects was clearly observed in females but not in males. From the results of these two test, it is possible to speculate that high=columnar and hyperfunctioning thyroidal follicular cells might exist focally in most cases of Hashimoto's thyroiditis.     

High incidence of chronic lymphocytic thyroiditis in apparently healthy school children: epidemiological and clinical study.

An epidemiological survey on the incidence of juvenile chronic lymphocytic thyroiditis was performed in 10,220 apparently healthy school children in Ishikawa district, Japan. The subject of present study included 6,244 school children (2,831 boys and 3,413 girls, ages 6-18 yrs.) in Kanazawa City and 3,976 children (2,055 boys and 1,921 girls, ages 6-18 yrs.) in Wajima City. The first group was selected as a representative of urban area and the second group as that of seaside area. Children who have goiter or firm thyroid were selected for testing antithyroglobulin and anti-microsomal antibodies in sera. Final diagnosis of chronic lymphocytic thyroiditis was made on histological specimen obtained by needle biopsy on the antibody positive subjects. The overall incidence of chronic lymphocytic thyroiditis in these children was 3.0 per 1,000, whereas the incidence in adolescent girls was as high as 8.2 per 1,000. There was a considerable sex difference in the prevalence, the ratio of female to male was 6.5:1, and the incidence increased with age. The incidence in seaside area was 5.3 per 1,000 that was significantly higher than in urban area, 1.4 per 1,000 (p less than 0.005). Histologically, 26 of 30 cases (87%) were classified as focal thyroiditis and 4 cases (13%) were diffuse thyroiditis. Serum T4-I and T3 values within normal range in all patients, but resting TSH was elevated in 1 of 23 cases and TSH response to TRH was exaggerated in 3 of 23 cases. Impaired organification of iodide was observed in 6 of 32 cases by iodide-perchlorate discharge test. The present study demonstrates that juvenile chronic lymphocytic thyroiditis is highly prevalent among apparently healthy school children and early recognition of the disease with preventive care for hypothyroidism in future should be stressed.     

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A 51-year-old woman presented with a painful, rapidly enlarging thyroid gland. The serum concentrations of the thyroid hormones were initially at the upper limit of normal, and the uptake of radioactive iodine by the thyroid was completely depressed. Although subacute thyroiditis was suspected, a biopsy specimen from the thyroid showed malignant disease and no evidence of inflammation. At the time of right subtotal lobectomy metastatic breast carcinoma was diagnosed. Thus, primary or secondary malignant disease of the thyroid can simulate thyroiditis and present a serious problem in differential diagnosis.     

Development of an animal model of autoimmune thyroid eye disease

In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we have examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroiditis with considerable follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in controls. None of the NOD animals developed any orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the receptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose tissue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital changes or thyroiditis were observed in control BALB/c mice. We have induced orbital pathology having many parallels with human TED, only in BALB/c mice, suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for the development of TED.