Determination of the Relationship Between the Development and Recurrence of Subacute Thyroiditis and Human Leukocyte Antigen Subtypes.

Background: There are several studies investigating the role of human leukocyte antigens (HLA) in the development and recurrence of subacute thyroiditis (SAT). The HLA subtypes associated with SAT were usually determined in a population-based manner and HLA-B*35, HLA-B*18:01, HLA-C*04:01, and HLA-DRB1*01 were detected to play a role in the disease susceptibility and prognosis. The aim of this study was to determine HLA alleles associated with the tendency of recurrence and prevention of SAT within the Turkish population. Methods: This prospective study was conducted with 51 SAT patients and 720 healthy bone marrow donor volunteers. HLA-A, -B, -C, -DRB1, and -DQB1 were genotyped using next-generation sequencing. Results: The frequency of HLA-A*02:09, HLA-B*35:01/35:02/35:03, HLA-C*04:01, HLA-DRB1*12:01, and DRB1*13:03 were associated with an increased risk of SAT development (Odds Ratio: 22.4, 9.5, 10.3, 4.2, and 3.5, respectively). While HLA-A*02:09, HLA-B*35:01, HLA-B*44:02 HLA-C*07:18, and HLA-C*16:04 were associated with nonrelapsing SAT, HLA-DR*12:01was associated with relapsing SAT. HLA-B*35:02, HLA-B*35:03, and HLA-C*04:01 were more frequent both in relapsing and nonrelapsing groups according to control group. The frequency of HLA-B*18:01, reported as a risk factor previously, was similar in the SAT and control groups (p = 0.959). HLA-DRB1*11:01 was associated with a lower risk of SAT development. Conclusions: Along with -B*358 and -C*04, HLA-A*02:09 was detected as an important risk factor for SAT development in our population. HLA-DRB1*11:01 appears to be the protective HLA subtype against SAT. HLA-A*02:09, HLA-B*35:01, HLA-B*44:02, HLA-C*07:18, HLA-C*16:04, HLA-DQ*06:03, and HLA-DR*12:01 subtypes can establish a tendency to relapsing or nonrelapsing SAT.

The effects of circulating MIR22-3p and MIR16-1-3p levels in different stages of subacute thyroiditis.

Subacute thyroiditis (SAT) is an inflammatory thyroid disease with a frequency is 5% among all thyroid diseases. miRNAs are endogenous, non-coding RNAs ranging in length from 19 to 25 nucleotides. They play an important role in the posttranscriptional regulation of gene expression. In this study, we aimed to investigate whether the expression levels of two circulating miRNAs, MIR22 and MIR16-1, can be used as a parameter in the diagnosis and follow-up of SAT disease. Fifty patients diagnosed with SAT and 41 healthy controls were included in this study. Expression levels of miRNAs were determined by real time-PCR method. Expression data of miRNAs were calculated by fold change (2-ΔΔCt) method. The statistical significance of miRNA expression was evaluated by t-test. The expression levels of MIR22-3p and MIR16-1-3p were not found to be statistically different between SAT patients and controls and also between the patients in different stages (hyperthyroid, euthyroid, and hypothyroid) of the disease. According to correlation analyses, we observed a positive strong correlation between erythrocyte sedimentation rate (ESR) and the expression levels of MIR22-3p and MIR16-1-3p (r = 0.960, p = 0.000 and r = 0.865, p = 0.006, respectively), and a positive strong correlation between fT4 and the expression levels of MIR22-3p in SAT patients in euthyroid stage (r = 0.712, p = 0.047). In this study, we showed that the expression levels of MIR22-3p and MIR16-1-3p have correlation with clinical characteristics of SAT disease. Our results suggest that MIR22 and MIR16-1 may be effective in the pathogenesis of SAT.

Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Background: Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. Objective: This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. Methods: A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed by next-generation sequencing. Results: The frequencies of HLA-B*35 and HLA-C*04 alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (HLA-B*35: 13 [93%] vs. 40 [40%], p < 0.001; HLA-C*04: 13 [93%] vs. 43 [43%], p < 0.001, respectively). More severe thyrotoxicosis was seen in patients having HLA-B*35 and HLA-C*04 homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], p = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], p = 0.07). Conclusions: The frequencies of HLA-B*35 and HLA-C*04 alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for HLA-B*35 and HLA-C*04 was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.

Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown. Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining. Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells. Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.

Strong Correlation between HLA and Clinical Course of Subacute Thyroiditis-A Report of the Three Siblings.

Subacute thyroiditis (SAT) is a thyroid inflammatory disease with susceptibility associated with the presence of human leukocyte antigen (HLA)-B*35, -B*18:01, -DRB1*01 and -C*04:01. Previous viral infection is considered as a triggering factor in genetically predisposed individuals. The influence of HLA on the SAT course was previously suggested. We aim to present the three siblings-female twins and their brother-with very close onset but different clinical courses of SAT, which appeared to be HLA-dependent. The HLA profile in the reported three siblings is strongly correlated with both SAT and Graves' disease (GD), however the coexistence of particular sets of high risk and protective alleles seems to be crucial for the GD development and the SAT course. The co-occurrence of HLA-DRB1*15:01 and/or -B*07:02, possibly together with the lack of HLA-A*01:01 and -B*41:01 seems to be key factors protecting against the development of GD with high TRAb levels, as well as against the recurrent SAT course and steroid dependence.

The Risk of Recurrence of Subacute Thyroiditis Is HLA-Dependent.

The frequency of recurrence of subacute thyroiditis (SAT) is rather high, reaching 20⁻30%. The reason for SAT relapse is still unknown. Recently, we have demonstrated the association between SAT and the presence of HLA-B*18:01, DRB1*01, and C*04:01, apart from the previously known HLA-B*35. The aim of the present study was to evaluate the correlation between SAT-associated HLA haplotypes and the risk of SAT recurrence. HLA-A, -B, -C, -DQB1 and -DRB1 were genotyped using a next-generation sequencing method in 49 SAT patients. The patients were divided into the following HLA groups: 1. HLA-B*35 and/or HLA-C*04, but without any other of the analyzed antigens; 2. HLA-DRB1*01, regardless of the co-presence of HLA-B*35 or -C*04:01, but without HLA-B*18:01; 3. HLA-B18 only, without any other antigen; 4. HLA-B*18:01 plus -B*35, regardless of the presence of any other analyzed antigens. The recurrence rate was compared between the groups. The recurrence rate was significantly increased in patients with HLA-B*18:01 plus HLA-B*35. In conclusion, the risk of SAT recurrence was HLA-dependent and the determining factor was the co-presence of HLA-B*18:01 and -B*35. In such high-risk patients, the steroid treatment regimen should be intensified with a slower dose reduction.

TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells.

Tumor necrosis factor alpha (TNF-α) regulates the expression of proinflammatory cytokines and apoptosis in thyroids. miR-155-5p is upregulated in circulating microvesicles in patients with autoimmune thyroiditis. However, the function and molecular mechanisms of TNF-α and miR-155-5p in the initiation and progression of subacute thyroiditis are largely unknown. Herein, we determined serum TNF-α levels in subacute thyroiditis patients and normal healthy controls by ELISA assay. Proliferation and apoptosis of rat thyroid follicle FRTL-5 cells were determined by MTT, TUNEL, and annexin V staining assays. Protein levels and phosphorylation status were assessed by immunoblotting. miR-155-5p expression was determined by the real-time quantitative PCR. Serum TNF-α was significantly upregulated in patients with subacute thyroiditis compared to that in normal healthy controls. In rat thyroid follicle FRTL-5 cells, TNF-α treatment led to a reduction of cell proliferation and an induction of apoptosis. It also increased IL-6 expression and phosphorylation of JAK2 and STAT3. Importantly, we demonstrated that serum miR-155-5p was upregulated in subacute thyroiditis patients and TNF-α stimulated the expression of miR-155-5p in FRTL-5 cells. We found that miR-155-5p inhibited the proliferation and induced apoptosis of FRTL-5 cells and increased the expression of IL-6 in FRTL-5 cells. Our results demonstrated that serum TNF-α and miR-155-5p were upregulated in patients with subacute thyroiditis, and TNF-α inhibited proliferation and induced apoptosis of rat thyroid follicle FRTL-5 cells via modulating the IL-6-JAK2/STAT3 pathway and miR-155-5p signaling. Our findings suggest that miR-155-5p might be a novel biomarker of subacute thyroiditis.

Simultaneous occurrence of subacute thyroiditis and Graves' disease.

BACKGROUND: Rare cases of Graves' disease occurring years after subacute thyroiditis (SAT) have been reported. Here, we present the first known case of simultaneous occurrence of Graves' disease and SAT. PATIENT FINDINGS: A 41-year-old woman presented with 10 days of neck pain, dysphagia, and hyperthyroid symptoms. Neck pain had initially started at the base of the right anterior neck and gradually spread to her upper chest, the left side of her neck, and bilateral ears. Physical examination revealed a heart rate of 110 beats/minute and a diffusely enlarged tender thyroid gland without evidence of orbitopathy. There was a resting tremor of the fingers and brisk deep tendon reflexes. Laboratory values: thyrotropin<0.01 mcIU/mL (nL 0.39-5.33), free thyroxine 2.0 ng/dL (nL 0.59-1.60), free T3 6.6 pg/mL (nL 2.3-4.2), thyroglobulin 20.1 ng/mL (nL 2.0-35.0), thyroglobulin antibody 843 IU/mL (nL 0-80), thyroperoxidase antibody 130 IU/mL (nL 0-29), thyroid stimulating hormone receptor antibody 22.90 IU/L (nL<1.22), thyroid stimulating immunoglobulins 299 units (nL<140), erythrocyte sedimentation rate 120 mm/h (nL 0-20), and C-reactive protein 1.117 mg/dL (nL 0-0.5). Human leukocyte antigen (HLA) typing revealed DRB1, DR8, B35, B39, DQB1, DQ4, and DQ5. A thyroid ultrasound showed an enlarged heterogeneous gland with mild hypervascularity. Fine-needle aspiration (FNA) biopsies of both thyroid lobes revealed granulomatous thyroiditis. The thyroid scan showed a diffusely enlarged gland and heterogeneous trapping. There was a focal area of relatively increased radiotracer accumulation in the right upper pole. The 5-hour uptake ((123)I) was 6.6% (nL 4-15). The patient was symptomatically treated. Over the next several weeks, she developed hypothyroidism requiring levothyroxine treatment. SUMMARY: This case illustrates a rare simultaneous occurrence of Graves' disease and SAT. Previous case studies have shown that Graves' disease may develop months to years after an episode of SAT. A strong family history of autoimmune thyroid disorders was noted in this patient. Genetic predilection was also shown by HLA typing. CONCLUSION: Although the occurrence of SAT with Graves' disease may be coincidental, SAT-induced autoimmune alteration may promote the development of Graves' disease in susceptible patients. Genetically mediated mechanisms, as seen in this patient by HLA typing and a strong family history, may also be involved.

Expression of transgenic FLIP on thyroid epithelial cells inhibits induction and promotes resolution of granulomatous experimental autoimmune thyroiditis in CBA/J mice.

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by transfer of thyroglobulin-primed in vitro activated splenocytes. Thyroid lesions reach maximal severity 20 d later, and inflammation resolves or progresses to fibrosis by d 60, depending on the extent of thyroid damage at d 20. Depletion of CD8+ T cells inhibits G-EAT resolution. We showed that expression of Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP) transgene (Tg) on thyroid epithelial cells (TECs) of DBA/1 mice had no effect on G-EAT induction but promoted earlier resolution of G-EAT. However, when CBA/J wild-type donor cells were transferred to transgenic CBA/J mice expressing FLIP on TECs, they developed less severe G-EAT than FLIP Tg- littermates. Both strains expressed similar levels of the FLIP Tg, but endogenous FLIP was up-regulated to a greater extent on infiltrating T cells during G-EAT development in DBA/1 compared with CBA/J mice. After transient depletion of CD8+ T cells, FLIP Tg+ and Tg- CBA/J recipients both developed severe G-EAT at d 20. Thyroid lesions in CD8-depleted Tg+ recipients were resolving by d 60, whereas lesions in Tg- littermates did not resolve, and most were fibrotic. FLIP Tg+ recipients had increased apoptosis of CD3+ T cells compared with Tg- recipients. The results indicate that transgenic FLIP expressed on TECs in CBA/J mice promotes G-EAT resolution, but induction of G-EAT is inhibited unless CD8+ T cells are transiently depleted.

Familial occurrence of painful subacute thyroiditis associated with human leukocyte antigen-B35.

INTRODUCTION: Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid that is presumed to be virally induced in genetically predisposed individuals. A strong association has been suggested between human leukocyte antigen (HLA)-B35 and patients who developed SAT. However, familial occurrence of SAT associated with HLA-B35 is reported only rarely. CASE-REPORTS: We report three sibs, (two brothers and one sister) living in the same Lebanese town, who developed SAT during an 18-month-period. All tested positive for HLA-B35. DISCUSSION: The family described here represents the first Third World third familial report of SAT associated with HLA-B35. It highlights the probably underestimated importance of genetic predisposition to SAT in families.

Subacute thyroiditis developed in identical twins two years apart.

A 34-year-old woman was referred to our hospital complaining of sore throat and arthralgia. She had low-grade fever, tachycardia, and goiter with tenderness. Laboratory data revealed thyrotoxicosis and tests for acute inflammatory markers were positive. Thyroidal radioactive iodine uptake was below normal. Ultrasonography of thyroid revealed mild thyroid enlargement and hypoechogenic areas consistent with tenderness. Subacute thyroiditis was diagnosed and prednisone was administered. Two years later, her identical twin sister, who lives separately, was referred to our hospital because of neck pain, low-grade fever, and palpitation. She exhibited the same clinical picture as her twin sister, and was also diagnosed as having subacute thyroiditis. Although the cause of subacute thyroiditis remains unclear, viral infection has been implicated in the onset of subacute thyroiditis in genetically predisposed individuals. We could not identify the viruses, but heterozygotes for HLA-B35, which has been reported to be linked with subacute thyroiditis, were found in the twins. This supports the suspicion that genetic factors, including this HLA haplotype, play a critical role in the onset of subacute thyroiditis.

Chemokine expression during development of fibrosis versus resolution in a murine model of granulomatous experimental autoimmune thyroiditis.

Severe granulomatous experimental autoimmune thyroiditis (G-EAT) in DBA/1 or CBA/J wild type (WT) mice at day 19 progresses to fibrosis by day 35, but severe G-EAT in DBA/1 interferon (IFN)-gamma-/- mice or less-severe G-EAT at day 19 in WT mice resolves by day 35. To study the role of chemokines in autoimmune diseases and fibrosis, profiles of chemokines and chemokine receptors were analyzed in DBA/1 WT versus IFN-gamma-/- and CBA/J thyroids, which have distinct outcomes of autoimmune inflammation. Gene expression of CXC chemokine ligand 1 (CXCL1) and CXC chemokine receptor 2 (CXCR2) paralleled neutrophil infiltration and thyrocyte destruction in DBA/1 WT or CBA/J thyroids, and gene expression of CC chemokine ligand 11 (CCL11), CCL8, and CC chemokine receptor 3 paralleled eosinophil infiltration in IFN-gamma-/- thyroids. Gene and protein expression of CXCL10, CXCL9, and CXCR3 was significantly lower in IFN-gamma-/- compared with DBA/1 WT thyroids. Moreover, immunostaining showed that CXCL10 was expressed by thyrocytes and inflammatory cells, and strong expression of CXCL10 by thyrocytes was as early as day 7. High expression of CCL2 was only observed in severely destroyed DBA/1 WT or CBA/J thyroids, which would develop fibrosis. Thus, the differential expression of chemokines may direct distinct cellular populations in DBA/1 WT versus IFN-gamma-/- thyroids. Up-regulation of CXCL10 by thyrocytes suggests its role in regulating the recruitment of specific subsets of activated lymphocytes to the thyroid during autoimmune inflammation. The early expression of CXCL1, CXCL10, and CCL2 may suggest their involvement in the initiation and perpetuation of disease in severe G-EAT thyroids, which progress to fibrosis.

[Cerebral venous thrombosis associated to subacute De Quervain's thyroiditis in a carrier for the G20210A mutation of the prothrombin gene]. / Trombosis venosa cerebral asociada a tiroiditis subaguda de De Quervain en una paciente con la mutación G20210A del gen de la protrombina.

INTRODUCTION: Recently, thyrotoxicosis has been described as a risk factor for cerebral venous thrombosis (CVT) in some reported cases. We present a case of CVT associated to a subacute De Quervain's thyroiditis in a young female who was an heterozygous carrier for the G20210A mutation of the prothrombin gene. CASE REPORT: A 42-year-old female with irrelevant past medical history developed a thrombosis of the superior sagital and right transverse sinus in the initial phase of a subacute thyroiditis. Diagnosis was made by thyroid radioactive iodine uptake, and cerebral computerized tomography scan, magnetic resonance imaging, and magnetic resonance angiography. Treatment with aspirin and corticosteroids was started until thyroid function was normalized. When CVT diagnosis was made, the patient was treated with anticoagulation. Two months later, magnetic resonance imaging showed resolution of the CVT. The patient was diagnosed as an heterozygous carrier for the G20210A mutation of the prothrombin gene by genetic studies. CONCLUSIONS: Subacute thyroiditis might act as a risk factor for CVT, increasing the thrombotic risk in the presence of other acquired or hereditary prothrombotic factors, such as the G20210A mutation of the prothrombin gene in our patient.

Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35.

Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as enlargement and tenderness of the thyroid. The patient had an elevated erythrocyte sedimentation rate, low thyrotropin (TSH) and elevated thyroxine and triiodothyroinine levels with suppressed 131I thyroidal uptake. He was diagnosed to have SAT. In the patient's family three sisters and one brother also had had SAT, as probably did the deceased father. Because of the familial occurrence HLA-typing was performed. All affected family members were heterozygous for HLA-B35. The family members lived more than 50 miles apart in different regions of The Netherlands and had SAT at different time points between 1986 and 2002, which in combination with HLA-B35 seems to highlight the importance of genetic influences as a risk factor for the development of SAT in this family. In conclusion, the case described here represents the second familial incidence and largest family reported so far with occurrence of SAT in association with HLA-B35.

Familial occurrence of subacute thyroiditis.

Although subacute thyroiditis (de Quervain's thyroiditis) is presumed to be caused by a viral infection, only 2 familial occurrences of subacute thyroiditis have been reported in the literature. Typical and severe subacute thyroiditis was diagnosed in an older sister who was hospitalized for 8 days. During this period her younger sister nursed her. Three weeks after, the same clinical picture occurred in the younger sister. We postulate that subacute thyroiditis might occur by transmission of possible viral infection in genetically predisposed individuals.

Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis.

Subacute granulomatous thyroiditis (SAT) is a self-limiting systemic inflammatory disorder with possible transient expression of thyroid antibodies. Persistent hypothyroidism is uncommon. The interleukin-1 receptor antagonist IL-1ra is an inhibitor of IL-1 activity and allele 2 of the IL-1ra gene is associated with inflammatory diseases and IL-1ra production. Forty-eight subjects with SAT were investigated. Polymorphisms of IL-1ra, IL-1beta-511 and TNFalpha genes were studied with respect to thyroid peroxidase antibodies (TPOab), thyroglobulin antibodies, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum IL-1ra levels were measured. An increased allelic frequency (43% vs 22%, p=0.039) and carriage rate (79% vs 41%, p=0.018) for IL-1ra allele 2 were observed with expression of TPOab in 14 (29.2%) subjects compared with those with negative findings. The carriage rate for both IL-1ra allele 2 and IL-1beta-511 allele 2 was also increased with TPOab expression (71% vs 27%, p=0.004, respectively). No difference in allele frequency or carriage rate was found compared with healthy controls. Serum IL-1ra levels correlated with S-CRP (r=0.41, p=0.004) and ESR (r=0.34, p=0.016), but the association with genes or thyroid antibodies was statistically insignificant. S-CRP levels and ESR were lower and negatively correlated with expression of TPOab (r=-0.27, p=0.046 and r=-0.32, p=0.017). This study describes the multiplicity of the mechanisms responsible for the severity of the acute-phase response during the course of SAT. IL-1ra may have a significant anti-inflammatory role in SAT. Presence of IL-1ra allele 2 increases the risk of developing TPOab.

TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis.

OBJECTIVE: Autoimmunity plays an important role in the development of thyrotrophin (TSH) receptor antibodies and the pathogenesis of Graves' disease and Hashimoto's thyroiditis. On the other hand, subacute thyroiditis is a self-limited inflammatory disease of presumed viral aetiology. The aim of this study was to examine whether subacute thyroiditis triggers TSH receptor antibody-associated thyroid disorders. PATIENTS: We reviewed 1,697 patients with subacute thyroiditis seen between 1985 and 1995. DESIGN AND MEASUREMENTS: We measured antibodies which inhibit the TSH binding to the TSH receptor (TBIAb), thyroid stimulating antibodies (TSAb) and antibodies that block TSH action (TBAb). Other thyroid autoantibodies were also determined. RESULTS: TBIAb became positive in 38 patients following subacute thyroiditis. Thyroid function after the development of TBIAb appeared to be influenced by the bioactivity of the antibody. Hyperthyroidism developed in the presence of TSAb, and so did hypothyroidism in the presence of TBAb, although 21 patients did not have thyroid dysfunction despite high titres of TBIAb. Fifteen out of 17 patients recovered from hyperthyroidism or hypothyroidism after the disappearance of TBIAb sometimes even without medication. TBIAb-positive patients had a high incidence of a family history of thyroid disease and positive anti-thyroid microsomal antibodies. An ophthalmopathy similar to Graves' disease was also observed in 3 patients. CONCLUSIONS: Subacute thyroiditis may trigger autoreactive B cells to produce TSH receptor antibodies, resulting in TSH receptor antibody-associated thyroid dysfunction in some patients.

Susceptibility to subacute thyroiditis is genetically influenced: familial occurrence in identical twins.

Subacute thyroiditis is thought to be virally induced in genetically predisposed individuals because a strong association has been suggested recently between HLA-B35 and patients in whom subacute thyroiditis has developed. Two identical twin brothers were seen at our clinic with the same symptoms and date of onset of hyperthyroidism and enlargement and tenderness of the thyroid, which gave us a unique opportunity to study the genetic predisposition and treatment of this thyroid disease. Diagnostic criteria for subacute thyroiditis were met in both twins, including hyperthyroxinemia, suppression of thyroidal 123I uptake, increased erythrocyte sedimentation rate, transient painful goiter, and absence of antimicrosomal antibodies. Twin B was treated with corticosteroids, and a nonsteroidal anti-inflammatory agent was prescribed for Twin A. The mode of treatment used did not make a difference in affecting the course of the disease. The erythrocyte sedimentation rate was normal after 2 months from onset of symptoms. Results of viral studies were inconclusive. The same HLA typing was found in each twin: A3, B18, B35, Cw4, DR2, DRw10, DQw1. Thus, each was heterozygous for HLA-B35. We reviewed the literature and found a strong association between HLA-B35 and subacute thyroiditis in various ethnic groups tested. Our experience with these identical twins provides additional evidence to suggest that HLA-35 and perhaps Cw4 confer genetic susceptibility in acquiring subacute painful thyroiditis in a possible dominant mode of inheritance.

Recurrence of subacute thyroiditis over 10 years after the first attack in three cases.

We saw a total of 4 episodes of the recurrence of subacute thyroiditis in 3 patients out of 222. The recurrent episodes were similar to the first episodes of subacute thyroiditis. The titers of various viral antibodies were not increased significantly during the clinical course of the recurrence. Regarding the HLA typing, A26, B35 and C3 were positive in all 3 patients. The association between the occurrence of subacute thyroiditis and the presence of HLA-B35 and C3 has hitherto been reported, although the association of HLA-A26 with recurrent type of subacute thyroiditis was observed and described for the first time in this report. It is suggested that HLA-A26 may somehow be related to the predisposition to the recurrence of subacute thyroiditis which developed after more than 10 years.