The microbiota and autoimmunity: Their role in thyroid autoimmune diseases.

Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject.

Identifying predictors of a difficult thyroidectomy.

BACKGROUND: A Thyroidectomy Difficulty Scale (TDS) was previously developed that identified more difficult operations, which correlated with longer operative times and higher complication rates. The purpose of this study was to identify preoperative variables predictive of a more difficult thyroidectomy using the TDS. METHODS: A four item, 20-point TDS, was used to score the difficulty of thyroid operations. Patient and disease factors were recorded for each patient. Difficult thyroidectomy and non-difficult thyroidectomy (NDT) patients were compared. A final multivariate logistic regression model was constructed with significant (P<0.05) variables from a univariate analysis. RESULTS: A total of 189 patients were scored using TDS. Of them, 69 (36.5%) suffered from hyperthyroidism, 42 (22.2%) from Hashimotos, 34 (18.0%) from thyroid cancer, and 36 (19.0%) from multinodular goiter. Among hyperthyroid patients, the DT group had a greater number preoperatively treated with Lugols potassium iodide (81.6% DT versus 58.1% NDT, P=0.032), presence of ophthalmopathy (31.6% DT versus 9.7% NDT, P=0.028), and presence of (>4 IU/mL) antithyroglobulin antibodies (34.2% DT versus 12.9% NDT, P=0.05). Using multivariate analysis, hyperthyroidism (odds ratio [OR], 4.35, 95% confidence interval [CI], 1.23-15.36, P=0.02), presence of antithyroglobulin antibody (OR, 3.51, 95% CI, 1.28-9.66, P=0.015), and high (>150 ng/mL) thyroglobulin (OR, 2.61, 95% CI, 1.06-6.42, P=0.037) were independently associated with DT. CONCLUSIONS: Using TDS, we demonstrated that a diagnosis of hyperthyroidism, preoperative elevation of serum thyroglobulin, and antithyroglobulin antibodies are associated with DT. This tool can assist surgeons in counseling patients regarding personalized operative risk and improve OR scheduling.

Primary Intrathyroidal Non-Hodgkin Lymphoma: A Case Report.

Primary thyroid lymphoma (PTL) is a rare disease characterized by the appearance of a rapidly growing solid mass in the cervical region. A major risk factor is chronic autoimmune thyroiditis with lymphocytes infiltrating the thyroid gland. The lymphoproliferative disease is seen more frequently in the females. PTL usually develops in the sixth and seventh decades of life. We present a case of a 66-year-old woman with diffuse primary B-cell thyroid lymphoma with no prior evidence of underlying autoimmune thyroid pathology. The initial localization of the lymphoproliferative disease was in the thyroid gland, but the involvement of regional cervical lymph nodes was also found at the time of diagnosis. After histological verification with immunohistochemistry and staging by imaging, chemotherapy was initiated according to the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, Oncovin® (vincristine), prednisone) protocol. An excellent therapeutic response was achieved with lymphoma remission after six cycles under the mentioned protocol. Thyroid autoantibodies became positive 18 months after rituximab treatment, possibly reflecting the transient suppressive effects of the immunotherapy. The patient was subsequently kept followed up by a multidisciplinary team in the light of possible lymphoma recurrence and/or development of thyroid dysfunction. This case report demonstrates possible challenges for the diagnosis, treatment, and follow-up of this rare thyroid lesion. At the time of diagnosis, the clinical presentation of the disease, the ultrasound image, and the cytological result may be similar to other low-grade thyroid carcinomas or secondary metastatic involvement of the gland. The initial lack of underlying thyroid autoimmunity makes this distinction even more challenging. Furthermore, despite the rapid resolution, regular long-term monitoring for recurrence is required.

Ultrasound-guided microwave ablation for benign thyroid nodules results in earlier and faster nodule shrinkage in patients with Hashimoto's thyroiditis than in those with normal thyroid function.

Objectives: Given that the histological features of the thyroid parenchyma in patients with Hashimoto's thyroiditis (HT) differ from those of the normal thyroid gland, HT may affect the effectiveness of ultrasound-guided microwave ablation (MWA) for benign thyroid nodules (BTNs). The present study aimed to compare the effectiveness of MWA for the treatment of BTNs in patients with both BTNs and HT and those with BTNs and normal thyroid function, based on changes in the volume reduction ratio (VRR) of the BTNs. Methods: Patients who had achieved a VRR ≥50% after MWA for BTN (July 2020-June 2021), followed up for 12 months, and their data were retrospectively analyzed. Results: A total of 213 nodules were identified in 185 patients, including 167 in the "BTN" group and 46 in the "BTN + HT" group. A comparison of the fitting curves for VRR-follow-up time revealed that the VRR increased with time after MWA, although the relationship was nonlinear. Piece-wise linear regression model analysis of the threshold effect of VRR and follow-up time in the two groups indicated that the inflection point of the "BTN" group occurred at 2.1 months: VRR increased fastest within 2.1 months of MWA (rate of change: 32.9% per month; P < 0.001), following which the rate of change was slower and maintained at 1.0% per month (P = 0.006). In the "BTN + HT" group, the inflection point occurred 1.5 months after MWA, with the most significant increase occurring in this period (rate of change: 41.5% per month; P < 0.001), followed by a rate of 2.8% per month (P < 0.001) after 1.5 months. Conclusions: The relationship between VRR and follow-up time for ultrasound-guided MWA for BTN is nonlinear and exhibits a threshold effect. The current results indicated that the VRR in both groups increased before and after the inflection point, although the rate of change was greater before than after the inflection point. The inflection point occurs earlier in patients with BTN + HT than in those with BTN yet normal thyroid function, and this difference may be related to the "oven effect" involved in the development of HT.

A Rare Case of Hashimoto's Encephalopathy With Mosaic Turner Syndrome.

Mosaicism in Turner syndrome (TS) is a 20%-30% occurrence, with 45, X plus at least another cell line. The haploinsufficiency of the X chromosome is usually responsible for the higher risk of autoimmunity in TS, exhibiting mainly as thyroiditis, type 1 diabetes, etc. Though Hashimoto's thyroiditis is commonly seen in patients with TS, the concurrence of encephalopathy in these patients is significantly rare and has not been reported. We present a case of a young female with mosaic TS who presented with altered mental status. The initial workup was negative for stroke and pulmonary embolism and cerebrospinal fluid (CSF) analysis did not show any infectious etiology. Thyroid peroxidase (TPO) antibodies (Abs) and thyroglobulin Abs were elevated. As the patient's mental status deteriorated, there was a concern for Hashimoto's encephalopathy (HE), hence the patient was started on high-dose IV steroids. Within 24 hours, the patient responded to the IV steroids and an improvement in mentation was noted. HE is a rare immune-mediated disorder, characterized by impaired brain function. The onset of which can be rapid or slowly developing over the course of many years but responds effectively to steroids. Turner syndrome is associated with a high incidence of autoimmune disorders, thus in the setting of a negative workup for more obvious causes, HE should be a consideration when encountered in a clinical scenario.

A Rare and Challenging Case of Neck Infection - Thyroid Abscess.

Acute suppurative thyroiditis (AST) is serious and rare infection of the thyroid gland, often it can progress to thyroid abscess. Both anatomical defects and underlying thyroid disorders are attributed to etiopathogenesis of the disease. Bacteria usually reach the gland either by lymphatic spread or via hematogenous routes. If untreated it has fatal outcome and had serious complications. The mainstay of treatment is usually a combination of intravenous antibiotics and drainage, and sometimes surgery.

A Case of Steroid-Responsive Encephalopathy.

Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy, is associated with autoimmune-mediated thyroiditis. Onset is typically gradual often with evolution over the course of months. Characteristic symptoms include impaired concentration and memory, delusions, hallucinations, personality changes, incoordination, tremor, hemiparesis, seizures, and speech difficulties. Diagnosis is predicated upon discovery of elevated anti-thyroid antibodies, specifically anti-thyroid peroxidase (TPO) or anti-M antibodies. Some patients may also present with subclinical hypothyroidism but many are euthyroid. Of note, neither thyroid function tests or antibody titers correlate with disease severity. Other common laboratory findings include elevations in sedimentation rate, liver enzymes, and cerebrospinal fluid (CSF) protein. Radiological work-up, including cerebral angiography, is often normal. Successful treatment includes administration of steroids and/or intravenous immunoglobulin (IVIg) or plasmapheresis. We describe a case of a 74-year-old male who presented for evaluation of abrupt onset confusion ultimately determined to be a consequence of autoimmune-mediated thyroiditis.

Association of Autoimmune Hashimoto's Thyroiditis with Systemic Lupus Erythematosis.

SLE (systemic lupus erythematosus) can be associated with other autoimmune disorders with overlapping clinical symptoms. We present a case of a 22-year-old male with recurring exertional dyspnea, chest pain, dry cough and chills, which on further testing revealed large pericardial effusion and bilateral pleural effusions along with laboratory abnormalities consistent with a diagnosis of overlap of SLE with serositis and Hashimoto's thyroiditis. SLE patients with underlying hypothyroidism are slow to respond to standard therapy unless the underlying hypothyroidism is adequately treated.

Molecular Insights Into the Relationship Between Autoimmune Thyroid Diseases and Breast Cancer: A Critical Perspective on Autoimmunity and ER Stress.

The etiopathologies behind autoimmune thyroid diseases (AITDs) unravel misbehavior of immune components leading to the corruption of immune homeostasis where thyroid autoantigens turn foe to the self. In AITDs lymphocytic infiltration in the thyroid shows up a deranged immune system charging the follicular cells of the thyroid gland (thyrocytes) leading to the condition of either hyperthyroidism or hypothyroidism. The inflammation in AITDs consistently associate with ER function due to which disturbances in the ER protein homeostasis leads to unfolded protein response (UPR) that promotes pathogenesis of autoimmunity. The roles of ER stress in the instantaneous downregulation of MHC class I molecules on thyrocytes and the relevance of IFN γ in the pathogenesis of AITD has been well-documented. Thyroglobulin being the major target of autoantibodies in most of the AITDs is because of its unusual processing in the ER. Autoimmune disorders display a conglomeration of ER stress-induced UPR activated molecules. Several epidemiological data highlight the preponderance of AITDs in women as well as its concurrence with breast cancer. Both being an active glandular system displaying endocrine activity, thyroid as well as breast tissue show various commonalities in the expression pattern of heterogenous molecules that not only participate in the normal functioning but at the same time share the blame during disease establishment. Studies on the development and progression of breast carcinoma display a deranged and uncontrolled immune response, which is meticulously exploited during tumor metastasis. The molecular crosstalks between AITDs and breast tumor microenvironment rely on active participation of immune cells. The induction of ER stress by Tunicamycin advocates to provide a model for cancer therapy by intervening glycosylation. Therefore, this review attempts to showcase the molecules that are involved in feeding up the relationship between breast carcinoma and AITDs.

The proportional changes of B regulatory cells and suppressor T cells in peripheral blood of patients with Hashimotos' thyroiditis / 中华内分泌代谢杂志

Objective To explore the proportional changes of regulatory B lymphocyte cells (Bregs) and suppressor T lymphocyte cell (Ts) in the peripheral blood of patients with Hashimotos' thyroiditis (HT).Method Sixty-one cases of HT and 38 healthy subjects with matched age and gender were recruited.Flow cytometry technology was used to detect the proportional changes of CD19+ CD24+ CD27 + B cells,CD19+ CD24hi CD38hi B cells,CD19+ IL-10+B cells,and CD8+CD28-T cells.Result Compared with control group,CD19+CD24+CD27+B cells in HT group increased significantly(P＜0.05).With the increase of thyroid peroxidase antibody,CD19+ CD24hi CD38hi B cells were decreased significantly.With the increase of antithyrogloblin antibody (TGAb),CD8 + CD28-T cells were decreased markedly (P＜0.05).TT3 was positively related with CD19 + CD24hi CD38 hiB cells while TT4 had a negative correlation with CD8+ CD28-T cells and positive correlation with CD19+ CD24+ CD27+ B cells.Logistic regression analysis showed that TGAb and FT4 were independent risk factors for decreased CD8+ CD28-T cells in lymphocyte percentage(P＜0.05).TSH was an independent risk factor for the decreased proportion of CD19+ CD24hi CD38hiB cell.FT4 was the independent risk factors for increased CD19+CD24+CD27+B cells(P＜0.05).Conclusion The percentage of Ts cells in patients with HT was lowered,while the different phenotypic Bregs cells showed various changes.Thyroid autoantibodies and thyroid function were closely associated with the immunological changes in HT patients.

Autoinmunidad tiroidea: Mecanismos patogénicos comunes y distintivos en tiroiditis de Hashimoto y enfermedad de Graves / Thyroid Autoimmunity: Common and Distinctive Pathogenic Mechanisms in Hashimotos Thyroiditis and Graves Disease

Las enfermedades tiroideas autoinmunes (ETA) son los desórdenes más frecuentes que llevan a la disfunción de la glándula tiroidea. Incluyen varias formas clínicas como Tiroiditis de Hashimoto (TH) y Enfermedad de Graves (EG). La relación entre TH y EG ha sido objeto de debate por décadas. Si bien, muy diferentes en su clínica, algunos las consideran los lados opuestos de una misma moneda. En su patogénesis tienen aspectos en común, como la predisposición genética demostrado por la ocurrencia en una misma familia y en un mismo individuo. Sin embargo, diferencias en el microambiente local determinan la diferente expresión fenotípica o el viraje de una a otra patología. El objetivo de esta monografía es investigar similitudes y diferencias entre TH y EG en las distintas etapas que llevan al desarrollo de autoinmunidad. Los autores declaran no poseer conflictos de interés.(AU)

Autoimmune thyroid disease (ATD) is the most common disorder that leads to thyroid gland dysfunction. ATD manifests in various clinical forms, such as Hashimotos Thyroiditis (HT) and Graves Disease (GD). The relation between HT and GD has been discussed for decades. Even if they greatly differ in their clinical features and treatment, some people believe they are the opposite sides of the same coin. In their pathogenesis, they share some mechanisms, such as genetic susceptibility, shown by the fact that they tend to occur both in the same person and within the same family. However, differences in the local micro-environment can determine the distinct phenotypic expression or the switch from one disease to the other. The aim of this monograph was to investigate similarities and differences between HT and GD at the diverse stages leading to the development of autoimmunity. No financial conflicts of interest exist.(AU)

Graves' disease associated with Hashimoto's thyroiditis / 대한내분비학회지

Hashimotos thyroiditis and Graves disease have been thought to be the autoirnmune diseases having their distinct and separate clinical and pathologic features. Because of the partial and complete simi1arity in histologic feature, it has been hypothesized that Hashimoto's thyroiditis and Oraves disease may be interrelated. Several patients who had been diagnosed as Graves disease showed features of hypothyroidism, and were proven to have histologie features of Hashimotos thyroiditis in their thyroid tissue. Two meehanisms had been suggested to explain tbis phenomenon. One is that the combined Hashimotos thyroiditis in Graves' disease may become predominant with time, The other is that the amount of TSH receptor blocking antibody may increase in the course of Graves disease. Early recognition of these patients would be impartant to estabilish therapeutic plan. Futhermcee, extensive study of these patients would give more understanding of the mechanism of these diseases. Here we report 5 cases of clinically diagnosed Graves disease with pathologic features of Hashimotos thyroiditis or focal lymphocytic thyroiditis.

A Case of Hashimotos Thyroiditis with Anti-Triiodothyronine Autoantibody / 대한내분비학회지

Autoantibodies against thyroid hormones can be detected in the sera of patients with both thyroidal and non-thyroidal disorders. These antibodies interfere with the radioimmunoassay of serum total and free thyroid hormone concentrations, resulting in a discrepancy between the measured hormone levels and clinical features. This can in turn lead to an erroneous diagnosis and patients may receive unnecessary treatment from physicians who are unaware of the presence of the autoantibodies. We experienced a woman having Hashimotos' thyroiditis with a spurious elevation of total T3 and free T3 values according to one-step analog-tracer radioimmunoassay who was had been treated as Graves' disease in past. Through the use of a polyethylene glycol precipitation method, she was subsequently revealed to have anti-triiodothyronine autoantibodies. We report this case with a review of related literature.

A Case of Autoimmune Hemolytic Anemia & Pericardial Effusion Developed in Hashimoto's Thyroiditis Patient / 대한내분비학회지

Hashimotos thyroiditis has been associated with a various autoimmune disorders. The immunologic mechanisms involved in the pathogenesis of these disorders have not always been thought to be the same. Although it was demonstrated that there were high prevalence of abnormal thyroid function and autoantibody in autoimmune hemolytic anemia(AIHA) and Fisher-Evans syndrome(FES), AIHA combined with Hashimotos thyroiditis is rare in Korean literature. It was suggested that a common immunologic mechanism may be involved in the pathogenesis of both disease and the possibility of multiple autoimmune syndrome might present in autoimmune hematologic disorders. We experienced a 74-year old woman with a 12-year history of a hypothyroidism due to Hashimotos thyroiditis was hospitalized with sudden development of warm AIHA with positive Direct & Indirect Coombs test and pericardial effusion. Her thyroid function test showed subclinical hypothyroidism with the maintenance dosage of levothyroxine(100pg/day). With glucocorticoid and plasmapheresis, AIHA and pericardial effusion were corrected successfully. It is suggested that the prudent immunologic study is needed for the anemia developed in patients with Hashimotos thyroiditis with or without hypothyroidism.

Expression and influencing factors of CD54 in Hashimotos thyroiditis / 第三军医大学学报

Objective To dectect the expression of CD54 in thyroid tissue of Hashimotos thyroiditis patients,and expression changes of CD54 on thyroid cells interferred by different agents.Methods The thyroid tissues from 41 cases of Hashimotos thyroiditis were collected and 26 normal thyroid tissues served as normal controls.All thyroid tissues were identified by pathological examination.The positive expression rate and area of CD54 were investigated by immunohistochemical method and quantitative analysis of image analysis system in all thyroid tissues.The expression changes of CD54 in the isolated thyroid cells interferred by 100,500,1 000 pg/ml IL-1? or 10 mg/L NaI or 1 000 pg/ml IL-1? and 10 mg/L NaI for 48 h were detected by flow cytometry.Results The positive expression rate of CD54 in Hashimotos thyroiditis tissues was much more than that of control tissues(P

Clinical Significance and Immunological Characteristics of Blocking TSH Receptor Antibodies in Patients with Hashimoto's Thyroiditis / 대한내분비학회지

BACKGROUND: TSH receptor blocking antibody (TRBAb) is a pathogenic factor in the vast majority of patients with primary myxedema. It has been reported that TRBAbs are found in some patients with chronic goitrous autoimmune thyroiditis (Hashimoto's thyroiditis), but the significance or the role of TRBAb in Hashimotos thyroiditis is not clear, We recently reported that hTSHR-CHO cells which express the functional human TSH receptors are more sensitive and are better in detecting functional TSH receptor antibodies in Graves patients than FRTL-5 cells. We are to investigate the biological role of TRBAb in Hashimotos thyroiditis by measuring thyroid stimulation blocking antibody (TSBAb) activities of Hashimoto's IgG's using hTSHR-CHO cells. Moreover, we are to see if there is any difference in epitope recognition between Hashimotos TRBAb and myxedema's TRBAb by measuring TSBAb activities with mutant receptor expressing cell lines, Mcl+2 and Mc 2 in those patients. METHOD: We measured TSBAb activities of IgGs from patients with primary myxedema (PM, n= 10) and those with hypothyroid (n 20) or euthyroid (n 17) Hashimoto's thyroiditis (HT) using wild type hTSHR-CHO cells (WT) and two chimeric receptor expressing cell lines, Mcl+2 and Mc2. RESULTS: TSBAb activities measured by WT were higher in hypothyroid HT than in euthyroid HT (30.0+-23.2% vs. 6.1+-28.7, p<0.05), and TSBAb-positive rate tend to be higher in the former (20%, 5/20) than in the latter (0%, 0/17, p=0.07). TRBAbs from PM (n=4) had high TBII activities and had persistent blocking activities despite of the replacement of amino acid residue 8~165 of extracellular domain of TSHR with those of rat LH/CGR (Mcl +2). However, TRBAbs from HT (n=4) had no TBII activity at all and lost blocking activities when measured with Mcl+2. CONCLUSION: TRBAbs are found in 20% of hypothyroid patients with Hashimotos thyroiditis in assay using hTSHR-CHO cells, and they seem to play a role in the development of hypothyroidism in some patients with Hashimotos thyroiditis. TRBAbs of Hashimotos thyroiditis are different in epitope recognition from TRBAbs of primary myxedema.