Hashimoto's Encephalopathy: Case Series and Literature Review.

PURPOSE OF REVIEW: To describe the clinical manifestations of Hashimoto's encephalopathy (HE) and discuss its pathogenesis in light of recent research. RECENT FINDINGS: The pathogenesis of HE is uncertain. Available evidences point towards an autoimmune etiology due to vasculitis or other inflammatory process. Detection of thyroid antibodies - antithyroid peroxidase and anti-thyroglobulin are essential for diagnosis. Autoimmune encephalitis including Anti-IgLON5 disease needs to be excluded in suspected cases with appropriate tests for neuronal surface antibodies. Detection of thyroid autoantibodies is nonspecific, as these can be detected in some normal individuals and in other autoimmune diseases. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels in younger males with very high levels of thyroid antibodies. The role of the thyroid autoantibodies in the central nervous system (CNS) tissue damage remains unclear and these can act only as markers for diagnosis. Conversely, they have a role to play in determining the thyroid pathology - more glandular fibrosis associated with thyro-peroxidase antibody than with the thyroglobulin antibody. HE is a syndrome characterized by altered mental status, confusion, hallucinations, delusions, and sometimes seizures, in association with high serum anti-thyroid antibody concentration that is usually responsive to glucocorticoid therapy. Diagnosis requires the exclusion of other causes of encephalopathies and encephalitis including autoimmune encephalitis associated with neuronal surface antibodies and paraneoplastic ones. Diagnosis also is dependent on the demonstration of thyroid autoantibodies in serum. Since there is no direct pathophysiologic link between antithyroid antibodies, Hashimoto thyroiditis and the cerebral syndrome, the nomenclature HE could be misleading. The response to steroids led to a renaming of the syndrome to steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), though some cases do not respond to steroids. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels (IgG4-related disease). This is characterized by a higher incidence in men (5:1) than in women, onset at a younger age, more intense thyroid inflammation and higher antithyroid antibody titters. Such patients have excessive production of IgG4 + plasmacytes, which infiltrate various organs leading to their fibrosis and sclerosis, sometimes resulting in inflammatory tumors. HE is treated with corticosteroids along with treatment of the dysthyroid condition, if any. There are yet no guidelines regarding steroid dose and/or duration.

The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and Nutrition Examination Survey (NHANES), 2007-2012.

BACKGROUND: Selenium has been shown to influence the pathological processes and physiological functions of thyroid. Although growing evidence has shown that selenium can improve the treatment of Hashimoto's thyroiditis (HT), there is a need to evaluate the association between dietary selenium intake and HT in a large cross-sectional study. This study explored the association between dietary selenium intake and HT based on the National Health reand Nutrition Examination Survey (NHANES) database (2007-2012). METHODS: A total of 8756 of 30,442 participants were included in the study. Dietary selenium intake was the independent variable, while HT was the dependent variable. In addition, the relative importance of the selected variables was determined using the XGBoost model. A smooth curve was constructed based on the fully adjusted model to investigate the potential linear relationship between dietary selenium intake and HT. Smooth curves were also constructed to explore the linear/non-linear relationship between dietary selenium intake and thyroid peroxidase antibody (TPOAb)/ thyroglobulin antibody (TgAb). RESULTS: The mean age of the enrolled participants was 44.35 years (± 20.92). The risk of HT was significantly reduced by a 35% per-unit increase in dietary selenium intake after fully adjusting for covariates according to the model (log2-transformed data; OR 0.65; 95% CI 0.51, 0.83). The XGBoost model revealed that dietary selenium intake was the most important variable associated with Hashimoto's thyroiditis. Dietary selenium intake (Log2-transformed) was negatively correlated with TPOAb levels [- 16.42 (- 22.18, - 10.65), P < 0.0001], while a non-linear relationship was observed between dietary selenium intake and TgAb with an inflection point of 6.58 (95.67 µg, Log2-transformed). CONCLUSION: Dietary selenium intake is independently and inversely associated with HT risk. Moreover, dietary selenium intake is negatively correlated with TPOAb levels and non-linearly correlated with TGAb levels. Therefore, dietary selenium intake may be a safe and low-cost alternative for the prevention and treatment of HT.

Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

Analysis of Therapeutic Effect and Influencing Factors of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma.

OBJECTIVES: The current study sought to explore the effects of ultrasound (US)-guided radiofrequency ablation (RFA) on papillary thyroid microcarcinoma (PTMC) and influencing factors. METHODS: PTMC patients were assigned to observation (US-guided RFA) and control (surgical operation) groups. A series of operation-related indexes (operation time, intraoperative bleeding, wound closure time, hospital stay, and expenses), visual analogue scale score, lesion size, and thyroid function-related indexes (thyroid-stimulating hormone [TSH], free triiodothyronine*** [FT3], free thyroxine [FT4]), inflammatory factors, and thyroglobulin antibody (TgAb) were assessed and compared. After a 6-month follow-up period, the complications and recurrence were recorded, in addition to analyses of postoperative recurrence cumulative incidence and evaluation of recurrence risk factors. RESULTS: Operation-related indexes of the observation group were relatively decreased compared with the control group. In addition, the lesion volume in the observation group was lower compared to that in the control group at the 6th month after operation, whereas the volume reduction rate was higher. There were no significant differences in regard to thyroid function-related indexes in the observation group before/after operation. After operation, serum TSH levels and inflammatory factors, and TgAb levels were all diminished, while the FT3 and FT4 levels were both elevated in the observation group relative to the control group, and postoperative recurrence cumulative incidence was lower in the observation group. TSH and TgAb were established as the independent risk factors for recurrence after RFA in PTMC patients. CONCLUSIONS: Our findings highlighted that US-guided RFA exhibits better efficacy, safety, and postoperative recovery and lower recurrence risk for PTMC.

Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum.

As previously demonstrated, serum beta-human chorionic gonadotropin (ß-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum ß-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum ß-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum ß-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between ß-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and ß-hCG levels for HG. Versus those in the control group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum ß-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that ß-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum ß-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, ß-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

Association between thyroid autoimmunity and the decline of ovarian reserve in euthyroid women.

RESEARCH QUESTION: Is thyroid autoimmunity (TAI) associated with the decline of ovarian reserve in euthyroid women? DESIGN: Case-control study. Data from 4302 euthyroid women with normal ovarian reserve (NOR) and low ovarian reserve (LOR), including biochemical premature ovarian insufficiency (POI) and overt POI, were retrospectively analysed. The prevalence and effect of TAI on ovarian reserve was evaluated between women with NOR and LOR. Status of ovarian insufficiency and TSH levels was further stratified for analysis. The correlation between anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) titres and ovarian reserve markers was also determined. RESULTS: The prevalence of positive TAI and TgAb was equally distributed between women with NOR and LOR (P = 0.080, P = 0.172); the prevalence of TPOAb positivity was higher in the LOR group (P = 0.005). After stratifying ovarian reserve and TSH, positive TAI, TPOAb and TGAb were significantly associated with overt POI when TSH was >2.5 µIU/ml (all P < 0.001); no association was observed with biochemical POI or overt POI when TSH was ≤2.5 µIU/ml. No correlation was found between TPOAb, TGAb titres and AMH (P = 0.218, P = 0.368, respectively), and bilateral AFC (P = 0.184, P = 0.315, respectively) in patients with LOR; only TPOAb titre was positively correlated with FSH (P = 0.039). CONCLUSIONS: Among the whole population of euthyroid women, TAI was not associated with low ovarian reserve but was significantly associated with overt POI in women with TSH>2.5 µIU/ml. Further basic studies on underlying mechanisms are needed.

Presence or severity of Hashimoto's thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank.

PURPOSE: The influence of Hashimoto's thyroiditis (HT) on calcitonin (Ct) production is unresolved question. The aim of this study was to explore if basal Ct levels are influenced by the presence/severity of HT or correlated with clinical phenotypes of HT patients. METHODS: We included 467 HT patients and 184 control participants, from Croatian Biobank of HT patients (CROHT), in this retrospective study. Calcitonin levels between HT patients and controls were compared using Mann-Whitney test. Ct levels between two subgroups of HT patients, divided by intake of levothyroxine (LT4) therapy, were additionally tested to take into account the illness severity. Spearman rank correlation test was used to analyze correlations between Ct levels and 14 relevant phenotypes. RESULTS: We have not detected significant differences in median Ct levels between HT patients and controls (2.2 vs 2.35 pg/mL, respectively, P = 0.717) nor in-between two subgroups of HT patients (P = 0.347). We have not detected statistically significant correlations between Ct levels and clinical phenotypes, although we identified three weak nominal correlations: negative correlation of Ct with TgAb in all HT patients (r = - 0.1, P = 0.04); negative correlation of Ct with age in subgroup of HT patients without LT4 therapy (r = - 0.13, P = 0.04); positive correlation of Ct with BSA in subgroup of HT patients on LT4 therapy (r = 0.16, P = 0.042). CONCLUSION: Our results suggest that HT patients of all disease stages preserve Ct production as healthy individuals and there is no need for Ct measurements in the absence of a nodule. Additional confirmation and clarification of observed nominal correlations are needed due to potential clinical relevance of TgAb and age-dependent Ct decrease in HT women.

The prediction effects of thyroid function in the severity of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated inflammatory disorder affecting the peripheral nervous system (PNS), is usually complicated with autoimmune diseases including thyroid diseases. Herein, we explored roles of thyroid function and thyroid autoantibodies in the disease severity and its short-term prognosis of GBS. In addition, we further investigated the predictive value of thyroid function for GBS respiratory insufficiency. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 219 GBS patients. According to the thyroid function, the enrolled subjects were divided into 2 groups, that is, patients with abnormal thyroid function (case group) and those with normal thyroid function (control group). The clinical characteristics, disease severity, and short-term prognosis of the patients in 2 groups were compared. In addition, we also divided the 219 GBS patients into mechanical ventilation (MV) group and non-MV group according to whether MV was performed within 1 week after admission. The clinical characteristics, disease severity, short-term prognosis, Erasmus GBS respiratory insufficiency score (EGRIS), and the thyroid function were compared in the two groups. RESULTS: We found that GBS patients with abnormal thyroid function had longer duration of hospitalization, higher frequency of cranial nerve damage, and higher incidence of weakened tendon reflexes. Medical Research Council (MRC) scores on admission, at nadir, and at discharge were lower, and Hughes Functional Grading Scale (HFGS) scores on admission and at discharge were higher in GBS patients with abnormal thyroid function group. More patients in the abnormal thyroid function group had myelin, axonal, and myelin-axonal injuries. In the MV group, the time from onset to admission, MRC scores on admission, and the levels of free triiodothyronine (FT3) were lower; the levels of thyroglobulin antibody (TgAb) and EGRIS were significantly higher than those in the non-MV group. The combination of EGRIS and FT3 serum levels to predict GBS patients with MV, the area under the curve (AUC) was 0.905 (95% CI: 0.861 to 0.948, P < 0.05), sensitivity was 88.9%, and specificity was 84.7%. CONCLUSION: Our results suggest that the serum FT3 levels are negatively correlated with disease severity; the serum FT3 might be a biomarker for the incidence and severity of GBS. Both EGRIS and serum FT3 have a predictive value for the occurrence of acute respiratory insufficiency in GBS patients, and the combination of these two indicators can more accurately predict the risk of acute respiratory insufficiency in GBS patients.

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OBJECTIVES: To examine the expression of serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in children with immune thrombocytopenia (ITP). METHODS: A total of 120 children with ITP who were admitted from October 2019 to October 2021 were enrolled as the ITP group. A total of 60 children without ITP were enrolled as the non-ITP group. According to the clinical classification of ITP, the children in the ITP group were further divided into a newly diagnosed ITP group, a persistent ITP group, and a chronic ITP group. The clinical data were compared between the ITP group and the non-ITP group and between the children with different clinical classifications of ITP. The expression levels of serum TGAb and TPOAb in children with ITP were measured and their association with the clinical classification of ITP was analyzed. RESULTS: Compared with the non-ITP group, the ITP group had significantly lower levels of CD3+, CD4+, and platelet count (PLT) and significantly higher levels of CD8+, TGAb, and TPOAb (P<0.05). The children with chronic ITP had significantly lower levels of CD3+, CD4+, and PLT and significantly higher levels of CD8+, TGAb, and TPOAb than those with newly diagnosed ITP or persistent ITP (P<0.05). The logistic regression analysis showed that CD3+, CD4+, CD8+, TGAb, and TPOAb were the influencing factors for chronic ITP (P<0.05). A decision curve was plotted, and the results showed that TGAb combined with TPOAb within the high-risk threshold range of 0.0-1.0 had a net benefit rate of >0 in evaluating the clinical classification of ITP in children. CONCLUSIONS: TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.

Pre-Operative Antithyroid Antibodies in Differentiated Thyroid Cancer.

OBJECTIVE: To evaluate the significance of antithyroglobulin and antithyroid peroxidase antibody levels associated with locoregional metastatic disease in patients with well-differentiated thyroid cancer. METHODS: Patients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected: age, sex, pre-operative thyroid-stimulating hormone, thyroglobulin, antithyroglobulin antibody (TgAb), antithyroid peroxidase antibody (TPOAb), the extent of surgery, T-stage, N-stage, extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion, and multifocal disease. The relationships between disease status and pre-operative TPOAb, TgAb, thyroglobulin, and thyroid-stimulating hormone were analyzed. RESULTS: A total of 405 patients (mean age, 52 years) were included in the study, of which 66.4% were women. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (P < .01), with a stronger correlation to N1b versus N1a disease (P = .03). The presence of ETE was inversely related to the TgAb titer (P = .03). TPOAb was associated with a lower T-stage (P = .04), fewer LNM (P = .04), and a lower likelihood of ETE (P = .02). From multivariable analysis, TgAb ≥40 IU/mL was an independent predictive factor for a higher N-stage (P < .01 for N0 vs N1; P = .01 for N1a vs N1b), and ENE (P < .01). TPOAb ≥60 IU/mL was associated with a lower T-stage (P = .04 for T <3) and absence of ETE (P = .01). CONCLUSION: Elevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T- and N-stage. Pre-operative antithyroid antibody titers may be useful to inform the disease extent and features.

Autoimmune thyroid disease in children with diabetes and adolescents: A single center study from south Punjab.

OBJECTIVE: To evaluate the prevalence of autoimmune thyroid disease in children with diabetes. METHODS: The descriptive cross-sectional study was conducted from January to December 2019 at the Children Hospital and the Institute of Child Health, Multan, Pakistan, and comprised paediatric type 1 diabetes mellitus patients of both genders. Blood samples were obtained for detailed testing of thyroid functions tests. Data was analysed using SPSS 20. RESULTS: Of the 161 paediatric subjects, 83(51.6%) were boys. The overall mean age was 9.7±4.3 years. Thyroid peroxidase antibody was positive in 34(21.1%) patients and thyroglobulin antibody in 27(16.7%). Both antibodies were positive in 17(10.5%) patients. Six (3.7%) patients had evidence of subclinical hypothyroidism, 8(4.9%) had overt hypothyroidism and 1(0.62%) had hyperthyroidism. CONCLUSIONS: The prevalence of autoimmune thyroid disease among children and adolescents with type 1 diabetes mellitus was 21%, with hypothyroidism being more prevalent compared to hyperthyroidism.

Excellent diagnostic performance of FNA-Tg in detecting lymph nodes metastases from papillary thyroid cancer.

Background: Thyroglobulin washout of fine needle aspiration (FNA-Tg) has proved to be useful in detecting lymph node metastases from papillary thyroid cancer; however, the influences of thyroid gland, Hashimoto thyroiditis, serum thyroglobulin (Tg) and anti-TG antibody on the diagnostic performance of FNA-Tg are controversial. Patients & methods: We retrospectively collected the FNA-Tg results of 176 preoperative or postoperative patients (356 lymph nodes) who finally were diagnosed with papillary thyroid cancer. The diagnostic abilities of FNA-Tg were evaluated and compared under different circumstances. Results: The diagnostic performance of FNA-Tg was uninfluenced irrespective of the status of thyroid gland or serum anti-TG antibody. However, high serum Tg was positively correlated with FNA-Tg (Exp(B) = 1.57; 95% CI: 1.209-2.309; p = 0.001). Conclusion: FNA-Tg was an excellent diagnostic tool, but it should be interpreted with caution only if serum Tg is higher than 10 ng/ml.

Gastric parietal cell and thyroid autoantibodies in patients with burning mouth syndrome.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in burning mouth syndrome (BMS) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 884 BMS patients and in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 12.3%, 21.6%, and 22.7% of 884 BMS patients and 1.8%, 2.3%, and 2.9% of 442 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. BMS patients had significantly higher frequencies of GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). We also found that 20 (2.3%), 130 (14.7%), and 181 (20.5%) BMS patients and 3 (0.7%), 8 (1.8%), and 6 (1.4%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 255 TGA/TMA-positive BMS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.8%, 5.1%, and 7.1% of these TGA/TMA-positive BMS patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 37.5% of 884 BMS patients have serum GPCA/TGA/TMA positivity. Moreover, 12.3%, 21.6%, and 22.7% of 884 BMS patients have the serum GPCA, TGA, and TMA positivities, respectively. Only 5.1% and 7.1% of TGA/TMA-positive BMS patients have hyperthyroidism and hypothyroidism, respectively. It needs further studies to know whether GPCA-positive BMS patients may finally become as having autoimmune atrophic gastritis.

Thyroid disorders in Taiwanese children with Down syndrome: The experience of a single medical center.

BACKGROUND/PURPOSE: Thyroid disorders are common in children with Down syndrome (DS), however, such data have rarely been reported in Taiwanese children. This study presents our experience with the management of these children. METHODS: Between 2006 and 2016, 51 children (31 boys and 20 girls) with DS were enrolled. Thyroid function was evaluated and natural course of thyroid status were analyzed. RESULTS: Of 51 patients with DS, 2 had congenital hypothyroidism due to dyshormonogenesis. Of the remaining 49 patients, 30 (61%) had euthyroidism (EuT), and 19 (39%) had subclinical hypothyroidism (SH). Eighteen (37%) had detectable thyroid antibodies. It occurred at any age and the incidence was not affected by sex. The mean follow-up duration for 39 DS children was 3.8 ± 2.4 years. Of the 26 children who had EuT at enrollment and were followed up, 22 remained EuT, 2 developed SH, 1 developed overt hypothyroidism, and 1 developed overt hyperthyroidism. Of the 13 patients with SH who were followed up, 1 was treated for high thyroid-stimulating hormone levels, 8 became EuT, and 4 maintained SH status. Children with DS and persistent SH had significantly higher maximum thyroid-stimulating hormone levels during follow-up than did those with transient SH. Fluctuation in thyroid status during follow-up was not uncommon in children with DS. CONCLUSION: The prevalence of thyroid disorders is higher in Taiwanese children with DS than in the general population. Because symptoms of hypothyroidism overlap those inherent to DS, regular follow-up of thyroid function in children with DS is indicated.

Polymorphisms in TSHR gene and the risk and prognosis of autoimmune thyroid disease in Tunisian population.

BACKGROUND: Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. TSHR is considered as candidate gene in GD. This finding prompted us to investigate the association of TSHR gene polymorphism with the risk and the prognosis of AITD in Tunisia. METHODS: A total of 84 healthy controls and 91 patients with AITD (69HT and 22 GD) were genotyped for TSHR rs74067403A>G polymorphism and 134 healthy controls and 149 patients with AITD (98 HT and 51 GD) were genotyped for TSHR rs1054708 T>C polymorphism. RESULTS: For rs1054708, we found an association between HT, AITD and the heterozygous genotype TC, the mutated genotype CC and the genotypes presented the mutated allele C (TC+CC) and with mutated allele C. The heterozygous genotype TC and the genotypes that presented the mutated allele C of rs1054708 are associated with male patients with AITD evenly the heterozygous genotype TC is associated with age of onset of disease. CONCLUSIONS: These preliminary results suggest that TSHR rs1054708 polymorphism may be a protective factor against HT and AITD. This polymorphism can affect the etiology of AITD between men and women and also by age.

Gastric parietal cell and thyroid autoantibodies in patients with atrophic glossitis.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of presence of serum GPCA, TGA, and TMA in atrophic glossitis (AG) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 1064 AG patients and in 532 age- and sex-matched healthy control subjects. RESULTS: We found that 26.7%, 28.4%, and 29.8% of 1064 AG patients and 2.3%, 2.1%, and 2.6% of 532 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. AG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). We also found that 67 (6.3%), 181 (17.0%), and 340 (32.0%) AG patients and 3 (0.6%), 10 (1.9%), and 8 (1.5%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 373 TGA/TMA-positive AG patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 78.6%, 8.0%, and 13.4% of these TGA/TMA-positive AG patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 55.3% of 1064 AG patients have serum GPCA/TGA/TMA positivity. Because part of GPCA-positive AG patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive AG patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these autoantibody-positive AG patients should be referred to medical doctors for further management.

Gastric parietal cell and thyroid autoantibodies in oral precancer patients.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) may be present in oral mucosal disease patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 131 oral precancer patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects. RESULTS: We found that 131 oral precancer patients had higher frequencies of serum GPCA (10.7% vs. 2.3%, P = 0.012, statistically significant), TGA (4.6% vs. 2.3%, P = 0.498), and TMA (8.4% vs. 2.3%, P = 0.054, marginal significance) positivities than 131 healthy control subjects. We also found that 1 (0.8%), 6 (4.6%), and 16 (12.2%) oral precancer patients had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) autoantibody in their sera, respectively. Of 10 TGA/TMA-positive oral precancer patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 80%, 10%, and 10% of these 10 TGA/TMA-positive oral precancer patients had normal, lower, and higher serum TSH levels, respectively. We also found a significantly higher GPCA positive rate in 26 smokers consuming >20 cigarettes per day than in 61 smokers consuming ≤20 cigarettes per day (P = 0.008). CONCLUSION: Approximately 17.6% of 131 oral precancer patients have serum GPCA/TGA/TMA positivity. Only approximately 20% of TGA/TMA-positive oral precancer patients have either hypothyroidism or hyperthyroidism.

Blood profile of atrophic glossitis patients with thyroglobulin antibody/thyroid microsomal antibody positivity but without gastric parietal cell antibody positivity.

BACKGROUND/PURPOSE: Our previous study found that 304 of 1064 atrophic glossitis (AG) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCAÖ¾TGA+/TMA+AG patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. METHODS: The mean blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCA-negative, TGA-negative, and TMA-negative AG patients (GPCAÖ¾TGAÖ¾TMAÖ¾AG patients) or 532 healthy control subjects. RESULTS: We found significantly lower MCV and lower mean blood Hb and iron levels as well as significantly greater frquencies of microcytosis, macrocytosis, blood Hb, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in 304 GPCAÖ¾TGA+/TMA+AG patients than in 532 healthy control subjects. However, no significant differences in the MCV and mean blood Hb, iron, vitamin B12, folic acid, and homocysteine leve1s as well as no significant differences in the frequencies of microcytosis, macrocytosis, blood Hb, iron, and folic acid deficiencies, and hyperhomocysteinemia were discovered between 304 GPCAÖ¾TGA+/TMA+AG patients and 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. The 304 GPCAÖ¾TGA+/TMA+AG patients had a significantly greater frquency of serum vitamin B12 deficiency than 476 GPCAÖ¾TGAÖ¾TMAÖ¾AG patients. CONCLUSION: The disease of AG itself plays a significant role in causing anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia, serum iron and folic acid deficiencies, and hyperhomocysteinemia in GPCAÖ¾TGA+/TMA+AG patients.

Recurrent aphthous stomatitis - Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management.

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregulated disease. Factors that modify the immunologic responses in RAS include genetic predisposition, viral and bacterial infections, food allergies, vitamin and microelement deficiencies, systemic diseases, hormonal imbalance, mechanical injuries, and stress. Our previous study found the presence of serum gastric parietal cell antibody, thyroglobulin antibody, and thyroid microsomal antibody in 13.0%, 19.4%, and 19.7% of 355 RAS patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 20.9%, 20.1%, 4.8%, 2.6%, and 7.7% of 273 RAS patients, respectively. Therefore, it is very important to examine the complete blood count, serum autoantibody, hematinic, and homocysteine levels in RAS patients before we start to offer treatments for RAS. Because RAS is an immunologically-mediated disease, topical and systemic corticosteroid therapies are the main treatments of choice for RAS.

Assessment of thyroid function in children, adults and pregnant and lactating women after long-term salt iodisation measurements.

Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.