Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

Acetazolamide as an effective treatment for pilomotor seizures in autoimmune encephalitis.

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti-LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE-associated pilomotor seizures. Six patients with AE (five anti-LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2-days-ON, 4-days-OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self-reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged .56 seizures/day ON, and 3.81 seizures/day OFF (p = .004). The two outpatients reported seizure reductions from 3-5/day to 2/week, and 15-20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings.

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

Nutritional Management of Hashimoto's Thyroiditis: A Case Report.

Introduction: Hashimoto's thyroiditis (HT) is prevalent in about 1 in 1000 people. A 39-year-old female diagnosed with HT was having unsuccessful symptom resolution with conventional thyroxine (T4) replacement therapy. In 60 days, there was a remarkable reduction of thyroid antibodies (Ab), improvement of thyroid hormones, and cardiometabolic biomarkers following a Paleolithic diet (PD). Case Description: A patient unable to lose weight or alleviate gastrointestinal and neurological symptoms after maintaining clinical thyroid stimulating hormone (TSH) levels through conventional T4 medication therapy saw significant reductions in thyroglobulin (47.5%) and thyroid peroxidase (28.9%) Abs, and significant improvement in TSH (36.4%) total T4 (21.5%) and total T3 (33.3%) after 60-day treatment intervention with the PD. Improvements were also seen in HDL (31.6%), LDL (8.9%), total cholesterol (14.9%), and weight (11.5%). The client adhered to a weekly step process of avoidance of foods that have known hypersensitivities and consumed high-quality fats, fermented foods, filtered water, and green tea, and took a daily nutritional supplementation of vitamin D used in conjunction with a homemade turmeric spice blend. Upon final follow-up, the client had a remarkable reduction in symptoms. Conclusion: The Paleolithic diet may be used as a nutritional therapeutic protocol in those with HT with who have complications reducing weight and alleviating gastrointestinal and neurological symptoms no adverse events. Future research should be performed on larger, more diverse populations to develop population-based clinical practice guidelines. Specific areas of research, such as the long-term effects of the PD on HT, comparisons with conventional treatments, and exploring the mechanisms by which PD influences HT symptoms and markers will be beneficial to this research.

Autoimmune Encephalitis following Checkpoint Inhibitor Therapy in a Patient with Metastatic Melanoma in Complete Remission.

The use of immune checkpoint inhibitors (ICIs) in cancer is increasing. Their side effects are mainly due to the triggering of autoimmunity, which are mild or moderate and include skin rash, colitis, hepatitis, endocrine disorders, myositis, interstitial lung disorder, etc., in most cases during the course of therapy. Autoimmune encephalitis (AE) is rare in cancer patients treated with ICIs. Fifty patients with ICI-related encephalitis were identified in a recent review. Herein, we report a case of pembrolizumab associated with AE with a favorable short-term prognosis. A 68-year-old man with malignant metastatic melanoma achieved complete remission after pembrolizumab treatment. However, 10 months after pembrolizumab cessation due to grade 3 diarrhea, he developed confusion, an altered mental status, progressive memory loss, and gait disturbance. He was admitted to the neurologic department, and a comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, and blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, a high dose of intravenous steroids, and intravenous immunoglobulins. The patient improved, and he is now well with a performance status of 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission, and the AE showed a good response after the treatment was performed.

Cardiometabolic Risk Factors in Atorvastatin-Treated Women with Euthyroid Autoimmune Thyroiditis.

INTRODUCTION: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. METHODS: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later. RESULTS: At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness. CONCLUSION: The obtained results indicate that euthyroid women with Hashimoto's thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.

A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis.

A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis Biva Bhakat1 , Jyotirmoy Pal2 , Sukdeb Das3 , Sumit Kr Charaborty4 1,3Nil Ratan Sircar Medical College, Kolkata, 2 RG Kar Medical College and Hospital, 4 North Bengal Medical College, Siliguri Introduction: Hashimoto thyroiditis (HT) is an autoimmune disease that destroys thyroid cells by antibody and call-mediated immune processes. Hashimoto thyroiditis is the commonest cause of goitre in iodine-sufficient regions.[1] The aetiology of Hashimoto disease is very poorly understood. Most patients develop antibodies to a variety of thyroid antigens, the most common of which is anti-thyroid peroxidase (anti-TPO). Many also form antithyroglobulin (anti-Tg) and TSH receptor blocking antibodies (TBII). These antibodies attack the thyroid tissue, eventually leading to inadequate production of thyroid hormone. There is a small subset of the population, around 10-15% with the clinically evident disease, that are serum antibody-negative.[2][3] The mechanisms underlying the assumption that vitamin D is linked with autoimmunity are not clear but probably are associated with its anti-inflammatory and immunomodulatory functions. The dendritic cells are antigen-presenting cells originating from bone marrow and also a primary target for the immunomodulatory activity of vitamin D. 1,25[OH]2D has direct immunomodulatory effects at the level of the T cell vitamin D receptor. Together, these immunomodulatory effects can lead to the protection of target tissues, such as thyroid cells in autoimmune diseases. Considering that in HT, a disorder of T cell-mediated immunity, immunologic attack is triggered when thyrocytes express MHC class II surface HLA-DR antigens, a process induced by the production of Th1 type inflammatory cytokines (especially IFN-γ). Moreover, at another stage, after being activated by T cells, B cells' ongoing proliferation might be inhibited and apoptosis might be induced by 1,25[OH]2D. Thus, 1,25[OH]2D might decrease antibodies that react with thyroid antigens. The exact levels of vitamin D that are sufficient to improve the immune regulatory function and lead to an effective immune response, should be investigated. Several clinical studies have reported a low vitamin D status in AITD or HT, indicating an association between vitamin D deficiency and thyroid autoimmunity. If supplementation of the Vitamin D decreased thyroid antibody titres in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D deficiency. [4] So, our study tries to assess any potential therapeutic role of vitamin D in the management of patients with Hashimoto's thyroiditis. AIMS AND OBJECTIVES: Most studies have shown an association between low vitamin D status and pathogenesis of AITD, especially HT. However, there are only few preliminary interventional studies for HT. whether vitamin D supplementation is beneficial for AITD or HT, should be evaluated. Treatment of HT mainly based on thyroid hormone supplementation, so if a beneficial role of vitamin D supplementation is identified/ confirmed, it will be helpful in the treatment of patients with HT and may be a part of treatment of HT patients. AIMS AND OBJECTIVES: Evaluating the role of vitamin D on an excessive thyroid immune response. MATERIALS AND METHODS: Study area: N.R.S. Medical college and hospital, Kolkata (Department of General Medicine). STUDY PERIOD: 1 year (January,2019 to December,2019 Sample size: 100 patients both male and female. Sample Design: Patients attending outpatient dept in N.R.S medical college. STUDY DESIGN: Prospective, hospital based, single centre study. INCLUSION CRITERIA: Newly diagnosed patients (age >18 years and of both sexes) with HT and vitamin D deficiency. EXCLUSION CRITERIA: Patients suffering from: Other autoimmune diseases. Chronic illnesses like diabetes mellitus, chronic kidney disease, chronic liver disease, malignancy. Pregnancy Study tools: Estimation from serum: TSH. Free thyroxine (FT4) 25 hydroxy vitamin D Anti-thyroid peroxidase (anti-TPO) antibody' Study techniques: This is a prospective study conducted in N.R.S Medical college, Kolkata, India. Total 100 adult patients of both sexes diagnosed with HT and vitamin D deficiency (vit D<30 ng/ml)12, having none of the exclusion criteria and getting treatment on out-patient department basis, who gave informed consent were included in our study. Blood samples drawn for anti TPO antibody and 25hydroxy vitamin D from all the participants. The correlations between serum Vit D and anti TPO antibody were measured and presented by correlation coef ficient (r2). Study participants are randomly assigned into two groups by random permuted block. Cholecalciferol supplement given in the dose of 60,000 IU weekly for 8 weeks in one group (n = 50). Another group (n = 50) were given placebo (empty soft gelatine capsule). At the onset of the study, patients were requested to keep their habitual diet and routine level of physical activity throughout the study period and not to take any medication that might affect their reproductive physiology. Compliance to the consumption of supplement and placebo was examined by empty blister packets. However, 2 patients from cholecalciferol group and 1 patient from control group lost to follow up. After 8 weeks blood anti TPO antibody level measured in both the groups (n = 48 & 49 in 2 group). The change in the mean value of anti TPO antibody measured and statistical significance of the change checked. Results considered significant or non-significant when P> or < 0.05, respectively. TSH, T4 measurement Performed with chemiluminescence using ADVIA Centaur XP Immunoassay System. Work plan: Study was done over 12 months. Data collected and compilation done and then statistical analysis done by standard statistical method. STATISTICAL ANALYSIS: For statistical analysis data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism version 5. p-value ≤ 0.05 was considered for statistically significant. The Negative Correlation was found between Serum 25 hydroxy vitamin D (ng/ml) vs Serum TSH (mU/L) which was statistically significant. Distribution of mean serum anti-TPO antibody level (IU/ml) [mean±SD] in both groups before and after intervention Reduction of serum anti-TPO antibody level in cholecalciferol group is 30.5% and reduction of serum anti-TPO antibody level in placebo group is 16.5%. DISCUSSION: This study is carried out with the total no. of 100 outdoor based patients of diagnosed Hashimoto's Thyroiditis (elevated Anti-thyroid peroxidase antibody) and vitamin D deficiency (vit D < 30 ng/mL)12 in Nil Ratan Sircar medical college and hospital within the mentioned study period. The study focussed on evaluating the role of vitamin D on an excessive thyroid immune response i.e. the effect of vitamin D supplementation on thyroid autoimmunity and that low vitamin D levels and the risk of HT are closely associated and the potential application of vitamin D in the treatment of AITD. The result demonstrates a negative Correlation between Serum 25 hydroxy vitamin D (ng/mL) vs anti TPO antibody (IU/ml) which was statistically significant. Pearson Correlation Coefficient (r)= -0.775, p value = 0.0001. Goswami et al. conducted a community-based survey on 642 adults to investigate the relationship between serum vitamin D concentrations and thyroid autoimmunity. Their results highlighted a significant inverse association between 25(OH)D3 and TPO Ab levels [40]. This inverse correlation was substantiated in the following studies.[5-8] As regards thyroid function in the context of HT, Mackawy and co-workers demonstrated a strong negative association between serum vitamin D concentrations and TSH levels, leading to speculate that vitamin D deficiency in HT patients could be associated with a progression towards hypothyroidism (TSH > 5.0 m UI/L) [45]. Our study also demonstrates negative Correlation between Serum 25 hydroxy vitamin D (ng/mL) vs Serum TSH (mU/L) and the result was statistically significant. Pearson Correlation Coefficient (r) = -0.301, p value = 0.003. So, the results indicate that vitamin D deficiency is a risk factor of Hashimoto's thyroiditis. Mean (mean± s.d.) Serum anti TPO antibody (IU/ml) before intervention was 545.06± 230.82 and after cholecalciferol supplementation the mean value decreased to 378.6± 160.49. So, there is a 30.5% reduction in the mean value of anti TPO antibody level. Difference of mean Serum anti TPO antibody (IU/mL) was statistically significant (p < 0.0001). In the placebo group the mean Serum anti TPO antibody (IU/ml) (mean ± s.d.) of patients was 686.97± 290.19 and after 8 weeks of placebo the mean value was 573.1 ± 254.09. So, in the placebo group the reduction is only 16.5%. Difference of mean Serum anti TPO antibody (IU/ml) was statistically significant (p < 0.0001). Therefore, in line with the hypothesis the data contributes clearer understanding that vitamin D supplementation results in a reduction of thyroid autoimmunity. This result also supports the previous research. Simsek et al. prospectively evaluated 82 patients with HT randomized in two groups: the first group treated with cholecalciferol for one month and the second group without vitamin D replacement. Their results showed that TPO Ab and Tg Ab levels were significantly decreased by the vitamin D replacement therapy in the first group [46]. These findings were also confirmed by other prospective studies and randomized controlled trials.[9-11] So, the result of our studyclearly indicates that vitamin D supplementation could exert a positive effect on thyroid function as well as thyroid autoimmunity Limitations: Vitamin D status is not measured at the end of 8 weeks because of economic constraints. So, it is difficult to determine the optimal level of vitamin D needed for improving the evolution of this immunological disorder. Cholecalciferol is used in HT patients in our study, although active form calcitriol might be more beneficial as vitamin D binding protein level may affect the conversion of inactive vitamin D form and thus alters its function on immune cells. HT patients with normal vitamin D level have been excluded from the study, so from our study we cannot comment on beneficial effect of vit D supplementation in HT patient with normal vit D level. As we used empiric dose of levothyroxine in both the groups instead of a fixed dose, we could not analyze the potential role of vitamin D supplementation in reduction of serum TSH in HT There is still a gap in the knowledge regarding the potential of vitamin D supplementation in the treatment of HT patients whether vitamin D supplementation will help in decreasing the replacement dose of levothyroxine or whether it will stop the need of levothyroxine replacement if used in early stages of HT. CONCLUSIONS: The 8 weeks randomized; double-blind, placebo-controlled clinical trial demonstrates a negative correlation between Serum 25 hydroxy vitamin D vs anti TPO antibody level. Treatment with 60,000 IU cholecalciferol weekly for 8 weeks, is associated with significant decrease in antithyroid antibody titers. It also improved serum TSH level compared with the placebo, i.e. supplementary treatment with cholecalciferol seems to have beneficial effects on AITD. However, large multicentre studies are needed to investigate the impact of vitamin D supplementary treatment on meaningful long-term clinical end points in AITD. References Dana L. Mincer; Ishwarlal Jialal. StatPearls [Internet]. Hashimoto Thyroiditis. Treasure Island (FL): StatPearls Publishing; 2020 Jan. Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr 2019;15(2):124-134. Yuan J, Sun C, Jiang S, et al. The pevalence of thyroid disorders in patients with vitiligo: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2018;. Front Endocrinol (Lausanne). 2018; 9:803. Yoo WS, Chung HK. Recent advances in autoimmune thyroid diseases. Endocrinol Metab (Seoul) 2016;31(3):379-385. Ke W, Sun T, Zhang Y, et al. 25-Hydroxyvitamin D serum level in Hashimoto's thyroiditis, but not Graves' disease is relatively deficient. Endocr J 2017;64(6):581-587. Shin D, Kim KJ, Kim D, et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J 2014; 55:476-481. ElRawi HA, Ghanem NS, ElSayed, N.M.; et al. Study of vitamin D level and vitamin D receptor polymorphism in hypothyroid egyptian patients. J Thyroid Res 2019. Kim CY, Lee YJ, Choi J, et al. The association between low vitamin d status and autoimmune thyroid disease in korean premenopausal women: the 6th korea national health and nutrition examination survey, 2013-2014. Korean J Fam Med 2019;40:323-328. Chaudhary S, Dutta D, Kumar M, et al. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labelled randomized controlled trial. Indian J Endocrinol Metab 2016;20:391-398. Krysiak R, Szkróbka W, Okopie´n, B. The effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D Status. Exp. Clin. Endocrinol. Diabetes 2017;125:229-233. Krysiak R, Kowalcze K, Okopie´n B. Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status. 2018;71:367-373. Mazokopakis EE1, Papadomanolaki MG, Tsekouras KC, et al. Is vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis? Hell J Nucl Med. 2015;18(3):222-7.

Autoimmune Thyroiditis Shifting from Hashimoto's Thyroiditis to Graves' Disease.

In 15-20% of cases, Graves' disease (GD) shifts to Hashimoto's thyroiditis (HT), while the shift from HT to GD is rare. We present a case of a patient in whom HT shifted to GD, along with a literature review. A 50-year-old woman with myxedema was diagnosed with Hashimoto's disease due to hypothyroidism and the presence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb); she also had thyroid stimulating antibodies (TSAb) without any signs of GD. Although thyroid hormone replacement therapy improved her thyroid function, 2 months later, hyperthyroidism appeared and did not improve after discontinuation of the replacement therapy. The patient was diagnosed with GD, which improved with antithyroid agent administration. To date, only 50 cases regarding conversion from HT to GD have been reported. The median age is 44 years (range, 23-82 years), and the median time of conversion is 7 years (range, 0.1-27 years). The male-to-female ratio of HT conversion to GD is 1:9, closer to that of regular GD (1:10) than that of general HT (1:18). All patients received thyroid hormone replacement therapy for hypothyroidism due to HT. Continuous evaluation of TSAb levels is recommended in HT, particularly in cases of TSAb-positive and those under replacement, since it may help predict conversion to GD. Evaluating the clinical characteristics of patients with HT preceding GD is crucial to ensure appropriate treatment and reduce the risk of adverse events.

Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) as a differential diagnosis of Creutzfeldt-Jakob disease.

INTRODUCTION: Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) is characterised by a wide range of neuropsychiatric symptoms and elevated thyroid antibodies. SREAT can mimic sporadic Creutzfeldt-Jakob disease (sCJD) and distinguishing between both entities is important because SREAT responds to corticosteroids. MATERIAL AND METHODS: Data of patients reported to the National Reference Centre for the Surveillance of CJD in Göttingen, Germany between August 1994 and October 2008 was retrospectively reviewed. In the case and control groups, 49 patients had SREAT and 48 had sCJD with elevated thyroid antibodies. RESULTS: Antibodies against thyroid peroxidase were the most common antibodies in both SREAT (86%) and sCJD (88%), followed by antibodies against thyroglobulin (SREAT, 63.3%; sCJD, 39.6%; p = 0.020) and TSH-receptor-antibodies (SREAT, 14.3%; sCJD, 2.1%; p = 0.059). Epileptic seizures were observed more frequently in the SREAT group (SREAT, 44.9%; sCJD, 12.5%; p < 0.001). Dementia (SREAT, 61.2%; sCJD, 100%; p < 0.001), ataxia (SREAT, 44.9%; sCJD, 89.6%; p < 0.001), visual impairment (SREAT, 22.4%; sCJD, 50%; p = 0.005), extrapyramidal disorder (SREAT, 32.7%; sCJD, 60.4%; p = 0.006), myoclonus (SREAT, 38.8%; sCJD, 81.3%; p < 0.001) and akinetic mutism (SREAT, 6.1%; sCJD, 37.5%; p < 0.001) were observed more frequently in sCJD. Cerebrospinal fluid (CSF) pleocytosis was observed more frequently in SREAT patients (SREAT, 33.3%; sCJD, 6.4%; p = 0.001), as was a pathological increase in protein concentration (SREAT, 68.8%; sCJD, 36.2%; p = 0.001). CONCLUSIONS: In a case of encephalopathy, the diagnosis of SREAT should also be considered in suspected cases of CJD so as to be able to start corticosteroid treatment quickly.

Steroid responsive encephalopathy associated with autoimmune thyroiditis as a cause of acuteencephalopathy.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), known as Hashimoto's encephalopathy (HE), represents a heterogeneous group of neurological and neuropsychiatric symptoms associated with a presence of antithyroid antibodies in case of other causes of encephalopathy were excluded. Clinical symptoms most commonly includes acute onset of encephalopathy, behaviour changes and cognitive dysfunction, epileptic seizures as well as cerebellar and extrapyramidal symptoms. Corticoids provides rapid and sustained therapeutic benefit in most patients and only a few patients require other immunosuppressive therapy such as plasmapheresis, intravenous immunoglobulins, or others. We present the cases of two patients with acute onset of encephalopathy, status epilepticus based on SREAT, with rapid improvement after steroid treatment.

Guillain-Barré syndrome with transition from hashimoto's to graves' disease: a case report.

BACKGROUND: On rare occasions, there can be a transition from Hashimoto's to Graves' disease. However, there are no reported cases of transition from Hashimoto's to Graves' disease triggered by the onset of Guillain-Barré syndrome. CASE PRESENTATION: Sixteen years prior, a 55-year-old woman was diagnosed with Hashimoto's disease and followed up without medication. One week after the appearance of signs of intestinal inflammation, weakness in the extremities was observed, and a cerebrospinal fluid test was positive for anti-GM1 IgG antibody, leading to the diagnosis of Guillain-Barré syndrome. In addition, hyperthyroidism was observed at the time of admission, and Graves' disease was diagnosed based on autoantibodies and thyroid echoes. Numbness in the extremities was relieved by high-dose intravenous gamma globulin. CONCLUSION: With the onset of Guillain-Barré syndrome, helper T cells became predominantly type 1, effector B cells increased in number, and thyroid-stimulating antibodies were produced, leading to the conclusion that Hashimoto's disease progressed to Graves' disease. Therefore, it is necessary to pay attention to the transition of thyroid function during Guillain-Barré syndrome.

Autoimmune encephalitis and CSF anti-AMPA GluR3 antibodies in childhood: a case report and literature review.

Acute autoimmune encephalitis is a severe neurological disorder presenting with altered level of consciousness, confusion, irritability, headache, vomiting, and in some cases seizures. An infective event precedes by 1-2 weeks the onset of the symptoms. Cognitive impairment is considered the cardinal symptom. The autoimmune encephalitis comprises an increasingly group of inflammatory brain disorder caused by an underlying abnormal immune response to the CNS to the infective agent. In children, several antibodies have been recorded as causative agent. Among these, GAD65, MOG, and NMDAR antibodies are more commonly reported and with less frequency, the Dopamine-2 receptor, GABA A receptor, GABA B receptor, and Glycinereceptorandm-GluR5. We report here a 10-year-old male with acute autoimmune encephalitis with altered status of consciousness and severe cerebral involvement at the brain-MRI. Serum and cerebrospinal fluid disclosed the presence of anti-AMPA-GluR3 antibodies suggesting a possible pathogenetic correlation with the disorder presented by the proband. Precocious treatment with intravenous methylprednisolone and immunoglobulin resulted in progressive but constant improvement. At 3-month follow-up, the clinical condition of the child and the neuro-radiological brain anomalies returned to the normal. At the 2-year follow-up, no recurrence or other disturbances were reported.

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.

Gluten-free diet attenuates the impact of exogenous vitamin D on thyroid autoimmunity in young women with autoimmune thyroiditis: a pilot study.

Although both exogenous vitamin D and a gluten-free diet were found to reduce thyroid antibody titers, no study investigated interactions between gluten intake and vitamin D status in patients with autoimmune thyroid disorders. The aim of the present study was to assess whether the gluten-free diet determines the effect of vitamin D treatment on thyroid autoimmunity and thyroid function in young women with autoimmune (Hashimoto's) thyroiditis. The study compared two groups of euthyroid premenopausal women with this disorder, matched for thyroid antibody titers: 31 women with non-celiac gluten sensitivity complying for at least 12 months with the gluten-free diet and 31 unaffected sisters of women with non-celiac gluten sensitivity remaining without any dietary intervention. Plasma titers of thyroid peroxidase and thyroglobulin antibodies, as well as plasma concentrations of thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitive C-reactive protein were measured at entry and after a six-month follow-up. Moreover, at both time points, the structure parameters of thyroid homeostasis were assessed. Although exogenous vitamin D decreased titers of thyroid peroxidase and thyroglobulin antibodies and increased 25-hydroxyvitamin D levels in each treatment group, this effect was less pronounced in patients on the gluten-free diet than in patients not following any dietary recommendations. Only in the latter group of patients, vitamin D increased SPINA-GT. Treatment-induced changes in thyroid peroxidase and thyroglobulin antibodies correlated with the impact of treatment on 25-hydroxyvitamin D levels. The obtained results suggest that gluten-free diet may impair beneficial effects of exogenous vitamin D in individuals with Hashimoto's thyroiditis.

Hashimoto's encephalopathy presenting as Wernekinck commissure syndrome: A case report.

The Wernekinck commissure syndrome is extremely rare in a clinical setting. This condition has been previously reported in association with midbrain infarction, midbrain hemorrhage, demyelinating pseudotumor, and optic neuromyelitis spectrum disease, but not with Hashimoto's encephalopathy. Herein, we report the case of a 44-year-old hypertensive man who developed cerebellar ataxia, internuclear ophthalmoplegia, and cognitive decline. Magnetic resonance imaging (MRI) of the brain revealed brain stem damage involving Wernekinck commissure. Initially, this patient was diagnosed with acute midbrain infarction in another hospital. However, his symptoms did not improve after the administration of anti-platelet aggregation drugs, statin, and free radicals scavenging treatment. Re-examination of cranial MRI revealed abnormal signals in the left parietal lobe. After a series of investigations that excluded cerebral infarction and neurodegenerative diseases, Hashimoto's encephalopathy was finally diagnosed. The patient's symptoms improved remarkably after treatment with methylprednisolone and γ-globulin. To the best of our knowledge, there are no other reports on the onset of Wernekinck commissure syndrome in the clinical manifestations of Hashimoto's encephalopathy.

Vitamin D Implications and Effect of Supplementation in Endocrine Disorders: Autoimmune Thyroid Disorders (Hashimoto's Disease and Grave's Disease), Diabetes Mellitus and Obesity.

Background and Objectives: Vitamin D deficiency is involved in numerous pathologies, including endocrine pathology. The purpose of this review consists of presenting the role of vitamin D in the pathophysiology of certain endocrine disorders, autoimmune thyroid disorders (Hashimoto's disease and Grave's disease), diabetes mellitus, and obesity, and whether its supplementation can influence the outcome of these diseases. Materials and Methods: Review articles and original articles from the literature were consulted that corresponded with the thematic. Results: Vitamin D deficiency is frequently encountered in endocrine disorders and supplementation restores the normal values. In Hashimoto's disease, vitamin D deficiency appears to be correlated with a higher titer of anti-TPO antibodies and with thyroid volume, and supplementation was associated with reduction of antibodies in some studies. In other studies, supplementation appeared to reduce TSH levels. In Grave's disease, there was a significant correlation regarding vitamin D levels and thyroid volume respective to the degree of exophthalmos. In diabetes mellitus type 2 patients, supplementation led to some improvement of the HOMA-IR index and HbA1c, whereas obesity data from literature do not report significant beneficial findings. Conclusions: Vitamin D deficiency is highly prevalent in endocrine disorders and its supplementation appears to have numerous beneficial effects.

FEATURES OF MANAGEMENT OF AUTOIMMUNE THYROIDITIS IN CHILDREN: A CASE REPORT.

The article reflects the main links of pathogenesis and diagnostic criteria for autoimmune thyroiditis (AIT) and subclinical hypothyroidism as well as presents formulated features of signs and symptoms, diagnosis, and therapy of this disease in children. Here, we present a case report of an adolescent patient with AIT that was treated with L-thyroxine. The feature of this case was the development of laboratory-confirmed drug-induced hyperthyroidism against the background of hypersensitivity to the drug, what required correction of the therapy.

Management of autoimmune encephalitis.

PURPOSE OF REVIEW: Autoimmune encephalitides are established diagnoses in contemporary neurology. Their management poses a regular challenge for almost all neurologists. One may ask if the concept of 1st line and 2nd line treatment is still up to date, which new data on the antibody-defined encephalitis types exist, and how to organize long-term management. RECENT FINDINGS: The 1st line/2nd line concept of initial immunological intervention is accepted worldwide. A randomized controlled trial confirmed that one 1st line compound (intravenous immunoglobulins) is superior to a placebo in patients with antibodies against leucine-rich glioma inactivated protein 1. Rituximab, a 2nd line compound, is increasingly and apparently successfully used in treating different types of autoimmune encephalitis. It may find its place even earlier in the treatment cascade. Long-term management needs to be improved and is under development. SUMMARY: There have been no groundbreaking new developments in the field. The published experience confirms existing suggestions. Aspects of long-term management including rehabilitation measures and counseling about driving eligibility require further research.

Tofacitinib treatment for refractory autoimmune encephalitis.

To treat intractable cases of autoimmune encephalitis, the need for novel immunotherapy that penetrates the blood-brain barrier (BBB) is increasing. Tofacitinib is a Janus kinase (JAK) inhibitor used to treat refractory immune-mediated diseases that effectively penetrates the BBB. Accordingly, tofacitinib could be a new option for patients with refractory autoimmune encephalitis. Patients treated with tofacitinib were selected from Seoul National University Hospital cohort for autoimmune encephalitis from April 2019 until July 2020. We retrospectively analyzed the efficacy of tofacitinib in patients with autoimmune encephalitis who showed insufficient responses to multimodal conventional immunotherapies. Tofacitinib was administered orally at a dose of 5 mg twice daily. A total of eight patients were treated with tofacitinib; two had good responses (clinical global impression-improvement score [CGI-I] = 1 or 2), three had partial responses (CGI-I = 3), and three showed no significant improvements (CGI-I = 4) in response to tofacitinib. The two good responders showed the improvement of chronic autoimmune meningoencephalitis and the cessation of the new-onset refractory status epilepticus in anti-myelin oligodendrocyte glycoprotein (MOG)-associated disorder, which was previously intractable to anesthetics and the other immunotherapies. No patients had serious side effects. Our findings suggest the potential of tofacitinib as a therapeutic option for central nervous system autoimmune diseases.

Orbital inflammatory disorders: new knowledge, future challenges.

PURPOSE OF REVIEW: This review aims to bring together recent advances in basic, translational and clinical research on the pathogenesis and treatment of orbital inflammatory conditions. RECENT FINDINGS: Basic science studies provide mechanistic insights into why the orbit is targeted for inflammation by autoimmune inflammatory disorders. Using Graves' disease as a test case reveals that endocrine pathways, such as the TSH and IGF1 receptor pathways play important roles in stimulating orbital inflammation. Furthermore, orbital tissues contain high concentrations of retinoids - byproducts of the visual pathway that diffuse across the sclera and can activate de novo transcription of inflammatory cytokines. Such cytokine expression places the orbit in a hyper-inflammatory 'resting' state, prone to respond to any additional systemic or local pro-inflammatory signals. The HIF2A--LOX pathway appears important for orbital tissue fibrosis. Lastly, bench-to-bedside studies of the IGF1R pathway have led to an FDA-approved drug, teprotumumab that represents a novel treatment approach for Graves' orbitopathy. Unfortunately, high drug costs and misplaced insurance company 'step-therapy' policies may block patients from receiving therapy that can protect vision and improve quality of life. SUMMARY: Improved understanding of orbital inflammatory conditions has led to a new drug and promises additional breakthroughs. Translational research is successful, but requires time, resources, and patience.