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New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction and Objectives: Recent studies have indicated a potential association of hypertension with Hashimoto's thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood., Methods: We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genome-wide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies., Results: Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10 -5 ) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10 -3 ). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10 -5 ) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10 -3 ) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications., Conclusion: The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cui, Chen, Xu, Mao and Chen.)

Introduction: Autoimmune encephalitis (AE) comprises a group of inflammatory brain disorders mediated by autoimmune responses. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and anti-γ-aminobutyric acid-B receptor (GABABR) encephalitis are the most prevalent forms, characterized by the presence of antibodies against neuronal cell-surface antigens. Efgartigimod, an antagonist of the neonatal Fc receptor, has proven efficacy in myasthenia gravis treatment. This clinical case report describes the clinical progression and functional outcomes of AE in three patients who received efgartigimod treatment., Case Presentations: Case 1 was a 60-year-old man exhibiting memory impairment and psychiatric disturbances over 11 days. Case 2 was a 38-year-old man with a 1-month history of rapid cognitive decline and seizures. Case 3 was a 68-year-old woman with mental behavioral changes and seizures for 4 months. Anti-GABABR, anti-LGI1, and anti-NMDAR antibodies were confirmed in the respective patients' cerebrospinal fluid or serum. All three patients experienced marked and swift symptomatic relief after four cycles of efgartigimod treatment, with no complication., Conclusion: Current first-line and second-line treatments for AE have limitations, and efgartigimod has demonstrated potential in the rapid and efficacious treatment of AE, emerging as a promising option for the management of this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yang, Qian, Zhang, Zhao, Shu, Li, Li, Ding, Shi, Liu, Cheng and Niu.)

Background: There are established associations between viral and autoimmune encephalitis as well as between autoimmune encephalitis and demyelinating central nervous system (CNS) diseases. Here, we report the evolution from varicella zoster virus (VZV) encephalitis to limbic autoimmune encephalitis (AIE) to multiple sclerosis (MS) in one patient., Case Report: A woman in her mid-thirties presented with headache, aphasia, and a generalized tonic-clonic seizure. Cerebrospinal fluid (CSF) VZV polymerase chain reaction was positive and treatment with acyclovir was administered for VZV encephalitis. Five months later, the patient presented with cognitive deficits and MRI showed new bilateral hippocampal T2-hyperintensities. CSF analyses revealed pleocytosis and neuropil antibodies in tissue-staining. A diagnosis of limbic AIE was established and treatment with IV steroids and IV immunoglobulins initiated. One year later, the patient developed paresthesia of both legs and magnetic resonance imaging studies now showed new supratentorial and spinal demyelinating lesions. The patient was diagnosed with MS and treatment was changed to rituximab., Conclusions: This unique case report links three important neuroimmunological entities in characterizing the evolution from infectious to autoimmune encephalitis to multiple sclerosis in one patient. Identification of such rare clinical constellations is critical for correct treatment choice and provides important novel insights into the pathophysiology of neuroimmunological disorders including viral triggers and overlap manifestations of autoimmune CNS diseases., (© 2024. The Author(s).)

Purpose: Recommended pharmacotherapy for hypothyroidism in Hashimoto's thyroiditis (HT) is oral supplementation with levothyroxine (LT-4). However, serum thyrotropin (TSH) levels within normal range are not consistently achieved with LT-4 medication., Patients and Methods: We report on 35 HT patients with LT-4 therapy in this retrospective evaluation. In general, we recommend that a maximum of two sips of water, which would then amount to < 50 mL, be ingested at the same time as LT-4. We report on follow up examinations measuring TSH and antibodies against thyroid peroxidase (TPOAb) after 6 months to five years., Results: After median time of 643 days (range 98-1825) we found in 35 HT patients a statistical significant reduction of serum TSH (p < 0.001) and TPOAb (p = 0.006). The patients median body weight was 71 kg (range 48-98) and a daily LT-4 dosage was used with median 69.1 µg (range 25-150). This results in a daily LT-4 dose of median 1.01 µg/kg bodyweight (range 0.3-2.3)., Conclusions: The reduction of water ingestion to a maximum of two sips, which is <50 mL, combined with LT-4 supplementation helps to achieve euthyroidism in HT. In addition, it reduces the L-T4 medication dosage needed to lower TSH serum levels and decreases TPO antibodies in HT., (© 2024. The Author(s).)

Background: Although Hashimoto's thyroiditis (HT) is one of most common autoimmune thyroid diseases, its treatment remains focused on symptom relief. The soluble epoxide hydrolase (sEH) shows potential functions as a drug target in alleviating some autoimmune diseases; however, we seldom know its role in HT., Methods: The protein expression of sEH and related downstream molecules were evaluated by immunohistochemistry, Western blotting, ELISA, or immunofluorescence staining. RNA sequencing of tissue samples was performed to analyze differential genes and dysregulated pathways in HT and controls. The thyroid follicular epithelial cells (TFECs) and rat HT model were used to verify the biological function of sEH and the inhibition role of adamantyl-ureido-dodecanoic acid (AUDA) in HT., Results: The sEH was significantly upregulated in HT patients compared with healthy individuals. Transcriptome sequencing showed cytokine-related pathways and chemokine expression; especially chemokine CXCL10 and its receptor CXCR3 were aberrant in HT patients. In TFECs and a rat HT model, blocking sEH by AUDA inhibitor could effectively inhibit the autoantibody, proinflammatory nuclear kappa factor B (NF-κB) signaling, chemokine CXCL10/CXCR3 expression, and type-1 helper CD4+ T cells., Conclusion: Our findings suggest that sEH/NF-κB p65/CXCL10-CXCR3 might be promising therapeutic targets for HT., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Background: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE., Case Description: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months., Conclusions: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Hashimoto's thyroiditis (HT) is a prevalent autoimmune thyroid disease, necessitating further research to identify effective treatment strategies. Two key pathophysiological factors of HT are inflammation and oxidative stress. Petunidin (PET) is an anthocyanin with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect and mechanism of PET on HT. C57BL/6N mice were injected with thyroglobulin emulsified with adjuvant to establish the HT animal model. Our results showed that PET administration decreased the concentrations of TPOAb, TgAb, T3, T4, IgG, IgA and IgM in HT mice, accompanied by significant alterations in follicle shape and increased lymphocyte infiltrations. Additionally, the apoptosis rate, ROS level, MDA content, CD4+ level, IFN-γ and IL-17A levels, as well as the concentrations of IFN-γ and IL-17, were elevated in HT mice and reduced by PET treatment. Furthermore, HT patients exhibited higher levels of NOX4 and PKM2, which were positively correlated with TPOAb, IFN-γ, and IL-17 concentrations. In HT mice, PET therapy decreased the expression of PKM2 and NOX4 proteins. In summary, PET can improve thyroid dysfunction by suppressing apoptosis, oxidative stress and Th1/Th17 differentiation through regulation of the NOX4/PKM2 axis in HT mice, suggesting its promising potential for HT intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed., Patient Concerns, Diagnoses, and Interventions: We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate)., Outcomes and Lessons: Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Thyroid hormones are known to affect the biosynthesis and degradation of antioxidant compounds, suggesting a possible link between hypothyroidism and oxidative stress. However, there is no clear consensus in the literature regarding this association. The aim of this study was to evaluate oxidative stress markers (extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis) in patients with hypothyroidism due to autoimmune (Hashimoto's thyroiditis) or nonautoimmune thyroid disease rendered euthyroid after levothyroxine replacement., Subjects and Methods: The study included 116 patients admitted to the Taksim Training and Research Hospital (Istanbul, Türkiye). Of these, 50 had hypothyroidism due to Hashimoto's thyroiditis (HT group), 30 had nonautoimmune hypothyroidism (NAIH group), and 36 were healthy controls (control group). All participants were women. Extracellular thiol-disulfide homeostasis and intracellular glutathione homeostasis tests were assessed as oxidative stress markers., Results: Thiol-disulfide homeostasis in both HT and NAIH groups was shifted toward the oxidative spectrum. Compared with the control group, the HT and NAIH groups had lower levels of native (p < 0.001 and p = 0.001, respectively) and total (p = 0.002 and p = 0.012, respectively) thiol, as well as a lower native thiol/total thiol ratio (p < 0.001 for both). The HT group also had higher disulfide levels than the control group (p = 0.027). Reduced glutathione (GSH) and oxidized glutathione (GSSG) values were comparable across all three groups, but the HT and NAIH groups had higher GSSG/GSH (p < 0.001 for both) and GSSG/(GSH+GSSG) ratios (p = 0.003 and p = 0.005, respectively), along with lower GSH/(GSH+GSSG) ratio (p = 0.001 and p = 0.002, respectively) than the control group., Conclusion: Levothyroxine replacement was ineffective in ameliorating oxidative stress in patients with hypothyroidism due to Hashimoto's thyroiditis or nonautoimmune causes, as extracellular thiol-disulfide homeostasis was notably altered in these patients compared with healthy controls. The findings of this study suggest that oxidative stress remains a prevailing issue in patients with autoimmune or nonautoimmune hypothyroidism even after euthyroidism is restored., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Super refractory status epilepticus (SRSE) is a condition associated with high rates of mortality and morbidity. We report the treatment protocol of magnesium sulphate infusion adapted for the management of a case of super refractory status epilepticus that lasted for 4 weeks. A young lady presented in altered sensorium with a history of fever followed by uncontrolled seizures of 2 weeks duration. Her serum tested weakly positive for GABA-B receptor antibody. Her seizures were not controlled despite being on multiple antiepileptics and anesthetic induction. Intravenous magnesium infusion was initiated and serum magnesium was titrated up to a final target concentration of 3.8-6.5 mg/dl. Seizure control was achieved after 11 days of the infusion. This case is the longest reported successful use of magnesium sulfate infusion for control of super refractory status epileptics., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Background: Rituximab (RTX) resistance or early B-cells repopulation were observed in children but only few publications reported the use of Obinutuzumab and no recommendations were made concerning the dosage for children., Methods: This study was a single-center retrospective cohort study of all the children followed-up in the Pediatric Neurology Department of Necker-Enfants malades Hospital in Paris, France, and treated with obinutuzumab, between November 1, 2019, and November 1, 2021., Results: A total of eight children (three females, median age 4.5 years) were treated. Seven patients presented with autoimmune encephalitis and one with myeloradiculitis. The median delay of B-cell repopulation after a course of RTX was 87 days (range 41 to 160). A switch to obinutuzumab (anti-CD20) was performed for eight children. The median duration between the first RTX infusion and obinutuzumab administration was 6.6 months. The dosage regimen for obinutuzumab was one infusion of 1000 mg/1.73 m 2 , that is to say 580 mg/m 2 (maximum 1000 mg/infusion), by extrapolation from the adult dosage. The median delay of B-cell repopulation after one course of obinutuzumab was 230 days (range 66 to 303 days) vs 87 days after one course of RTX (P < 0.01). None of the patients presented side effects with obinutuzumab treatment. All patients had a favorable evolution at the last-follow up. Median follow-up was 1.6 years., Conclusions: This study reports the use of obinutuzumab in neurological inflammatory diseases in a pediatric population. Obinutuzumab seems to have a better biological efficacy than RTX with a longer time of B-cell repopulation., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest that could potentially influence or bias the submitted work exists., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding., Methods: This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist., Results: A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation., Discussion: This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions., Classification of Evidence: This provides Class IV evidence. It is a single observational study without controls.

Hashimoto's encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

Dipeptidyl peptidase-like protein 6 (DPPX) antibody encephalitis is a rare autoimmune encephalitis. Diagnosis and treatment of DPPX remain challenging, particularly in patients with refractory disease. Herein, we report the first case of anti-DPPX encephalitis treated with ofatumumab. The patient had a chronic insidious onset and predominantly presented with severe neuropsychiatric symptoms and the typical triad of symptoms (weight loss, central nervous system hyperexcitability, and cognitive dysfunction). Positive anti-DPPX antibodies in the serum (1:1,000) and cerebrospinal fluid (CSF) (1:100) were detected at the disease peak. The patient was unresponsive to four types of standard immunotherapies (intravenous globulin, plasma exchange, steroids, and tacrolimus), resulting in a treatment switch to ofatumumab. After five doses of injection and 12 months of follow-up, the patient improved well, with only a mild cognitive deficit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fu, Hu, Zhang and Li.)

We present a rare case of low titre GAD65 antibody-associated autoimmune encephalitis and status epilepticus in a young woman. She initially presented with left arm dystonic movements, contractures and status epilepticus. Due to the concern of autoimmune encephalitis and seizures, the patient received intravenous immunoglobulin empirically. After the detection of low serum GAD65 antibodies, the patient underwent immunomodulation therapy with significant improvement. This case demonstrated that in autoimmune encephalitis, it is important to monitor serum GAD65 antibodies levels and consider immunotherapy, despite mildly elevated serum levels. The patient's history of left arm dystonic movements without impaired awareness may have been due to limb dystonia, a presenting symptom of stiff person syndrome (SPS), despite SPS more commonly affecting axial muscles. This case further demonstrates that GAD65 antibody-related syndromes can manifest with different neurological phenotypes including co-occurrence of epilepsy with possible focal SPS despite low GAD65 antibodies titres., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: Antipsychotic medications (APMs) and selective serotonin reuptake inhibitors (SSRIs) are frequently utilized in patients with neuroinflammatory disorders, such as autoimmune encephalitis and multiple sclerosis (MS). This retrospective study investigates how in-hospital treatment with APMs and SSRIs in patients with these neuroinflammatory diseases are associated with differences in hospital length-of-stay (LOS) and mortality., Methods: We evaluated all the inpatients in the Stanford University Hospital from 2008 to 2023 diagnosed with either non-infectious encephalitis or MS and subdivided them into those who did or did not receive APMs or SSRIs while hospitalized. We then analyzed whether hospital LOS and mortality differed with these medications., Results: Among inpatients with non-infectious encephalitis (n = 114), those who were exposed to APMs had a significantly increased mean LOS (11.8 vs 20.9 days, p < 0.01). For inpatients with MS (n = 1095), treatment with an APM was associated with a significant increase in mean LOS (2.8 vs. 7.1, p < 0.00001). When comparing typical to atypical APMs given to subjects with MS, those who received atypical APMs showed a significant increase in LOS (4.3 vs 10.5, p < 0.01), although typical APMs showed significantly increased risk of mortality (p < 0.05). For inpatients with MS and SSRI use, there was a significant increase in mean hospital LOS (3.5 vs 5.3, p < 0.01), with a significant difference found in those who received fluoxetine or citalopram, but not sertraline or escitalopram. Finally, several healthcare disparities were found, including that Black patients were more likely to receive APMs, and those with MS were more likely to receive typical rather than atypical APMs. Conversely, Black patients with MS were less likely to receive SSRI treatment., Conclusions: There was a statistically significant increase in LOS associated with APM use in non-infectious encephalitis and MS, as well as with SSRI use in MS. These data reflect the importance of these medications in these neuroinflammatory disorders and suggest that further investigation into their risks and benefits would be warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Hashimoto encephalopathy presents with a myriad of neuropsychiatric features in the background of elevated antithyroid antibodies and it may or may not be associated with Hashimoto thyroiditis. It is a diagnosis of exclusion. Here, we present the case of a hypothyroid woman in her 30s, with a 5-year history of chronic progressive gait ataxia along with hand and head tremor, inattention and electroencephalogram (EEG) suggestive of interictal epileptiform discharges without any clinical seizures. The patient had very high titres of anti-thyroid peroxidase antibodies >2000 IU/mL and was on very high-dose levothyroxine replacement therapy. She responded to intravenous pulse corticosteroids. Improvement was noted both clinically and on subsequent EEGs. Pure cerebellar syndrome without frank encephalopathy can also be a rare presentation of Hashimoto encephalopathy. This highlights the importance of antithyroid antibodies testing even in cases of pure cerebellar syndrome to rule out Hashimoto encephalopathy associated ataxia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A gentleman in his 90s presented with a slowly enlarging goitre over 18 months, causing manifestations of superior vena cava obstruction, dysphagia and hoarseness of voice. Investigations were suggestive of a fibrosing thyroid pathology. Surgical management was avoided due to high surgical risk. Treatment included prednisolone and tamoxifen with palliative management in the event of further medical deterioration. This article illustrates the difficulties in diagnosing and managing fibrosing thyroid diseases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Considering the possible adverse effects of thyroid autoantibodies on the brain, the present study aimed to investigate whether there was a difference in mental health difficulties and mindfulness awareness levels between subclinical Hashimoto's thyroiditis patients with and without levothyroxine (LT4) use. A case-control study was conducted. The Strengths and Difficulties Questionnaire (SDQ) and the Mindful Attention Awareness Scale (MAAS) were used to screen mental health difficulties and mindfulness awareness. Scale scores were compared by performing correlation analysis between the groups with respect to LT4 use and thyroid autoantibodies. Levothyroxine alone does not affect scale results. Higher thyroid peroxidase antibody (TPOAb) titers were positively correlated with the behavioral problems subscale of the SDQ, while awareness level in patients was inversely correlated with higher thyroglobulin antibody (TgAb) levels., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 CO 2 /pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: The polyethylene glycol (PEG) methodology is used for investigating incongruities in laboratory assays, such as thyroid-stimulating hormone (TSH) measurements. The aim of the study is to investigate the practical application of PEG-TSH testing in cases of discrepancies between elevated TSH and normal free thyroxine (FT4) levels., Methods: A real-life observational study conducted in a tertiary medical center. The hospital's electronic database was queried for TSH tests performed in pediatric patients between 2015 and 2023. Of those, PEG-TSH were identified. Patients' clinical and biochemical characteristics and PEG-TSH-guided management were assessed., Results: In total, 2949 TSH tests were performed in 891 children and adolescents for various indications. Among them were 61 (2.1%) PEG-TSH results, mean age 7.1 ± 5.3 years, of 38 patients (4.3%), comprised of 16 with congenital hypothyroidism, 16 with subclinical hypothyroidism, and 6 with Hashimoto thyroiditis. Both the TSH and the PEG-TSH levels of patients with congenital hypothyroidism were higher than those of the other two groups (P = 0.021 and P = 0.009, respectively), with no group differences in FT4 levels. Spearman's correlation analysis revealed a strong association between TSH and PEG-TSH levels: r = 0.871, P < 0.001. In nearly one-half of the cases, clinical decisions made by clinicians (decreasing the dose or not initiating L-thyroxine treatment) were affected by the PEG-TSH results., Conclusion: Our findings support PEG-TSH testing for determining appropriate TSH levels and avoid unnecessary thyroid hormone treatment among children and adolescents. We propose the suitability of managing their clinical condition based upon age-appropriate clinical parameters and FT4 levels when their PEG-TSH levels are within the normal range., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The quality of the studies was assessed using the Cochrane risk bias assessment tool and the results were analyzed using Review Manager 5.3 software. The evidence was also evaluated for its strength using GRADE. A total of 18 randomized controlled trials were included in the study, involving 1247 patients. The primary outcomes of this study included overall efficacy, effectiveness in treating specific symptoms, and the Traditional Chinese Medicine symptom score. The secondary outcomes included the levels of FT3, FT4, and TSH, the size of the thyroid gland, and any adverse events. The results of the meta-analysis showed that CHM combined with WM has a better curative effect and a more effective reduction in clinical symptoms than WM alone: comprehensive efficacy [OR = 4.83; 95% CI (3.45, 6.76)], syndrome efficacy [OR = 5.95; 95% CI (3.94, 8.99)], TCM symptom score SMD = -1.49; 95% CI (-1.86, -1.11)], FT3 [SMD = 0.59; 95% CI (0.48, 0.71)], FT4 [SMD = 0.59; 95% CI (0.48, 0.71)], TSH SMD = -0.97; 95% CI (-1.35, -0.58)], and thyroid volume SMD = -0.25; 95% CI (-0.34, 0.15)]. The incidence of adverse events between the groups was not significantly different [OR = 1.00; 95% CI (0.14, 7.27)]. Because of the effectiveness of CHM, we support using CHM to improve clinical efficacy in the treatment of HTH. The results of our research suggest that the use of Chinese Herbal Medicine (CHM) in combination with Western Medicine (WM) may result in improved clinical efficacy in the treatment of hypothyroidism (HTH) compared to using WM alone.

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.

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.

Background: Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life., Methods: We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs)., Results: A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = -63.18, 95%CI = -91.73 to -34.62, P < .00001), TGAb content (MD = -68.56, 95%CI = -101.55 to -35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = -2.16, 95%CI = -3.14 to -1.19, P < .00001) had a significant effect., Conclusion: Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I 2  = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I 2  = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I 2  = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I 2  = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Objectives: Limitations in human cognition commonly result in clinical reasoning failures that can lead to diagnostic errors. A metacognitive structured reflection on what clinical findings fit and/or do not fit with a diagnosis, as well as how discordance of data can help advance the reasoning process, may reduce such errors., Case Presentation: A 60-year-old woman with Hashimoto thyroiditis, diabetes, and generalized anxiety disorder presented with diffuse arthralgias and myalgias. She had been evaluated by physicians of various specialties and undergone multiple modalities of imaging, as well as a electromyography/nerve conduction study (EMG/NCS), leading to diagnoses of fibromyalgia, osteoarthritis, and lumbosacral plexopathy. Despite treatment for these conditions, she experienced persistent functional decline. The only definitive alleviation of her symptoms identified was in the few days following intra-articular steroid injections for osteoarthritis. On presentation to our institution, she appeared fit with a normal BMI. She was a long-time athlete and had been training consistently until her symptoms began. Prediabetes had been diagnosed the year prior and her A 1c progressed despite lifestyle modifications and 10 pounds of intentional weight loss. She reported fatigue, intermittent nausea without emesis, and reduced appetite. Examination revealed intact strength and range of motion in both the shoulders and hips, though testing elicited pain. She had symmetric hyperreflexia as well as a slowed, rigid gait. Autoantibody testing revealed strongly positive serum GAD-65 antibodies which were confirmed in the CSF. A diagnosis of stiff-person syndrome was made. She had an incomplete response to first-line therapy with high-dose benzodiazepines. IVIg was initiated with excellent response and symptom resolution., Conclusions: Through integrated commentary on the diagnostic reasoning process from clinical reasoning experts, this case underscores the importance of frequent assessment of fit along with explicit explanation of dissonant features in order to avoid misdiagnosis and halt diagnostic inertia. A fishbone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic error. The case discussant demonstrates the power of iterative reasoning, case progression without commitment to a single diagnosis, and the dangers of both explicit and implicit bias. Finally, this case provides clinical teaching points in addition to a pitfall, myth, and pearl specific to overcoming diagnostic inertia., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Hypothyroidism is one of the most common endocrinopathies worldwide, the treatment of which is based on replacement therapy with levothyroxine. However, this seemingly simple treatment method is fraught with many difficulties and frequent dissatisfaction among patients. In fact, differences in response to levothyroxine probably depend on a complex interaction between individual, environmental, genetic, and epigenetic factors that are still not sufficiently understood. Immunological disturbances, underlying Hashimoto's disease, the most common cause of hypothyroidism, probably play a significant role in these relationships. Indeed, a growing number of studies indicate that autoimmunity through activation of low-grade inflammation can lead to impaired absorption, transport, metabolism, and action of thyroid hormones. This review provides an up-to-date overview of the causes responsible for both the difficulty in achieving target thyrotropin levels and persistence of nonspecific symptoms despite adequate hormone replacement from an immunoendocrine perspective. Understanding these mechanisms points to a new direction in the approach to hypothyroidism, indicating the need for new personalized treatment strategies.

In this case report we describe a pregnant woman with newly developed auditory hallucinations, initially seen by a psychiatrist of the psychiatric emergency service. The day after assessment , the patient developed epileptic seizures and was referred to the hospital. After additional blood and liquor tests and an MRI scan, an autoimmune encephalitis was diagnosed. She was treated with prednisolone and immunoglobulins. She made a full recovery and gave birth to a healthy son at term. In this article we describe the diagnostic considerations, the course and treatment, the importance of being alert to a somatic cause of psychiatric symptoms and of multidisciplinary collaboration.

Background: In recent years, the number of patients with Hashimoto's thyroiditis has been increasing, and traditional Chinese medicine ingredients and combinations have been applied to treat Hashimoto's thyroiditis to increase efficacy and reduce side effects during the treatment process., Objective: Shutiao Qiji Decoction is one of the Chinese traditional medicine prescriptions, which is commonly used to treat cancer, tumor, etc. It is also used for thyroid-related diseases in the clinic. Hashimoto's thyroiditis is an autoimmune disease. In this study, the mechanism of Shutiao Qiji Decoction in treating Hashimoto's thyroiditis was studied through network pharmacology and molecular docking verification., Method: Each Chinese medicine ingredient of Shutiao Qiji Decoction was retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The related genes of HT were searched from the UniProt and GeneCards databases. Meanwhile, we used Cytoscape to construct the protein-protein interaction (PPI) visual network analysis, and used the search tool to search the database of Interacting Genes (STRING) to build a PPI network. These key proteins were enriched and analyzed by molecular docking validation, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hashimoto's thyroiditis disease model was established in SD rats, and SQD was administered by gavage after the successful establishment of the model. After 6 weeks of continuous administration of the drug by gavage, tissue samples were collected and the thyroid and spleen tissues were visualized by HE staining to verify the therapeutic effect., Results: The results showed that there were 287 TCM active ingredients, 1920 HT-related disease targets, and 176 drug and disease targets in SQD. Through PPI analysis, GP analysis, and KEGG analysis of the common targets of drugs and diseases, we found their pathways of action to be mainly cancer action pathway, PI3K-AKT signaling pathway, and T-cell action pathway. The active ingredients of the drugs in SQD, malvidin, stigmasterol, porin-5-en-3bta-ol, and chrysanthemum stigmasterol, were docked with the related target proteins, MAPK, GSK3β, TSHR, and NOTCH molecules. The best binding energies obtained from docking were mairin with TSHR, stigmasterol with TSHR, poriferast-5-en-3beta-ol with MAPK, and chryseriol with GSK3β, with binding energies of -6.84 kcal/mol, -6.53 kcal/mol, -5.03 kcal/mol, and -5.05 kcal/mol, respectively. HE staining sections of rat thyroid and spleen tissues showed that SQD had a therapeutic effect on Hashimoto's thyroiditis and restored its immune function., Conclusion: It is verified by molecular docking results that Shutiao Qiji Decoction has a potential therapeutic effect on Hashimoto's thyroiditis in the MAPK/TSHR/NOTCH signal pathway, and that the main components, mairin, stigmasterol, poriferast-5-en-3beta-ol, and chryseriol play a role in it. SQD has been shown to have a good therapeutic effect on Hashimoto's thyroiditis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To assess the effect of daily zinc supplementation for 12 weeks on thyroid auto-antibodies - thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), and oxidative stress in children with autoimmune thyroid disease (AITD) compared to standard therapy., Methods: This open-labeled, parallel, randomized controlled trial was done in a tertiary care teaching institute in south India. Children aged 3-18 years with AITD were randomized to receive 25 mg elemental zinc daily for 12 weeks or standard therapy alone. The change in thyroid function tests (thyroid stimulating hormone, free T3, free T4), thyroid auto-antibody (TPOAb, TgAb) titers, oxidative stress markers (glutathione peroxidase, malondialdehyde, superoxide dismutase, and total antioxidant capacity) were compared., Results: Forty children, 20 in each arm, were recruited in the study. We observed a female-to-male ratio of 7:1. Median duration of disease was 2 (0.25, 4.25) years. A total of 37 (92.5 %) children were hypothyroid, two hyperthyroid, and one euthyroid at enrolment. A total of 13 children (32.5 %) had associated co-morbidities, most commonly type 1 diabetes mellitus and systemic lupus erythematosus, three (7.5 %) each. We did not find any significant change in thyroid function tests, thyroid auto-antibody titers, and oxidative stress markers. However, the requirement of levothyroxine dose was significantly increased in the control arm, compared to the zinc group (p=0.03). Only four (20 %) children had minor adverse effects like nausea, metallic taste, and body ache., Conclusions: Zinc supplementation did not have any effect on thyroid auto-antibodies and oxidative stress. Zinc-supplemented children did not require escalation in levothyroxine dose., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors., Methods: Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol (1, 25(OH) 2 D 3 ) at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR., Results: Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFβ) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation., Conclusion: The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hashimoto's thyroiditis (HT) is the prevailing form of autoimmune thyroiditis and the leading cause of hypothyroidism in iodine-sufficient regions worldwide. This study aims to evaluate the efficacy of vitamin D supplementation on HT through a meta-analysis of randomized controlled trials (RCTs)., Methods: The databases searched included PubMed, and others. We included RCTs that the treatment group received vitamin D, while the control group received either a placebo or no treatment. The studies measured the baseline and endpoint levels of 25-hydroxyvitamin D [25(OH)D], thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab). We performed a meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval (CI)., Results: A total of 12 studies involving 862 individuals were included. Vitamin D supplementation has a significant impact on reducing the titers of TPO-Ab (SMD = -1.084, 95% CI = -1.624 to -0.545) and TG-Ab (SMD = -0.996, 95% CI = -1.579 to -0.413) in patients with HT, and it also improves thyroid function by decreasing TSH level (SMD = -0.167, 95% CI = -0.302 to 0.031) and increasing FT3 (SMD = 0.549, 95% CI = 0.077-1.020) and FT4 (SMD = 0.734, 95% CI = 0.184-1.285) levels. Active vitamin D (calcitriol) significantly reduces the titer of TPO-Ab compared to naive forms of vitamin D (vitamin D2 or D3); treatment durations > 12 weeks result in a more effective reduction of TPO-Ab levels and a more significant increase in FT4 and FT3 levels in patients with HT (meta-regression P < .05)., Conclusion: Vitamin D supplementation may have beneficial effects on HT patients by modulating immune responses and improving thyroid function., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Encephalopathy can be associated with autoimmune disorders such as autoimmune thyroiditis, and it can present with a wide range of neuropsychiatric manifestations. However, it rarely presents with catatonia. We present the case of a middle-aged female with Hashimoto's thyroiditis presenting with catatonia. A literature review of previous similar cases highlighting significant points is also included. A 48-year-old female presented to the emergency department with catatonic symptoms that had worsened over the previous 5 days. A similar condition was reported to have occurred and resolved spontaneously 3 months earlier. On examination, the patient appeared uncooperative and unresponsive. She showed typical symptoms of catatonia, with a score of 21 points on the Bush-Francis Catatonia Rating Scale. Routine tests were within normal ranges except for an elevated level of C-reactive protein and an elevated erythrocyte sedimentation rate. Computed tomography, magnetic resonance imaging, and cerebrospinal fluid analysis were all normal. An electroencephalogram showed diffuse delta-theta range slowing with no epileptiform discharges. Lorazepam was initiated but did not control the catatonic symptoms. Re-evaluation revealed thyroid swelling and elevated levels of thyroperoxidase antibodies. IV methylprednisolone was therefore initiated and produced complete resolution of the catatonic symptoms in 4 hours. The patient was discharged and prescribed prednisone 1 mg/kg daily. At follow-up, the patient continued to show complete resolution of the catatonic symptoms. It is noteworthy that the patient developed hypothyroidism 6 months after this catatonic episode for which levothyroxine 50 mcg/d was prescribed. Encephalopathy associated with autoimmune thyroiditis can initially present with catatonic symptoms in euthyroid cases. The mainstay of treatment is steroids which result in complete resolution of the catatonic symptoms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Assessing severity of antibody-mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti-NMDAR-encephalitis one-year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort., Methods: We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome., Results: Thirty-four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6-12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti-NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow-up in patients with AE with a sensitivity of 79% at a cut-off value of 2 points (AUC 0.79, 95% CI 0.58-0.99, p = 0.04)., Interpretation: The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Hashimoto's encephalopathy is an uncommon cause of altered mental status in hospitalized patients and is challenging to diagnose, particularly in the presence of other psychiatric comorbidities. Corticosteroids are the primary treatment. Here, we present a patient with history of post-traumatic stress disorder and prior substance abuse admitted with profound altered mental status and agitation requiring admission to the intensive care unit and mechanical ventilation. He was treated with intravenous immunoglobulin (IVIG) instead of the standard steroid course because of concerns for worsening agitation. The patient had improvement with IVIG infusions, returned to a functional state, and has remained on IVIG therapy monthly since the initial episode without any disease recurrence., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Both prolactin excess and autoimmune (Hashimoto) thyroiditis may predispose to the development of cardiometabolic disorders. The aim of this study was to investigate whether autoimmune thyroiditis determines cardiometabolic effects of cabergoline. The study population consisted of 2 groups of young women: 32 women with euthyroid Hashimoto thyroiditis (group A) and 32 individuals without thyroid disorders (group B). Both groups were matched for age, body mass index, blood pressure, and prolactin levels. Plasma prolactin, thyroid antibodies, glucose homeostasis markers, plasma lipids, circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, and the urinary albumin-to-creatinine ratio were assessed before and after 6 months of cabergoline treatment. All women completed the study. Both groups differed in thyroid antibody titers, insulin sensitivity, high-density lipoprotein cholesterol, hsCRP, homocysteine, and the albumin-to-creatinine ratio. Although cabergoline treatment reduced prolactin levels, improved insulin sensitivity, decreased glycated hemoglobin, increased high-density lipoprotein cholesterol, decreased hsCRP, and reduced the albumin-to-creatinine ratio in both treatment groups, these effects (except for glycated hemoglobin) were more pronounced in group B than in group A. Only in group B, the drug decreased triglycerides, uric acid, fibrinogen, and homocysteine. In group A, hsCRP levels correlated with both baseline thyroid antibody titers and with other cardiometabolic risk factors. The impact of cabergoline on cardiometabolic risk factors depended on the degree of reduction in prolactin levels, while in group A additionally correlated with the effect of treatment on hsCRP. The obtained results suggest that coexisting autoimmune thyroiditis attenuates cardiometabolic effects of cabergoline in young women with hyperprolactinemia., (© 2023, The American College of Clinical Pharmacology.)

Hashimoto's thyroiditis (HT) is a common autoimmune disease affecting the thyroid gland, characterized by lymphocytic infiltration, damage to thyroid cells, and hypothyroidism, and often requires lifetime treatment with levothyroxine. The disease has a complex etiology, with genetic and environmental factors contributing to its development. Vitamin D deficiency has been linked to a higher prevalence of thyroid autoimmunity in certain populations, including children, adolescents, and obese individuals. Moreover, vitamin D supplementation has shown promise in reducing antithyroid antibody levels, improving thyroid function, and improving other markers of autoimmunity, such as cytokines, e.g., IP10, TNF-α, and IL-10, and the ratio of T-cell subsets, such as Th17 and Tr1. Studies suggest that by impacting various immunological mechanisms, vitamin D may help control autoimmunity and improve thyroid function and, potentially, clinical outcomes of HT patients. The article discusses the potential impact of vitamin D on various immune pathways in HT. Overall, current evidence supports the potential role of vitamin D in the prevention and management of HT, although further studies are needed to fully understand its mechanisms of action and potential therapeutic benefits.

Thyroid autoimmunity is associated with an increased risk of sexual dysfunction. The aim of this study was to compare sexual functioning and depressive symptoms in women with Hashimoto's thyroiditis receiving different treatments. The study included euthyroid women with autoimmune thyroiditis, untreated or receiving vitamin D, selenomethionine, or myo-inositol. Apart from measuring antibody titers and hormone levels, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II). In untreated women, the overall FSFI scores and domain scores for desire, arousal, lubrication, and sexual satisfaction were lower than in women receiving vitamin D, selenomethionine, and myo-inositol. In the vitamin D-treated women, the total FSFI scores and scores for desire and arousal were higher than in women receiving the remaining micronutrients. The BDI-II score was lowest in the vitamin D-treated women and highest in the untreated patients with thyroiditis. Vitamin D-treated women were also characterized by lower antibody titers and higher testosterone levels than the women receiving the remaining micronutrients. There were no differences in sexual functioning and depressive symptoms between the selenomethionine- and myo-inositol-treated women. The study results suggest that although all antibody-lowering treatments are associated with better sexual functioning and well-being in young women with euthyroid autoimmune thyroiditis, the greatest benefits are observed in patients receiving vitamin D.

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.