Causes of difficulties with adequate levothyroxine substitution - an immunoendocrine perspective.

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.

Incidence and prevalence of autoimmune diseases in China: A systematic review and meta-analysis of epidemiological studies.

Background: Autoimmune diseases account for a substantial burden of disease in high-income countries, including Europe and North America. However, their epidemiology remains under-researched in other regions. We examined the incidence and prevalence of eight autoimmune diseases in the adult Chinese population through a systematic review of epidemiological studies. Methods: We searched OvidSP MEDLINE and Google Scholar from 1995 to 2023 (inclusive) for articles on the incidence or prevalence of autoimmune thyroiditis (AT), Graves' disease (GD), type 1 diabetes mellitus (T1D), multiple sclerosis (MS), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We included studies from mainland China, Taiwan, Hong Kong or Macau. The study is registered with PROSPERO (CRD42021225842). Findings: We retrieved 2278 records, of which 62 studies (161 estimates) were included in the systematic review, and 42 studies (101 estimates) were included in the meta-analysis. Pooled fixed-effects estimates for incidence of CD, UC, MS, T1D and SLE were 0.22 (95% CI 0.21-0.23), 1.13 (1.10-1.17), 0.28 (0.26-0.30), 2.20 (1.70-2.84) and 4.87 (4.21-5.64) per 100,000 persons, respectively. For RA, one study estimate was included, with an incidence of 15.8 per 100,000 persons. Fixed-effects estimates for the prevalence of CD, UC, MS, SLE, RA, GD and AT were 3.73 (95% CI 3.68-3.78), 16.11 (15.93-16.29), 4.08 (3.95-4.21), 93.44 (92.27-94.63), 104 (103-106), 450 (422-481) and 2322 (2057-2620), respectively, per 100,000 persons. Across all conditions, women were almost twice as likely as men to be diagnosed with an autoimmune disease. Interpretation: There is marked variation in the frequency of autoimmune diseases among Chinese adults. We estimate that 2.7-3.0% (>31 million people) of the adult Chinese population have one or more autoimmune diseases, comparable to Western populations, with the majority of the burden from autoimmune thyroid diseases and rheumatoid arthritis.

A Malignant Duo: Mixed Medullary and Follicular Variant Papillary Thyroid Cancer.

Medullary thyroid cancer (MTC) is a relatively rare thyroid malignancy, constituting a small percentage of all thyroid cancer cases. Even more rare is the occurrence of mixed MTC and papillary thyroid cancer (PTC), found in a very small fraction of MTC cases. These cancers originate from different cell types with distinct developmental origins. The coexistence of MTC and PTC in the same patient raises questions about whether this occurrence is merely coincidental or if there is an underlying genetic link. We present the case of a woman with metastatic mixed MTC and PTC. A 61-year-old woman with a history of Hashimoto's disease was found to have bilateral thyroid nodules; the largest (1.7 cm) was in the right lobe. This nodule met fine needle aspiration (FNA) biopsy criteria and was found to have a follicular neoplasm of undetermined significance. The patient elected to pursue total thyroidectomy instead of lobectomy given the presence of bilateral nodules. Postoperative pathology showed mixed medullary carcinoma (pT3b) and follicular variant papillary thyroid microcarcinoma (pT1a) involving the right lobe with positive anterior and posterior margins and lymphovascular invasion. Preoperative calcitonin was not checked. However, post-thyroidectomy calcitonin was 1599 pg/mL. She underwent central and right lateral neck dissection which showed 27 out of 35 lymph nodes were positive for malignancy. Postoperative calcitonin dropped to 38.7 pg/mL. She then established care in our endocrine clinic. Screening for pheochromocytoma and primary hyperparathyroidism was normal. She underwent external beam radiation of the neck. A year after her initial surgery, her neck ultrasound and computed tomography (CT) studies show no signs of local or distant anatomic recurrence. Her thyroglobulin level remains undetectable, carcinoembryonic antigen (CEA) within normal range, and calcitonin stable at about 20 pg/mL. She is on levothyroxine 100 mcg daily with thyroid-stimulating hormone (TSH) at a suppression goal of <0.1 mIU/L. Mixed PTC and MTC is poorly studied due to its rarity. The origin of these mixed tumors is unclear, but some suggest that they arise from neoplastic changes of remnant multipotent cells in the thyroid. While patients with PTC often have a favorable prognosis following surgical therapy, MTC has a more aggressive course. We suggest monitoring patients like ours for both MTC and PTC, as if present in isolation. Our case highlights the clinical aspects of this condition and our current knowledge of its pathophysiology.

Surgical management of papillary thyroid carcinoma coexisting with Hashimoto's disease: a single-center retrospective cohort study.

Background: The mechanism and impact of Hashimoto's disease (HT) in patients with papillary thyroid carcinoma (PTC) remains a subject of ongoing debate. The optimal extent of thyroid resection is also controversial in cases of low-risk PTC. Objective: To investigate the clinical outcomes and prognoses associated with different extents of surgical resection in patients diagnosed with PTC coexisting with HT. Methods: We retrospectively analyzed data on the clinical features and treatment outcomes of patients with PTC concomitant with HT who underwent lobectomy with isthmusectomy and those who underwent total thyroidectomy at Peking University International Hospital between December 2014 and August 2023. Results: Twenty-one patients in group A underwent lobectomy with isthmusectomy and prophylactic central neck dissection, whereas twenty patients in group B underwent total thyroidectomy with prophylactic central lymph node (LN) dissection, except one who did not undergo LN dissection. Group A demonstrated shorter surgery time (105.75 min ± 29.35 vs. 158.81 min ± 42.01, p = 0.000), higher parathyroid hormone (PTH) levels on postoperative day 1 [26.96 pg/ml (20.25, 35.45) vs. 9.01 pg/ml (2.48, 10.93), p = 0.000] and a shorter postoperative hospital stay [2.95 d (2.0, 4.0) vs. 4.02 d (3.0, 5.0), p = 0.008] than those of group B, with statistically significant differences. Both groups exhibited similar recovery patterns in terms of PTH [32.10 pg/ml (22.05, 46.50) vs. 20.47 pg/ml (9.43, 34.03), p = 0.192] and serum calcium (2.37 mmol/L ± 0.06 vs. 2.29 mmol/L ± 0.19, p = 0.409) after 1 montsh following the surgery. According to the Kaplan-Meier curves, no significant difference in the 5-year disease-free survival rates were observed between patients in group A (100%) and group B (97.1%) (Log rank test: p = 0.420, Breslow test: p = 0.420). Conclusion: Lobectomy with isthmusectomy and prophylactic central neck dissection is a safe and feasible treatment option for patients with low-risk PTC coexisting with HT. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2300079115.

The Role of the Immune System in the Course of Hashimoto's Thyroiditis: The Current State of Knowledge.

The process of thyroid autoimmunization develops against the background of genetic predispositions associated with class II human leukocyte antigens (HLA-DR), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and forkhead transcription box protein P3 (FOXP3). Environmental factors, such as vitamin D deficiency, Zn, Se, and Mg, as well as infections, chronic stress, pregnancy, smoking, alcohol, medications, intestinal dysbiosis, and malnutrition, also play an important role. The first stage of autoimmunization involves the accumulation of macrophages and dendritic cells, as well as plasma cells. In the second stage, the mutual interactions of individual cells in the immune system lead to a decrease in the level of CD8+ in favor of CD4+, which intensifies the synthesis of T lymphocyte derivatives, especially Th1, Th17, Tfh, and Tc, reducing the level of Treg. Consequently, the number of the anti-inflammatory cytokines IL10 and IL2 decreases, and the synthesis of the pro-inflammatory cytokines IL-2, Il-12, Il-17, IL-21, IL-22, IFN-γ, and TNF-α increases. The latter two especially trigger the pyroptosis process involving the inflammasome. Activation of the inflammasome by IL-ß and IL-18 produced by macrophages is one of the mechanisms of pyroptosis in the course of Hashimoto's thyroiditis, involving Gram-negative bacteria and NLRC4. In the next step, the apoptosis of thyroid cells is initiated by the intensification of perforin, granzyme, and proteoglycan synthesis by Tc and NK cells. The current findings raise many possibilities regarding interventions related to the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines produced by both T and B lymphocytes. Furthermore, since there is currently no effective method for treating thyroid autoimmunity, a summary of the review may provide answers regarding the treatment of not only Hashimoto's thyroiditis, but also other autoimmune diseases associated with autoimmunity.

Thyroid Disorders.

This article includes a review of information primary care physicians need to know direct their evaluation and treatment of thyroid disorders that include sick euthyroid, hyperthyroidism, hypothyroidism, and subclinical thyroid disorders.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

OBJECTIVE: To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). METHODS: We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. RESULTS: Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). CONCLUSIONS: The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

A Silent Cause of Shock: Autoimmune Polyglandular Syndromes.

Addison's disease is a rare, autoimmune condition leading to destruction of the adrenal gland. Autoimmune conditions are known to commonly co-occur. When Addison's disease presents in the setting of autoimmune thyroid disease and/or type 1 diabetes, this condition is termed autoimmune polyendocrine syndrome type II, a rare endocrinopathy found in roughly 1.4-4.5 per 100,000 individuals. Here, we describe a clinical case presenting with hypotension refractory to fluid resuscitation and electrolyte derangements later diagnosed as autoimmune polyendocrine syndrome type II. LEARNING POINTS: Primary adrenal insufficiency may present clinically as shock refractory to fluid resuscitation.Autoimmune polyglandular syndrome type 2 is a rare autoimmune condition occurring in 1.5-4.5 per 100,000 individuals.The presence of an underlying autoimmune condition should raise suspicion for multiple concurrent autoimmune conditions.

Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis.

BACKGRUOUND: Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. METHODS: This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. RESULTS: Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. CONCLUSION: This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Do Brassica Vegetables Affect Thyroid Function?-A Comprehensive Systematic Review.

Brassica vegetables are widely consumed all over the world, especially in North America, Asia, and Europe. They are a rich source of sulfur compounds, such as glucosinolates (GLSs) and isothiocyanates (ITCs), which provide health benefits but are also suspected of having a goitrogenic effect. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on thyroid function, in terms of the potential risk for people with thyroid dysfunctions. We analyzed the results of 123 articles of in vitro, animal, and human studies, describing the impact of brassica plants and extracts on thyroid mass and histology, blood levels of TSH, T3, T4, iodine uptake, and the effect on thyroid cancer cells. We also presented the mechanisms of the goitrogenic potential of GLSs and ITCs, the limitations of the studies included, as well as further research directions. The vast majority of the results cast doubt on previous assumptions claiming that brassica plants have antithyroid effects in humans. Instead, they indicate that including brassica vegetables in the daily diet, particularly when accompanied by adequate iodine intake, poses no adverse effects on thyroid function.

Toll-like receptor 7 and tumor necrosis factor alpha polymorphisms in Egyptian patients with autoimmune thyroid diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto's thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves' disease.

Is Every Thyroid Antibody a Bad Sign?: The Complex Relationship of Antithyroid Antibodies and Obsessive-compulsive Symptoms.

Objective: : Several immunological factors are emphasized in the etiology of autoimmune thyroid diseases and obsessivecompulsive disorder. Obsessive-compulsive symptoms (OCS) are commonly seen in patients with autoimmune thyroid diseases. This study aims to evaluate the relationship between OCS and antithyroid antibodies. Methods: : The study included 145 patients with Hashimoto thyroiditis or Graves' disease and 42 healthy controls. Thyroid function tests and serum thyroid autobody levels (anti-thyroglobulin [TG], anti-thyroid peroxidase [TPO], and anti-thyroid stimulating hormone [TSH]) of the patients were measured. The socio-demographic data and OCS of the participants were evaluated with Dimensional OCS (DOCS). Results: : DOCS scores were higher in patients than in the control group. There was not found a significant relationship between free T3, free T4, and TSH levels and DOCS scores. Anti-TG positivity in females was associated with lower DOCS scores. Anti-TPO positivity in males had a positive correlation with DOCS scores. There was no correlation between sex and the presence of anti-TSH in terms of OCS severity. Univariate analysis found the highest OCS scores in anti-TPO positive, anti-TG, and anti-TSH negative patients. The group with the lowest OCS scores was found to be anti-TG positive, anti-TPO, and anti-TSH negative patients. Conclusion: : OCS severity could be affected by different thyroid autoantibody profiles in patients with autoimmune thyroid diseases. While anti-TG serves a protective role against OCS in females, the presence of anti-TPO may worsen the OCS in men. Additionally, the co-existence of different antithyroid antibodies may affect the severity of OCS differently according to sex.

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

BACKGRUOUND: Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. METHODS: This study included two types of research. RESULTS: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. RESULTS: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. CONCLUSION: This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease.

CONTEXT: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD). OBJECTIVE: This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD. METHODS: Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized ß values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs. RESULTS: We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis. CONCLUSION: Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential.

Seven thyroid imaging reporting and data systems for differentiating benign and malignant thyroid nodules under the context of Hashimoto thyroiditis / 中国医学影像技术

Objective To compare the value of 7 different thyroid imaging reporting and data systems(TI-RADS)for differentiating benign and malignant thyroid nodules under the context of Hashimoto thyroiditis(HT).Methods A total of 338 thyroid nodules in 200 HT patients were enrolled,including 167 benign and 171 malignant ones.Kwak-TIRADS,American Thyroid Association(ATA)guideline,American Association of Clinical Endocrinologists(A ACE)/American College of Endocrinology(ACE)/Associazione Medici Endocrinologi(AME)guideline,K-TIRADS of Korean Society of Thyroid Radiology,EU-TIRADS of European Thyroid Association,American College of Radiology(ACR)-TIRADS and 2020 Chinese guidelines for malignant risk stratification of thyroid nodules by ultrasound proposed by the superficial organs and vessels group of the ultrasound medicine branch of the Chinese Medical Association(C-TIRADS)were used for grading of benign and malignant thyroid nodules.Taken pathological results as gold standards,the diagnostic efficacy of 7 kinds of TI-RADS were analyzed.Results The sensitivity of Kwak-TIRADS,ATA guideline,A ACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS for differentiating benign and malignant thyroid nodules under the context of HT was 97.08％,98.25％,99.42％,95.91％,99.42％,90.06％and 99.42％,respectively,the specificity was 88.02％,83.23％,82.04％,88.02％,82.04％,86.83％and 84.43％,respectively,and the area under the curve(AUC)was 0.946,0.913,0.907,0.934,0.909,0.916 and 0.960,respectively.The sensitivity of C-TIRADS,EU-TIRADS and A ACE/ACE/AME guideline were all higher than that of K-TIRADS and ACR-TIRADS(all P＜0.05),and the specificity of Kawk-TIRADS and K-TIRADS were both higher than that of C-TIRADS,ATA guideline,EU-TIRADS and AACE/ACE/AME guideline(all P＜0.05),while AUC of C-TIRADS and Kawk-TIRADS were both higher than that of the rest 5 kinds of TI-RADS(all P＜0.05).According to Kwak-TIRADS,ATA guideline,AACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS,the malignant rate of different grades nodules identified with the same TI-RADS were significant different(all P＜0.05),which all raised with the increase of TI-RADS grade.Conclusion C-TIRADS and Kawk-TIRADS had better value for differentiating benign and malignant thyroid nodules under the context of HT,among which C-TIRADS had higher sensitivity and Kawk-TIRADS had higher specificity.

Psychopathological Analysis of Adolescent Girls With Autoimmune Thyroiditis.

AIM: Clinical studies indicate that there is an association between high levels of thyroid autoantibodies and psychiatric disorders, independent of impairment of thyroid function. Therefore, we aimed to investigate the association between thyroid autoimmunity and mood disorders in euthyroid girls with Hashimoto's thyroiditis (HT) in a case-control study. MATERIAL AND METHODS: We recruited 82 participants: 41 pubertal female patients with thyroiditis from endocrine outpatient clinics and a control group of 41 healthy pubertal girls from the University Hospital. Age ranged from 12 to 18 years; the diagnosis of HT was based on high levels of anti-TPO and/or anti-Tg antibodies associated with a hypoechogenic or normal thyroid ultrasound pattern. Other comorbidities known to affect mental and physical health were exclusion factors. All participants underwent a complete thyroid evaluation, assays of serum-free T4, TSH, anti-TPO antibodies, anti-Tg antibodies, and thyroid ultrasonography. They were then referred to a child psychiatrist. A psychiatric diagnosis was made in two steps. First, the Children's Depression Inventory (CDI) and Screen for Child Anxiety-Related Emotional Disorders (SCARED) tests were implemented according to the DSM-IV diagnostic criteria to be calculated. Second, the same psychiatrist conducted a K-SADS-PL semi-structured interview while unaware of the children's data. RESULTS: There was no significant difference in CDI score between patients with and without HT (p = 0.47). Patients with HT had significantly higher SCARED scores than patients without HT (p < 0.05). In the SCARED test, the subcategories of separation anxiety and social anxiety were significantly higher in the HT group (p = 0.04 and p = 0.01, respectively). During the K-SADS interview by the attending child psychiatrist, psychopathology diagnoses were detected in 27 of 41 patients (66%) with HT and in 8 of 41 individuals (19.5%) in the control group. Psychopathology was significantly higher in the HT group (p < 0.01). The incidences of depressive disorder, generalized anxiety disorder, and social phobia were significantly higher in the HT group than in the control group (p < 0.05). Multivariate logistic regression analysis revealed that the anti-TPO value was the most significant independent risk factor for the presence of depressive disorder (p < 0.01). CONCLUSION: This study described severe psychometric impairment in patients with euthyroid HT. We have demonstrated that autoimmune thyroid diseases, even in a euthyroid state, are associated with psychiatric disorders.

Hashimoto thyroiditis in a lingual thyroid: An interesting case.

Key Clinical Message: Whenever an enlarging mass is seen in throat, possibility of lingual thyroid should be considered. Thyroid function test should be done whenever ectopic thyroid is detected. Imaging (ultrasonography or Tc-99m scintigraphy) is adequate for diagnosis. Conservative treatment with levothyroxine helps in reducing size of lingual thyroid. Abstract: Hashimoto thyroiditis in lingual thyroid results in enlargement of the thyroid gland and oropharyngeal symptoms. Suppression therapy with levothyroxine results in reduction in size of the gland. We present an interesting case of Hashimoto disease in an adolescent female presenting as oropharyngeal mass.

Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.

This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.

Effects of Autoimmune Protocol (AIP) diet on changes in thyroid parameters in Hashimoto's disease.

INTRODUCTION AND OBJECTIVE: In the scientific world, the nutritional needs of persons with Hashimoto's autoimmune thyroid disease are discussed, and there is a lot of interest in the autoimmune protocol (AIP). The aim of the study was to check the effects of AIP on thyroid parameters in euthyroid patients with Hashimoto's disease. MATERIAL AND METHODS: Among 28 people with Hashimoto's (including 1 male) the consumption of nutrients, anthropometrics, symptoms of the disease, values of thyroid parameters: FT3, FT4, TSH, thyroid ultrasound and autoimmune aTPO, aTG were analyzed before and after 12 weeks of using the AIP diet. The impact of changes in the consumption of selected nutrients on changes in thyroid biochemical parameters were analyzed using multiple regression models, where the dependent variables of the created models were changes in thyroid biochemical parameters. RESULTS: After applying the AIP diet, the number of people reporting symptoms of malaise decreased, the levels of FT3 and FT4 as well as TSH decreased, remaining within the reference concentration range. aTG decreased slightly, but aTPO increased significantly. Ultrasound examination also showed a decrease in the volume of the thyroid gland. The body weight of the subjects decreased, which indicates a caloric deficit. CONCLUSIONS: Given the numerous advantages of the AIP diet, extending the observation time of the diet, along with its personalization in terms of food selection, energy and nutritional value, could show changes in both well-being and biochemical test results to a greater extent. The use of a personalized AIP protocol can improve the quality of life, a positive change in mental state, reduction of stress, and above all, the improvement of adverse ailments associated with Hashimoto's disease.

Autoimmune polyendocrine syndromes associated with autoimmune rheumatic diseases.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes, are a group of autoimmune diseases characterized by the co-occurrence of dysfunctions of several (at least two) endocrine glands. They develop under the influence of environmental factors in genetically predisposed people. Autoimmune polyendocrine syndromes may accompany autoimmune rheumatic diseases and worsen their course - APS-2 and APS-3 are the most common. The APS-2 includes the coexistence of, e.g. Hashimoto's disease, celiac disease and rheumatoid arthritis (RA). In APS-3, rheumatic diseases such as RA, systemic lupus erythematosus, and Sjögren's syndrome may coexist with Hashimoto's disease, type 1 diabetes and hypogonadism or other endocrinopathies. Undiagnosed endocrine diseases may be the reason for the intensification of metabolic disorders observed in the course of rheumatic diseases, cause the ineffectiveness of rheumatological treatment and also increase the frequency of bone fractures due to osteoporosis, cardiovascular complications and even miscarriages when coexistent, e.g. Hashimoto's disease with hypothyroiditis, which increases the risk of pregnancy loss. It is important to be able to conduct an extensive interview, paying attention to the symptoms of possible endocrinopathy as well as the features of other autoimmune disorders in the physical examination (e.g. vitiligo or darkening of the skin in Addison's disease). Depending on the history and physical examination, screening for various APSs is advised.