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Aims: Thyroid dysfunction and metabolic disturbances are common in major depressive disorder (MDD) patients. We aimed to assess the relationship between thyroid dysfunction, metabolic disturbances, and clinical symptoms in Chinese first-episode, drug-naïve (FEDN) MDD patients using undirected and Bayesian network methods., Methods: 1718 FEDN MDD patients were recruited. Serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and glucose were assessed. Blood pressure and body mass index were measured. Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety, and positive subscale of Positive And Negative Syndrome Scales were used to detect clinical symptoms. An undirected network with EBICglasso default and a directed acyclic graph (DAG) using the Bayesian network approach was conducted., Results: The prevalence rates of clinical symptoms, thyroid dysfunction, and metabolic dysfunction were as follows: anxiety (n=894, 52%), psychotic symptoms (171, 10%), subclinical hypothyroidism (SCH, n=1041, 61%), abnormal TgAb (n=297, 17%), abnormal TPOAb (n=438, 25%), hyperthyroidism (n=5, 0.3%), hypothyroidism (n=3, 0.2%), hyperglycemia (n=241, 14%), hypertriglyceridemia (n=668, 39%), low HDL-C (n=429, 25%), hypercholesterolemia (421, 25%), abnormal TC (357, 21%), abnormal LDL-C (185, 11%). overweight or obesity (n=1026, 60%), and hypertension (n=92, 5.4%). Both networks demonstrated serum TSH and TC levels and the severity of depression played an important role in the pathophysiology of MDD., Conclusions: MDD patients may have thyroid and metabolic dysfunction in the early stage. Targeting hypercholesterolemia, depressive symptoms, and SCH in MDD patients may hold promise in reducing clinical symptoms, metabolic disturbances, and thyroid dysfunction., 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 © 2023 Peng, Wang, Lang, Liu and Zhang.)

Isolated thyroid abscess is a rare entity in early childhood. Among thyroid disorders, thyroid abscess or acute suppurative thyroiditis constitutes about 0.7%-1% of all cases. The thyroid gland is normally resistant to infections due to its well-enveloped capsule, rich blood supply, and high iodine content.A child presented with tender neck swelling accompanied by fever for 3 days. Ultrasound of the neck showed features suggestive of left parapharyngeal abscess. Laboratory parameters including thyroid function test were within normal limits. Contrast-enhanced CT of the neck was done and showed an isolated thyroid abscess with no other abnormalities. The patient was started on intravenous antibiotics followed by incision and drainage of the abscess. The child improved symptomatically. This report discusses the differential diagnosis and management of this rare entity., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Common symptoms of overt hypothyroidism are non-specific and include fatigue, lethargy, and dry skin. Although the diagnosis is considered to be straightforward, no single symptom can be used to identify patients with overt hypothyroidism, while many patients with subclinical hypothyroidism are asymptomatic. A large population-based study on the spectrum of symptoms in subclinical hypothyroidism showed similar rates of thyroid disease-related symptoms compared with euthyroid subjects, while the TSH concentration had no impact on symptom score. Together, these findings make it challenging to attribute symptoms to their underlying cause. This is also true in the case of unexplained persistent symptoms in levothyroxine-treated patients. Although generally considered a life-long replacement therapy, successful thyroid hormone discontinuation resulting in euthyroidism has been reported in approximately one third of patients. Thus, we overtreat patients with (subclinical) hypothyroidism, highlighting the importance of reliable diagnostic criteria. The diagnostic process, including the implementation of robust TSH and FT4 reference intervals, is especially challenging in specific situations including aging, pregnancy, non-thyroidal illness, and central hypothyroidism. There is a clear need for improved adherence to current guidelines from scientific societies and for willingness to manage symptoms without a clear pathological correlate, especially in the case of mild TSH elevations. This review will highlight recent literature on this topic and offers some practice points., 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 © 2023 Jansen, Boelen, Heijboer, Bruinstroop and Fliers.)

Background: The hypothalamus-pituitary-thyroid axis coordinates brain development and postdevelopmental function. Thyroid hormone (TH) variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood. Methods: To get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder (BIP), and anxiety disorders (ANXs) in 497,726 subjects from U.K. Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyrotropin (TSH), and free thyroxine (fT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions. Results: Hypothyroidism was positively associated with an increased risk of major depressive disorder (MDD; OR = 1.31, p  = 5.29 × 10 -89 ), BIP (OR = 1.55, p  = 0.0038), and ANX (OR = 1.16, p  = 6.22 × 10 -8 ). Hyperthyroidism was associated with MDD (OR = 1.11, p  = 0.0034) and ANX (OR = 1.34, p  = 5.99 × 10 - ⁶). Genetically, strong coheritability was observed between thyroid disease and both major depressive ( r g  = 0.17, p  = 2.7 × 10 - ⁴) and ANXs ( r g  = 0.17, p  = 6.7 × 10 - ⁶). This genetic correlation was particularly strong at the major histocompatibility complex locus on chromosome 6 ( p  < 10 - ⁵), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor fT4 levels were genetically correlated with mood disorders. Conclusions: Our findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated through THs and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.

Background: Thyroid dysfunction is closely related to arrhythmia. However, the relationship between sensitivity to thyroid hormone and risk of arrhythmia remains unknown. This study aimed to investigate the association between the thyroid system complex index and risk of arrhythmia in patients with coronary heart disease (CHD)., Methods: This large, multicenter study included 28,413 patients with CHD. Central sensitivity to thyroid hormone was assessed by calculating the thyroid feedback quantile-based index (TFQI). Logistic regression was used to analyze the relationship between sensitivity to thyroid hormone and risk of arrhythmia. This study also assessed the relationship between sensitivity to thyroid hormone and risk of arrhythmia in different sexes, ages, and glucose regulation and blood lipid states., Results: Of the 28,413 participants, 8935 (31.4%) patients with CHD had arrhythmia. There was a remarkable association between TFQI and risk of arrhythmia (odds ratio [OR]: 0.783; 95% confidence interval [CI], 0.735-0.836). Furthermore, the association between the TFQI and risk of arrhythmia in women (OR: 0.731; 95% CI: 0.667-0.802) was stronger than that in men (OR: 0.894; 95% CI: 0.816-0.910), as well as higher in elder (OR: 0.779; 95% CI: 0.721-0.843) than middle-aged (OR: 0.789; 95% CI: 0.703-0.886) patients. Furthermore, the association was strong in the state of diabetes (OR: 0.635; 95% 0.569-0.709) and dyslipidemia (OR: 0.706; 95% CI: 0.644-0.774)., Conclusion: There is a remarkable association between sensitivity to thyroid hormone and risk of arrhythmia in patients with CHD, which is more pronounced among women and the elderly. The association is also stronger in CHD patients with dyslipidemia or diabetes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To study the epidemiological, clinical and evolutionary characteristics of autoimmune dysthyroidism in the endocrinology-diabetes department of the CNHU-HKM., Material and Method: This was a descriptive and analytical cross-sectional study of patients seen for thyroid pathology in the endocrinology diabetology department over a 10-year period. Patients with at least one abnormal TSH and positive anti-thyroid antibodies were included., Results: Over the study period, we recorded 2883 consultants, 347 of them having thyroid diseases, including 69 cases of autoimmune dysthyroidism divided into 54 cases of Graves' disease and 15 cases of Hashimoto's disease. Autoimmune dysthyroidism represented 2.39% of consultations and 19.89% of thyroid disorders. Graves' disease and Hashimoto's disease accounted for 1.87% (54 cases) and 0.52% (15 cases) of consultations respectively. Autoimmune dysthyroidism was more frequent in the 30-40 and 40-50 age groups. The most frequent symptoms of Graves' disease were asthenia (94.4%), weight loss (87.0%) and tachycardia (85.2%). In Hashimoto's disease, the main symptoms were asthenia (86.66%), goiter (66.6%) and weight gain (60%). High initial R-TSH antibody levels and iatrogenic hypothyroidism were found to be factors associated with extended follow-up of Graves' disease beyond 18 months., Conclusion: Autoimmune dysthyroidism is a frequent condition, with Graves' disease predominating. Their evolution under therapy is influenced by clinical, biological and ultrasonographic factors., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Introduction: The high prevalence of obesity and thyroid diseases worldwide justifies di per se their simultaneous coexistence. In recent decades, there has been a parallel and significant rise in obesity and thyroid diseases in industrialised countries, although the underlying mechanisms are complex and not well known., Material and Methods: The authors accomplished a comprehensive literature search of original articles concerning obesity and thyroid status. Original papers exploring the association between these two morbidities in children and adults were included., Results: A total of 79 articles were included in the present analysis. A total of 12% of obese children (mean age 10.9 ± 1.4 years) showed a thyroid disease, and they were younger than healthy obese children (10.9 ± 1.2 vs. 11.0 ± 0.4 years, p < 0.001). Isolated hyperthyrotropinaemia was the most frequent finding in children (10.1%). Autoimmune thyroid disease was more frequent in puberal age. Thyroid antibodies and subclinical hypothyroidism were more frequent in obese that in non-obese patients (7% vs. 3%, p < 0.001; 10% vs. 6%, p < 0.001). Among obese adults, 62.2% displayed a thyroid disease; those affected were younger (35.3 ± 6.8 vs. 41.0 ± 1.9 years, p < 0.001), heavier [body mass index (BMI): 39.4 ± 6.3 vs. 36.1 ± 2.3 kg/m², p < 0.001], and more frequently female (13% vs. 8%, p < 0.001). The most frequent disease was overt hypothyroidism (29.9%). BMI appears to be correlated with TSH levels in obese adults. Overt hypothyroidism was significantly more frequent in obese patients (7% vs. 3%, p < 0.005), but no difference was found in thyroid antibodies (15% vs. 14%, p = 0.178)., Conclusions: An undeniable relationship between obesity and thyroid impairments exists. Isolated hyperthyrotropinaemia is frequently seen in obese children, often followed by spontaneous resolution. Subclinical hypothyroidism should never be treated in children or adults with the aim of reducing body weight.

Introduction: Studies show a high prevalence of thyroid dysfunction in heart failure patients that could have an impact on clinical course and outcome., Materials: A total of 185 consecutive heart failure patients aged &gt;18 years (mean age 58.4 years; 57.3% males) underwent demographic, clinical, hematological, biochemical and thyroid profile assessment. Euthyroidism was defined as TSH of 0.5 to 4.94 mIU/L with fT3 and fT4 in normal range, hypothyroidism as TSH of &gt;4.94, and hyperthyroidism as TSH &lt;0.5 mIU/L. Patients were followed up till discharge/outcome. Data was analyzed using SPSS 21.0 software., Result: Prevalence of thyroid disorders was 28.6% (6.5% hyper and 22.2% hypothyroid). No significant association of thyroid disorders was seen with age, sex, comorbidities and NT-proBNP levels (p &gt; 0.05). Thyroid disorder was significantly associated with higher SBP, patients with NYHA 3/4, TSH, S. urea, S. creatinine and HDL levels and lower Hb, SGPT, TC and LDL levels (p &lt; 0.05). Mean duration of hospital stay of patients with thyroid disorder was 3.74±0.92 days as compared to 3.45±0.86 days for those without thyroid disorder (p = 0.050). There were 12 (6.5%) mortalities. No significant association of mortality was seen with thyroid disorder (p = 0.711)., Conclusion: There is high prevalence of thyroid disorders in heart failure patients which had a clinical impact too. Patients with thyroid disorder had higher NYHA and required longer hospitalization. Further studies to explore these relationships further are recommended. References Biondi B, Kahaly GJ. Cardiovascular involvement in patients with different causes of hyperthyroidism. Nat Rev Endocrinol 2010;6(8):431-443. Kuchulakanti PK, Bandaru S, Kuchulakanti A, et al. Association of subclinical hypothyroidism in heart failure: a study from South India. Br J Cardiol 2019;26:35. Jabbar A, Ingoe L, Thomas H, et al. Prevalence, predictors and outcomes of thyroid dysfunction in patients with acute myocardial infarction: the ThyrAMI-1 study. J Endocrinol Invest 2021;44(6):1209-1218., (© Journal of the Association of Physicians of India 2011.)

Introduction: Anemia frequently occurs during course of clinical thyroid diseases. Without proper diagnosis & effective treatment of underlying thyroid disease, it is often difficult to achieve complete correction of anemia., Aim: The present study was conducted to assess prevalence & types of anaemia in patients with thyroid disorders., Materials: A cross sectional study was conducted on 160 patients including both hypothyroid & hyperthyroid patients at OPD/IPD in SRN Hospital affiliated to MLN Medical college Prayagraj between July 2021 & August 2022. Blood samples were taken to estimate CBC, GBP with Retic count, S. ferritin, S. folate, S. Vitamin B12, Thyroid profile. Data was entered in MS Excel Spreadsheet & appropriate statistical package applied., Result: Out of 144 hypothyroid patients, 102 (70.83%) were found to be anaemic & out of 16 hyperthyroid patients, 6 (37.5%) were found to be anaemic. In 102 anaemic hypothyroid patients, 56 (54.9%)had normocytic normochromic, 25 (24.5%) had microcytic and 21 (20.5%) had macrocytic anaemia. In 6 anaemic hyperthyroid patients, 3 (50%) had normocytic normochromic, 2(33.33%) had microcytic and 1 (16.67%) had macrocytic anaemia., Conclusion: High prevalence of anaemia was found in patients with thyroid disorders. Anaemia is an uncommon finding in hyperthyroidism but when present may be similar to that present in hypothyroidism. The most common type of anaemia in both hyperthyroidism & hypothyroidism was found to be normocytic normochromic, followed by microcytic & least common being macrocytic. References Suhail N, Abu Alsel BT, Batool S. Prevalence and association of thyroid dysfunction with anemia/body iron status among northern border Saudi population. Int J Med Res Health Sci 2020;9(3):1-7. Peraka SA, Karre S, Ravuri S, et al., To evaluate prevalence of anemia in hypothyroid patients. J Diagn Pathol Oncol 2019;4(2):110-113., (© Journal of the Association of Physicians of India 2011.)

Coronavirus disease 2019 (COVID-19) was characterized as a pandemic in March, 2020 by the World Health Organization. COVID-19 is a respiratory syndrome that can progress to acute respiratory distress syndrome, multiorgan dysfunction, and eventually death. Despite being considered a respiratory disease, it is known that other organs and systems can be affected in COVID-19, including the thyroid gland. Thyroid gland, as well as hypothalamus and pituitary, which regulate the functioning of most endocrine glands, express angiotensin-converting enzyme 2 (ACE2), the main protein that functions as a receptor to which SARS-CoV-2 binds to enter host cells. In addition, thyroid gland is extremely sensitive to changes in body homeostasis and metabolism. Immune system cells are targets for thyroid hormones and T3 and T4 modulate specific immune responses, including cell-mediated immunity, natural killer cell activity, the antiviral action of interferon (IFN) and proliferation of T- and B-lymphocytes. However, studies show that patients with controlled hypothyroidism and hyperthyroidism do not have a higher prevalence of COVID-19, nor do they have a worse prognosis when infected with the virus. On the other hand, retrospective observational studies, prospective studies, and case reports published in the last two years reported abnormal thyroid function related to acute SARS-CoV-2 infection or even several weeks after its resolution. Indeed, a variety of thyroid disorders have been documented in COVID-19 patients, including non-thyroidal illness syndrome (NTIS), subacute thyroiditis and thyrotoxicosis. In addition, thyroid disease has already been reported as a consequence of the administration of vaccines against SARS-CoV-2. Overall, the data revealed that abnormal thyroid function may occur during and in the convalescence post-COVID condition phase. Although the cellular and molecular mechanisms are not completely understood, the evidence suggests that the "cytokine storm" is an important mediator in this context. Thus, future studies are needed to better investigate the pathophysiology of thyroid dysfunction induced by COVID-19 at both molecular and clinical levels., 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 © 2022 Rossetti, Cazarin, Hecht, Beltrão, Ferreira, Fortunato, Ramos and de Carvalho.)

Context: Thyroid peroxidase antibody (TPOAb) positivity is prevalent in women of reproductive age and predisposes to thyroid dysfunction, particularly hypothyroidism, which has adverse effects on pregnancy., Objective: This study aimed to report the rate of development of abnormal thyroid function among initially euthyroid TPOAb-positive women recruited into the TABLET trial, to identify factors associated with the development of hypothyroidism, and to compare outcomes between euthyroid and treated hypothyroid individuals., Methods: This observational cohort study, conducted at 49 UK hospitals between 2011 and 2016, included euthyroid TPOAb-positive women 16 to 40 years of age with a history of miscarriage or subfertility, planning pregnancy, randomized to levothyroxine 50 mcg daily or placebo. Abnormal thyroid function, conception rate, and live birth rate (LBR) ≥34 weeks were analyzed., Results: Among the women, 70/940 (7.4%) developed subclinical (SCH) or overt (OH) hypothyroidism: 27/470 taking levothyroxine and 43/470 placebo (relative risk [RR] 0.63; 95% CI, 0.39-1.00; P = 0.05); 83% of cases emerged prepregnancy. Baseline median serum TSH concentrations and TPOAb titers were significantly higher in those who developed hypothyroidism vs those who did not (P < 0.001). Treated SCH/OH demonstrated a higher failure-to-conceive rate compared with euthyroid women (adjusted RR 2.02 [1.56-2.62]; P < 0.001). The LBR ≥ 34 weeks was similar in the treated SCH/OH and euthyroid groups (adjusted RR 1.09 [0.77-1.55]; P = 0.6)., Conclusion: Approximately 7% of euthyroid TPOAb-positive women will develop hypothyroidism within 1 year preconception or in pregnancy. Conception rates are lower in women with treated SCH/OH compared with euthyroid women, but LBR are comparable. Thyroid function in TPOAb-positive women should be monitored regularly, when trying to conceive, to ensure prompt diagnosis and appropriate treatment initiation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose-response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis. Risk estimates from 22 of the 25 studies were included in the meta-analysis and pooled using random-effects models. Compared to euthyroidism, hyperthyroidism and hypothyroidism diagnoses were associated with higher (pooled risk ratio (RR): 1.12, 95% CI: 1.06-1.18, 3829 exposed cases) and lower risks (RR = 0.93, 95% CI: 0.86-1.00, 5632 exposed cases) of breast cancer, respectively. The increased risk after hyperthyroidism was greater among postmenopausal women (RR = 1.19, 95% CI 1.09-1.30) and the decreased risk after hypothyroidism was more pronounced among premenopausal women (RR = 0.69, 95% CI 0.53-0.89). Among women with no prior history of thyroid disease, every 1 mIU/L increase in TSH level was associated with a 0.8% (95% CI > 0-1.5%) lower risk of breast cancer. In conclusion, this meta-analysis supports an association between thyroid hormone levels and breast cancer risk, which could be modified by menopausal status.

Introduction: Autoimmune diseases account for a cumulative overall prevalence of about 3-5% worldwide. Among them, autoimmune thyroid diseases (ATDs) are the most common and comprise two main entities: Hashimoto's thyroiditis (HT) and Graves-Basedow disease (GD). The pathogenesis of ATDs remains not fully elucidated, however the role of microbioma has been proposed. Gut microbiota exert an important influence on the intestinal barrier, nutrient metabolism and immune system development and functions., Evidence Acquisition: In this review, we describe on the main features of ATDs in pediatrics, focusing on the reciprocal influence between gut microbiota, thyroid hormone metabolism and thyroid autoimmunity and consider the role of probiotics and other microbiota-targeted therapies in thyroid diseases with a perspective on pediatric endocrinology., Evidence Synthesis: Microbiome affects both endogenous and exogenous thyroid hormone metabolism and influences the absorption of minerals important to the thyroid function, which are iodine, selenium, zinc and iron. The alteration of the gut microbiota, with the consequent modifications in the barrier function and the increased gut permeability, seems involved in the development of autoimmune and chronic inflammatory diseases, including ATDs. The supplementation with probiotics showed beneficial effects on the thyroid hormone and thyroid function because this strategy could restore the intestinal eubiosis and the good strain microorganism proliferation., Conclusions: Even though the evidence about the interaction between microbiota and ATDs in pediatric patients is limited, the promising results obtained in the adult population, and in other autoimmune disorders affecting children, highlight the need of for further research in the pediatric field.

Aims: It is uncertain whether subclinical thyroid dysfunction is associated with cardiovascular disease (CVD) events and mortality in people with type 2 diabetes. The aim of this study was to determine whether undetected thyroid disease increases the risk of incident CVD and death in type 2 diabetes., Methods: One thousand two hundred fifty participants with type 2 diabetes (mean age 65.3 years, 56.5% males, median diabetes duration 8.0 years) without known thyroid disease and not taking medications known to affect thyroid function were categorised, based on baseline serum free thyroxine (FT4) and thyrotropin (TSH) concentrations, as euthyroid, overt hypothyroid (increased TSH, low FT4), subclinical hypothyroid (increased TSH, normal FT4), overt thyrotoxic (decreased TSH, raised FT4) or subclinical thyrotoxic (decreased TSH, normal FT4). Incident myocardial infarction, incident stroke, all-cause and cardiovascular mortality were ascertained during a mean 6.2-6.7 years of follow-up., Results: Most participants with newly-detected thyroid dysfunction had subclinical hypothyroidism (77.2%) while overt/subclinical thyrotoxicosis was infrequent. Compared to participants with TSH 0.34-2.9 mU/L, those with TSH > 5.1 mU/L were not at increased risk of incident myocardial infarction (adjusted hazard ratio (95% confidence limits) 1.77 (0.71, 2.87)), incident stroke (1.66 (0.58, 4.78)), all-cause mortality (0.78 (0.44, 1.37)) or cardiovascular mortality (1.16 (0.38, 3.58)). Independent baseline associates of subclinical hypothyroidism included estimated glomerular filtration rate and systolic blood pressure., Conclusions: Subclinical hypothyroidism was not independently associated with CVD events or mortality in community-dwelling people with type 2 diabetes despite its associations with CVD risk factors, questioning strategies to identify and/or treat mild thyroid dysfunction outside usual care., (© 2022. The Author(s).)

Autism spectrum disorder (ASD), with its high economic and societal costs, is a growing public health concern whose prevalence has risen steadily over the last two decades. Although actual increased incidence versus improved diagnosis remains controversial, the increased prevalence of ASD suggests non-inherited factors as likely contributors. There is increasing epidemiologic evidence that abnormal maternal thyroid function during pregnancy is associated with increased risk of child ASD and other neurodevelopmental disorders. Prenatal exposure to endocrine-disrupting chemicals such as per- and polyfluoroalkyl substances (PFAS) is known to disrupt thyroid function and can affect early brain development; thus, thyroid dysfunction is hypothesized to mediate this relationship. The concept of a potential pathway from prenatal PFAS exposure through thyroid dysfunction to ASD etiology is not new; however, the extant literature on this topic is scant. The aim of this review is to evaluate and summarize reports with regard to potential mechanisms in this pathway.

Chronic obstructive pulmonary disease (COPD), a group of diseases of distinct aetio-pathological consideration with different phenotypic presentations where smoking is the leading cause, all share the ultimate result of airflow limitation. This study aimed to evaluate thyroid function tests (TFT) in patients with COPD. Pulmonary function tests (PFT) were performed for 30 patients with obstructive lung disease and fifteen healthy control individuals. We measured SPO 2 to confirm COPD and assess the severity of the disease and assessed TT3, TT4, and TSH using the ELISA test. The values of VC, FVC, and FEV in the first second and PEF, TSH, and SPO 2 were lower in the COPD group than in the control group (P-value=0.001). In severe COPD (FEV 1 <50%), there was a significant reduction in T3 but not T4 or TSH compared to mild-moderate COPD patients. Thyroid dysfunction was observed in patients with COPD pointing to a metabolic response; patients with lower weight indices had a lower TSH and, consequently, T3., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Background: The research of cytokine-induced thyropathies in the midst of continuing coronavirus infection (COVID-19) pandemic is a very important and urgent problem. On the one hand, COVID-19 is often accompanied by a massive overproduction of cytokines, so we can expect an enhanced cytokines effects impact on the thyroid gland. On the other hand, it is possible that biological therapy with tocilizumab, which has a powerful immunosuppressive effect, plays a protective role to the development of cytokines-induced thyropathies amidst COVID-19. The results of the study should be the starting point for understanding the mechanisms of possible compromise of thyroid function during COVID-19., Aim: The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, FT3 and FT4 values, and patient survival., Materials and Methods: This retrospective, single-center study included 122 patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, FT3, FT4, antibodies to thyroid peroxidase, antibodies to the TSH receptor (AT-recTSH). The markers of the inflammatory process were assessed: interleukin-6, C-reactive protein, the degree of lung tissue damage according to multispiral computed tomography of the lungs, the percentage of blood oxygen saturation (SpO 2 ), the treatment outcomes., Results: Five (4%) patients were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with interleukin-6 ( r =-0.221; p =0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients ( p =0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]., Conclusion: Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. This study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate.

Objectives: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction., Methods: A population-based cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health-related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One-way analysis of variances or chi-square test was used for comparisons between oral health-related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health-related parameters and the abnormal results of TFTs., Results: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241-1.537, p < .0001); however, statistical significance was not found after adjusting for the other variables., Conclusions: Our study demonstrated that good oral health-related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health-related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies., (© 2021 Wiley Periodicals LLC.)

Background: Thyroid dysfunctions are highly prevalent and can worsen underlying cardiopathies, but despite that the routine screening of thyroid function in the Emergency Department (ED) setting is not generally recommended., Objective: To understand if staff training and implementation of rapid TSH screening (rTSH) could improve the management of patients arrived in the ED. Specifically, we aimed at evaluating the prevalence of undiagnosed thyroid diseases among ED patients; the effects of educational meetings in the clinical decision-making process; the usefulness of rTSH, in terms of variation of either the clinical work out or the existing treatment., Design: Retrospective case-control study of 9227 patients managed in the ED of an academic institution. rTSH was routinely available for all patients, who were divided into rTSH-YES and rTSH-NO groups., Results: We included 4243 and 4984  patients in the rTSH-YES and rTSH-NO group, respectively. Trained personnel uncovered a high prevalence of undiagnosed thyroid dysfunction (7%). The diagnosis in the ED of heart failure, history of thyroid diseases, contrast media/amiodarone administration and female gender were independently associated with an increased likelihood to have thyroid dysfunction. The rTSH improved the clinical outcome by (a) appropriate treatment of an underlying clinical condition causing ED entrance, (b) appropriate prophylaxis in patients requiring contrast media, (c) uncovering incorrect treatments, with 60% of patients on levothyroxine requiring a dose reduction., Conclusions: The rTSH in the ED revealed a high prevalence of untreated thyroid disorders with a major impact on following interventions. The training of a multidisciplinary team is crucial in driving the correct decision-making process., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

This systematic review and meta-analysis was conducted to evaluate the effect of COVID-19 on thyroid function and the role of thyroid hormones alterations in predicting the severity of COVID-19. Online databases, including Scopus, Medline/PubMed, EMBASE, Google Scholar, and Cochrane were searched up to August 2, 2022. After screening titles, abstracts, and full manuscripts, respectively, 30 reports were enrolled. The risk of bias (ROB) was evaluated using the QUADAS-2 tool. In addition, odds ratio (OR) and hazard ratio (HR) analysis for assessing the OR of abnormal thyroid function tests (TFT) in predicting the COVID-19 severity and poor outcomes. Among 30 enrolled studies, ROB of the current study is estimated low to moderate. The average number of patients in each study was 325 (range: 40-3,703), with an overall mean age of 57.6, and the female proportion of 40.4%. Overall, the pooled analysis showed that the prevalence of thyroid dysfunction among 9,707 COVID-19 cases was 15%. Among mild to moderate COVID-19 patients, 6.2% had abnormal TFT, and among patients who experienced severe to critical COVID-19, 20.8% had abnormal TFT. The pooled OR for abnormal TFT and the severity of COVID-19 obtained from 3,865 COVID-19 patients was 3.77 (2.03, 6.99). The pooled HR of TSH level of COVID-19 mortality was 1.57 (0.91, 2.72). Our results demonstrate a high prevalence of thyroid dysfunction in COVID-19, and that among patients severe cases had a 3.77-fold higher risk of abnormal TFT compared to mild to moderate COVID-19. Further studies are required to evaluate the longer-term prognostic role of thyroid dysfunction in severe COVID-19, and investigate potential therapeutic strategies., 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 © 2022 Darvishi, Nazer, Shahali and Nouri.)

Objective: To investigate the clinicopathological characteristics of papillary thyroid cancer (PTC) and identify risk factors for postoperative recurrence of PTC with recurrent laryngeal nerve (RLN) involvement., Methods: In total, 171 patients (112 women and 59 men, age: 18-80 years, and 65 patients aged ≥ 55) with T4a PTC with RLN involvement, treated at Beijing Tongren Hospital, Capital Medical University, from January 2006 to December 2020, were retrospectively examined. Clinicopathological characteristics, including voice analysis results, and survival outcomes were assessed. The Mann-Whitney U and Kruskal-Wallis H tests were used to analyze differences in acoustic parameters. The Kaplan-Meier method was used to calculate the overall survival (OS) and recurrence-free (RFS) rates. Univariate and multivariate Cox regression analyses were performed of the clinical data., Results: The postoperative follow-up period ranged from 12 to 196 months (mean: 66.18 months). Of the 171 patients, 16 had recurrence and 8 died of thyroid-related diseases. The 5-year OS rate was 95.22%. The 5-year RFS rate was 89.38%. Jitter and shimmer were higher and maximum phonation time was shorter in patients with preoperative vocal cord paralysis (VCP) than in those without RLN involvement, and in those with RLN involvement but without preoperative VCP. Acoustic parameters were similar in patients with no preoperative VCP and those without RLN involvement. Voice analysis results did not differ between cases with RLN adhesion and RLN invasion. Univariate analysis showed that age at onset ≥ 55 years, preoperative RLN palsy, and esophageal invasion were risk factors for postoperative recurrence of PTC with RLN involvement. Multivariate analysis showed that onset age ≥ 55 years (OR 4.52, 95% confidence interval: 1.44-14.19, P = 0.010) was an independent risk factor for recurrence., Conclusions: PTC patients with RLN invasion can achieve good outcomes. Preoperative voice analysis may offer insights into RLN function. Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in T4a PTC patients., 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 © 2022 Chen, Zhong, Hou, Ma, Shi, Feng, He, Lin, Lian, Shen, Wang and Fang.)

Objective: To evaluate whether sex differences in the associations of subclinical hypothyroidism (SH) and subclinical hyperthyroidism (SCH) with the risks of major adverse cardiovascular events (MACE) and fractures., Methods: The PubMed, EmBase, and Cochrane Library databases were searched for eligible studies from inception until November 2021. The relative risk (RR) ratio with the 95% confidence interval (CI) was used to identify sex differences in the associations of SH and SCH with the risks of MACE and fractures. All analyses were performed using a random-effects model., Results: Twenty-four cohort studies (in 3,480,682 patients) were selected for meta-analysis. There were no sex differences in the associations of SH and SCH with the risks of atrial fibrillation, all-cause mortality, cardiac death, coronary heart disease, heart failure, MACE, stroke, fracture. Subgroup analyses indicated a greater risk of MACE in men than in women with SH if follow-up was ≥10.0 years (RR ratio 2.44; 95% CI 1.17-5.10; P = 0.017). The risk of any fracture was greater in men than in women with SH if follow-up was <10.0 years (RR ratio 1.17; 95% CI 1.03-1.34; P = 0.017) and in studies with a high level of adjustment (RR ratio 1.16; 95% CI 1.02-1.32; P = 0.022). However, the risk of hip fracture was lower in men than in women with SH on pooling of studies with low adjustment (RR ratio 0.53; 95% CI 0.29-0.97; P = 0.039)., Conclusions: There may be sex-related differences in the risks of MACE, any fracture, and hip fracture in patients with SH.

Cardiovascular diseases (CVD) and thyroid dysfunction are two of the most prevailing disorders in the world that are closely interlinked. Actions of thyroid hormones are mediated via thyroid receptors present in the myocardium and the vascular tissue. Primary mechanism that links thyroid dysfunction with CVD is the modification of cardiovascular risk factors (dyslipidemia, blood pressure, coagulation parameters, etc.) resulting in endothelial and left ventricular systolic and diastolic dysfunction. Both overt and subclinical hyperthyroidism and hypothyroidism may cause adverse alterations in cardiac function. Hyperthyroidism gives rise to palpitation, atrial fibrillation, systolic hypertension, and heart failure, whereas hypothyroidism increases diastolic hypertension, pericardial effusion, and the risk of ischemic heart disease via altering lipid and coagulation parameters. Early recognition and treatment of thyroid dysfunction may prevent adverse cardiovascular events in patients with or without pre-existing CVD. Certain cardiac conditions and medications can cause alterations in thyroid function that may predispose an individual to higher morbidity and mortality. In certain situations, thyroid dysfunction treatment may have cardiovascular benefits. This study deals with the interplay between cardiovascular and thyroid dysfunctions associated with clinical implications and management strategies., (© 2022 Sanyal Debmalya et al., published by Sciendo.)

Introduction: Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services., Aims: To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic., Methods: A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1 st January 2016 and 31 st December 2021 at a tertiary paediatric endocrine centre in the United Kingdom., Results: Overall, 244 children whose first presentation was within the timeframe of interest were included in this study, with a median age (range) of 11.5 (6.1, 16.8) years. Of these, 43 (18%) were hyperthyroid and 201 (82%) were hypothyroid. The greatest number of thyroid presentations occurred in 2021 (n=60, 25% of total over time period) and the fewest in 2020 (n=10, 4% of total over time period). Prior to this, the median (range) number of presentations per year was 34 (28, 39). There were no statistically significant differences in biochemistry, antibody status or other clinical characteristics between those who presented with hyperthyroidism prior to the pandemic or after. In those with hypothyroidism, baseline biochemistry was similar between the 2 groups, but the presence of other autoimmune conditions was greater pre-pandemic (17.2% vs 15.0%, p=0.03). In addition, patients were more likely to have transient thyroid dysfunction, which did not require treatment post-pandemic (70.0% vs 49.6%, p=0.0086)., Conclusions: Although overall rates of presentation with thyroid dysfunction have not altered since the first wave of the COVID-19 pandemic, presentations with transient thyroid dysfunction, not requiring ongoing treatment have increased. Further research regarding the relationship between COVID-19 and thyroid function in children and young people, is needed., 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 © 2022 McCowan, Wild, Lucas-Herald, McNeilly, Mason, Wong, Ahmed and Shaikh.)

Background: The influence of thyroid-stimulating hormone (TSH) on gestational outcomes have been studied and checked whether differing TSH levels are relevant on human reproduction outcomes. International guidelines recommend TSH values <2.5 mIU/L in women trying to conceive, since values above this level are related to a higher frequency of adverse reproductive outcomes. This study aimed to evaluate whether TSH values correlate with different gestational outcomes in euthyroid infertile women without autoimmune thyroid disease., Methods: A retrospective cohort study was conducted involving 256 women who underwent in vitro fertilization (IVF) treatment. The participants were divided into two groups: TSH 0.5-2.49 mIU/L (n=211) and TSH 2.5-4.5 mIU/L (n=45). The clinical data, hormonal profiles and reproductive outcomes were compared between groups. Additionally, a systematic review with meta-analysis following the PRISMA protocol was carried out in PubMed/MEDLINE, EMBASE, and SciELO, with no time or language restrictions, for articles comparing TSH groups named "low TSH" (<2,5 mIU/L) and "high TSH" (≥2.5 mIU/L). A meta-analysis of proportions was performed with pooled estimates expressed as relative risk (RR) of events and a random effects model., Results: Age, BMI, free thyroxine levels (FT4) hormonal profile and IVF outcomes were not different between groups, neither gestational outcomes (p=0.982). Also, no difference was observed when the TSH and FT4 levels were compared between patients with positive or negative gestational outcomes (p=0.27 and p=0.376). Regarding the systematic review with meta-analysis, 17 studies from 2006 to 2022 were included, and added by this original retrospective research comprising 13.247 women undergoing IVF. When comparing the proportions of clinical pregnancy between the TSH groups, no significant difference was found (RR 0.93, 95% CI 0.80-1.08), with high between studies heterogeneity ( I² : 87%; τ 2 : 0.0544; p<0.01). The number of deliveries was not significantly different between groups, despite a trend towards higher frequency in the high-TSH group (RR 0.96, 95% CI 0.90-1.02)., Conclusion: Variation in TSH levels within the normal range was not associated with pregnancy and delivery rates in women, without autoimmune thyroid disease, who underwent IVF treatment., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD 42022306967., 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 © 2022 d’Assunção, Montagna, d’Assunção, Caldas, Christofolini, Barbosa, Negreiros, Laganà, Oliveira and Bianco.)

Background: The association of autoimmune bullous diseases (AIBDs) with thyroid disorders remains to be profoundly investigated., Objective: To evaluate the epidemiological association between six AIBDs and thyroid disorders., Methods: A population-based cross-sectional study enrolled patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with these six AIBDs were compared with six age- and sex-matched control groups regarding the prevalence of thyroiditis and hyperthyroidism. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for thyroid disorders., Results: The study population included 1,743, 251, 106, 126, 860 and 103 patients with BP, MMP, EBA, PG, PV and PF respectively. The corresponding control groups consisted of 10,141, 1,386, 606, 933, 5,142 and 588 matched controls respectively. A significant association was found between thyroiditis and BP (OR, 1.98; 95% CI, 1.18-3.35; P = 0.010), MMP (OR, 7.02; 95% CI, 1.87-26.33; P = 0.004) and PV (OR, 2.73; 95% CI, 1.45-5.15; P = 0.002). With regards to hyperthyroidism, PF was the only AIBD to demonstrate significant comorbidity (OR, 2.42; 95% CI, 1.13-5.21; P = 0.024). EBA and PG were not found to cluster with any of the investigated thyroid conditions., Conclusion: Patients with BP, MMP, PV and PF experience an elevated burden of thyroid disorders. Patients with these AIBDs presenting with suggestive symptoms may be carefully screened for comorbid thyroid disorders., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: It is unclear whether levels of hypothyroid symptoms in pregnant women with (sub)clinical thyroid dysfunction differ from euthyroid controls and whether free thyroxine (fT4)/thyrotropin (TSH) changes throughout pregnancy affect hypothyroid symptom levels. The objective was twofold: (1) To compare hypothyroid symptom levels between thyroid dysfunction subgroups and a carefully defined reference group; (2) to assess the association between fT4/TSH changes throughout pregnancy and hypothyroid symptom levels adjusted for depressive symptoms. Methods: The current study was a longitudinal prospective cohort study in 1800 healthy pregnant women. At each trimester of pregnancy, hypothyroid symptoms were assessed with a 12-item symptom hypothyroidism checklist and depressive symptoms with the Edinburgh Depression Scale. Thyroid dysfunction was defined using the 2.5-97.5th fT4/TSH percentile of thyroid peroxidase antibodies-negative women. Euthyroid controls consisted of women with appropriate fT4 levels within the 10-90th percentile and with a normal TSH level. Hypothyroid symptom mean scores were compared between controls and several thyroid dysfunction subgroups. Growth mixture modeling was performed to evaluate possible longitudinal trajectories of hypothyroid and depressive symptoms. The association between hypothyroid symptom trajectories (adjusted for depression) and fT4/TSH changes was assessed with multivariate logistic regression analysis. Results: Women with overt hypothyroidism (fT4 < 2.5th, TSH >97.5th) and hypothyroxinemia (fT4 < 2.5th, TSH: 2.5-97.5th) showed higher hypothyroid symptom levels compared with the euthyroid controls and women with subclinical hypothyroidism (SCH, fT4: 2.5-97.5th, TSH >97.5th), because 82% of these SCH women had fT4 levels in the euthyroid range. Two groups of hypothyroid and depressive symptoms were defined: a persistently low and persistently high symptom group. fT4 decreased in 98% of the women from the first to third trimester and per unit pmol/L fT4 decrease (not TSH increase), the likelihood to present persistently high hypothyroid symptoms increased with 46%, adjusted for depression. Conclusions: A properly defined euthyroid control group distinguishes women with hypothyroid symptoms. An fT4 decrease toward end term is associated with persistently high hypothyroid symptom levels. Clinicians should be aware of the importance of fT4 stratification in SCH women.

Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes., Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up., Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses., Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes., Significance Statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands., Subjects and Methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC., Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures., Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

Introduction: Thyroid hormones influence neuromuscular function, and it has been thought that this might contribute to degeneration of motor neurons., Methods: We used case-control methods to investigate the prevalence of thyroid dysfunction (hyperthyroidism and hypothyroidism) in ALS patients followed in our centre, between 2015 and 2020. Data from patients with neuromuscular disorders not derived from thyroid dysfunction, followed within the same time frame, were used as controls. Thyroid dysfunction was defined by previous thyroid replacement medication managed by an endocrinologist. We used odds ratios (OR) with a 95% confidence interval (CI) to compare 579 ALS patients and 415 age-gender-matched disease controls. Additionally, we provide a summarized review of the literature., Results: Hypothyroidism (prevalence of 5.0 versus 8.6%; OR = 0.56, 95% CI 0.34-0.92, p = 0.023), hyperthyroidism (prevalence of 0.3 versus 1.2%; OR = 0.28, 95% CI 0.06-1.47, p = 0.134) and overall thyroid dysfunction (prevalence of 5.4 versus 9.9%; OR = 0.52, 95% CI 0.32-0.84, p = 0.015) were less prevalent in ALS patients than in controls, but similar to the national epidemiological data for thyroid disease. Our data are in line with the findings of most previous studies., Conclusions: We conclude that thyroid dysfunction is not associated with ALS., (© 2022. Fondazione Società Italiana di Neurologia.)

Objective: Evidence for the association between subclinical thyroid dysfunction before conception and its pregnancy outcomes is inconsistent. Thus, we evaluated the relationship between preconception thyroid-stimulating hormone (TSH) levels and adverse pregnancy outcomes., Design: Retrospective cohort study., Methods: A total of 50,217 women without prior thyroid disease who became pregnant within 1 year after undertaking a routine TSH test in the Chongqing Municipality of China (2010-2016) were studied. Restricted cubic spline regression and logistic regression were used to estimate the association between preconception TSH levels and pregnancy outcomes. The main outcomes were individual and composite adverse pregnancy outcomes (CAPOs) comprising pregnancy loss, small for gestational age, large for gestational age, and preterm birth., Results: Incidence of CAPO was 24.19%. Increased preconception TSH level was positively associated with CAPO (odds ratio [OR]/SD: 1.04, 95% confidence interval [CI]: 1.01-1.07) when TSH was ≥2.1 mIU/L, positively associated with pregnancy loss (OR/SD: 1.06, 95% CI: 1.01-1.12) when TSH was <2.1 mIU/L, negatively and positively associated with preterm delivery when TSH levels were <1.3 mIU/L (OR/SD: 0.90, 95% CI: 0.83-0.97) and >3.0 mIU/L (OR/SD: 1.08, 95% CI: 1.00-1.17), respectively. Women with subclinical hypothyroidism before conception were at a higher risk for CAPO (adjusted odds ratio [aOR]: 1.12, 95% CI: 1.04-1.22), while those with subclinical hyperthyroidism had a higher risk of preterm delivery (aOR: 1.31, 95% CI: 1.01-1.70)., Conclusions: Nonlinear associations were indicated between preconception TSH levels and pregnancy outcomes. Subclinical thyroid dysfunction before conception was associated with an increased risk of adverse pregnancy outcomes., (© 2021 John Wiley & Sons Ltd.)

Hypothyroidism and obesity are common coexisting illnesses which have an impact on each other. Data from India suggests that about a third of individuals with obesity have overt hypothyroidism and about one-tenth have subclinical hypothyroidism. Multiple mechanisms have described how both thyroid and obesity could have a significant impact on each other. A moderately elevated TSH, elevated T3 and a lower T4 is classically described thyroid dysfunction in patients with obesity. This article will detail the epidemiology, pathogenesis and the clinical implications of weight gain and thyroid dysfunction with a special focus on women.

Background: Multiple factors contribute to the pathogenesis of childhood vitiligo. The characteristics in a different population under modified environmental factors need further reevaluation. The present study aimed to reevaluate the clinical and laboratory features in consequent children vitiligo patients., Materials and Methods: We retrospectively reviewed consequent children vitiligo patients who visited Children's Hospital of Fudan University (National Children's Medical Center of China). The prevalence rate of thyroid dysfunction, circulating autoantibodies, serum IgE, and associated factors were analyzed., Results: A total of 244 consequent vitiligo patients were included, of which 20 children had personal autoimmune history. Two hundred and nineteen of the 244 patients took a thyroid function test, and the abnormal rate was only 3.7% (8/219). The elevated IgE rate was 31.7% (52/157), the antinuclear antibody (ANA) positive rate was 9.8% (12/123), and the extractable nuclear antigens (ENA) positive rate was 4.4% (4/91), respectively. The elevated IgE was significantly associated with atopic disease history and male gender. Of note, personal autoimmune history showed a significant inverse association with elevated IgE., Conclusions: Thyroid dysfunction rate was low among the consequent children vitiligo patients. Personal autoimmune history was inversely associated with elevated IgE. Various clinical characteristics and pathogenesis might contribute to different long-term outcomes of vitiligo., (© 2022 the International Society of Dermatology.)

Objectives: It is well recognized that overt thyroid dysfunction is associated with changes in body mass index (BMI). However, there is ongoing debate regarding the influence of thyroid stimulating hormone (TSH) on BMI, in euthyroid subjects. The aim of this study is to examine the association of TSH with BMI in an outpatient population without evidence of thyroid disease., Methods: Cross-sectional study conducted in an Endocrinology Department. We identified the latest TSH and BMI measurements in 923 patients from the reference euthyroid population. All patients with positive thyroid autoimmunity and nodules were excluded. We performed a linear regression analysis using SPSSv.025., Results: 923 adult patients were evaluated. 79.4% were males, with a mean age of 67.6 years old. Mean TSH level was 1.78 mIU/L and mean BMI was 29.2 kg/m 2 . A significant negative correlation between serum TSH concentration and BMI was evident (p=0.04; r=-0.067). Statistical significance was lost when performing subgroup analysis, for males and females (p=0.19 and p=0.075), elderly (≥65 years) and non-elderly (p = 0.55 and p = 0.32) and also obese (BMI ≥30 kg/m 2 ) and non-obese (p=0.39 and p=0.13) ., Conclusions: The relationship between BMI and TSH is not consensual in the literature. This study included a large cohort sample of euthyroid patients, majority men and with negative autoimmunity. Our results support the hypothesis that variation in thyroid status within the normal range, could have a negative effect on BMI, contrary to most published studies., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Patients with isolated leukopenia pose difficulties in diagnosis because there is no related guideline in the literature. In this study, our aim was to evaluate the clinical and laboratory associations of isolated, nonspecific (not related to neutropenia) leukopenia. In this retrospective data review study, patients who were admitted to Hacettepe University Hematology Outpatient Clinic between 2014 and 2019 due to leukopenia were evaluated. The patients with anemia (other than iron deficiency) or thrombocytopenia were excluded. Clinical and laboratory data and the final diagnoses (if present) of the remaining cases and especially of those without neutropenia (the most difficult group to diagnose) were evaluated. One hundred sixty-nine patients were included in the study. One hundred forty-four (85.2%) patients were female and 25 (14.8%) were male. One hundred ten of them had 1500/µL or higher neutrophil count. In these nonneutropenic cases, the etiological factors contributing to leukopenia were as follows: iron deficiency anemia (21.8%), other autoimmune/autoinflammatory diseases (17.3%), autoimmune thyroid disease (21.8%), autoimmune laboratory tests (2.7%), drugs (12.7%), infection (5.5%), hematopoietic disorder (2.7%), hypersplenism (2.7%), radiotherapy sequel (1.8%), and B12 deficiency (1.8%). No etiology was recognized in 44 patients. On the other hand, the etiological factors in patients with neutrophil count <1500/µL were as follows; iron deficiency anemia (10.2%), other autoimmune/autoinflammatory diseases (17%), autoimmune thyroid disease (5.1%), autoimmune laboratory tests (8.5%), drugs (8.5%), infection (6.8%), hematopoietic disorder (11.9%), hypersplenism (1.7%), radiotherapy sequel (1.7%), and B12 deficiency (1.7%). No etiology was recognized in 25 patients. Physicians ordered bone marrow examination more frequently in patients with neutropenia. If isolated antinuclear antibody positivity was also considered in favor of autoimmunity, 91/169 (53.8%) cases had an autoimmune diagnosis or laboratory finding. In the present study, the most frequent reasons of isolated leukopenia in nonneutropenic patients are found as iron deficiency anemia, other autoimmune/autoinflammatory diseases, and autoimmune thyroid disease. In neutropenic patients, the most frequent reasons of isolated leukopenia are found as iron deficiency anemia, autoimmune/autoinflammatory diseases, and hematopoietic disorders. Therefore, autoimmunity is detected as an important factor leading to isolated leukopenia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Obesity is strongly associated with chronic low-grade inflammation. Obese patients have an increased risk to develop thyroid autoimmunity and to became hypothyroid, suggesting a pathogenetic link between obesity, inflammation and autoimmunity. Moreover, type 2 diabetes and dyslipidemia, also characterized by low-grade inflammation, were recently associated with more aggressive forms of Graves' ophthalmopathy. The association between obesity and autoimmune thyroid disorders may also go in the opposite direction, as treating autoimmune hyper and hypothyroidism can lead to weight gain. In addition, restoration of euthyroidism by L-T4 replacement therapy is more challenging in obese athyreotic patients, as it is difficult to maintain thyrotropin stimulation hormone (TSH) values within the normal range. Intriguingly, pro-inflammatory cytokines decrease in obese patients after bariatric surgery along with TSH levels. Moreover, the risk of thyroid cancer is increased in patients with thyroid autoimmune disorders, and is also related to the degree of obesity and inflammation. Molecular studies have shown a relationship between the low-grade inflammation of obesity and the activity of intracellular multiprotein complexes typical of immune cells (inflammasomes). We will now highlight some clinical implications of inflammasome activation in the relationship between obesity and thyroid 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 © 2022 Le Moli, Vella, Tumino, Piticchio, Naselli, Belfiore and Frasca.)

Preconception counseling is an essential tool for preventing adverse pregnancy outcomes associated with thyroid dysfunction. The high prevalence of thyroid disease among women of reproductive age, and the increased risk of adverse pregnancy outcomes associated with thyroid dysfunction, emphasize the necessity for well-established screening and treatment criteria in the preconception period. We therefore conducted a literature review for relevant information on the screening, diagnosis and treatment of subclinical and overt hypothyroidism in women seeking pregnancy. While screening for thyroid disease is recommended only in the presence of risk factors, iodine supplementation should be recommended in most regions, with higher doses in areas with severe deficiency. Known hypothyroid women should be counseled about increasing their levothyroxine dose by 20-30% in the case of suspected or confirmed pregnancy (missed menstrual cycle or positive pregnancy test). Treating subclinical hypothyroidism appears to be beneficial, especially in the presence of autoimmunity or in patients undergoing artificial reproductive techniques. Regarding the management of TPOAb negative SCH women or euthyroid women with positive TPOAb, further research is necessary in order to make evidence-based recommendations.

Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis., 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 © 2022 Jiang, Lu, Gao, Lv and Li.)

Objective: To explore the relationship between thyroid dysfunction, thyroid-stimulating hormone (TSH) levels, and risks of atrial fibrillation (AF) in studies and conduct a dose-response meta-analysis on the correlation between the TSH levels and risk of AF., Methods: Thirteen studies from 5 databases with 649 293 subjects (mean age, 65.1 years) were included. The dose-response meta-analysis was conducted by comparing the risk ratios (RRs) and 95% confidence intervals (CIs) for incident AF associated with different levels of TSH (vs TSH level of 0 mU/L) across studies. Data were collected until October 25, 2021., Results: Subclinical hyperthyroidism, subclinical hypothyroidism, and clinical hyperthyroidism were associated with an increased risk of AF (RR, 1.70; 95% CI, 1.11-2.62; RR, 1.23; 95% CI, 1.05-1.44; and RR, 2.35; 95% CI, 1.07-5.16, respectively), whereas clinical hypothyroidism was not associated with the significantly increased risk of AF (RR, 1.20; 95% CI, 0.72-1.99). A nonlinear relationship was observed in 2 models (crude model, P nonlinear < .001; adjusted model, P nonlinear  = .0391) between the TSH levels and risks of AF., Conclusions: Our study indicated that subclinical hyperthyroidism, subclinical hypothyroidism, clinical hyperthyroidism were associated with the risk of AF, and the results for the TSH levels and risk of AF were mixed, which showed a U-shaped relationship., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Introduction: The incidence of thyroid carcinoma has grown significantly over the last few decades. A possible explanation is the increased diagnosis of small thyroid microcarcinoma (TMc). TMc reach a maximum diameter of ≤1 cm, identified during histopathology examination following a thyroidectomy performed for reasons not pertaining to malignancy. This study aims to investigate the prevalence of papillary thyroid microcarcinoma (PTMc) according to the benign pathology that refers patients to surgery and its trend evolution., Methods: Retrospective cohort analysis of 1815 patients who underwent total thyroidectomy for non-malignant diseases in the 2005-2020 period., Results: The mean age of the subjects was 53.5 years, with a higher proportion of women (1481, 82.1%). A total of 167 PTMc (9.3%) were incidentally discovered. A multivariate logistic regression analysis was performed, showing no differences in prevalence according to sex or age in patients with PTMc compared to final benign histology. Multinodular goiter increases the risk of PTMc with an odds ratio of 2.2 (p = 0.001) compared to Hashimoto's thyroiditis and Graves' disease (GD). There is a statistically significant increase in the incidence of PTMc in the group operated in the 2017-2020 vs. 2005-2008 period (p = 0.005)., Conclusion: The overall prevalence of PTMc in patients who underwent thyroid surgery for the benign disease was 9.3%. Thyroid nodular hyperplasia was the most frequent benign pathology associated with PTMc compared to Hashimoto's or GD. Gender and age were not correlated with the prevalence of TMc. Over the years, surgical findings of PTMc have grown, particularly in the 2017-2020 period., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ongoing COVID-19 pandemic calls for extensive research on various medical topics. Since the beginning of the pandemic, multiple studies investigated the impact of SARS CoV-2 on thyroid function. However, crucial data, such as trend progression over time or influence of commonly used drugs, might still be missing. We checked the thyroid function in 174 patients with PCR-confirmed COVID-19. Our research covered three separate time points of hospitalization (days 1, 4, and 10). We did not exclude patients treated with glucocorticoids but, instead, compared them with patients not treated with steroids. We correlated the results of thyroid function tests with markers of systemic inflammation. We checked if abnormal thyroid function can predict unfavorable outcomes defined as combined primary endpoint and/or secondary endpoints; the combined primary endpoint was the occurrence of death, mechanical ventilation, non-invasive ventilation, vasopressor infusion, or prolonged hospital stay, and the secondary endpoint was any of the listed events. In general, 80.46% of evaluated patients displayed abnormalities in thyroid function tests over at least one time point throughout the observation. We noticed a high prevalence of features typical for thyroid dysfunction in non-thyroidal illness (NTI). Free triiodothyronine (fT3) concentration was significantly lower in the group requiring glucocorticoids. Patients displaying abnormal thyroid function were statistically more likely to meet the predefined combined primary endpoint. We found that fT3 measured at admission could be perceived as an independent predictor of endpoint completion for all analyzed groups. Thyroid involvement is common in COVID-19. Our study supports the idea of thyroid function abnormalities being important clinical tools and allowing early recognition of possible detrimental outcomes of the 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 © 2022 Świątkowska-Stodulska, Berlińska and Puchalska-Reglińska.)

Subclinical thyroid dysfunction is defined by serum thyroid-stimulating hormone (TSH) levels either greater or less than the reference range with normal thyroxine (T4) concentrations, and consists of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper). For the proper diagnosis of SCH, it is most important to be able to correctly evaluate the serum TSH levels, which have numerous unique characteristics. We also need to be versed in TSH harmonization, which was recently launched world-wide. In this review, we will attempt to determine the best clinical approaches to the treatment of subclinical thyroid dysfunction based on recent guidelines published from several countries and novel findings of several recent large-scale clinical studies.

Thyroid disease instances have rapidly increased in the past few decades; however, the cause of the disease remains unclear. Understanding the pathogenesis of thyroid disease will potentially reduce morbidity and mortality rates. Currently, the identified risk factors from existing studies are controversial as they were determined through qualitative analysis and were not further confirmed by quantitative implementations. Association rule mining, as a subset of data mining techniques, is dedicated to revealing underlying correlations among multiple attributes from a complex heterogeneous dataset, making it suitable for thyroid disease pathogenesis identification. This study adopts two association rule mining algorithms (i.e., Apriori and FP-Growth Tree) to identify risk factors correlated with thyroid disease. Extensive experiments were conducted to reach impartial findings with respect to knowledge discovery through two independent digital health datasets. The findings confirmed that gender, hypertension, and obesity are positively related to thyroid disease development. The history of I 131 treatment and Triiodothyronine level can be potential factors for evaluating subsequent thyroid 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 © 2022 Liu and Zhang.)