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Resistance to thyroid hormone beta (RTHβ) caused by germline mutations in genes encoding thyroid hormone receptor beta (TRβ) is a rare disorder. Little information is available regarding the clinical experience of this syndrome in Japan. We retrospectively reviewed the records of 34 patients with RTHβ (21 adult females and 13 adult males) with positive TRβ mutations identified at our division between 2000 and 2020. Of the 24 patients with available clinical history, 10 (41.7%) received inappropriate treatments such as antithyroid drugs, thyroidectomy, or radioactive iodine. Diagnostic delay and inappropriate management of RTHβ are still present in Japan. Every patient except one demonstrated thyroid hormone profiles indicative of syndrome of inappropriate secretion of thyrotropin (SITSH), characterized by a hormonal profile of hyperthyroxinemia with a non-suppressed TSH concentration. Since the most common forms of hyperthyroidism including Graves' disease feature elevated thyroid hormone levels with suppressed TSH concentrations, early diagnosis of SITSH is critical for preventing inappropriate management. One patient positive for anti-thyroglobulin antibody (Tg-Ab) and anti-thyroperoxidase antibody (TPO-Ab) showed remarkably elevated TSH (>200 μIU/mL) despite thyroid hormone concentrations within the reference ranges. At least one thyroid autoantibody (Tg-Ab, TPO-Ab, or thyrotropin receptor antibodies) was identified in 37.9% (11/29) of the patients tested. One patient developed overt Graves' disease nine years after ‍RTHβ diagnosis. These findings suggest that RTHβ is frequently comorbid with additional autoimmune thyroid disorders. ‍Further research is required to identify the most appropriate treatments for RTHβ patients who develop a second thyroid ‍disorder.

Objective: To evaluate the prevalence of autoimmune thyroid disease (AITD) in diabetic children in south Punjab. Methods: This was an observational cross sectional study from Jan 2019 to Dec 2019 in the outpatient diabetic clinic of the department of pediatric endocrinology at Children Hospital and The Institute of Child Health Multan. A total of 161 consecutive patients of both genders with TIDM were enrolled in this study after taking informed consent. Blood samples for Thyroid functions testes including thyroid stimulating hormone (TSH), free thyroxin (fT4), Thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TG-Ab) and glycosylated hemoglobin (HbA1C) level were sent. Results: Among diabetic children males were 83 (51.6%). Age range was 2-15 years. Mean age and standard deviation was 9.7± 4.3. TPO-Ab was positive in 34 patients (21.1%) and TG-Ab in 27 patients (16.7%), whereas both antibodies were positive in 17 patients (10.5%). Six patients (3.7%) had evidence of subclinical hypothyroidism, 8 patients (4.9%) had overt hypothyroidism and 1 patient (0.62%) had hyperthyroidism Conclusion: The prevalence of AITD among children and adolescents with type 1 diabetes mellitus was 21.1% in our study. Hypothyroidism was more prevalent in these children compared to hyperthyroidism. All diabetic children should be screened for AITD. Thyroid functions should be checked where TPO antibody is positive. Keywords: Autoimmune thyroid disease, anti thyroid peroxidase antibody, anti thyroglobulin Continuous...

Background. Hashimoto’s thyroiditis (HT) is an auto-immune condition characterized with lymphocytic and fibroblastic infiltration of the thyroid gland. The rate of uric acid and HDL cholesterol – so called as uric acid to HDL ratio (UHR) has been shown to be elevated in inflammatory conditions diseases. We aimed to compare UHR and other laboratory parameters of the patients with HT to those values in healthy controls. Methods. The patients diagnosed with HT by medical history, physical examination, elevated thyroid autoantibodies in serum and characteristic sonographic findings in outpatient internal medicine clinics of our institution were enrolled to the present retrospective study. Age and sex matched healthy volunteers were enrolled as controls. UHR of the HT patients and control subjects were compared. Results. The mean UHR of the HT group was 11% ± 4 %, while UHR of the control group was 8% ± 2% (p Conclusion. We suggest that UHR is a reliable and useful marker for HT. Therefore, it may be helpful in establishing the diagnosis of HT in addition to other diagnostic tools.

Objectives/hypothesis Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. Study design Retrospective cohort. Methods Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. Results Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P Conclusion HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. Level of evidence 3 Laryngoscope, 2021.

Four anti-thyroglobulin autoantibodies (TgAb) assays were evaluated for their reference interval, method agreement, concordance etc. Prevalence of TgAb and anti-thyroid peroxidase was studied in differentiated thyroid cancer (DTC) and control. Reference intervals for TgAb assays varied from method to method due to varied assay designs. For TgAb correlation coefficients ranged from 0.74 to 0.99 whereas concordance ranged from 81 to 96.1%. Prevalence of thyroid antibodies mainly TgAb was increased in DTC primarily in females. Use of sensitive immunoassays is recommended for thyroid autoantibody measurement. Diagnosis and follow-up are difficult in DTC with coexisting thyroid autoimmunity. Hence, careful monitoring with regular surveillance is suggested.

Toxicological studies show that exposure to disinfection byproducts, including trihalomethanes (THMs), negatively affects thyroid function; however, few epidemiological studies have explored this link. This study included 2233 adults (ages ≥20 years) from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) who were measured for blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), or bromoform (TBM)] and serum thyroid function biomarkers [thyroid-stimulating hormone, free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb)]. Multivariable linear regression models showed positive associations between blood TCM, BDCM, and total THMs (the sum of all four THMs) concentrations and serum FT4, whereas inverse associations were found between blood DBCM and total brominated THM (Br-THM; the sum of BDCM, DBCM, and TBM) concentrations and serum TT3 (all p < 0.05). Besides, positive associations were observed between blood TCM concentrations and FT4/FT3 ratio, between BDCM, DBCM, and Br-THM concentrations and TT4/TT3 ratio, and between DBCM and Br-THM concentrations and FT3/TT3 ratio (all p < 0.05). Blood THM concentrations were unrelated to the serum levels of thyroid autoantibodies TgAb or TPOAb. In summary, exposure to THMs was associated with altered serum biomarkers of thyroid function but not with thyroid autoimmunity among U.S. adults.

OBJECTIVES: To assess free thyroxine (fT4), thyroid stimulating hormone (TSH), and anti thyroid peroxidase antibodies (anti TPO abs) in adult Celiac disease patients and non-celiac controls and to find out any statistically significant difference in their corresponding means between the two groups. METHODOLOGY: The study design was analytical cross sectional. Sixty adult patients of celiac disease (CD) and 30 apparently healthy non-celiac adults were included in the study. CD patients had earlier been diagnosed by elevated levels of serological evidence of elevated (greater than 15X ULN) anti tissue transglutaminase (TTG) (IgA class) antibodies. CD was ruled out in the control group by normal levels of the antibodies. TSH, fT4 and anti TPO abs were obtained from all individuals of CD patient and control groups. RESULTS: Mean age of Celiac disease in patients was 23.85±5.43 years. Mean age of individuals in the control group was 24.26±5.55 years. Statistically significant difference in mean TSH and anti-TPO abs levels between the CD patient group and control group (p values of 0.03 and 0.038, respectively) was present. No statistically significant difference was seen between mean fT4 of patients and control group (p=0.74). Subclinical and overt hypothyroidism was present in 10% and 5% of CD patients, while anti TPO abs was positive in 16.6% of CD patients. CONCLUSION: There is a considerably high prevalence of subclinical and overt hypothyroidism as well as serological evidence of thyroid dysfunction in adult patients of CD.

Objective Mandatory universal salt iodization in China was implemented 20 years ago. However, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown. Methods A nationally representative cross-sectional study with 26 166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urinary iodine concentration (UIC) were measured. Results The median UIC was 178.7 μg/L, indicative of adequate iodine status. pHowever, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalence of thyroid disorders was as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for thyroid peroxidase antibodies, and 14.55% were positive for thyroglobulin antibodies. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for thyroid peroxidase antibodies and thyroglobulin antibodies. Conclusion Iodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies remain prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.

BACKGROUND The objectives of the study were to investigate whether the incidence of antithyroid antibodies (ATAs) is related to an adverse outcome in the in-vitro fertilization and embryo transfer (IVF-ET) in terms of quality of oocytes retrieved, fertilisation, cleavage, embryo quality and implantation rate (primary outcome) as compared to patients without anti-thyroid antibodies and also evaluate the association of ATAs with abortion rate, biochemical pregnancy and clinical pregnancy (secondary outcome). METHODS A total of 52 women having anti-thyroid peroxidase antibody (anti- TPO Ab) level ≥ 35 IU/mL (Cases) and 21 women having anti-TPO Ab level < 35 IU/mL (Controls) undergoing IVF / ICSI from Jan 2014 to Dec 2014 at Milann – The Fertility Centre, Bangalore, were retrospectively analysed. RESULTS There was no difference among the cases and controls for the primary outcome, viz. maturation rate, fertilisation rate, cleavage rate, implantation rate, and embryo quality. However, the abortion rate and biochemical pregnancy rate were significantly higher in the cases than in controls (P = 0.027 for each parameter). On the other hand, the clinical pregnancy rate was significantly lower among the cases (P = 0. 045). CONCLUSIONS There was no statistically significant difference in the primary outcome among the two groups. The secondary outcome of abortion rate and biochemical pregnancy rate was significantly higher in the cases than controls. The clinical pregnancy rate was significantly lower among the cases as compared to controls. Clinical Significance - Anti-TPO Ab acts as a prognostic factor and is disadvantageous to the pregnancy outcome following IVF-ET. KEY WORDS Abortion Rate, Clinical Pregnancy Rate, Fertilisation Rate, Implantation Rate, IVF/ICSI, Oocyte Maturation Rate

Objective Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Methods We conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. Results One hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004). Conclusion Thyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.

To evaluate the United Arab Emirate National Newborn Screening Programme we compared coverage, timeliness of programme indicators [age at sampling, recall and treatment initiation, timing of specimen delivery and laboratory results] and specimen quality with international st and ards. Recall rate, sensitivity, specificity, positive predictive values and relative incidence rates for phenylketonuria [PKU] and congenital hypothyroidism [CH] were calculated. Investigations for hypothyroidism included thyroid function studies [T3, T4, fT4 and TSH], technetium-99m thyroid scan when possible and thyroglobulin and thyroid antibodies when indicated. PKU investigations included plasma amino acids and measurement of biopterin defects. In the 6 years before December 2000, 138, 718 neonates were screened. Relative incidences for CH and for classic PKU were 1: 1570 and 1: 20, 050 respectively

The review deals with the role of innate and adaptive, local and systemic immunity, cellular and humoral factors in the pathogenesis of autoimmune thyroid diseases (AITD). The importance of lymphoid infiltration of the thyroid gland, cytokines and autoantibodies, the role of thyroid hormones as modulators of the immune response, trace elements and dysregulation of apoptosis in the development of AITD is considered. Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) have been shown to be closely pathophysiologically related and have similar immune-mediated mechanisms, such as the production of autoantibodies to thyroid antigens and lymphocytic infiltration of the thyroid gland. Loss of immune tolerance to thyroid peroxidase, thyroglobulin and thyroid-stimula­ting hormone autoantigens is the basis for the development of AITD. Emphasis is placed on the role of cytokines, which are produced by both immune system cells and thyroid follicular cells. Imba­lance between Th17 lymphocytes and regulatory T cells (Treg) has a significant effect on the progression of AITD. An increase in Th17 lymphocytes may play a more important role in the pathogenesis of HT, whereas a decrease in Treg may be strongly involved in GD. Insufficiency of Treg that impairs immunological tolerance and causes abnormal cytokine production can lead to the initiation of apoptosis, which plays a role in the pathogenesis of GD and HT. Induction of apoptosis by HT leads to destruction of thyrocytes, while apoptosis in GD cause damage to thyroid infiltrating lymphocytes., Представленный обзор посвящен роли естественного и адаптивного, локального и системного иммунитета, клеточных и гуморальных факторов в патогенезе аутоиммунных заболеваний щитовидной железы (АЗЩЖ). Рассмотрены значение лимфоидной инфильтрации щитовидной железы (ЩЖ), цитокинов и аутоантител, роль тиреоидных гормонов как модуляторов иммунного ответа, микроэлементов и нарушения регуляции апоптоза в развитии АЗЩЖ. Показано, что болезнь Грейвса (БГ) и тиреоидит Хашимото (ТХ) тесно связаны патофизиологически и имеют подобные иммуно­опосредованные механизмы — продукция аутоантител к антигенам ЩЖ и лимфоцитарная инфильтрация ЩЖ. Потеря иммунной толерантности к аутоантигенам ЩЖ тиреоидной пероксидазе, тиреоглобулину и рецептору тиреотропного гормона является основой развития АЗЩЖ. Отмечается роль цитокинов, продуцируемых как клетками иммунной системы, так и непосредственно фолликулярными клетками ЩЖ. Значительное влияние на прогрессирование АЗЩЖ имеет дисбаланс между Th17-лимфоцитами и регуляторными Т-клетками. Увеличение количества Th17-лимфоцитов может играть важную роль в патогенезе ТХ, тогда как пониженное содержание Treg может быть значительно связано с развитием БГ. Недостаточность Тreg, которая нарушает иммунологическую толерантность и вызывает аномальную продукцию цитокинов, может вызвать инициацию апоптоза, который играет определенную роль в патогенезе БГ и ТХ. Индукция апоптоза при ТХ приводит к разрушению тироцитов, тогда как апоптоз при БГ приводит к повреждению тиреоидных инфильтрирующих лимфоцитов., Наведений огляд присвячений ролі вродженого та адаптивного, локального та системного імунітету, клітинних та гуморальних чинників в патогенезі автоімунних захворювань щитоподібної залози (АЗЩЗ). Розглянуті значення лімфоїдної інфільтрації щитоподібної залози (ЩЗ), цитокінів та автоантитіл, роль тиреоїдних гормонів як модуляторів імунної відповіді, мікроелементів та порушення регуляції апоптозу у розвитку АЗЩЗ. Показано, що хвороба Грейвса (ХГ) та тиреоїдит Хашимото (ТХ) тісно пов’язані патофізіологічно і мають подібні імуноопосередковані механізми — продукцію автоантитіл до антигенів ЩЗ і лімфоцитарну інфільтрацію ЩЗ. Втрата імунної толерантності до автоантигенів ЩЗ тиреоїдної пероксидази, тиреоглобуліну та рецептора тиреотропного гормона є основою розвитку АЗЩЗ. Наголошується на ролі цитокінів, які продукуються як клітинами імунної системи, так і безпосередньо фолікулярними клітинами ЩЗ. Значний вплив на прогресування АЗЩЗ має дисбаланс між Th17-лімфоцитами та регуляторними Т-клітинами. Збільшення кількості Th17-лімфоцитів може відігравати важливу роль у патогенезі ТХ, тоді як знижений вміст Treg може бути значно пов’язаний із розвитком ХГ. Недостатність Тreg, яка порушує імунологічну толерантність і викликає аномальну продукцію цитокінів, може спричинити ініціацію апоптозу, який відіграє певну роль у патогенезі ХГ та ТХ. Індукція апоптозу при ТХ призводить до руйнування тироцитів, тоді як апоптоз при ХГ призводить до пошкодження тиреоїдних інфільтруючих лімфоцитів.

Introduction : Over the past several years new evidence on the management of hypothyroidism has emerged, which has influenced recommendations from professional bodies. The presentation of hypothyroid patients has also changed, and new cases are increasingly diagnosed by indiscriminate screening, often identifying cases with minor biochemical disturbances. Little is known about the physician responses and attitudes to this changing landscape. THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) is a large-scale survey of European physicians who treat patients with hypothyroidism. Here we document current practices of Polish physicians relating to the use of thyroid hormones in hypothyroid and euthyroid patients. Material and methods: Members of the Polish Society of Endocrinology were invited to participate in the web-based THESIS survey. Results: In total 423 (54.6% of the 774 invited) physicians completed the survey. The majority of respondents (74.2%) would prescribe thyroid hormones for euthyroid patients for certain indications, such as female infertility with elevated thyroid antibodies (63.4%), simple goitre (40.9%), unexplained fatigue (12.1%), obesity (9.7%), hypercholesterolaemia (9.0%), and depression (9.2%). Nearly all physicians (96.0%) declared that the treatment of choice for hypothyroidism is levothyroxine (LT4). However, around one-third (30.3%) were also using LT4 and liothyronine (LT3) combination treatment; LT3 alone was rarely prescribed (1.7%), and none prescribed desiccated thyroid extract. The majority of respondents preferred LT4 tablets. Among alternative formulations, liquid LT4 was most commonly recommended for patients unable to take LT4 in the fasting state (26.0%) and patients with malabsorption (19.9%). Respondents considered prescribing dietary supplements (such as selenium and iodine) in hypothyroid patients with coexisting autoimmune thyroiditis (29.6%) or at the patients’ request (32.2%). LT4 + LT3 combination therapy was used by 32.2% when symptoms persisted notwithstanding normal serum TSH concentration. Psychosocial factors, comorbidities, and the burden of chronic disease were considered as the most likely causes of persistent symptoms. Conclusions: Apart from clinical practice recommendations, other factors influence the thyroid hormone therapy patterns. Moreover, certain areas of clinical practice were identified (the use of thyroid hormones in euthyroid subjects and the use of dietary supplements), which are not in accordance with the current evidence.

Purpose Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. Methods We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. Results Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto’s thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto’s thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto’s thyroiditis patients with major molecular response. Conclusions Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

OBJECTIVE Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients. DESIGN 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared. PATIENTS 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high-dose intravenous GCs. MEASUREMENTS Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post-therapy (week 12). RESULTS 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels. CONCLUSIONS Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients.

Thyroid-associated orbitopathy (TAO) is one of the most common autoimmune inflammatory disorders of the orbit. The presence of anti-thyroid antibodies is believed to play a role in the pathogenesis and clinical status of the TAO patients. Herein, we review the usefulness of TPOAb as a biomarker for TAO.A systematic search in MEDLINE library was conducted. Results: Twenty studies were included. TPO is expressed in orbital tissues, and the polymorphism rs11675434 SNP has proven to be associated with clinically evident TAO. Studies in pediatric patients have shown a positive correlation between high TPOAb levels and TAO. In contrast, results in adults are inconsistent. Some studies imply a protective role of TPOAb, yet the majority did not find any association. Some authors have suggested an implication of TPOAb in the pathophysiology of TAO in TRAb-negative patients.The role of TPOAb in TAO remains unclear and controversial.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia with or without bleeding. Mild to moderate thrombocytopenia can be seen with thyrotoxicosis and hypothyroidism. This study was conducted to assess prevalence of thyroid dysfunction in ITP and impact on treatment and outcomes. This prospective study included patients more than 12 years old, diagnosed as ITP. Serum Thyroxine (T4) and Thyroid Stimulating Hormone levels and anti-thyroid peroxidase (TPO) antibodies were done by electro- chemiluminescence immunoassay. A total of 168 patients were enrolled, with thyroid function tests available in 146 patients. Mean age was 30.6 years, with 67.8% females (n = 114). Sixty percent patients had chronic ITP and 25% had persistent ITP. Overall prevalence of thyroid disease was 25.7% in the study population, with overt hypothyroidism seen in 21 (16.4%) patients, subclinical hypothyroidism in 9 (7.0%) patients and subclinical thyrotoxicosis in 3 (2.3%) patients, while no patient had overt thyrotoxicosis. Thyroid status of the patients did not correlate with duration of ITP or response to treatment. Presence of anti TPO antibodies was associated with abnormal thyroid function and chronic ITP. The prevalence of thyroid dysfunction is increased in ITP patients. Many such cases have anti TPO antibodies, suggesting autoimmune pathology. Role of glucocorticoids, estrogens and systemic illness in these findings must be further studied before firm conclusion can be drawn about their routine inclusion in diagnostic work up.

To investigate the prognostic factors of extraocular muscle restriction in patients with thyroid eye disease (TED), 65 patients with TED and restrictive myopathy were evaluated. Demographics, clinical activity score (CAS), smoking status, thyroid disease status, thyroid hormone status, thyroid autoantibody status, orbital computed tomography (CT) scan at initial presentation, and treatment regimens were assessed. The movements of the most severely affected extraocular muscles were categorized into five grades. The patients were divided into the improved and the not-improved group based on the improvement in the limitation of the extraocular muscle excursion (LOM) throughout the follow-up, and the groups were compared using clinical factors. The mean LOM significantly improved from 2.3 ± 1.1 to 1.7 ± 1.2 after 1 year of follow-up. The excursion of the most restricted muscle improved in 32 patients but not in 33 patients during the follow-up. The initial concentration of the thyroid-stimulating antibody (TSAb) was significantly lower in the improved (229.3 ± 114.1) than in the not-improved group (345.0 ± 178.6) (P = 0.02) Age, sex, smoking status, CAS, thyroid status, and muscle thickness on the CT scan did not significantly differ in the groups. This study showed that the initial concentration of TSAb is a factor affecting the recovery of restrictive myopathy.

Background: Hypothyroidism during pregnancy has an adverse effect on both mother and child. The maternal and foetal risk is higher in TPOAb (Thyroid peroxidase antibody) positive women compared to women with negative TPO Ab. The recent ATA (American Thyroid Association) guidelines recommend that pregnant women with TSH (Thyroid Stimulating Hormone) concentration above 2.5mU/L should be evaluated for TPOAb status and LT4(levothyroxine) treatment should be considered with TSH values between 2.5mU/L and 4.0mU/L only when TPOAb status is positive. Materials and Methods: All the pregnant women booked in first trimester underwent testing for TSH levels and subsequently for anti TPO Ab if TSH levels were between 2.5-4 mIU/ml. The hospital based prevalence of women with anti TPO Ab positive status was determined. These pregnancies were followed till term and the maternal and foetal complications associated with TPO Ab positive and negative status were compared. Results: Total of 400 pregnant women were included. The hospital prevalence of women with anti TPO antibodies in first trimester of pregnancy with TSH values between 2.5- 4 mIU/ml was found to be 23.5%. Anti TPO antibody positive status was significantly more associated with antenatal complications especially GDM and IUGR as compared to patients with anti TPO antibody negative status (47.8% v/s 23.2%, p value 0.001). Conclusion: Women with TPO Ab positive status are to be vigilantly monitored for early detection and management of various antenatal complications. Determining anti TPO Ab status helps in avoiding unnecessary treatment of the women with TPO Ab negative status and TSH between 2.5-4mIU/ml. Keywords: Antenatal complications, Anti TPO Ab, Hypothyroidism.

Ibrahim Y Allam,1 Sihem Lazreg,2 Mohamed Shafik Shaheen,1 Mohamed Fahmy Doheim,1 Mai A Mohammed1 1Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 2Cabinet Ophtalmologie, Alger Centre, Algiers, AlgeriaCorrespondence: Ibrahim Y AllamOphthalmology Department, Faculty of Medicine, Alexandria University, El Maram Building, 3 rd Mostafa Kamel St., Smouha, Alexandria, 21615, EgyptTel +201001233126Fax +2034210443Email ibrahimallam2007@gmail.comBackground: This study aimed to compare ocular surface parameter changes in active and inactive thyroid eye disease (TED) patients and controls.Methods: This is an observational clinical study that included 60 eyes divided into three groups following clinical activity score (CAS) assessment. The first group (Group A) comprised 20 eyes with active TED (CAS score ≥ 3/7), while the second group (Group B) comprised 20 eyes with inactive TED (CAS score < 3/7) and the third group (Group C) comprised 20 eyes of controls without dry eye manifestations. The palpebral fissure height, degree of proptosis, degree of lagophthalmos, ocular surface disease index (OSDI), Schirmer test without anesthesia, corneal fluorescein staining (CFS), non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), lipid layer thickness (LLT), meiboscore, meibomian gland dysfunction (MGD), and thyroid antibodies were assessed and data were compared between study participants.Results: The mean OSDI was 40.0 ± 5.80 in Group A, which significantly differed from Group B with a mean of 26.5 ± 5.10 (p=0.02). There were significant differences between the two groups regarding palpebral fissure height (p=0.02), amount of proptosis (p=0.008), and degree of lagophthalmos (p=0.001). Similarly, active TED patients had more decreased tear secretion than inactive TED patients (p=0.012). Moreover, active TED patients showed a significant increase in Meibomian gland loss areas in both upper and lower eyelids compared with inactive TED patients (p=0.001). Corneal fluorescein staining also revealed a statistically significant difference between the studied groups (p=0.0001).Conclusion: This study showed differences regarding ocular surface parameter changes between both active and inactive TED and compared to controls. Further studies are needed to confirm these results.Keywords: thyroid eye disease, dry eye disease, ocular surface, thyroid antibodies

Background: Hypothyroidism is a common endocrine disorder that is managed by a wide range of physicians. There are no data on the pattern of clinical management of hypothyroidism in the Middle East and Africa (MEA) region. Objectives: We sought to document current practices in the management of primary hypothyroidism in the MEA region and compare these with international recommendations and practices elsewhere. Materials and Methods: A convenience sample of physicians practicing in the MEA in relevant disciplines were invited to take a web-based survey consisting of previously validated multiple-choice questions dealing with investigation and treatment of an index case of overt primary hypothyroidism in general and in three special situations. Results: Out of complete 397 responses, 368 were eligible for inclusion in the analysis. The majority were endocrinologists and internal medicine specialists; 82.2% of them have been in clinical practice for 10 years or more. Overt hypothyroidism would be treated using L-T4 alone by 97.2% of respondents; 1.7% would use a combination of L-T4 and liothyronine (L-T3) therapy. The rate of replacement would be gradual (66.5%), an empiric dose, adjusted to achieve target levels (14.7%); or a calculated full replacement dose (18.5%). A target thyroid-stimulating hormone (TSH) of 2.0–2.9 mU/L was favored in the index case of overt hypothyroidism (by 34.4%) followed by a target of 3.0–3.9 mU/L (by 26.0%) of respondents. However, a target of 4.0–4.9 mU/L was the most commonly selected TSH target for an octogenarian (by 33.5% of respondents). Persistent hypothyroid symptoms despite achieving a target TSH would prompt testing for other causes by 86.9% of respondents, a change to L-T4 plus L-T3 therapy by 5.8%, and an increase in the thyroid hormone dose by 4.6%. Evaluation of persistent symptoms would include measurements of complete blood count (82.4%), complete metabolic panel (68.7%), morning cortisol (65.3%), Vitamin B12 levels (54.5%), and serum T3 levels (27.9%). Subclinical disease with a TSH 7.8 mU/L would be treated without further justification by 9.0% of respondents, or in the presence of positive thyroid peroxidase antibodies (65.3%), hypothyroid symptoms (65.0%), high low-density lipoprotein (51.7%), or a goiter (36.7%). The TSH target for a newly pregnant patient was 2.0–2.4 mU/L for 28.5% of respondents, with 15.8% preferring a TSH target of 1.5–1.9 mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 62.9% and every 8 weeks by an additional 17.6%. A hypothyroid patient with a TSH of 0.5 mU/L who becomes pregnant would receive an immediate L-T4 dose increase by only 28.5% of respondents. Conclusions: The survey revealed that (1) nearly exclusive preference for L-T4 alone for therapy, (2) use of age-specific TSH targets for replacement therapy, (3) a low threshold for treating mild thyroid failure, (4) complacent and variable attention to TSH targets in the pregnant and prepregnant woman, and (5) a highly variable approach to both the rate and means of restoring euthyroid status for overt disease. Both alignments with and divergence from guidelines were detected. The results should help in directing focused educational activities in the region, providing a baseline for future monitoring of practices.

Background Painless thyroiditis (PT) is characterized by transient hyperthyroidism with a low Tc-99m uptake. We herein describe 11 cases of PT that occurred during treatment with potassium iodide (KI) for Graves' disease (GD). Patients and Method From August 2016 to December 2018, 11 women with GD who developed PT during treatment with KI were enrolled. Of these patients, 10 discontinued antithyroid drug (ATD) because of side effects and began KI, and 1 patient switched from thiamazole to KI because she was planning a pregnancy. The mean patient age was 40.1 years old. Thyroid function tests, thyroid autoantibodies including anti thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb), and M22-TRAb, and the 99mTc uptake were evaluated at the time of PT. Results All 11 women patients presented with transient thyrotoxicosis in which 99mTc scans revealed a low uptake of 0.34% ±0.15% (normal 0.70%-1.02%). M22-TRAb was absent in all cases except for one (2.4 IU/L), whereas TgAb and TPOAb were present in 10 and 6 cases, respectively. Ten patients returned to a euthyroid status without passing through the post-hypothyroid phase, and one patient underwent total thyroidectomy during the euthyroid phase of PT. Only four patients require beta-blocker therapy. All patients with KI-induced PT except 1 displayed GD remission during a mean observation period of 23.3 months, and 1 patient had recurrence of GD after PT. Conclusion We encountered 11 GD patients who developed PT during treatment with KI, which was initiated after ATD had been discontinued due to side effects.

Subclinical hypothyroidism (SH) is defined as serum thyroid-stimulating hormone (TSH) above the upper limit of the reference range in the presence of normal free T4 concentrations. Depending on the degree of TSH elevation, SH could be defined as mild (TSH, 4.5-10 mIU/L) or severe (TSHgt;10 mIU/L). While there is a general consensus to treat children with serum TSH levels above 10 mU/L, the management of the mild form is uncertain and should be individualized. In this mini-review, we present a brief review of SH in children based on extensive literature review and long-standing clinical experience. This review provides the prevalence, causes, clinical presentation, consequences, investigation, and up-to-date therapeutic approach of SH in children. Generally, the purpose of the review is to provide pediatricians with an update of this common and continuously evolving condition.

Hypothyroidism can cause significant reproductive morbidity and its association with ovarian cyst formation is rare and when it occurs in children, it is referred to as Van Wyk and Grumbach syndrome. An 18-year-old girl was referred to our emergency services with suspicion of torsion ovarian cyst with USG findings as she had pain abdomen and vomiting of 3 days duration. She was provisionally prepared for laparoscopic surgery but on revaluation by USG bilateral thecaleutein cysts measuring 7x6.8x3.5 cms (right) and 10x6.8 x3.2 cms (left) were diagnosed. Her TSH level was 483 mI U/L . On probing she revealed past history of diagnosis of hypothyroidism and discontinuation of thyroxin therapy after taking for 6 months. Her anti TPO antibodies were >1300 IU/mL. USG thyroid revealed features suggestive of Hashimoto’s thyroiditis. She was counselled and started on thyroxin therapy with a dose of 4µg/kg and after 2 months of follow up the ovarian cysts have regressed and ovaries appeared normal on USG.

We investigated whether more advanced climacteric stage in the mid-40s is associated with thyroid autoimmunity and dysfunction.This cross-sectional cohort study included 2,569 46-year-old women. Thyroid hormone, thyroid peroxidase antibodies, and follicle-stimulating hormone levels were determined. Using menstrual history and follicle-stimulating hormone levels, the participants were divided into climacteric (n = 340) and preclimacteric (n = 2,229) groups. Women diagnosed with premature ovarian insufficiency (menopause by 40 y of age) were excluded. The use of thyroid medication was evaluated from the medication reimbursement register. The prevalence of thyroid medication use, laboratory-based thyroid dysfunction, and thyroid peroxidase antibody positivity was compared between the two groups. The association between climacteric status and thyroid disorders was investigated using a logistic regression model including smoking and thyroid antibody status.At 46 years old, climacteric women used thyroid medication more often than preclimacteric women (9.1% vs 6.1%; P = 0.04). There was no difference in the prevalence of subclinical or clinical hypothyroidism and hyperthyroidism in nonmedicated participants (5.5% vs 5.0%; P = 0.7) or thyroid peroxidase antibody positivity (14.0% vs 15.0%, P = 0.7). In the regression model, being climacteric (OR = 1.6; 95% CI 1.1-2.3; P = 0.02) and antibody positivity (OR 4.9; 95% CI 3.6-6.6; P 0.001) were associated with a higher prevalence of thyroid dysfunction.More advanced climacteric stage in the mid-40s was slightly associated with thyroid dysfunction but not thyroid autoimmunity.Video Summary:http://links.lww.com/MENO/A771.

Clinical studies have investigated the prevalence of gestational diabetes mellitus (GDM) in women with subclinical hypothyroidism (SCH). While some studies demonstrate a clear association, others do not. It is possible this may be due to varied diagnostic criteria for SCH and the presence of thyroid antibodies (TA). We conducted a meta-analysis, separating patients diagnosed with SCH using a diagnostic cut-off 4.0 mIU/L and determined the association with GDM and factored TA status into our analysis. A computerised search of five databases including PubMed, Embase, Cochrane Library, Web of Science and CINAHL returned 787 records. Two independent reviewers assessed abstracts and full texts against pre-specified inclusion and exclusion criteria. Ten cohort studies were included in the final analysis. The diagnostic criteria for SCH and incidence of GDM were extracted from each study. Study quality and risk of bias was assessed by two reviewers. TSH levels 4.0 mIU/L saw a significant increase in the odds of GDM, regardless of TA status (OR = 1.60, 95% CI 1.33–1.93). Women with TSH levels >4.0 mIU/L have an increased odds of GDM regardless of TA status but at TSH levels

The current meta-analysis aimed to evaluate the association of thyroid dysfunction and autoimmunity with gestational diabetes mellitus (GDM). A comprehensive search from PubMed, Embase, MEDLINE, and Cochrane databases until November 2020 was conducted. Fixed-effect model was used to combine the results when I2 was 50%. A total of 44 studies were included in the meta-analysis. Low FT4 levels were closely related with GDM in the first and second trimesters of gestation. Hypothyroxinemia (OR: 1.45; 95% CI: 1.25, 1.68; P

Objective Serum lipids have been shown to regulate inflammatory and immune processes, but little is known about their association with thyroid autoimmunity. This study aimed to investigate the association of serum lipids with thyroid autoantibody positivity in the general population with normal thyroid-stimulating hormone (TSH) levels. Methods Data regarding the 7,688 subjects’ baseline characteristics were retrospectively collected. All subjects were categorized into four groups according to thyroid autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) positivity and serum lipid levels were compared. Binary logistic regression models were used to evaluate the risk of TgAb or TPOAb positivity with increasing serum lipid levels. Results In 6,456 included subjects, after adjusting for confounders, the risk of TgAb positivity was positively associated with increasing low-density lipoprotein cholesterol (LDL-C) levels (OR 1.10, 95%CI 1.02–1.19, P = 0.014) and negatively correlated with the increasing high-density lipoprotein cholesterol (HDL-C) levels (OR 0.80, 95%CI 0.67–0.96, P = 0.014). In female subjects, the association between increasing LDL-C (OR 1.15, 95%CI 1.05–1.26, P = 0.004) or HDL-C levels (OR 0.74, 95%CI 0.60–0.91, P = 0.005) and TgAb positivity become more pronounced. Moreover, there was a positive correlation between LDL-C levels and TPOAb positivity (OR 1.14, 95%CI 1.02–1.26, P = 0.016). Conclusion We have shown the associations of HDL-C and LDL-C with thyroid autoantibody positivity in the general population with normal TSH levels in a gender-dependent manner. This study highlights that serum lipids may be new predictors of thyroid autoimmunity even when TSH is within the reference range.

Objective The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been few clinical reports based on a large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves’ disease (GD), Hashimoto’s thyroiditis (HT) and T1DM patients with AITD. Methods Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by RIA. Results The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P < 0.05) but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P < 0.0001). Conclusions An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.

Objective: To compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC. Methods: A total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups. Results: Of the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037). Conclusion: Although preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC. Refereed/Peer-reviewed

Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto’s thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized‑controlled study was performed in patients with HT assigned to two groups. Se‐treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD‐1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se‐treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.

Background: Thyroid peroxidase (TPO) gene mutation leads to a change in enzyme built structure resulting in the anti-TPO autoantibodies production that may cause thyroid destruction. Aim: To evaluate the association of three single nucleotide polymorphisms (SNPs) of the TPO gene and anti-TPO levels in Egyptian patients with autoimmune hypothyroidism and correlate them with the disease severity. Methods: Two hundred patients with newly discovered autoimmune hypothyroidism were included in the study (100 with subclinical hypothyroidism and 100 of them with overt hypothyroidism) and 100 healthy individuals as a control group were genotyped by PCR-REFLP. Results: The TT genotype of rs2071400 C/T and the T allele were significantly more frequent in patients with subclinical hypothyroidism and overt hypothyroidism than in the control group. But there were no significant differences in the TT genotype and T allele between subclinical and overt hypothyroidism patients. As regards TPO rs732609 A/C polymorphism, the CC genotype of rs732609 A/C and the C allele were significantly increased in patients with subclinical hypothyroidism and overt hypothyroidism than in controls. There was a significant difference in the CC genotype and C allele between subclinical and overt hypothyroidism patients. Concerning TPO rs1126797 C/T polymorphism, there were no significant differences of genotype or allele frequencies between patients groups and control group. Conclusion: We found an association of rs2071400 C/T and rs732609A/C polymorphisms with autoimmune hypothyroidism and correlated anti-TPO levels with different genotypes in hypothyroid patients. Also, we found an association of rs732609A/C polymorphism with the disease severity.

Purpose We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes. Methods This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed. Results We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity. Conclusion Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.

Previous studies have reported reduced bone mineral density (BMD) in patients with hyperthyroidism. We assessed the association of BMD in children and adolescents with Graves' disease (GD) after correcting for potential confounders affecting BMD such as age, sex, and pubertal status. Forty-four children and adolescents with GD and 172 age- and sex-matched healthy controls were enrolled in this study. We analyzed auxological features, BMD, and levels of thyroid hormone, thyroid-stimulating hormone, and thyroid autoantibodies. We measured BMD by dual-energy X-ray absorptiometry at the time of diagnosis in all patients. The mean age of all patients with GD (9 boys and 32 girls) was 12.1 ± 2.2 years (range, 7.0-16.0). Their initial mean free T4 and thyroid-stimulating hormone levels were 3.51 ± 1.56 ng/dL and 0.04 ± 0.03 IU/L, respectively. The mean BMD Z-scores of the lumbar spine (LS), femoral neck, and total body less head of patients with GD were significantly lower than those of control subjects. Eleven patients (26.8%) had low bone density (LS BMD Z-scores-2.0). To identify correlations of patient characteristics with BMD Z-scores at each site, alkaline phosphatase had a significant negative correlation with BMD Z-scores at LS and femoral neck, but not total body less head (r = -0.441; p = 0.004 and r = -0.351; p = 0.025, respectively). Children and adolescents with newly diagnosed GD had lower bone mass than their healthy peers. These results suggest that BMD measurement at initial evaluation may be necessary in this population.

Background: Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH).Methods: We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center.Results: A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both PP=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy.Conclusion: PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

The pathogenesis of Hashimoto’s thyroiditis (HT) is unclear, although some studies have identified an association between vitamin D deficiency and thyroid autoantibody positivity. This study aimed to investigate vitamin D status, and its relationships with thyroid autoantibody positivity and HT, via a large epidemiological survey. The epidemiological survey was conducted in Tianjin, China. All participants underwent testing for serum 25-hydroxyvitamin D (25OHD), thyroid function, and thyroid autoantibodies, and some participants underwent testing to evaluate CD4+ T-cell differentiation and concentrations of related cytokines. The study included 1812 participants and revealed prevalences of 13.1% for thyroid peroxidase antibodies (i-TPOAb) and 14.0% for thyroglobulin antibodies (i-TgAb). Logistic regression analysis revealed that thyroid autoantibody positivity was associated with sex, age, and 25OHD classification. An increased likelihood of i-TPOAb positivity was associated with 25OHD deficiency (odds ratio [OR]: 2.428, 95% confidence interval [CI]: 1.383–4.261) and 25OHD inadequacy (OR: 1.198, 95% CO: 0.828–1.733; p = 0.008). An increased likelihood of i-TgAb positivity was associated with 25OHD deficiency (OR: 2.366, 95% CI: 1.366–4.099) and 25OHD inadequacy (OR: 1.263, 95% CI: 0.883–1.807; p = 0.009). Relative to healthy subjects, patients with HT had significantly higher proportions of Th1 and Th17 cells, as well as higher concentrations of related cytokines. This study revealed that vitamin D deficiency was associated with thyroid autoantibody positivity, and that vitamin D deficiency seems to be involved in the pathological mechanism underlying HT. Large randomized controlled trials are needed to investigate the effects of vitamin D supplementation on HT.

Iodine deficiency is still the main cause of preventable thyroid disorders, worldwide. To optimize iodine intake, programs of voluntary or mandatory iodization of salt have been implemented in several iodine-deficient countries and iodine sufficiency has been achieved in many. Despite the clear beneficial effects on thyroid health, some concerns have been raised on the presumed detriment of iodine prophylaxis on thyroid autoimmunity. Very recent studies aimed at evaluating the long-term consequences of iodine supplementation on thyroid autoimmunity and related dysfunction, have clearly demonstrated that the early post-iodization increase in thyroid antibody positivity is largely transient and not clinically relevant, since the prevalence of overt thyroid dysfunction has remained reassuring low over two decades. The recommended iodine intake is therefore safe with regard to thyroid autoimmunity, the benefits largely outweighing the risks in a population with a stable median iodine concentration not exceeding 300 μg/L. Thus, a possible increase in thyroid autoimmunity should not represent a limitation to promoting iodine supplementation in the general population, also taking into account the steady rise in prevalence of autoimmune disorders which has occurred in the last few decades because of environmental factors other than iodine.

Background. The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto’s thyroiditis (HT) patients without central nervous system involvement. Methods. 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. Results. The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. Conclusions. There were changes in the brain’s bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain’s bioelectrical activity in the course of HT may be associated with an autoimmune process.