UNASSIGNED: The risk factors linked to hand osteoarthritis (OA) that contribute to its distinct symptoms and clinical presentation are not thoroughly understood. This study aimed to examine whether the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), associate with hand OA and symptomatic hand OA in the Third National Health and Nutrition Examination Survey (NHANES III).
UNASSIGNED: We included 2,429 persons from NHANES III ≥60 years of age. Data on hand OA or symptomatic hand OA were examined with respect to their associations with TPOAb and TgAb. Log-binomial and modified Poisson regression models were fit to examine the associations between the anti-thyroid autoantibodies and hand OA or symptomatic hand OA.
UNASSIGNED: Higher levels of TPOAb were associated with a higher prevalence of symptomatic hand OA in the unadjusted (PR = 1.182, p = 0.024) and adjusted models after controlling for age, gender, and diabetes (PR = 1.174, p = 0.039). This association was no longer significant when positive TPOAb was considered a categorical variable with four levels and compared with negative TPOAb. TgAb showed a trend toward being positively associated with symptomatic hand OA (p < 0.10). When positive TgAb was considered a categorical variable with four levels and compared with negative TgAb, the highest quartile was associated with a higher prevalence of symptomatic hand OA than negative TgAb in the unadjusted (PR = 2.242, p = 0.008) and adjusted models (PR = 2.045, p = 0.038). There was no significant association between TPOAb or TgAb and hand OA.
UNASSIGNED: Higher levels of TPOAb may be associated with the presence of symptomatic hand OA in persons ≥60 years old. Persons ≥60 years old with the highest quartile levels of TgAb may be more likely to present with symptomatic hand OA.

Autoimmune thyroid diseases (AITDs) pose significant challenges in clinical practice, representing one of the most common endocrine abnormalities. Vitamin D deficiency has been linked as one of the contributing factors to the etiology of AITDs. This systematic review evaluates the effects of vitamin D supplementation on thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels in adults with AITDs. Using a PICO (population, intervention, comparison, and outcome) framework and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, seven relevant studies were identified from an initial pool of 1,469 articles. The population comprised individuals with thyroid autoimmunity, as evidenced by at least one elevated positive thyroid autoimmune marker and intervention involved the supplementation of vitamin D, regardless of the dose or method of administration. All randomized clinical trials within the last 10 years, which fit the study criteria, were included. These studies showed varying results based on follow-up duration. Short-term studies (three months or less) demonstrated no significant changes in mean TSH, T3, or T4 levels compared to the control group with vitamin D supplementation. However, all of the long-term studies (greater than three months) indicated significant improvements compared to the control in mean TSH, T3, and T4 levels. Additionally, all long-term studies that compared TSH, T3, and T4 to baseline levels revealed significant changes by the trial\'s end. Despite these promising findings, the review highlights limitations, including small sample sizes, short study durations, and the need for further research to establish optimal dosing and treatment duration for vitamin D in AITD management. The overall findings suggest that vitamin D supplementation may play a part in thyroid hormone regulation in AITD, particularly with prolonged administration.

Metformin inhibits the secretory function of overactive anterior pituitary cells, including lactotropes. In women of childbearing age, this effect was absent if they had coexisting autoimmune (Hashimoto) thyroiditis. The current study was aimed at investigating whether autoimmune thyroiditis modulates the impact of metformin on the plasma prolactin concentration in men. This prospective cohort study included two groups of middle-aged or elderly men with drug-induced hyperprolactinemia, namely subjects with concomitant Hashimoto thyroiditis (group A) and subjects with normal thyroid function (group B), who were matched for baseline prolactin concentration and insulin sensitivity. Titers of thyroid peroxidase and thyroglobulin antibodies, levels of C-reactive protein, markers of glucose homeostasis, concentrations of pituitary hormones (prolactin, thyrotropin, gonadotropins, and adrenocorticotropic hormone), free thyroxine, free triiodothyronine, testosterone, and insulin growth factor-1 were measured before and six months after treatment with metformin. Both study groups differed in titers of both antibodies and concentrations of C-reactive protein. The drug reduced the total and monomeric prolactin concentration only in group B, and the impact on prolactin correlated with the improvement in insulin sensitivity and systemic inflammation. There were no differences between the follow-up and baseline levels of the remaining hormones. The results allow us to conclude that autoimmune thyroiditis mitigates the impact of metformin on prolactin secretion in men.

The pathogenesis and manifestation of autoimmune thyroid diseases (AITDs), Graves\' disease (GD), and Hashimoto\'s disease (HD) are associated with T cell activation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a crucial role in the regulation of T cell activation. DNA methylation levels of eight CpG sites in the CTLA4 gene and expression levels of soluble CTLA-4 were examined. Methylation levels of +22 CpG and CT60 CpG-SNPs in patients with GD and HD with the CT60 GG genotype were lower than those in control subjects. Methylation levels of the-15 CpG sites were lower in patients with intractable GD than those in GD patients in remission. These results suggest that demethylation of +22 CpG and CT60 CpG-SNPs may be associated with susceptibility to GD and HD in subjects with the CTLA4 CT60 GG genotype, and that demethylation of -15 CpG may be associated with the intractability of GD.

There is growing evidence suggesting an association between severe acute respiratory coronavirus syndrome coronavirus 2 (SARS-CoV-2) infection and various extrapulmonary diseases since the advent of coronavirus disease 2019 (COVID-19) pandemic. However, case reports of fulminant type 1 diabetes mellitus (FT1D) following SARS-CoV-2 infection are limited. We encountered a 44-year-old Japanese woman who developed FT1D accompanied by subclinical thyrotoxicosis caused by autoimmune thyroid disease (AITD) approximately one week after SARS-CoV-2 infection. The patient developed fever and flu-like symptom 4 days before transportation and tested positive then for the SARS-CoV-2 antigen self-test. She subsequently developed sudden thirst, polyuria, and fatigue of 1 day duration and was urgently brought to our emergency room. Laboratory findings indicated diabetic ketoacidosis (DKA) without marked elevation of serum glycated hemoglobin (HbA1c) levels (glucose, 930 mg/dL; HbA1c, 7.4%). Her insulin secretory capacity was almost completely depleted, and islet-specific autoantibodies were negative. Endocrine examinations revealed subclinical thyrotoxicosis, which was positive for thyroid stimulation hormone receptor antibodies. Based on these results, the patient was diagnosed with FT1D accompanied by AITD and immediately started on intensive insulin therapy with a basal-bolus subcutaneous insulin regimen. Human leukocyte antigen analysis revealed haplotypes, indicating susceptibility to both FT1D and AITD. Further studies are required to elucidate the causal relationship between SARS-CoV-2 infection, FT1D, and AITD. However, clinicians must be vigilant about possible development of FT1D and AITD to enable accurate diagnosis and treatment of patients with DKA during the COVID-19 pandemic.

BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown.
OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D.
METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence.
RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (β: 0.0456, P-value: 0.0140) and overt PolyA (β: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed.
CONCLUSIONS: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

One of the sensitive markers for autoimmune thyroid disease (AITD) clinical identification is thyroid-stimulating hormone receptor antibodies (TRAbs). To quickly distinguish TRAb with distinct antigenic epitopes, a straightforward and uncomplicated technique has not yet been created. The objective of this study is to search for molecular diagnostic targets for different types of AITD {Graves\' disease (GD), Graves\' orbitopathy (GO), GD with third-degree goiter [GD(3)], hypothyroidism combined with positive TRAb [HT(TRAb+)]} as molecular diagnostic targets. Following action on thyroid cells, differential genes (DEGs) generated by TRAb with distinct antigenic epitopes were detected and identified by RNA sequencing (RNA-Seq), bioinformatics analysis, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) in the serum of patients with AITD. Using the 5-ethynyl-2\'-deoxyuridine (EdU) assay, the effect of coculturing thyroid cells with different antigenic TRAb epitopes on the cells\' capacity to proliferate was investigated. Bioinformatics analysis and RT-qPCR validation identified one GD key gene alpha 2-HS glycoprotein (AHSG), two GO key genes [adrenoceptor alpha 1D (ADRA1D) and H2B clustered histone 18 (H2BC18)], two GD(3) key genes [suppressor of cytokine signaling 1 (SOCS1) and cytochrome b-245 beta (CYBB)], and one HT(TRAb+) key gene (MASP2). Correlation analysis and ROC curves showed that the abovementioned genes could be used as molecular diagnostic targets for different types of AITD. Finally, EdU results showed that TRAb inhibited thyroid cell proliferation in the HT(TRAb+) group compared with the normal control group, whereas the remaining three groups promoted thyroid cell proliferation, with a statistically significant difference (P < 0.05). We identified six key genes for different types of AITD, which have diagnostic value for different types of AITD. Meanwhile, we found that TRAbs with different antigenic epitopes in AITD have different biological functions.NEW & NOTEWORTHY We identified six molecular targets of different types of AITD [GD, GO, GD(3), and HT(TRAb+)], which have diagnostic value for different types of AITD. Meanwhile, we found that TRAb with different antigenic epitopes extracted from the sera of patients with AITD had different biological functions, which also provided a new idea for further research on the mechanism of action of TRAb with different antigenic epitopes in AITD.

BACKGROUND: Bioassays provide information on the functionality of thyrotropin receptor antibodies (TSH-R-Ab) and thus may offer more clinical utility than binding assays.
OBJECTIVE: In this prospective, blinded, US-based study, the clinical performance of several TSH-R-Ab assays was compared.
METHODS: US endocrinology clinic.
METHODS: One hundred sixty-two unselected, consecutive, well-documented patients with various thyroid diseases and healthy controls.
METHODS: Blinded TSH-R-Ab measurements.
METHODS: Sensitivity and specificity of 4 TSH-R-Ab assays.
RESULTS: The 4 TSH-R-Ab assays were negative in all 42 patients without autoimmune thyroid disease (AITD). In 104 patients with Graves\' disease (GD), irrespective of the disease duration, TSH-R-Ab positivity was present in 65 (63%), 67 (65%), and 87 (84%) for the Cobas and Immulite binding assays and stimulatory TSH-R-Ab [thyroid-stimulating immunoglobin (TSI)] bioassay, respectively (TSI vs Immulite P < .0025, TSI vs Cobas P < .0009). Fifteen newly diagnosed GD patients were all positive in the TSI bioassay, but only 11 (73%) were positive in the Cobas and Immulite binding assays. Nine GD patients with biochemical subclinical hyperthyroidism were TSI-positive but Immulite- and Cobas-negative. Two GD patients were blocking TSH-R-Ab [thyroid-blocking immunoglobin (TBI)]-positive and TSI-negative, and the Immulite and Cobas were positive in both. Additional serum samples from AITD patients that consisted of 30 TBI-positive and 10 TSI-positive samples were blindly tested in the binding assays. Only 6 of the 10 TSI-positive samples were positive in both binding assays, and 30 and 28 of the TBI-positive samples were positive in the Cobas and Immulite assays, respectively.
CONCLUSIONS: Binding TSH-R-Ab assays are less sensitive than TSI bioassays and are not specific for stimulating antibodies. Measuring the function of TSH-R-Ab in a bioassay can provide useful information to clinicians.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM.
METHODS: In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb.
RESULTS: Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04).
CONCLUSIONS: Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

OBJECTIVE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.
METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.
RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).
CONCLUSIONS: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.