Thyroid Peroxidase Autoantibodies Research Articles

Exploring the role of autoantibodies in Iraqi females with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy that affects 5-10% of women during their reproductive years. Clinicians characterize it by the occurrence of ovarian cysts, oligomenorrhea, amenorrhea, and either clinical or biochemical evidence of hyperandrogenism. Recent research suggests a potential link between autoantibodies and PCOS development. Aim of study: This study investigated the relationship between autoantibodies and Polycystic ovary syndrome (PCOS). Materials and methods: The study involved a total of 150 female participants diagnosed with PCOS, aged between 20 to 35, and a control group of 150 individuals. We utilized chemiluminescent immunoassays to measure Anti-thyroid antibodies thyroglobulin (TG) and thyroid peroxidase (TPO). We conducted IgM and IgG for anti-cardiolipin (ACL) and β-2 glycoprotein I (B2GPI) using the enzyme-linked immunosorbent assay (ELISA). To measure lupus (La), we employed coagulation time. To assess the serum levels of total antibodies Ig (M, G, A), Serum amyloid A (SAA), High-Sensitivity C-reactive protein (hs-CRP), and Procalcitonin (PCT), we used nephelometry methods. Results: In our findings, patients showed a significantly higher level of TPO autoantibodies (91.9±14.7) compared to the control group (12.4±5.1). This difference was highly significant (<0.001). Similarly, we observed high levels of anti-TG antibodies in patients (50.4±10.3) compared to the control group (30.6±7.2). This points out the important role of both TPO and TG antibodies in this context. Moreover, the level of IgM for ACL was significantly higher in patients (19.2±4.2 AU/dl) than in controls (3.3±1.0 AU/dl). The level of IgG for ACL was also higher in patients (22.5±2.3 AU/dl) compared to controls (3.3±1.0 AU/dl). These increases in ACL antibodies in patients suggested a risk factor for the disease. Additionally, Serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) were significantly higher in patients, with measurements of 66±10.4 (AU/ml) and 55±12.5 (AU/ml) respectively, compared to controls who had measurements of 3.6±1.9 (AU/ml) and 2.3±0.98 (AU/ml) respectively, which was highly significant (<0.001). Procalcitonin (PCT) was also highly significant in patients (40±6.3 AU/ml) compared to the control group (6.4±2.6 AU/ml). Lastly, the concentration of total IgG antibodies was significantly higher in patients (25.3±2.6 AU/dl) than in controls (4.3±1.0 AU/dl), with a significant difference (P=0.006). Conclusion: High concentrations of autoantibodies in patients suggest a risk factor and positive associations with the disease.

FRI553 ICI-induced Thyroid Ophthalmopathy With De Novo Graves’ Disease

Abstract Disclosure: S.I. Moctezuma: None. J. Perlman: None. J.S. Mammen: None. Background: Immune checkpoint inhibitors frequently target the thyroid gland. However, immune checkpoint inhibitor (ICI)-induced Graves’ disease (GD) is rare. To our knowledge, there are no reported cases of thyroid eye disease after immune checkpoint inhibitor therapy in patients with newly positive anti-thyroid antibodies. Clinical Case: An 81-year-old man developed thyroiditis within three weeks of a single dose of ipilimumab/nivolumab for the treatment of metastatic cholangiocarcinoma. ICI therapy was discontinued for cardiotoxicity. He presented one year later with onset of periorbital edema, pain with downgaze, redness, irritation and progressive proptosis with diplopia. He did not have a prior history of thyroid disease. Thyroid function tests before the start of ICI therapy revealed euthyroidism [TSH 2.982 uIU/mL (0.55 - 4.78)]. Symptoms of palpitations, weight loss, and hyper-defecation that characterized his initial presentation with thyroiditis were absent at the time of onset of eye disease. At presentation of thyrotoxicosis his TSH was <0.01 uIU/mL, free T4 3.6 ng/dL (0.89 - 1.76) total T3 190 ng/dL (60-180) Thyroid-peroxidase autoantibodies (TPOAb) and thyroid-stimulating immunoglobulin (TSI) were negative. When his visual symptoms appeared, TPOAb remained negative while a repeat TSI antibody was positive [0.64 IU/L (0.00 - 0.55)]. Thyroid ultrasound at the time of thyroiditis revealed a heterogeneous gland without discrete nodules and a normal vascular flow. Most cases of ICI-induced GD have been reported at the start of therapy, particularly in the first 6 weeks, although thyrotoxicosis has been described to occur as late as 224 days after starting PD-1 inhibitor. GD is more frequently reported with combination anti-CTLA-4 and anti-PD-1 therapy. Patients with thyroid ICI-induced adverse events experience either isolated hypothyroidism or thyroiditis spontaneously evolving towards hypothyroidism. However, ICI-induced GD is more likely to have a relapsing-remitting disease. In 2021, Peiffert et al. described the antibody profile for 243 patients with ICI-induced thyrotoxicosis. In this case series, 5 patients developed thyrotoxicosis with positive thyrotropin-receptor antibodies (TRAb). Only 2 patients had a typical clinical presentation of GD. TSI antibodies were not reported. Furthermore, none of the patients with positive TRAb had Graves’ ophthalmopathy. Conclusion: Our case demonstrates the acquisition of auto-antibodies capable of mediating Graves’ disease, and raises the possibility that thyroid eye disease-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy. These symptoms developed as late as one year after initiation of therapy. As with sporadic cases, this can occur in the absence of clinically significant hyperthyroidism. Presentation: Friday, June 16, 2023

Thyroid peroxidase antibody titers, thyroid function, and iodine nutrition status of pregnant normotensive and preeclamptic women in Eastern Cape South Africa

Autoimmune thyroid disease, one of the main risk factors for hypothyroidism, is associated with adverse pregnancy outcomes. The burden of autoimmune thyroid disease in pregnancy and its association with thyroid function among normotensive pregnant women and pregnant women with hypertension in South Africa are not known. This study aimed to establish the magnitude of thyroid peroxidase autoantibodies in pregnancy in the Eastern Cape of South Africa and its relationship with iodine nutrition status and preeclampsia. Overall, 60 randomly selected normotensive pregnant controls at term and 120 pregnant participants with preeclampsia in the third trimester of pregnancy going to the Mthatha Regional Hospital and the Nelson Mandela Academic Hospital in the Eastern Cape Province who had complete data on thyroid peroxidase antibody titers, urinary iodine concentrations, serum thyroid-stimulating hormones, and free triiodothyronine, free thyroxine, and thyroglobulin levels were enrolled in this unmatched case-control study. The cases and controls had similar mean chronological age (23.8 vs 24.0 years), body mass index (29.4 vs 28.8 kg/m2), and median parity (both 1) (P>.05). The controls had a higher mean gestational age than participants with preeclampsia (38.5 vs 33.7 weeks, respectively; P<.001). Both participants with preeclampsia and normotensive participants had median thyroid peroxidase antibody levels consistent with a negative thyroid autoimmune status. Participants with preeclampsia had higher but nonstatistically significant median thyroid peroxidase antibody (2.14 vs 1.77 IU/L), thyroglobulin (25.9 vs 21.3 µg/L), and thyroid-stimulating hormone (2.4 vs 2.3 mIU/L) levels (P>.05) and significantly lower median urinary iodine concentration (123.4 vs 188.6 µg/L), free thyroxine (13.2 vs 14.1 pmol/L), and free triiodothyronine (4.3 vs 4.6 pmol/L) levels (P<.05) than normotensive controls. Thyroid peroxidase antibodies were positively correlated with thyroglobulin, urinary iodine concentration, and thyroid-stimulating hormone. In the rural Eastern Cape of South Africa, pregnant women in the third trimester of pregnancy have thyroid peroxidase antibody titers that show negative thyroid autoimmune status. Insufficient iodine intake, other than thyroid autoimmune disease, seems to be the underlying cause of the lower free triiodothyronine and free thyroxine levels observed among women with preeclampsia.

Most Patients With Autoimmune Chronic Spontaneous Urticaria Also Have Autoallergic Urticaria, but Not ViceVersa.

Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell-activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]-anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG-anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE). To investigate the rates of CSU patients with aaCSU and aiCSU. We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]-anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both. Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment. Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology.

Prevalence of Thyroid Peroxidase and Thyroglobulin Autoantibodies in the Swedish Population.

Autoimmune thyroid disease (AITD) may be detected prior to clinical symptoms through the presence of autoantibodies against thyroid peroxidase (TPOab), thyroglobulin (TGab), or both.The present study aimed to develop a novel radiobinding assay (RBA) for TPOab and to determine the prevalence of TPOab and TGab in the Swedish population.Patient samples from 27 newly diagnosed Graves' disease patients in longitudinal follow-up and 124 AITD autoantibody-positive children in prospective follow-up for increased risk of type 1 diabetes were included to validate the novel RBA for TPO. The results of RBA were compared with those obtained by commercial radioimmunoassay (RIA) and electrochemiluminescence (ECL). Furthermore, 476 serum samples from adult blood donors and 297 from 13-year-old school children were analyzed for the presence of TPOab and TGab.Receiver operating characteristics analysis for the novel TPOab resulted in an area under curve (AUC) value of 0.82 (p<0.0001), a sensitivity of 77.8%, and a specificity of 91.9% in adult blood donors, and an AUC value of 0.70 (p<0.0001), a sensitivity of 53.2% and a specificity of 95.3% in the 13-year-old school children, respectively. TPOab levels in RBA correlated with both ECL (r=0.8950, p<0.0001) and RIA (r=0.9295, p<0.0001). The prevalence of TPOab and TGab was 6.3% and 7.6% in adult blood donors and 2.9 and 3.7% in 13-year-old school children.In conclusion, a novel RBA for the determination of TPOab was developed and validated with current methodologies. This study also reports an increasing prevalence of thyroid autoantibodies from adolescence to adulthood.

Exposure of Akwesasne Mohawk women to polychlorinated biphenyls and hexachlorobenzene is associated with increased serum levels of thyroid peroxidase autoantibodies

ABSTRACT Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and dichlorodiphenyltrichloroethane (p,p’-DDT) were reported to influence immunological activity. As endocrine-disrupting chemicals (EDC), these pollutants may disrupt normal thyroid function and act as catalysts for development of autoimmune thyroid disease by directly and indirectly affecting levels of thyroid peroxidase antibodies (TPOAbs). Native American communities are disproportionately exposed to harmful toxicants and are at an increased risk of developing an autoimmune disease. The aim of this study was to determine the association between POPs and TPOAbs in serum obtained from Native American women. This assessment was used to measure whether increased risk of autoimmune thyroid disease occurred as a result of exposure to POPs. Data were collected from 183 Akwesasne Mohawk women, 21–38 years of age, between 2009 and 2013. Multivariate analyses were conducted to determine the association between toxicant exposure and levels of TPOAbs. In multiple logistic regression analyses, exposure to PCB congener 33 was related to elevated risk of individuals possessing above normal levels of TPOAbs. Further, HCB was associated with more than 2-fold higher risk of possessing above normal levels of TPOAbs compared to women with normal levels of TPOAbs. p,p’-DDE was not associated with TPOAb levels within this study. Exposure to PCB congener 33 and HCB was correlated with above normal levels of TPOAbs, a marker of autoimmune thyroid disease. Additional investigations are needed to establish the causes and factors surrounding autoimmune thyroid disease which are multiple and complex.

Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study.

Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se's role in AITD in Indonesian children with DS. This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearman's rank correlation (r s). All results with p<0.05 were considered statistically significant. Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

Screening for Adrenocortical and Thyroid Peroxidase Antibodies to Look for Underlying Autoimmune Etiologies in Women under 35 with Idiopathic Dimished Ovarian Reserve

Background: Autoimmune disorders are more common in premature ovarian insufficiency (POI) than in the general population. The most important association is with autoimmune Addison’s disease. Measurement of adrenocortical antibodies (ACA) and/or 21-hydroxylase antibodies (21-OH) is recommended in every POI patients as they appear to be the marker with the highest diagnostic sensitivity for autoimmune POI. Also thyroid peroxidase autoantibodies (TPO-Ab) should be assayed due to the common association between thyroid disease and POI. The underlying etiologies of diminished ovarian reserve (DOR) in young women can be expected to be similar to the etiology of POI since they represent a continuum in the phenotypic expression of premature ovarian aging. Methods: This pilot case-control study was conducted between January 2019 and April 2020. The study group consisted of patients under the age of 35, who was infertile and diagnosed with idiopathic DOR by ovarian reserve tests during infertility work up. Controls were patients of the same age range who diagnosed with isolated tubal factor or male infertility and had functional ovarian reserve test results during infertility work up. Patients with a history of ovarian surgery, cancer, genetic or autoimmune disease were excluded. Abnormal ovarian reserve tests are defined as antral follicle count &lt;5 and anti-mullerian hormone (AMH) &lt;1.2 ng/dL corresponding to group 3 according to POSEIDON criteria. In total, 35 DOR patients and 35 controls were included in the study. ACA and TPO-Ab screening were performed in serum samples using indirect immunofluorescence method. Demographics and family history of autoimmune diseases were also evaluated. Results: A higher rate of ACA positivity was detected in the DOR group (34.3%) compare to controls (17.1%), although it was not found to be statistically significant (p = 0.101, p &lt; 0.05). The incidence of family history of autoimmune diseases in first degree relatives was positively correlated with ACA positivity (p = 0.006, p &lt; 0.05). In DOR group, autoimmune disease history in the family was significantly higher in ACA (+) patients compared to ACA (–) individuals (p = 0.03, p &lt; 0.05). TPO-Ab positivity rates were similar between 2 groups (17.1% vs 20%, p = 0.759, p &lt; 0.05). Conclusions: Even if there is no specific treatment option yet for autoimmune ovarian damage, screening for ACA or 21-OH antibodies may be considered in young women with idiopathic DOR, especially those with a family history of autoimmune disease, based on knowledge that identification of women with autoimmune POI is clinically important for the identification of subclinical autoimmune Addison’s cases.

Thyroid Peroxidase Autoantibody in Subclinical and Overt Hypothyroidism: A Hospital Based Retrospective Study

Introduction:Thyroid peroxidase (TPO) is a key enzyme of thyroid hormone biosynthesis as it catalyzes the iodination and the coupling steps. Subclinical hypothyroidism is the condition of increased Thyroid Stimulating Hormone (TSH) and normal levels of serum free thyroxine (ft4) and free triiodothyronine (ft3) levels. Subclinical hypothyroidism can be progressed to overt hypothyroidism in which ft3 and ft4 levels are decreased along with an increment of TSH levels. Materials and methods: This was the hospital-based retrospective study conducted on the patients who had undergone thyroid function test measurements along with thyroid peroxidase autoantibody level in serum. The study duration was eight months (January 2022 to August 2022). All the data were entered in Microsoft Excel version 10 and analyzed in SPSS version 22 accordingly. Results: In the study among 424 patients, 73.8% were female and 26.2% were male. Firstly, our study revealed subclinical hypothyroidism was predominant (41.7%), followed by euthyroidism (34.7%) overt hypothyroidism (20.3%), and overt hyperthyroidism (3.3%). Secondly, there was no statistically significant difference in age (P value: 0.26) and gender (0.64) between subclinical and overt hypothyroidism. There was no statistically significant difference in serum anti-TPO antibodies level between subclinical (median 6.25) and overt hypothyroidism (median 6.12) (P value: 0.92) when median and interquartile ranges were compared. Correlation analysis revealed a significant positive correlation of TPO antibodies with TSH (0.27, 0.00) and no significant negative correlation with fT4 (-0.02, 0.46) and fT3 (-0.05, 0.37). Conclusion: The current study revealed the elevation of thyroid peroxidase autoantibodies in both subclinical and overt hypothyroid patients though subclinical hypothyroidism was predominant.

Assessment of Antinuclear Antibodies, Anti-Beta 2-Glycoprotein-1, and Thyroid Peroxidase Autoantibody Levels in Human Immunodeficiency Virus Sero-positive Pregnant Women at Nnamdi Azikiwe University Teaching Hospital, Nnewi Nigeria

Abstract Background: Pregnancy is associated with biochemical alterations and may be compounded by human immunodeficiency virus (HIV) infection potentially affecting pregnancy outcome. Aims: This study evaluated some biochemical parameters that could possibly affect pregnancy outcomes in HIV-infected women. Patients, Materials and Methods: The study involved 136 HIV sero-positive on highly active antiretroviral therapy (HAART) and 137 HIV sero-negative pregnant women, recruited from the Antenatal Clinic of Nnamdi Azikiwe University Teaching Hospital, Nnewi. Antinuclear antibodies (ANAs), anti-beta 2-glycoprotein-1 (βGP1), and thyroid peroxidase autoantibody (TPOab) were analysed using the enzyme-linked immunosorbent assay methods. Results: TPOab in HIV sero-positive subjects (104.9 ± 51.06 IU/mL) was significantly higher (P &gt; 0.05) compared with controls (89.5 ± 33.5 IU/mL). ANA and βGP1 in test group (0.89 ± 0.31; 12.94 ± 8.9, respectively) did not change significantly (P &gt; 0.05) compared with the controls (0.84 ± 0.27; 10.37 ± 9.6, respectively). There were no significant changes in measured biochemical parameters between trimesters (P &gt; 0.05). Furthermore, there were no significant differences in measured biochemical parameters between subjects with different APGAR scores in all subject groups. Conclusion: HIV infection affected TPOab level but had no impact on ANA, bGP1, and APGAR score in HIV pregnancy under HAART.

Thyroid dysfunction and anti-thyroid antibodies in systemic sclerosis patients

Aim of the workTo assess the frequency of thyroid dysfunction and thyroid auto-antibodies in systemic sclerosis (SSc) patients. Patients and methodsThis study included thirty-three SSc patients and 30 matching controls. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti thyroglobulin (ATG) and anti thyroid peroxidase autoantibodies (ATPO) were measured in the sera of patients and controls. ResultsThe mean age of the patients was 45.9 ± 13.05 years; 28 females and 5 males (F: M 5.6:1) and a disease duration of 4.58 ± 3.84 years. The FT3, FT4, TSH tended to be higher in patients (T3: 2.8 ± 0.66 pg/ml; T4: 1.5 ± 0.65 ng/ml; TSH: 1.9 ± 2.1ul/ml) than in controls (p = 0.07, p = 0.21 and p = 0.24 respectively) while the ATG level in patients was 40 ± 21.3 IU/ml and ATPO 36.7 ± 88.2 IU/ml. Four patients had hypothyroidism (12 %); 3 (9 %) subclinical hypothyroidism (SCHT) and 1 (3 %) clinical hypothyroidism (CHT). ATG was positive in one patient and in 2 controls while ATPO was positive in two patients compared to one control. Both antibodies were positive in one patient. ATPO was associated with SCHT in one (3 %) and with overt hypothyroidism in another (3 %). The thyroid profile, ATG and ATPO were comparable between females and males (p = 0.34, p = 0.23, p = 0.96, p = 0.77 and p = 0.35 respectively) and all were similar between lcSSc and dcSSc except TSH (lower in dcSSc; p = 0.03). Muscle weakness was significantly higher among ATPO positive patients (p = 0.005) while thyroid dysfunction was significantly associated with arthralgia (p = 0.007). ConclusionThyroid dysfunction mainly hypothyroidism is more frequent among SSc patients.

Granulomatous myopathy: Sarcoidosis and beyond.

Non-necrotizing granulomatous inflammation is a rare but easily recognized histopathological finding in skeletal muscle biopsy. A limited number of diseases are known to be associated with non-necrotizing granulomatous myopathy. Once identified, a careful evaluation for evidence of extramuscular granulomatosis and other signs suggestive of sarcoidosis is warranted as about half of the patients have sarcoid myopathy. In addition, the presence of granulomatous myopathy should trigger a search for clinical and pathological clues of inclusion body myositis (IBM), which accounts for most of the remaining patients and can coexist with sarcoidosis. Recognizing the features of IBM in patients with granulomatous myopathy can potentially spare the patients from unnecessary exposure to immunosuppressive therapies. In patients whose granulomatous myopathy remain unexplained, further investigations should aim at identifying myasthenia gravis and other autoimmune disorders, especially those known to cause granulomatous inflammation in other organs. Laboratory investigations should include acetylcholine receptor, antimitochondrial, antineutrophil cytoplasmic, thyroglobulin, and thyroid peroxidase autoantibodies. In the appropriate clinical context, exposure to immune checkpoint inhibitors and chronic graft-vs-host disease can be causes of granulomatous myopathy. In cases of unexplained granulomatous myopathy, natural killer/T-cell lymphoma should be considered and careful histopathological examination for atypical cells and appropriate immunostaining is crucial. Identifying the etiology of granulomatous myopathy in each patient can guide appropriate treatment.

Impact of anti-thyroid peroxidase and anti-thyroglobulin antibodies on the gestational outcome of euthyroid pregnancies: A retrospective study.

Thyroglobulin (anti-TG) and/or thyroid peroxidase (anti-TPO) autoantibodies are associated with higher rates of poor gestational outcomes. To demonstrate the impact of anti-TPO and anti-TG autoantibodies on the gestational outcomes of euthyroid pregnant women with a history of poor gestational outcome and thyroid gland disorders. This retrospective study included totally 75 euthyroid pregnant, 30 of women with high thyroid autoantibodies (Anti-TPO/Thyroglobulin-positive group) and 45 of them without autoantibodies (control group). We could not demonstrate significant differences between two groups in terms of risk factors/co-morbidities, obstetric complications, gestational outcomes, and birth data (p> 0.05). However, enhanced miscarriage rates were observed among the Anti-TPO/Thyroglobulin-positive and control groups without significance (36.7% and 17.8% respectively, p= 0.116). High neonatal intensive care unit (NICU) admission rates were found for control and Anti-TPO/Thyroglobulin-positive groups (16.2% and 21.1%, respectively) (p= 0.720). Clinically, we compared the two groups in terms of the existence and the types of goiter (diffuse and nodular), and demonstrated that nodular goiter was statistically more frequent in the control group (40.0% vs. 8.7%, p= 0.015). Alongside, relatively high hereditary thrombophilia and type-2 diabetes mellitus rates were found in the Anti-TPO/Thyroglobulin-positive group (20.0% and 20.0%). Thyroid autoantibody positivity is likely a risk factor for early pregnancy loss and NICU admission.

Increased Incidence of Hashimoto Thyroiditis in Selenium Deficiency: A Prospective 6-Year Cohort Study.

In 2015, we reported an increased prevalence of thyroid disease in a county of low habitual selenium (Se) intake in comparison to a neighboring county with higher intake in a cross-sectional survey in Shaanxi Province, China. To explore longitudinal effects of low Se status, a prospective cohort study was conducted in the same area from 2013 to 2019, and thyroid peroxidase autoantibodies (TPO-Abs) and disease incidence were compared. A total 1254 individuals from 1500 reinvited participants were successfully enrolled. Venous blood, fingernails, and urine samples were collected and analyzed to evaluate thyroid status, TPO-Abs, serum Se, and urinary iodine. Diagnosis of Hashimoto thyroiditis (HT) was based on elevated thyrotropin, presence of TPO-Abs, and ultrasound characteristics. Se deficiency was categorized using a serum concentration of 80 µg/L as a threshold, and tested by logistic regression for a relationship to TPO-Abs and HT. Se deficiency was observed in 46.2% of participants from the adequate-Se county (Ziyang) and in 89.7% from the low-Se county (Ningshan). Se concentrations in fingernails differed strongly by residency (Ziyang vs Ningshan; 678.7 vs 364.3 μg/kg; Z = -9.552; P < .001). Newly diagnosed HT in Ziyang was less frequent than in Ningshan (0.09% vs 0.31%; χ 2 = 4.350; P = .037). The conversion rate to seropositive TPO-Abs was 10.2% in Ningshan vs 5.6% in Ziyang. Excluding iodine as confounding factor, low-Se was confirmed as a risk factor for HT (relative risk [95% CI]; 3.65 [1.03-12.90]; P < .05). The data indicate an increased incidence of TPO-Ab seroconversion with low Se supply and support the hypothesis that Se deficiency contributes to HT as a modifiable risk factor.

Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes.

Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. Autoantibodies to the parietal cell autoantigen, H+ /K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6-9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3-2.8; p=0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9-5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5-5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6-26.7) by age 20 years and was 47.3% (95% CI, 41.3-53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.

Hashimoto Thyroiditis, Anti-Parietal Cell Antibodies: Associations With Autoimmune Diseases and Malignancies.

BackgroundHashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT patients: a) the prevalence of APCA in an attempt to define their clinical phenotype and b) any possible associations of APCA with other autoimmune diseases and malignancies.MethodsThis is a single-center, case-control study, conducted at a University Hospital. The study included patients with HT diagnosed between November 2017 and November 2020. Excluded were patients <18 years old, with sonographic features of HT but negative thyroid peroxidase (TPOAbs) or thyroglobulin autoantibodies (TgAbs), Graves’ disease, Down or Turner’s syndrome.ResultsA total of 840 patients with HT were included in the study, from whom 180 (21.4%) had positive APCA. A total of 79 patients (9.4%) had one or more organ-specific autoimmune diseases and 61 (7.3%) had a systemic autoimmune disease. Autoimmune diseases were more frequent in female than in male patients (17.9% versus 10.9%, p = 0.05). APCA-positive patients were older than APCA-negative (54.1 ± 13.5 versus 49.0 ± 14.6, p <0.001) and had more often positive TPOAbs (93.3% versus 83.9%, p=0.001). Gastric neoplasms were documented only in APCA-positive patients (p <0.001). A higher frequency of organ-specific autoimmune diseases was observed in the APCA-positive group (14.4% versus 8%, p = 0.024). In the subgroup of patients with additional autoimmune diseases (n = 140), younger age and positive APCA were independently associated with the presence of organ-specific autoimmunity (OR 0.954, 95% CI 0.927–0.982 and OR 3.100, 95% CI 1.256–7.652, respectively). Papillary thyroid cancer (PTC) occurred in 3.5% of patients (26/29 women). Positive family history for thyroid autoimmunity and negative TPOAbs were the only independent risk factors for PTC among women (OR 3.228, 95% CI 1.173–8.887 and 0.315, 95% 0.113–0.881, respectively).ConclusionThis study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Finally, this study showed an association between APCA and gastric neoplasms in these patients.

Pediatric stiff limb syndrome with polyautoimmunity of anti-GAD-65, anti-islet cell, and thyroid peroxidase antibodies: A case report and review of literature

We report an early childhood onset Stiff Limb Syndrome (SLS) in association with unusual polyautoimmunity of GAD-65, anti-islet cell, and Thyroid Peroxidase (TPO) autoantibodies, who has achieved a nearly complete neurological recovery following combined immunotherapy, symptomatic and physical therapy. The patient had normal MRIs of the brain and spinal cord and a negative paraneoplastic work-up. Subsequently, she developed hypothyroidism requiring levothyroxine supplementation. We then conducted an extensive review of literature and identified 52 previously reported pediatric Stiff Man Syndrome (SMS)/Stiff Person Syndrome (SPS) or SLS cases, which has demonstrated a common association with other systemic autoimmune conditions. In the available literature, screening for concurrent autoimmunity has only been reported infrequently. We found that a paraneoplastic process is extremely rare in pediatric cases. Timely diagnosis and initiation of immunotherapy are critical to a favorable outcome. Therefore, we recommend to include SMS/SPS or SLS as an important differential diagnosis for MRI-negative myelopathy. Further clinical and research efforts should be focused on understanding the role of both genetic predisposition and environmental insults in the autoimmunity of pediatric SMS/SPS or SLS.

Anti-thyroglobulin Antibodies as a Possible Risk Factor for Graves' Disease After Radioiodine Treatment for Toxic Nodular Goiter: Case Report

BackgroundThe manifestation of Graves' disease (GD) in patients treated with radioactive iodine (RAI) for hyperfunctioning thyroid nodules (RAI-induced GD or post-RAI GD) remains a long-standing challenge in radionuclide therapy. Known risk factors for post-RAI GD include preexisting subclinical hyperthyroidism, positive thyroid peroxidase autoantibodies (TPOAb), positive TSH receptor autoantibodies (TRAb) or otherwise undiagnosed GD. However, these risk factors are not present in all patients with post-RAI GD, and therefore it cannot always be predicted in a reliable manner if a given patient has a high risk for RAI-induced GD or not.Case PresentationWe describe the case of a 64 year-old woman known for hyperthyroidism due to toxic nodular goiter; she was treated initially with carbimazole, and then, due to recurrence, underwent RAI treatment. Three months later, symptomatic hyperthyroidism persisted. Diagnosis of new-onset GD was made based on typical ultrasound findings and newly-positive TRAb. Our patient had only positive thyroglobulin antibodies (TgAb) before RAI treatment, whereas TPOAb were negative.ConclusionsIn the literature, TgAb have never been reported as a possible risk factor for RAI-induced GD. The present case suggests that the assessment for pre-existing autoimmunity in patients considering RAI for hyperfunctioning thyroid nodules should probably also include TgAb.

Autoimmune thyroid patients with CTLA-4 (+49A/G) GG/AG genotypes have high seropositivity to thyroid peroxidase than thyroglobulin

Despite increasing burden of autoimmune thyroid disease (AITD) in India, there is paucity of data for the genetic susceptibility in Indian population which represents an important aspect to uncover the genetic factors for the cause or progression of different forms of AITD. It is known that production of auto-antibodies to thyroglobulin (TG) and thyroid peroxidase (TPO) is a characteristic feature of AITD. Production of high titres of auto-antibodies against TG and TPO is one the hallmarks of AITD that often precedes the development of clinical disease. The gene coding for cytotoxic T lymphocyte antigen-4 (CTLA-4) is considered an important candidate gene for susceptibility to AITD and also determines seropositivity. Earlier studies have demonstrated that polymorphic variants in CTLA-4 gene are linked to determine seropositivity. Hence, this study investigates a relationship between CTLA-4 (+49A/G) genotypes and seropositivity to anti-TPO and anti-TG antibodies in AITD patients. A total of 85 Indian participants were included and genotyped for CTLA-4 (+49A/G) single nucleotide polymorphism and further analyzed for seropositivity of TPO and TG auto-antibodies in mean age group of 35.76 ± 12.42 years of both the genders. The TPO seropositivity was reported higher in G allele containing genotypes GG and AG (66.66% and 58%, respectively) compared to AA (44.8%) genotype. Whereas, TG auto-antibodies showed highest seropositivity for genotype AA (55.17%) compared to AG (36%) and GG (16.6%). Higher median titre values were observed for TPO antibodies with GG genotype (1587.461 U/mL). In contrast to this, higher titres of auto-antibodies to TG were observed for individuals with AA genotype (520.746 U/mL). In conclusion, this study demonstrates a relationship between CTLA4 (+49A/G) genotype and seropositivity to thyroid auto antigens TPO and TG in Indian patients with clinical manifestation of Hashimoto's thyroiditis and Graves' disease, two different forms of AITD.

Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism.

Background:B12 (cobalamin) deficiency has been reported in hypothyroid patients with variable prevalence rates thus routine screening of hypothyroid patients was recommended by some and discouraged by others. We aimed to assess the prevalence of B12 deficiency among hypothyroid patients and to evaluate for pernicious anemia and celiac disease as etiologies.Methods:A total 133 patients were included. Thyroid hormones and thyroid peroxidase (TPO) autoantibodies were measured. Serum B12 was measured and if deficient, intrinsic factor antibodies (IFAB) and tissue transglutaminase (tTG) antibodies were evaluated.Results:Our study included 45 patients with overt hypothyroidism (OH), 48 patients with subclinical hypothyroidism (SCH), and 40 patients as controls. Mean age was 34.3 years and 82% were females. TPO antibodies were positive in 73.5% of OH and 51.1% of SCH patients. B12 deficiency was detected in 33.3%, 47.9%, and 37.5% of OH, SCH, and controls, respectively with no significant difference (P = .334). Borderline-to-low B12 level was more prevalent in the OH and the SCH groups compared to controls (68.9%, 85.4%, and 57.5%, respectively; P = .014). Among B12-deficient hypothyroid patients, 7.5% had positive IFAB and 13.3% had positive tTG antibodies. We did not find a significant association of TPO positivity and B12 deficiency (OR, 0.69; 95% CI 0.3-1.57; P = .147).Conclusion:We did not find a higher prevalence of B12 deficiency among hypothyroid patients nor an association with TPO positivity. Borderline B12 levels were more prevalent among hypothyroid patients.