Effect of anti-thyroid antibodies on recurrent miscarriage: A meta-analysis.

SETTING: Previous studies addressed the association between anti-thyroid antibodies and recurrent miscarriage (RM), however, the role of anti-thyroid antibodies in RM patients is debatable. OBJECTIVES: Therefore, we conducted this meta-analysis and the aim of this current study was to assess whether anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-TG) antibody positivity was associated with RM. DESIGN: A meta-analysis was conducted. PARTICIPANTS: Recurrent miscarriage patients. METHODS: STATA 12.0 software were applied to compute odds ratios (ORs)/relative risks (RRs) and 95% CIs regarding association between anti-TPO and anti-TG antibodies and the prevalence of RM. RESULTS: N = 28 studies (8875 participants) explored effect of anti-thyroid antibodies on RM. Analysis of the 28 studies revealed significant association between anti-TPO, anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.02; 95% CI: 1.63-2.51, p < 0.001; I2 = 44.3%, p value for Q test = 0.004). Analysis of the 20 studies revealed significant association between anti-TPO antibodies and the prevalence of RM with a random effects model (OR/RR = 1.59; 95% CI: 1.25-2.03, p < 0.001; I2 = 43.1%, p value for Q test = 0.022). Analysis of the 14 studies revealed significant association between anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.25; 95% CI: 1.56-3.23, p < 0.001; I2 = 49.2%, p value for Q test = 0.019). CONCLUSIONS: Based on the currently available analysis, our findings suggest that women with anti-TPO and/or anti-TG antibodies have a higher risk of RM than that in negative antibody women. Further investigation is needed to better clarify the exact role of the anti-thyroid antibodies in RM and whether treatment is of benefit. LIMITATIONS: First, differences from various detection methods and reagents used in different studies may affect the diagnostic interpretation of anti-thyroid antibodies, which might influence the accuracy of this meta-analysis. Second, positive anti-thyroid antibodies seem likely to be part of a more general disorder of maternal immune system, due to restrictions of funding and condition, a complete autoantibody screening investigation is hardly to conduct in all participants, and this could be a possible limitation of all included studies. Third, there is no mention of thyroxine therapy on RM, making the meta-analysis even more limited.

Vitamin D and the Thyroid: A Critical Review of the Current Evidence.

Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a risk factor for the development of many thyroid disorders, including autoimmune thyroid diseases and thyroid cancer. However, the interaction between vitamin D and thyroid function is still not fully understood. This review discusses studies involving human subjects that (1) compared vitamin D status (primarily determined by serum calcidiol (25-hydroxyvitamin D [25(OH)D]) levels) with thyroid function assessed by thyroid stimulating hormone (TSH), thyroid hormones, and anti-thyroid antibody levels; and (2) evaluated the effect of vitamin D supplementation on thyroid function. Due to the many inconsistencies in the results between the studies, it is still difficult to draw a definite conclusion on how vitamin D status affects thyroid function. Studies in healthy participants observed either a negative correlation or no association between TSH and 25(OH)D levels, while the results for thyroid hormones showed high variability. Many studies have observed a negative association between anti-thyroid antibodies and 25(OH)D levels, but equally many studies have failed to observe such an association. Regarding the studies that examined the effect of vitamin D supplementation on thyroid function, almost all observed a decrease in anti-thyroid antibody levels after vitamin D supplementation. Factors that could contribute to the high variability between the studies are the use of different assays for the measurement of serum 25(OH)D levels and the confounding effects of sex, age, body-mass index, dietary habits, smoking, and the time of year when the samples were collected. In conclusion, additional studies with larger numbers of participants are needed to fully understand the effect of vitamin D on thyroid function.

The detection of up-regulated anti-thyroid antibodies and autoimmune thyroid diseases in patients with autoimmune encephalitis: a retrospective study of 221 patients.

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy.

PURPOSE: Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy. METHODS: This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. RESULTS: Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). CONCLUSIONS: Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.

Higher baseline TSH levels predict early hypothyroidism during cancer immunotherapy.

BACKGROUND AND PURPOSE: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that enhance the immune response against cancer cells. ICIs are generally well tolerated, although endocrine immune-related adverse events (irAEs) are common. We investigated the risk factors for thyroid irAEs in patients treated with ICIs. Moreover, we evaluated the clinical outcome of subjects who became hypothyroid compared to euthyroid patients. PATIENTS AND METHODS: We retrospectively analyzed a series of 195 consecutively subjects treated with ICIs for metastatic tumors at the University of Naples "Federico II" between January 2014 and March 2020. Only subjects tested for thyroid function before and during the treatment with ICIs were included. RESULTS: In the 96 patients treated with ICIs who were included [66 males, median age: 62 years (27-87)], thyroid irAEs occurred in 36 (37.5%), 16 (16.7%) a transient thyrotoxicosis, and 20 (20.8%) an hypothyroidism (in nine subjects hypothyroidism was preceded by a transient thyrotoxicosis). Only baseline TSH levels above 1.67 mIU/L and positive anti-thyroid antibodies (Ab-T) were associated with a higher risk of hypothyroidism. Patients with hypothyroidism during ICI treatment showed an improved 2-year PFS (HR = 0.82 CI 0.47-1.43; p = 0.0132) and OS (HR = 0.38 CI 95% 0.17-0.80; p = 0.011) compared to euthyroid patients. CONCLUSIONS: Baseline TSH levels above 1.67 mIU/L and presence of Ab-T are risk factors for the development of thyroid irAEs. Patients affected by thyroid irAEs showed a longer survival than patients who remained euthyroid.

Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal.

PURPOSE: Primary ovarian insufficiency (POI) represents ovarian dysfunction related to very early aging of the ovaries. While the cause of POI in a majority of clinical cases remains undefined, autoimmunity is responsible for approximately 4-30% of POI cases. In the present paper, we aim to provide a critical appraisal and update review on the role of autoimmunity in POI patients. METHODS: A literature review was conducted for all relevant articles reporting on POI and autoimmunity. PubMed/MEDLINE and the Cochrane library were searched for the best available evidence on this topic. RESULTS: Patients with POI and coexisting autoimmunity are indistinguishable from those with negative autoimmune screen with regard to age of onset, prevalence of primary amenorrhea, or their endocrine profiles. A specific noninvasive reliable diagnostic test for the diagnosis of an autoimmune etiology is lacking; therefore, patients should be screened for the most common autoantibodies, i.e., steroid cell antibodies, anti-ovarian antibodies, and anti-thyroid antibodies. Moreover, treatment strategies to POI infertility are lacking and controversial. CONCLUSIONS: Nowadays, guidelines for the treatment of autoimmune POI are not available. Moreover, since diagnostic and treatment strategies to POI infertility are still lacking and controversial, further large clinical studies are needed to investigate the true impact of autoimmunity on POI and to identify the selected groups of patients who are most likely to benefit from immunossuprresive treatment.

[Relationship of the ovarian reserve with autoimmune thyroid diseases in the reproductive period].

AIM: To compare ovarian reserve in healthy women of reproductive age - carriers of antithyroid antibodies (ATA) and in healthy women of reproductive age negative for ATA. MATERIALS AND METHODS: 70 healthy women of young reproductive age in the state of euthyroidism (from 18 to 38 years old) were examined. Participants were divided into equal groups (n=35) depending on the status of the presence of antithyroid antibodies (AT-TPO, AT-TG). On the 2nd-4th days of the menstrual cycle, the following markers of the ovarian reserve were determined: serum levels of anti-Müllerian hormone (AMG), inhibin B, FSH, LH, estradiol, testosterone and progesterone, as well as ultrasound parameters - the number of antral follicles and the volume of the ovaries. In addition, to determine the predisposition to premature ovarian failure, an analysis was performed to the number of CGG repeats in the FMR1 gene. RESULTS AND DISCUSSION: Statistically significantly differs such parameters as the level of estradiol and testosterone, while the differences were not clinically significant. All the parameters evaluated were within the normal range, the main predictors of the ovarian reserve (levels of AMG and inhibin B, the number of antral follicles) remained in the normal range. An increase in the number of repeats of CGG in the FMR1 gene was not detected in any of the participants in the study. CONCLUSION: In healthy young reproductive age women, the status of ATA does not have a direct effect on the ovarian reserve.

The impact of autoimmunity-related early ovarian aging on ICSI cycle outcome.

The aim of this study was to investigate the impact of anti-thyroid peroxidase antibodies (Anti-TPO) on the in vitro fertilization and embryo transfer (IVF-ET) outcome in women with poor ovarian reserve but normal thyrotropin levels. A total of 300 patients with poor ovarian reserve undergoing ICSI cycle from April 2015 to December 2017 were analyzed retrospectively. Subjects were divided into two groups: Group 1: Women with early ovarian aging, Group 2: Women with age related poor ovarian reserve. All subjects underwent anti-thyroid peroxidase antibody (anti-TPO) analysis. The impacts of age and anti-TPO positivity on cycle outcome were assessed. There were no significant differences in basal FSH, basal AMH levels, and antral follicle count between the two main groups. Groups were also comparable in terms of the duration of ovarian stimulation, peak estradiol level, starting gonadotropin dose, total gonadotropin dose, and number of oocytes retrieved. Clinical pregnancy and cycle cancelation rates were significantly higher in group with age-related poor ovarian reserve. While autoimmune thyroid disease rate was significantly higher in group with early ovarian aging. Anti-TPO positivity was a risk factor for poor cycle outcome [RR: 2.8 (95% CI: 1.2-6.3)]. Early ovarian aging may be associated with poorer cycle outcome compared to group with age-related poor ovarian reserve. This difference may be associated with high rate of autoimmunity which led to the impaired endometrial receptivity.

Women with Subclinical Hypothyroidism Are at Low Risk of Poor Pregnancy Outcome in Japan.

Maternal subclinical hypothyroidism may be associated with adverse pregnancy outcomes, although not consistently across regions. Here, we sought to determine the effect of elevated thyroid-stimulating hormone (TSH) on pregnancy outcomes in Japanese women without known medical complications. TSH was determined by dried blood spots at 8-20 weeks of gestation, and 3.0-10.0 µU/mL of TSH was considered as elevated TSH (eTSH). A retrospective study involving 167 cases of eTSH was conducted. Five hundred and seventy eight of controls with normal TSH and without thyroid antibodies were selected. We compared a composite adverse maternal outcome comprised of spontaneous abortion, premature delivery, gestational diabetes mellitus (GDM), placental abruption, and pregnancy-induced hypertension, as well as composite adverse neonatal outcome including stillbirths, heavy for date, light for date, and a low Apgar score (< 7) at 5 minutes between two groups. The incidence of GDM was significantly higher in eTSH (p < 0.01); however, composite adverse maternal and neonatal outcome did not differ between groups (p = 0.19 and p = 0.50, respectively). Although 27 out of 167 cases in eTSH have antibodies, composite adverse outcome did not differ between eTSH with antibodies and controls (p = 0.64 and p = 0.50, respectively). Additionally, composite adverse maternal and neonatal outcome did not differ between the group larger than the median of TSH in eTSH (n = 81) and controls (p = 0.43 and p = 0.98, respectively). Thus, elevated TSH is not associated with overall adverse pregnancy outcomes in women without known medical complications.

A cross-sectional study of thyroid function in 66 patients with bipolar disorder receiving lithium for 10-44 years.

OBJECTIVES: An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross-sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years. METHODS: The study was performed in 66 patients (21 males, 45 females) with bipolar mood disorder, receiving lithium for 10-44 (21 ± 9; mean ± standard deviation) years. Thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) were measured by the microparticle enzyme immunoassay. Thyroid peroxidase (TPO) antibodies, thyroglobulin (TG) antibodies, and TSH receptor (TSH-R) antibodies were measured by the radioimmunoassay. RESULTS: Some features of hypothyroidism were found in ten (22%) female patients (seven received levothyroxine and three had increased TSH). No abnormality in thyroid hormones was found in male patients. A significant percentage of patients had abnormally high levels of anti-TPO, and anti-TG antibodies, which correlated with TSH and fT3 concentrations. There were no differences in thyroid function between patients receiving lithium for 10-20 years and those taking the drug for more than 20 years. CONCLUSIONS: These results confirm the greater susceptibility of female subjects for disturbances of thyroid hormones during lithium therapy, with one-fifth of them showing some features of hypothyroidism. Abnormally high levels of anti-TPO and anti-TG antibodies were shown in a significant proportion of patients. However, in contrast to the effect of lithium on kidney function, our results do not show an association between the duration of lithium therapy and thyroid dysfunction.

The impact of the presence of antithyroid antibodies on pregnancy outcome following intracytoplasmatic sperm injection-ICSI and embryo transfer in women with normal thyreotropine levels.

PURPOSE: The aim of our study was to investigate the impact of anti-thyroid peroxidase antibodies (Anti-TPO) on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET) in general groups and in subgroups divided according to AMH level and age. METHODS: A total of 114 patients positive for anti-thyroid peroxidase antibodies (Anti-TPO+ group) and 495 infertile women negative for anti-thyroid peroxidase antibodies (Anti-TPO- group) undergoing IVF with ICSI from April 2010 to April 2012 were analyzed retrospectively. RESULTS: There were no significant differences in age, BMI, basal FSH, LH, AMH levels and duration of infertility between the two main groups. No significant differences in terms of the days of ovarian stimulation, estradiol level in day 8, total gonadotropin dose, number of oocytes retrieved, available embryos and blastocysts, number of embryos transferred nor in rates of fertilization, implantation, clinical pregnancy, live birth and abortion rate between two main groups were found. The only statistically significant difference among the groups with different anti-TPO antibodies levels was found in basal FSH concentration and BMI. Among the clinical outcomes of IVF with respect to the different anti-TPO levels, the only significant difference was found for the number of oocytes retrieved. Analysis of the baseline parameters in relationship to age categories and AMH levels found significant differences between women positive and negative for thyroid antibodies with respect to basal FSH and LH levels for women >37 years and for basal FSH in AMH <0.6 subgroup. CONCLUSIONS: The present study reveals that patients with anti-TPO antibodies showed no significant differences in fertilization, implantation, pregnancy rates, live birth rates and no higher risk for miscarriage following IVF-ET when compared with those negative for anti-thyroid antibodies.

Immune-related thyroid dysfunction in patients with non-small cell lung cancer.

Background: Immune-related thyroid dysfunction (irTD) is a common immune-related adverse event (irAE). The potential biomarkers of irTDs and their impact on the clinical outcomes of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) remain unclear. We aimed to identify potential biomarkers of irTDs and reveal the association between irTDs and the clinical outcomes in patients with NSCLC treated with ICIs. Methods: We conducted a retrospective study on 126 patients with NSCLC, who were treated with pembrolizumab, sintilimab, atezolizumab, or camrelizumab, as first-line therapy, at the First Affiliated Hospital, College of Medicine, Zhejiang University, between July 2019 and February 2023. Anti-thyroid antibodies (ATAs), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), serum interleukin-6 (IL-6), thyroid ultrasonography, overall survival (OS), and progression-free survival (PFS) were the main indicators. Results: Most (92.9%) irTD cases occurred no later than one year after ICIs initiation. Patients with irTDs had higher positive rates for ATAs and TPOAb [33.3% vs. 1.3%, and 30.3% vs. 1.3%, both P<0.01, odds ratio (OR) =39.81, and OR =35.46, respectively]. Irregular echo pattern and diffuse changes were more common in patients with irTDs (70.7% vs. 47.2%, and 19.5% vs. 1.4%, P<0.05 and P<0.01, OR =2.70, and OR =17.21, respectively). OS and PFS were similar in patients with and without irTDs (P>0.05). Conclusions: The ATAs, TPOAb, and abnormal thyroid ultrasonographic findings (irregular echo patterns and diffuse changes) are potential biomarkers of irTDs. Patients with NSCLC treated with ICIs (pembrolizumab, sintilimab, atezolizumab, and camrelizumab) who developed irTDs had no advantage in terms of clinical outcomes compared to euthyroid patients.

Long-term exposure to organochlorine pesticides and thyroid status in adults in a heavily contaminated area in Brazil.

Organochlorine (OC) pesticides are endocrine disruptors altering the thyroid hormonal system. The aim of this study is to investigate the relationship between exposure to OC pesticides and thyroid status in adults from a rural area in Rio de Janeiro, Brazil, heavily contaminated with OC pesticides. A cross-sectional study was carried out in 303 men and 305 women >14 years old. Concentrations of 19 OC pesticides and levels of free thyroxine (T4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH), anti-thyroperoxidase (TPOAb) and anti-thyroglobulin (TgAg) antibodies were analyzed in serum samples. Associations between OC pesticides concentrations and values of biochemical thyroid parameters were determined using multivariate regression models stratified by gender. Prevalence of subclinical hyperthyroidism and the presence of TPOAb antibodies were higher than those described for euthyroid populations elsewhere. After adjusting for confounders, total T3 levels were associated with lower concentrations of endosulphan 2 in men and with higher alpha-chlordane, p,p'-dichlorodiphenyltrichloroethane (DDT), endosulphan 2, and methoxychlor in women. Levels of free T4 showed inverse association with beta-hexachlorocyclohexane (HCH) and p,p'-DDT in men, and were positively associated with hexachlorobenzene (HCB), heptachlor, o,p'-DDT, and p,p'-DDT in women. TSH levels were associated with higher beta-HCH in men. A positive association was observed between exposure methoxychlor in males and presence of TPOAb, but no association with TPOAb was found in women. These results suggest that OC pesticides can affect the thyroid system through gender-specific mechanisms that may differ among compounds. Further detailed investigations and health monitoring should be warranted for this population.

Impact of Vitamin D on Immunopathology of Hashimoto's Thyroiditis: From Theory to Practice.

Hashimoto's thyroiditis (HT) is a common autoimmune disease affecting the thyroid gland, characterized by lymphocytic infiltration, damage to thyroid cells, and hypothyroidism, and often requires lifetime treatment with levothyroxine. The disease has a complex etiology, with genetic and environmental factors contributing to its development. Vitamin D deficiency has been linked to a higher prevalence of thyroid autoimmunity in certain populations, including children, adolescents, and obese individuals. Moreover, vitamin D supplementation has shown promise in reducing antithyroid antibody levels, improving thyroid function, and improving other markers of autoimmunity, such as cytokines, e.g., IP10, TNF-α, and IL-10, and the ratio of T-cell subsets, such as Th17 and Tr1. Studies suggest that by impacting various immunological mechanisms, vitamin D may help control autoimmunity and improve thyroid function and, potentially, clinical outcomes of HT patients. The article discusses the potential impact of vitamin D on various immune pathways in HT. Overall, current evidence supports the potential role of vitamin D in the prevention and management of HT, although further studies are needed to fully understand its mechanisms of action and potential therapeutic benefits.

Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.

Background: Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. Methods: We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Results: At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). Conclusion: In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

Celiac And Autoimmune Thyroid Disease In Patients With Anti-Gad Positive Type-1 Diabetes Mellitus.

BACKGROUND: Type-1 diabetes mellitus (T1DM) and autoimmune thyroid disease can occur concomitantly and patients with TIDM have a high risk of other autoimmune conditions like thyroid disease and celiac disease. This study aimed to analyze the association of anti-GAD positive T1DM with anti-thyroid antibodies and celiac disease. METHODS: This cross-sectional study was conducted at the Department of Paediatric Endocrinology & Diabetes, National Institute of Child Health, Karachi Pakistan from July 2022 to December 2022. A total of 115 children of both genders aged between 1-18 years having known T1DM were analyzed. Children with chronic kidney disease or chronic liver disease were excluded. Those children were also not included whose parents/caregivers did not wish their children to be part of this research. The blood sample of each child was taken in a sterilized container and sent to an institutional laboratory for biochemical investigations. RESULTS: In a total of 115 patients, 67 (58.3%) were female and 48 (41.7%) males. The mean age was 8.87±3.43 (ranging between 1.5-17 years). The mean HbA1c was 11.86±7.31%. It was found that anti-GAD IgG was having signification association with celiac disease (p<0.001). Significant correlation of anti-GAD positive antibodies with Ttg-IgG antibodies (correlation coefficient=0.303, p=0.001), thyroid peroxidase antibodies (correlation coefficient=0.228, p=0.001). CONCLUSIONS: High proportions of children with anti-GAD positive T1DM patients were found to have thyroid disorders and celiac disease. A significant correlation was found between anti-GAD positive antibodies, celiac disease and anti-thyroglobulin antibodies.

Autoimmune Polyglandular Syndrome with Refractory Gait Disturbance.

Autoimmune polyglandular syndrome (APS) causes autoimmune diseases of multiple organs and can also present with neurological symptoms. We here report a 58-year-old man who presented with progressive gait disturbance that had started 7 years ago. He had spasticity, reduced deep sensations, and truncal cerebellar ataxia. Laboratory examinations revealed autoantibody-related cobalamin deficiency and the presence of anti-thyroid antibodies and anti-glutamic acid decarboxylase antibodies. His gait worsened after cobalamin replenishment, but additional steroid therapy was effective. APS can cause refractory gait disturbance that requires not only cobalamin replenishment but also immunotherapy.

[Is thyroid autoimmunity associated with subclinical atherosclerosis in young women with type 1 diabetes mellitus?]

INTRODUCTION: It has been hypothesized that autoimmunity may contribute to cardiovascular complications and may be an important trigger for processes leading to atherosclerosis, especially in type 1 diabetes mellitus (T1DM). This pilot study aimed to answer the question of whether markers of thyroid autoimmunity are associated with increased carotid intima-media thickness (cIMT) in young, asymptomatic T1DM women. MATERIAL AND METHODS: The study population consisted of 102 women, including 72 with T1DM and 30 healthy controls. All patients had thyroid hormones within the normal range. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO-positive (T1DM aTPO+) (n = 41) and an aTPO-negative (T1DM aTPO-) (n = 31) group. In all patients, aTPO, thyroglobulin antibody (aTG) titres, thyroid-stimulating hormone (TSH), free thyroxine (FT3), free triiodothyronine (FT4), lipid parameters, glycated haemoglobin, thyroid ultrasonography, and cIMT assessment were evaluated. The association of cIMT with different risk factors related to thyroid autoimmunity was determined. RESULTS: Carotid intima-media thickness was significantly greater in T1DM aTPO+ females (0.66 ± 0.10 mm) than in T1DM aTPO- (0.59 ± 0.11 mm) and healthy controls (0.58 ± 0.10 mm) (p = 0.007, p = 0.001, respectively). In all women cIMT was significantly, positively correlated with aTPO (p = 0.005, r = 0.273), Hashimoto's thyroiditis (HT) duration (p = 0.00015, r = 0.367), levothyroxine dose per week (p = 0.006, r = 0.269), and ultrasound features of HT (p = 0.004, r = 0.281) and inversely with fT3 concentration (p = 0.014, r = -0.243) and FT3/FT4 ratio (p = 0.042, r = -0.201). A logistic regression analysis showed that HT duration (OR: 1.102, 95% CI: 1.008-1.206, p = 0.032) and a positive history family of HT (OR: 3.909, 95%CI: 1.014-15.071, p = 0.045) were risk factors for increased cIMT. However, multivariate regression analysis showed that the studied parameters related to thyroid autoimmunity are not independent risk factors for increased cIMT. CONCLUSIONS: We expanded the data on cIMT in young women with T1DM and showed that thyroid autoimmunity, and in particular the duration of exposure to anti-thyroid antibodies, despite adequate levothyroxine substitution, is associated with subclinical atherosclerosis in young women with T1DM. However, thyroid-related parameters are not independent risk factors for increased cIMT in euthyroid women.