Search Results (50)

Background/Objectives: Hashimoto’s thyroiditis (HT) is the most common cause of hypothyroidism during childhood and adolescence. Children and adolescents with HT have an increased susceptibility to the development of thyroid nodules and thyroid cancer. Among the genetic causes of thyroid cancer, the 677C>T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is also reported. This study investigated for the first time the association between the 677C>T polymorphism (rs1801133) of the MTHFR gene and HT in children and adolescents. Methods: This case–control study included 130 children and adolescents with HT and 130 healthy controls. The 677C>T polymorphism of the MTHFR gene was studied in all participants with Restriction Fragment Length Polymorphism (RFLP) methodology for genetic variance analysis. Results: Children and adolescents with HT presented approximately 2.5 times more frequently the T allele sequences (CT and TT variants) and the T alleles in total for the 677C>T polymorphism of the MTHFR gene compared to the healthy population (OR: 2.56, CI: 1.53–4.21 and OR: 2.57, CI: 1.59–4.16, respectively). Children and adolescents with HT and T allele sequences (CT and TT variants) exhibited abnormal thyroglobulin antibodies (anti-TG) two times more frequently compared to those with the wild-type (CC) sequence in the same population (OR: 2.13, CI: 1.04–4.389). Conclusions: Children and adolescents with HT showed an increased frequency of T allele sequences (CT and TT variants) and total T alleles of the 677C>T polymorphism of the MTHFR gene compared to the healthy population. Full article

Objectives: The aim of this study was to find correlations between vitamin D deficiency and thyroid autoimmune pathology in a group of patients from Dobrogea, a non-endemic geographical area, with a high degree of sunshine. An important factor in maintaining immunological balance is the intake of an adequate level of vitamin D. Multiple studies have suggested that vitamin D deficiency is associated with a higher incidence of autoimmune diseases. Recent studies have analyzed the possible effect of this factor in promoting autoimmunity, as the serum level of BAFF often increases among patients with systemic autoimmune diseases. Methods: This study included 80 patients with autoimmune thyroid pathology from the Dobrogea area. The entire study group (n = 80) was divided according to the established diagnosis into two study groups: Group 1 included 62 patients with CAT (chronic autoimmune thyroiditis), and Group 2 included 18 patients with GD (Graves’ disease). Results: Vitamin D study average values of 25-OH-vitamin D found statistically significant differences between vitamin D values in the two groups (p = 0.018). Determination of BAFF (B-cell-activating factor) serum levels among patients with CAT and GD obtained a lower mean value of BAFF for the CAT group compared with the GD group. The evolution of BAFF serum level related to the serum levels of the antithyroid antibodies ATPO (antithyroidperoxidase) and ATG (antithyroglobulin) was also analyzed. In the patients with GD, BAFF was not correlated with the value of ATPO or ATG, but in the patients with CAT, a correlation was found between the value of BAFF and the level of ATG but not the ATPO level. Conclusions: This study analyzed BAFF serum levels in patients with CAT and GD. The results indicate that BAFF acts as a stimulatory factor of immunoglobulin production in autoimmune diseases. These results require clarifying the role and therapeutic benefits of supplementing vitamin D intake in patients with autoimmune diseases. Full article

Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disease influenced by genetic factors and environmental triggers that affect immune system function. Data suggest that vitamin D may also play a role in the etiopathogenesis of HT. Methods: This retrospective study included patients admitted to the Endocrinology and Metabolic Diseases Outpatient Clinic. Data from individuals aged 18 years and older were analyzed, including serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and vitamin D. HT was diagnosed based on the presence of anti-TPO and/or anti-TG antibodies, while individuals with negative results for both were classified as non-HT. Thyroid function was categorized as euthyroid if TSH levels were between 0.55 mU/L and 4.78 mU/L and fT4 levels were between 0.89 ng/dL and 1.76 ng/dL; hypothyroid status was defined as TSH > 4.78 mU/L. Vitamin D levels were classified as deficient (<50 nmol/L), insufficient (50–74.9 nmol/L), or sufficient (≥75 nmol/L). Results: Of the total participants, 25,018 did not have HT, while 27,800 were diagnosed with HT. Vitamin D level was significantly higher in the HT group than the non-HT group (41.43 nmol/L and 39.44 nmol/L, p < 0.001). Vitamin D deficiency was present in 65.5% of the non-HT group and 62.1% of the HT group (p < 0.001). Subgroup analyses based on thyroid function showed that vitamin D levels were highest in the euthyroid HT group and similar in the euthyroid non-HT, hypothyroid non-HT, and hypothyroid HT groups (p < 0.001). Conclusions: In conclusion, while vitamin D levels were higher in the HT group compared to the non-HT group, no clinically significant association between vitamin D levels and HT or autoantibody positivity was observed. Vitamin D deficiency was more prevalent in the hypothyroid group compared to the euthyroid group. This study suggests that although vitamin D deficiency may not be directly involved in the pathogenesis of HT, it may still play a role in modulating immune activity or influencing the disease phenotype.. Full article

Turner syndrome (TS) is a genetic disorder caused by abnormalities in one of the X chromosomes. Individuals with TS have a higher incidence of autoimmune thyroid disorders, particularly Hashimoto’s disease, leading to thyroid dysfunction, most commonly hypothyroidism. Hormonal imbalance, growth hormone deficiency, and reduced physical activity contribute to muscle weakness in TS patients, and thyroid dysfunction can exacerbate these effects. The purpose of this study was to evaluate whether thyroid factors affect muscle strength in female patients with TS. The study included 70 women with TS and 88 age- and weight-matched controls. TS diagnoses were genetically confirmed (mosaic karyotypes: n = 20; monosomy X: n = 37; structural abnormalities: n = 7). The main criterion for exclusion from the study was unbalanced thyroid function. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid antibodies (anti-thyroid peroxidase antibodies (aTPO), anti-thyroglobulin antibodies (aTG)) were measured, and muscle strength was assessed using hand-held dynamometry. In TS patients, higher TSH levels were positively correlated, and higher fT4 levels were negatively correlated with muscle strength. No such correlations were found in controls. Thyroid compensation may impact musculoskeletal health in TS. Lower-normal TSH levels are associated with reduced muscle strength, and autoimmune thyroid changes like aTPO and aTG may contribute to muscle deterioration. Further research is needed to confirm these findings. Full article

Background/Objectives: Structural incomplete response (SIR) (persistence/recurrence) may occur in 2–6% of low-risk differentiated thyroid cancer (DTC)-cases and in 67–75% of high risk. Regarding locoregional disease, surgery is the optimal therapeutic modality if the smallest dimension of the targeted node is ≥8 mm or ≥10 mm (central or lateral compartment). In the presence of smaller nodes, contraindications or the patient’s unwillingness for reoperation, active surveillance (AS) or minimally invasive treatments (MITs) may be considered. Methods: We retrospectively studied eight DTC patients with SIR confirmed by ultrasound (U/S)-guided fine-needle aspiration cytology (FNAC) and the measurement of Thyroglobulin (Tg) in the washout fluid. Fourteen malignant lesions were ablated by radiofrequency (RF). We assessed prior to RF ablation (RFA) and consecutively at one month, three months and, then, every three months the volume of each lesion, serum Tg and Anti-Tg antibodies and calculated the volume reduction ratio (VRR). Results: Patients were followed for a mean period of 13.25 months (range: 4–24) after RFA was performed. The targeted lesions reduced significantly from a median volume of 0.24 mL (range: 0.09–0.9) to 0.02 mL (range: 0–0.03) (p < 0.05), with a median VRR of 94.5% (range: 78–100%) and concomitant significant biochemical remission (decrease in serum Tg from a median of 1.05 ng/mL to 0.2 ng/mL, p < 0.05). In one patient with an aggressive radioiodine (RAI)-refractory histological variant, re-recurrence was documented, which was successfully re-ablated by RF. In two patients, Horner syndrome was diagnosed as an RFA complication, which was totally resolved within six months. Conclusions: RFA may be considered as an effective and safe MIT in selective DTC patients with SIR, especially in cases of smaller lesions. Additional prospective studies are needed, including aggressive DTC histological variants towards a tailored therapeutic approach. Full article

Background: Thyroglobulin (Tg) is the specific tumor marker for epithelial thyroid cancer. It holds significant value in the postoperative period, and somehow, the goal of surgery in papillary thyroid cancer (PTC) undergoing total thyroidectomy is to achieve undetectable levels of postoperative thyroglobulin (uTg). Methods: This is a retrospective single-center study in which first basal Tg values were evaluated post-surgery in PTC patients undergoing total thyroidectomy. Patients with elevated antithyroglobulin antibodies were excluded. The impact of various demographic, clinical, therapeutic, tumor-stage related, and histopathological variables on the achievement of undetectable thyroglobulin levels (uTg, <1 ng/mL) was studied. A descriptive and logistic regression-based bivariate and multivariate analysis was planned using STATA vs. 16.1. program. The significance level was stated at 0.05. Results: Basal athyroglobulinemia was obtained in 89.6% of 202 patients operated on between January 2015 and June 2023 in a single referral institution. Due to the limited number of cases with detectable Tg, multivariate analysis could not be performed. The main factors that favored its achievement on bivariate analysis were a smaller tumor size (p = 0.003), no need for extended resections due to local invasion beyond the thyroid gland (p = 0.003) or neck dissection (p = 0.039), absence of distant metastases (p = 0.000), and a lower MACIS score (p < 0.000). Conclusions: The achievement of uTg was closely related to factors related to tumor stage (tumor diameter, lymph node spread, and metastatic disease), and it was not influenced by differences in epidemiological data, clinic manifestations, preoperative diagnosis, multifocality, or the presence of aggressive cytological variants. Full article

Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia. Full article

Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25–41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy. Full article

Background: The increasing incidence of autoimmune diseases in type 1 diabetes mellitus (T1DM) patients highlights the influence of human leukocyte antigen (HLA) haplotypes on their development. This study aims to determine genetic predisposition to autoimmune diseases in T1DM patients, including thyroid disease and celiac diseases, and explore its correlation with vitamin D deficiency. Methods: A cross-sectional study involving thirty-six T1DM children was conducted. Typing was performed for the HLA A, B, C, DP, DR, and DQ loci. Regression analysis linked DR-DQ haplotypes to T1DM and the associated conditions. Results: The most frequent predisposing alleles and haplotypes were HLA-DR3 (70.27%), DQ2 (70.27%), DR3-DQ2 (70.27%), DQB1*02:01 (70.27%), A02 (54.05%), whereas the most prevalent protecting allele was DPB1*04:01 (52.63%). Positive correlations were observed between positive anti-thyroid peroxidase antibodies and the absence of protective alleles (DPB1*04:02, p = 0.036; DPB1*04:01, p = 0.002). Associations were found between the absence of DPB1*04:01 and anti-thyroglobulin antibodies (p = 0.03). HLA allele DPB1*03:01 was linked with vitamin D deficiency (p = 0.021). Positive anti-transglutaminase antibodies correlated with C03:03 (p = 0.026) and DRB1*04:01-DQA1*03-DQB1*03:01 (p < 0.0001) and the lack of DQA1*01:03-DQB1*06:03-DRB1*13:01 (p < 0.0001). Conclusions: The predisposing T1DM haplotypes were associated with the presence of anti-transglutaminase and anti-thyroid antibodies, indicating a genetic predisposition to autoimmune diseases. Full article

Background/Objectives: The interplay between thyroid function and kidney graft function following kidney transplantation remains incompletely understood. Thyroid disorders are more prevalent in kidney transplant recipients than in the general population and are associated with poorer outcomes. Methods: This prospective, single-center study was designed to estimate thyroid function (thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxine (FT4), as well as anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), and thyroid-stimulating immunoglobulin (TSI)) and its influence on kidney graft function among a cohort of 23 kidney transplant recipients during a follow-up period of 12 months. Results: Significantly increased levels of T4 and T3 were observed 12 months post-transplantation, with FT3 levels increasing significantly after 6 months. The prevalence of immeasurably low anti-Tg antibodies rose during follow-up. Initially, 8% of patients showed positive TSI, which turned negative for all after 6 months. A statistically significant correlation was found between the initial TSH and the estimated glomerular filtration rate (eGFR) value 6 months after transplantation (p = 0.023). The graft function was stable. Proteinuria was statistically significantly lower 12 months after transplantation. Conclusions: Identifying additional risk factors, understanding their impact on kidney graft function, and recognizing cardiovascular comorbidities could enhance patient care. Notably, this study marks the first prospective investigation into thyroid function after kidney transplantation in Croatia, contributing valuable insights to the global understanding of this complex interplay. Full article

Hashimoto’s thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods. Full article

Introduction: Vulvar lichen sclerosus (VLS), a chronic inflammatory skin disorder, often coexists with autoimmune thyroid disease (AITD). VLS presents with subtle symptoms including vulvar itching and discomfort. Clinically, a “Figure 8” pattern involving the labia minora, clitoral hood, and perianal region is often observed. It is prevalent both in pre-pubertal girls and women aged 40–60, and the link between VLS and AITD remains unclear, with proposed causes including autoimmune, hormonal or genetic factors, and environmental triggers. This study addresses the lack of research on the association in children, aiming to investigate the largest group of underage girls to date. Aim: This study aimed to investigate the coexistence of thyroid autoimmune diseases in girls diagnosed with vulvar lichen sclerosus (VLS) and to assess the presence of antibodies for specific thyroid autoimmune diseases. Materials and Methods: Our study was conducted from July 2020 to February 2021, involving a sample of 55 girls aged 2–18 years old, all free from systemic diseases. The study group comprised 20 girls previously diagnosed with vulvar lichen sclerosus (VLS), while the control group included 35 girls without VLS. Legal guardians completed questionnaires detailing the medical history of their children. Blood samples were collected from all participants and subjected to biochemical analysis. The presence of human IgG antibodies against thyroid peroxidase and IgG antibodies against thyroglobulin was assessed using the immunoenzymatic method with commercially available ELISA kits. Results: In the study group, common symptoms included itching, soreness, burning sensation, excoriation, and erythema or pallor of the skin and perineal mucosa. An evaluation of anti-thyroglobulin and anti-thyroid peroxidase antibodies revealed no statistical significance between the study and control groups (anti-TG p = 0.379, anti-TPO p = 0.96). Family history of autoimmune diseases showed no significant correlation with anti-thyroid antibodies in girls. Although no significant relation between VLS occurrence and antibody levels was found, it emphasizes the need for multidisciplinary medical care. Further research with larger patient groups is necessary. Full article

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto’s thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship. Full article

Background: Immune-checkpoint inhibitors (ICIs) are effective against various cancers; however, immune-related adverse events (irAEs) have been reported and the timing and risk factors are unknown. Therefore, we examined the incidence and timing of irAE occurrence. Methods: Patients who received ICIs at our hospital between 1 April 2016 and 31 March 2020 were enrolled. Patients were classified into an irAE group or non-irAE group. In addition, we examined the onset time and symptoms of irAEs for each ICI type. Results: A total of 80 patients received ICIs, of which 27 (33.8%) developed irAEs. The incidence of irAEs was 35.3% for nivolumab, 35.5% for pembrolizumab, and 28.6% for atezolizumab. The incidence of pneumonitis was 12.5%, 8.8% for dermatologic adverse events, and 6.3% for thyroid dysfunction. The earliest case of onset was after the 1st course, and the latest cases occurred after the 66th course. By the sixth course, 69% of the irAEs occurred. The positive rates for anti-thyroid peroxidase and anti-thyroglobulin antibodies were higher in the irAE group compared to the non-irAE group. Conclusions: Our findings suggest a high probability of irAEs occurring early in ICI treatment, with a diverse range of symptoms. This underscores the need for vigilant monitoring and tailored patient management during the initial courses of ICI therapy. Full article

Objective: Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. Methods: This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: “iron deficiency”, “thyroid function”, “thyroid disease”, “thyroid dysfunction”, and “hypothyroidism”. A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran’s Q testing and heterogeneity indices (I²) were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Results: Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: −0.24 mIU/L; 95% CI −0.41, −0.07; I² = 100%, p = 0.005), FT4 (MD: −1.18 pmol/L; 95% CI −1.43, −0.94; I² = 99%, p < 0.000001), and FT3 (MD: −0.22 pmol/L; 95% CI −0.32, −0.12; I² = 99%, p < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Conclusion: Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism. Full article