Search Results (8)

Background/Objectives: We aimed to explore long-term trajectories of thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves’ disease (GD) and to identify key factors associated with TRAb normalization. We also investigated whether these trajectories correlate with Graves’ orbitopathy (GO) comorbidity. Methods: We retrospectively reviewed 403 patients with GD who had an initial TRAb level ≥ 1.5 IU/L between 2010 and 2021, monitoring their TRAb levels for at least 3 years. K-means clustering was performed to categorize patients into distinct TRAb change patterns (A, B, C, D). We employed a Cox regression–based time-to-event model, expressing results as “Survival ratio” rather than the conventional Hazard ratio, to reflect the proportion of patients achieving TRAb normalization over time. Key variables included age, sex, initial TRAb, and GO comorbidity. Results: Four unique TRAb patterns emerged, differing primarily in baseline TRAb levels, duration of GD, and treatment approaches. Pattern A demonstrated the highest TRAb normalization rate (96%), whereas Patterns B (80%), C (29%), and D (13%) showed lower probabilities. Regrouping into A vs. BCD further emphasized the distinct normalization profile of Pattern A. A higher “Survival ratio” was observed in female patients and those with baseline TRAb < 6.14 IU/L. In contrast, patients whose TRAb levels were ≥6.14 IU/L frequently exhibited persistently elevated values over a decade. GO comorbidity did not significantly differ among the four patterns. Conclusions: K-means clustering revealed four unique TRAb change patterns in GD, with baseline TRAb (stratified by the median of 6.14 IU/L) and sex emerging as significant predictors of normalization. These findings highlight the importance of early TRAb monitoring and tailored therapeutic strategies, particularly for those with persistently elevated TRAb levels. Full article

Fetal and neonatal thyrotoxicosis occurs in up to 5% of pregnancies in mothers with Graves’ disease (GD). This condition is caused by stimulating antibodies against the thyrotropin receptor (TRAbs) that cross the placenta and may stimulate the fetal thyroid, typically in the second half of pregnancy. GD is often treated with radioiodine, resulting in hypothyroidism in most patients, but TRAbs can persist for several years. Even if a pregnant mother is hypothyroid after radioiodine therapy or surgery, her TRAbs can still, although rarely, induce fetal hyperthyroidism. In this review, we first present two cases of neonatal hyperthyroidism in mothers with GD who became hypothyroid after prior radioiodine therapy, identified through a 10-year analysis of the National Perinatal System in Slovenia. Based on these cases, we provide an overview of existing data on this rare clinical condition in neonates. We also discuss the underlying mechanisms and clinical outcomes based on currently available data. In conclusion, our review highlights the importance of careful monitoring during pregnancy in all women with GD, even in those well managed after radioiodine therapy or surgery. 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

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto’s thyroiditis (HT) and hyperthyroidism (Graves–Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described. Full article

Thyroid dysfunction is associated with both vitamin D deficiency and iodine; however, it is unclear whether they interact. This study aimed to investigate whether and to what extent the interactions between vitamin D and iodine contribute to the risk of thyroid disorder. Participants (n = 4280) were chosen using multistage, stratified random sampling from Shanghai. Fasting blood was drawn for the 25(OH)D and thyroid parameter tests. Spot urine samples were gathered to test for urine iodine. To evaluate the interactive effects of vitamin D and iodine, crossover analysis was carried out. Pregnant women with a high urinary iodine concentration (UIC) and severe vitamin D deficiency had a significantly higher risk of thyrotropin receptor antibody (TrAb) positivity (odds ratio = 2.62, 95% confidence interval (CI): 1.32, 5.22) in the first trimester. Severe vitamin D deficiency and high UIC interacted positively for the risk of TrAb positivity (relative excess risk due to interaction = 1.910, 95%CI: 0.054, 3.766; attributable proportion = 0.700, 95%CI: 0.367, 1.03). Severe vitamin D deficiency combined with excess iodine could increase the risk of TrAb positivity in pregnant women in the first trimester. Full article

This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO. Full article

Epstein–Barr virus (EBV) mainly persists in B cells, which differentiate into antibody-producing cells, and thus, EBV has been implicated in autoimmune diseases. We aimed to describe the EBV reactivation and its relevance to autoimmune disease, focusing on Graves’ disease, which is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies. Circulating autoreactive B cells that have evaded from the selection have difficulties differentiating to produce antibodies. However, once EBV infects such B cells and reactivates, the B cells may become plasma cells and produce autoantibody. We herein proposed an EBV reactivation-induced Ig production system, which is a distinct pathway from the antibody production system through germinal centers and bone marrow and has the following characteristics: 1. IgM dominance, 2. ubiquitous Ig production, and 3. the rescue of autoreactive B cells, which skews Ig production toward autoantigens. IgM autoantibodies induced by EBV reactivation may activate the classical complement pathway and injure healthy tissue, which supply autoantigens for the production of affinity-matured IgG autoantibodies. Antibodies induced by EBV reactivation may play important roles in the development and exacerbation of autoimmune diseases. Full article

Background and Objective. Current treatment options of Graves’ disease (GD) are often unsatisfactory. This study aimed at determining the independent baseline predictors of medical treatment failure in GD.
Material and Methods. A retrospective study of 194 patients with GD was carried out. According to the disease outcome, patients were divided into groups. The remission group included the patients who achieved long-term remission after initial antithyroid drug (ATD) treatment with no relapse (group 1) or after 2 or 3 courses of ATD therapy (group 2). The treatment failure group included the patients who underwent thyroid ablation due to relapse (group 3) or without ATD withdrawal (group 4).
Results. A family history of thyroid disorders was associated with greater odds of failure (P=0.046). Higher thyrotropin receptor antibodies (TRAb) levels and a larger goiter size (grade 2/ grade 3) at the onset of the disease were both independently associated with a greater likelihood of failure. The initial TRAb concentration of 30.2 U/L and the TRAb concentration of 12.97 U/L at the end of ATD therapy were found to be the best cutoff values predicting the treatment failure. A hypoechogenic thyroid after ATD therapy, but not before therapy, increased the likelihood of failure by nearly 7.5 times (P<0.001).
Conclusions. Higher TRAb levels and a larger goiter size at the onset of the disease were found to be the independent predictors of medical treatment failure in GD. Full article