Thyroid-stimulating Antibodies Research Articles

Proangiogenic effect of thyrotropin receptor stimulating antibody in human umbilical vein endothelial cells.

This study aims to investigate the role of TRAb in the angiogenesis associated with Graves' disease (GD) and to elucidate its underlying mechanisms. Human thyroid follicular epithelial cells (Nthy-ori 3-1) and human umbilical vein endothelial cells (HUVECs) were treated with the monoclonal thyroid-stimulating antibody M22 and thyroid-stimulating hormone (TSH) at various concentrations. Cell viability, migration, and tube formation were evaluated using CCK-8, wound healing, and tube formation assays, respectively. Protein expressions of TSHR receptor (TSHR) and phosphorylated AKT (p-AKT) in M22-induced HUVECs were quantified via Western blotting. Proteomic analysis was employed to identify changes in protein expression profiles and relevant signaling pathways in GD specimens. Immunofluorescence assays were conducted to detect and localize the expressions of CD34 and PROX1 in GD specimens and normal thyroid tissues. M22 stimulated the proliferation of Nthy-ori 3-1 cells and HUVECs in a dose-dependent manner, while TSH exhibited an inverted U-shaped dose-response effect. M22 also dose-dependently promoted angiogenesis, and more effectively induced tube formation in HUVECs compared to TSH, although the difference was not statistically significant. A total of 16 proteins were significantly upregulated and 24 were downregulated in M22-induced HUVECs. Notably, PROX1, the most significantly upregulated protein, is closely associated with angiogenesis. Immunofluorescence confirmed that PROX1 was significantly more expressed in thyroid tissues from GD patients compared to normal tissues adjacent to papillary thyroid cancer (PTC), and it co-localized with CD34. TRAb enhances angiogenesis and upregulates PROX1 expression in HUVECs, suggesting a novel possible mechanism for goiter formation in GD.

The TSH Receptor Antibody Reactome Contributes to Retro-Orbital Inflammation.

The thyroid eye disease (TED) of Graves disease is associated with high titers of stimulating TSH receptor antibodies, retro-orbital inflammation, fibroblast release of cytokines and chemokines, and adipogenesis, which in turn leads to proptosis, muscle fibrosis, and dysfunction. Part of this scenario is the induction of fibroblast proliferation and autophagy secondary to synergism between the TSH receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). While TED is well associated with thyroid-stimulating antibodies to the TSHR, which is also well expressed on fibroblasts, in fact the TSHR reactome has a variety of TSHR antibodies with varying biological activity. Therefore, we have now evaluated the possible role of neutral TSHR antibodies (N-TSHR-mAbs), directed at the hinge region of the TSHR, which do not induce cell proliferation but are known to have effects on multiple proteins in thyroid cells including stress-related signaling molecules. We examined the consequences of an N-TSHR-mAb acting on TSHR-expressing fibroblasts and found marked cell stress, which initiated signaling pathways involving inflammasome activation. This response ended in widespread cell death by pyroptosis through activation of caspase 8 and gasdermin D. Hence, not only can stimulating TSHR autoantibodies influence TED inflammation but the N-TSHR antibodies, representing more of the reactome, may also exaggerate the retro-orbital inflammatory response seen in TED.

Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves' Hyperthyroidism with Potassium Iodide.

Graves' hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal 123I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves' disease (GD) with a large goiter (>40 g), 131I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

The efficacy and safety of intravenous tocilizumab to treat Graves' ophthalmopathy: A systematic review and single-arm meta-analysis.

This study aims to evaluate the efficacy and safety of intravenous tocilizumab (TCZ) in the treatment of Graves' ophthalmopathy (GO). A comprehensive search was conducted across the Web of Science, PubMed, Embase, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and https://ClinicalTrials.gov databases from inception to April 2024. Randomized controlled trials (RCTs) and cohort studies that utilized intravenous TCZ for treating GO were included. Twelve studies encompassing 219 patients with active, steroid-resistant GO were analyzed. The meta-analysis demonstrated significant improvements in Clinical Activity Score (CAS) response (effect size [ES] = 0.98, 95% confidence interval [CI]: 0.93-1.00), proptosis response (ES = 0.50, 95% CI: 0.27-0.73), and diplopia response (ES = 0.48, 95% CI: 0.24-0.74). The ES for adverse events was 0.27 (95% CI: 0.22-0.33), with only three severe cases necessitating treatment discontinuation, and a low reactivation rate (ES = 0.01, 95% CI: 0.00-0.04). TCZ treatment led to a mean CAS reduction of 4.60 points (95% CI: 3.88-5.32) across 10 studies, a mean proptosis reduction of 2.04 mm (95% CI: 1.42-2.65) across 7 studies, and a mean decrease in thyroid-stimulating hormone receptor antibodies (TRAb) levels of 10.62 IU (95% CI: 4.67-10.62) across 5 studies. This meta-analysis provides robust evidence supporting the efficacy and safety of intravenous TCZ in patients with GO who are resistant to glucocorticoid therapy. The results highlight TCZ's comparable efficacy to glucocorticoids and suggest that TCZ could significantly expand clinical management options for GO. In the future, more high-quality, large-scale RCTs are still needed to confirm these findings.

8806 A Case of Autoimmune Thyroid Switching

Abstract Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None. Autoimmune thyroid disease comprises both hyper- and hypothyroid states including Graves' disease and Hashimoto's thyroiditis, respectively. The predominant antibody activity, demonstrable by thyrotropin receptor antibody, predicts the clinical presentation and treatment; thyrotropin receptor antibodies may act as a stimulatory or inhibitory stimulus upon the thyroid gland recognized as thyroid stimulating antibody(TSAb) and thyroid blocking antibody(TBAb). Rarely patients may transition from a hyperthyroid to a hypothyroid state and vice versa if the predominant antibody activity shifts which may occur due to a variety of mechanisms and characteristics related to each individual patient and treatment course. A 29 year old female presented to establish care for autoimmune thyroiditis. She was diagnosed with Graves' disease at age 19 when pregnant and treated with propylthiouracil; she switched to methimazole for the next six years when her thyroid function normalized and therapy discontinued. Two years later she became concerned with weight gain and her thyroid function was reevaluated demonstrating hypothyroidism and she was treated with levothyroxine 25mcg daily until presentation. Further labwork revealed undetectable TSI, and TPO antibody elevated at 177 u/mL. She became clinically and biochemically euthyroid on levothyroxine 50mcg daily. Switching between hyper- and hypothyroid states is a rare occurrence among patients with may attributable factors. Both antithyroid drugs including methimazole as well as replacement therapy with levothyroxine may alter the antibody milieu and so the predominant ratio and activity among TSAb and TBAb thereby leading to a shift in clinical presentation and thyroid state. Pregnancy may lead to hemodilution contributing to lessening of autoimmune activity which may return following delivery leading typically to a shift from TSAb to TBAb. Uncontrolled hyper- and hypothyroidism may affect dendritic activity leading to altered presentation and increased immune reactivity. The unlikely occurrence of switching from a hyperthyroid to a hypothyroid state based upon autoimmunity as in this patient was likely affected these factors. Recognition of this potential transition and associated factors would lead to beneficial monitoring and possibly development of assays more attuned to this phenomenon with better capability in maintaining a euthyroid state and potentially predicting a transition. Presentation: 6/3/2024

5039 Chronic Painful Hashimoto's Thyroiditis

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

Assessment of CD40L and TSAB serum level in Graves disease patients.

The autoimmune disorder known as Graves' disease. The condition is due to the binding of thyroid-stimulating immunoglobulins to the thyrotropin receptor located on the thyroid gland. The result is an excess of thyroidal hormones. symptoms of hyperthyroidism, and the formation of diffuse goiter. This research intends to quantify the levels of CD40L, TSAB in people who suffer from Graves' disease. It also aims to determine the relationship between TSAB and the duration of the disease, as well as analyze the role of CD40L as a predictive marker for Graves' disease using medcalc Statistical Software version 16.4.3 and SAS (2018). In a case-control study, randomly selected 90 graves disease patients were included, the randomly selected patients were divided equally and matched into a case group who have graves disease and graves disease-free patients as a control group. For both groups whole blood sample was examined to compare for (TSAB), and (CD40L) levels determination by ELISA technique. The average serum levels of CD40L showed a highly significant correlation (P value < 0.01) among the groups examined for Graves' disease. The patient group consisted of 13males (28.89%) and 32females (71.11%). No significant correlation was identified between TSAB and the duration of the condition. Thyroid stimulating antibody (TSAb) test and ultrasonography of the thyroid gland are valuable diagnostic techniques for autoimmune Graves' disease (GD). CD40L could potentially serve as a predictive diagnostic marker for Graves' disease. However, there is no observed link between the duration of the disease and the concentration of TSAB.

Efficacy of Anti-Thyroid Medications in Patients with Graves’ Disease

IntroductionGraves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use.MethodWe conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study.ResultsThe study sample consisted of 189 patients, 72% of whom were female. The patients’ median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001.ConclusionThe remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

Clinical Significance of Thyroid Autoantibodies in Differential Diagnosis and Predicting the Course of Programmed Cell Death Protein-1 Inhibitor-Induced Thyroid Dysfunction

ObjectiveThyroid immune-related thyrotoxicosis is one of the most common adverse effects in patients treated with programmed cell death protein-1 (PD-1) inhibitors. We investigated the significance of levels of serum anti-thyroglobulin antibodies (TgAbs), anti-thyroid peroxidase antibodies (TPOAbs), and thyroid-stimulating hormone receptor antibodies (TRAbs) in the identification of anti-PD-1-induced thyroid thyrotoxicosis. MethodsWe divided 161 patients with thyroid dysfunction who received PD-1 inhibitors at our hospital between January 2022 and June 2024 into 3 groups: primary hypothyroidism group, primary hyperthyroidism group, and destructive thyroiditis group. The characteristics of the 3 groups were determined, and the positivity rates of serum TgAbs, TPOAbs, and TRAbs were assessed. An additional 42 patients diagnosed with Hashimoto’s thyroiditis were selected as the control group for PD-1 inhibition-induced destructive thyroiditis. Age, sex, and time of transition from thyrotoxicosis to hypothyroidism in the 2 groups were compared. ResultsIn the primary hypothyroidism group, only 1 case was TPOAbs-positive (1/1%). In the destructive thyroiditis group, the positivity rate for TPOAbs or TgAbs was 92.9%, and TPOAbs and TgAbs were negative in the primary hyperthyroidism group. TRAbs were undetectable in all 3 groups. There were statistically significant differences in age, sex, and time from thyrotoxicosis to hypothyroidism in the PD-1 induced destructive thyroiditis and Hashimoto’s thyroiditis groups. ConclusionsIn patients with thyrotoxicosis caused by PD-1 inhibitors, serum TgAb, and TPOAb levels can be used to distinguish between primary hyperthyroidism and destructive thyroiditis. This study provides insights into novel treatment targets and effective management strategies for PD-1-induced thyrotoxicosis.

Identification and functionalization of thyrotropin receptor antibodies with different antigenic epitopes.

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

Subcutaneous Injections of Triamcinolone Acetonide for Upper Eyelid Retraction and Swelling Associated with Thyroid Eye Disease: A Retrospective Case Series Study.

To evaluate the efficacy of subcutaneous injection of triamcinolone acetonide (SCTA) in treating upper eyelid retraction and swelling in patients with thyroid eye disease (TED). This case series included consecutive patients (aged 16-69 years, monitored from June 2012 to December 2015) with TED-related eyelid symptom and without an enlarged extraocular muscle on magnetic resonance imaging (MRI). SCTA (0.5 mL, 40 mg/mL) was administered to target the orbital fat around the levator palpebrae superioris (LPS) muscle. Patients who did not exhibit improvement after the first trial received an additional injection. Follow-up was conducted for 12 months with 3-month intervals. Eyelid retraction, eyelid swelling, and eyelid lag were evaluated at each follow-up visit. In total, 116 eyelids of 102 patients were analyzed. SCTA led to significant improvement in 93% of eyes (108/116), disappearance of eyelid symptoms (74%, 87%, and 73% in retraction, swelling, and lag, respectively), and improvement of scores (from 1.64 to 0.12, 1.32 to 0.26, and 1.72 to 0.30, respectively). Improvement in eyelid symptoms was observed in eight eyes; however, additional steroid therapy was required in these cases due to the emergence of other extraocular muscle inflammation. Additional injection was required in 39.8% of patients. The clinical activity score was lower in the single SCTA group than in the multiple SCTA group (1.5 vs 0.9; p < 0.01). However, the levels of thyroid-stimulating hormone receptor antibody and MRI findings were not significantly different between the two groups. No elevation in intraocular pressure was observed. Eight female patients experienced menstrual disorder. SCTA effectively reduced LPS muscle enlargement and fat tissue swelling in patients with TED. A single SCTA was sufficient in almost 60% of the patients; nevertheless, follow-up is necessary to detect early signs of orbital inflammation even in eyelid-symptom-improved patients.

Stability analysis of a mathematical model for methimazole dosing in graves' hyperthyroidism: A dynamic approach

This study explores a novel mathematical model for analyzing methimazole (MMI) therapy in patients with Graves' disease, a common autoimmune cause of hyperthyroidism. The model leverages a system of ordinary differential equations to capture the interplay between key factors: methimazole concentration, thyroid-stimulating hormone (TSH), free thyroxine (FT4) concentration, thyroid-stimulating hormone receptor antibody (TRAb) concentration, and functional thyroid gland size (V). Thirteen parameters account for the underlying physiological processes. Stability analysis were employedby Lyapunov stability theory and LaSalle's principle, to demonstrate the model's asymptotic stability. This implies the system converges towards a steady state under defined conditions. Additionally, a clinically relevant chart is constructed based on FT4 levels and treatment duration.For model validation, patient data is utilized within SimBiology simulations implemented in MATLAB. These simulations offer valuable insights into the dynamic response of hyperthyroidism to MMI treatment. This approach holds promise for future applications in optimizing treatment strategies and facilitating personalized medicine approaches.

Clinical Changes and Autoantibody Level Changes in Thyroid Eye Disease Patients after Intravenous High-dose Steroid therapy

Purpose: To evaluate the effects of intravenous steroid therapy on the clinical activity score (CAS), exophthalmos, margin-reflex distance 1 (MRD1), and autoantibody levels in patients with thyroid eye disease.Methods: In this retrospective observational study, we enrolled 83 patients diagnosed with thyroid eye disease treated with intravenous steroid therapy. We assessed exophthalmos, MRD1, CAS, thyroid-stimulating antibody (TSAb), and thyroid-stimulating hormone receptor antibody (TSHR Ab) levels at baseline, 6 and 12 weeks after initiating therapy, and 2 months after therapy termination. Additionally, baseline serum selenium levels were examined to determine their impact on treatment efficacy.Results: TSAb, TSHRAb, and CAS levels showed a continuous decline from 443.22 to 341.03 specimen-to-reference control ratio (SRR%), 22.18 to 7.91 IU/L, and 3.37 to 1.88, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), up to 2 months following therapy termination. Exophthalmos did not show significant changes at any assessed time point up to 2 months after therapy termination. MRD1 decreased until 12 weeks after therapy initiation but showed no significant change 2 months later. No correlation was found between baseline serum selenium levels and changes in exophthalmos, MRD1, TSAb, TSHR Ab, or CAS.Conclusions: Intravenous steroid therapy was effective in reducing TSAb, TSHR Ab, and CAS levels up to 2 months after therapy termination. However, it had limited positive impact on exophthalmos or eyelid retraction. Baseline selenium levels did not correlate with the changes in any of the examined parameters.

Graves-PCD: protocol for a randomised, dose-finding, adaptive trial of the plasma cell-depleting agent daratumumab in severe Graves’ disease

IntroductionSevere Graves’ disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating hormone receptor-stimulating antibodies (TRAb), which are secreted from plasma...

Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease

PurposeThis study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED).Study designRetrospective study.MethodsThe thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses.ResultsThe TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement.ConclusionsTSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED.

Severity Identification of Graves Orbitopathy via Random Forest Algorithm.

This study aims to establish a random forest model for detecting the severity of Graves Orbitopathy (GO) and identify significant classification factors. This is a hospital-based study of 199 patients with GO that were collected between December 2019 and February 2022. Clinical information was collected from medical records. The severity of GO can be categorized as mild, moderate-to-severe, and sight-threatening GO based on guidelines of the European Group on Graves' orbitopathy. A random forest model was constructed according to the risk factors of GO and the main ocular symptoms of patients to differentiate mild GO from severe GO and finally was compared with logistic regression analysis, Support Vector Machine (SVM), and Naive Bayes. A random forest model with 15 variables was constructed. Blurred vision, disease course, thyroid-stimulating hormone receptor antibodies, and age ranked high both in mini-decreased gini and mini decrease accuracy. The accuracy, positive predictive value, negative predictive value, and the F1 Score of the random forest model are 0.83, 0.82, 0.86, and 0.82, respectively. Compared to the three other models, our random forest model showed a more reliable performance based on AUC (0.85 vs. 0.83 vs. 0.80 vs. 0.76) and accuracy (0.83 vs. 0.78 vs. 0.77 vs. 0.70). In conclusion, this study shows the potential for applying a random forest model as a complementary tool to differentiate GO severity.

Impending thyroid storm caused by hydatidiform mole

Introduction: Thyroid storm is a rare but life-threatening endocrine emergency. It is an acute exaggerated clinical manifestation of thyrotoxic state. We report an impending thyroid storm caused by a hydatidiform mole in a 14-year-old girl. This paper intends to describe hyperthyroidism secondary to molar pregnancy highlighting the rare but essential evaluation of hyperthyroidism. Case: A 14-year-old girl was consulted by the obstetric division to evaluate and manage hydatidiform mole with suspected hyperthyroidism. She had frequent palpitations and tremors for 1 week ago. She also complained of nausea and vomiting 1 week before admission to the hospital. We found a Burch-Wartofsky score of 25, which was categorized as an impending thyroid storm. Laboratory results showed mild anemia, low thyroid stimulating hormone (TSH) levels, high free thyroxine (T4) levels, and markedly elevated beta-human chorionic gonadotropin (beta-hCG) levels, normal Thyroid-stimulating hormone receptor antibodies (TRAb). Other laboratory parameters are mediocre. The ECG results showed sinus tachycardia. A mole tissue biopsy of the uterus confirms the morphology of the hydatidiform mole. These findings established the diagnosis of Impending Thyroid Storm caused by a hydatidiform mole. Conclusion: A hydatidiform mole can cause thyroid storm because the hormone hCG has similar structure to TSH. Doctors should always estimate the possibility of hyperthyroidism in a molar pregnancy.

The main principles of managing patients with Graves’ disease in clinical practice

BACKGROUND: Graves’ disease (GD) is a common cause of persistent thyrotoxicosis. In regions with adequate iodine intake, the incidence is 20–30 cases per 100,000 people. Modern treatment of GD includes antithyroid drugs, radioactive iodine therapy (RAI), and thyroidectomy. The choice of treatment strategy is based on the severity of thyrotoxicosis, the frequency of potential side effects, the availability of treatment options, and the likelihood of achieving sustained remission. Previous studies have demonstrated differences in approaches to diagnosis, treatment, and follow-up between countries and individual specialists.AIM: To conduct a survey on the current clinical practice of treating Graves’ disease in Russia.MATERIALS AND METHODS: An online survey was conducted among physicians in 2022-2023. The questions covered the principles of diagnosis, treatment, and dynamic observation of adult patients with Graves’ disease.RESULTS: The study involved 104 physicians of various specialties who treat patients with Graves’ disease. Approximately 99% of respondents chose the determination of thyroid-stimulating hormone receptor antibodies (TSHR-ab) to clarify the etiology of thyrotoxicosis, while only 60.6% of them chose thyroid scintigraphy. As the first-line treatment method, antithyroid drug therapy is chosen by 88.5%, while 13.5% of physicians use radioactive iodine therapy (RAI), and less than 1% of respondents refer patients to thyroidectomy. Thiamazole is most commonly used (99%), while propylthiouracil (PTU) is used in cases of allergy to thiamazole or during the first trimester of pregnancy. The «block-replace» scheme is preferred over the «block» scheme, with 72.1% compared to 28.8%, respectively. The majority of physicians (95.2%) initiate therapy with moderate doses of thiamazole (20–30 mg) and PTU (200–300 mg). Most physicians conduct dynamic monitoring of liver transaminase levels (57.7%) and complete blood count (78.8%). Conservative therapy is prescribed for a period of 12–18 months (88.5%) or up to 24 months (10.6%). Before discontinuing antithyroid drug therapy, 89.4% of respondents monitor thyroid hormone levels, 82.7% monitor TSHR-Ab levels, and 47.1% perform thyroid ultrasound. Repeat courses of conservative therapy are prescribed for up to 61.5% of respondents. Approximately 63.5% of surveyed physicians reported difficulties in referring patients for radical treatment due to a limited number of specialized institutions. Physicians cited patient unwillingness and the need to postpone pregnancy (81.6% and 24.3% respectively) as the main inhibitory factors for RAI. Thyroidectomy was associated with patient unwillingness (69.2%), as well as physician fear of laryngeal paralysis (48.1%) and postoperative hypoparathyroidism (49%).CONCLUSION: The results of the study demonstrated that physicians in their practice generally adhere to international recommendations for the treatment of Graves’ disease.

Principles and features of ultrasound hypoechogenicity in diffuse thyroid pathology.

For different thyroid diseases and hormonal metabolism, ultrasound (US) of the thyroid gland reveals hypoechogenicity. Despite the direct correlation of hypoechogenicity with the levels of thyroid-stimulating hormone and antibodies of thyroid peroxidase and thyroglobulin, ~20% of this correlation is inconsistent, thus restricting the comprehensive utilisation of this valuable diagnostic sign. Thus, it is necessary to investigate the additional circumstances affecting the extent and features of the US hypoechogenicity of the thyroid gland. The technique for assessing thyroid hypoechogenicity was based on the basic setting of the US mode and visual assessment in percentage of gray relative to a gradient gray scale. Doppler mode was used. US data were compared with the results of hormonal and immune blood tests. The study contains the morphofunctional basis of the various US hypoechogenicities detected in the diffuse pathology of the thyroid gland has been presented, and the principles and probable mechanisms of widespread and segmental hypoechogenicity formation are disclosed for the first time. Furthermore, a mandatory Doppler involving thyroid parenchyma blood flow intensity and peak systolic blood velocity of thyroid arteries, which indicates the magnitude of neurovegetative influence, has been suggested. The results of the study shows revealed that the evaluation of the importance and features of US hypoechogenicity in various diffuse thyroid pathologies is probably based on a single system involving neurohumoral regulation, segmental arrangement and compensatory reserve state of the gland parenchyma.

The evaluation of retrobulbar fat tissue in Graves' orbitopathy with shear-wave ultrasound elastography.

To evaluate retrobulbar adipose tissue of patients with active and inactive Graves' orbitopathy (GO) by shear-wave ultrasound elastography (SWE). Followed-up in our ophthalmology clinic due to GO, 72 eyes of 36 patients and 38 eyes of 19 healthy controls were included in this cross-sectional case-control study. Graves' patients were divided into two subgroups under clinical activity score (CAS): active Graves' orbitopathy (AGO) (CAS ≥ 3) and inactive Graves' orbitopathy (IGO) (CAS < 3). SWE measurement values of retrobulbar adipose tissue of all participants were recorded in meters/second, and the intergroup comparisons were performed. Thirty-four eyes of 17 patients in AGO, 38 eyes of 19 patients in IGO, and 38 eyes of 19 participants in the control group were included in the study. Mean values measured from retrobulbar adipose tissue through SWE were 1.00 ± 0.01m/sec in AGO, 1.16 ± 0.01m/sec in IGO, and 0.94 ± 0.01m/sec in the control groups. Even so, the mean SWE value was significantly higher in the IGO group than in the other groups (p < 0.001). Mean SWE values were significantly higher in the AGO group than in the controls (p = 0.008). In the correlation analysis performed, a significant positive correlation was found between SWE and Hertel exophthalmometer measurement values (p = 0.026, r = 0.212), and thyroid-stimulating hormone receptor antibody (TSHR-Ab) levels (p = 0.018, r = 0.224). We detected SWE values of retrobulbar adipose tissue high in GO, especially in the IGO group. Such a situation, which we associated with the development of fibrosis, may be an indicator of unresponsiveness to immunomodulatory treatments.