Thyroid-stimulating Immunoglobulin Levels Research Articles

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024

6581 Case of Conversion from Hashimoto’s Thyroiditis to Graves’ Disease: An Unusual Sequence

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: The two most common autoimmune thyroid diseases are Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is a destructive thyroiditis, via autoantibodies most commonly against the thyroid peroxidase enzyme (anti-TPO), while GD results in hyperthyroidism, due to TSH-receptor stimulating antibodies (TSAb) and Thyroid Stimulating Immunoglobulin (TSI). Case Report: A 23-year-old male presented to the clinic with complaints of weight gain, dry skin and excessive hair loss. His physical examination was non-contributory and laboratory evaluation revealed a TSH of 130 uIU/ml (ref: 0.45-4.5), free T4 (fT4) 0.4 ng/dl (ref: 0.82-1.77), and positive anti-TPO antibodies, for which he was started on levothyroxine (LT4) supplementation for newly diagnosed HT. Over the first five months on treatment, his TSH and T4 progressively improved to 31.8 uIU/ml and 1.48 ng/dl, respectively. Six months later, his TSH rapidly decreased to 0.01 uIU/ml, with an fT4 elevation to 2.45 ng/dl, alongside developing hyperthyroid symptoms like weight loss, insomnia and palpitations. Due to persistently positive anti-TPO antibody titers, his hyperthyroidism was considered iatrogenic, and LT4 dose was gradually reduced, but eventually required to be discontinued. A thyroid ultrasound depicted generalized increase in vascularity, consistent with active thyroiditis. He continued to have a significantly suppressed TSH <0.005 uIU/ml and elevated fT4, off all medications, and was also found to have multiple positive antibody titers [TSI of 1.02 IU/L (ref: < 0.55), thyroglobulin antibody of 351 IU/ml (< 0.9) and anti-TPO Ab >600 IU/ml (ref< 34)]. He was then diagnosed with new GD, and thyroid suppression therapy with 10mg/day of methimazole was initiated, to which he rapidly responded, with a TSH of 0.059 uIU/ml and reduced fT4 of 1.37 ng/dl. His diagnosis of GD was confirmed via an I-123 thyroid uptake scan which revealed a homogenous increased tracer uptake of 57% at 24 hours (ref 15-35%), following which he received definitive therapy for GD, with radio-active iodine (RAI) ablation with 20.6 mCi of I-131. Discussion: As HT and GD have a common autoimmunity-based pathophysiology, conversions between the two clinical states have been described, though HT to GD, as seen in our patient is much less common than the reverse conversion. Some described mechanisms include an antibody switch from thyrotropin receptor blocking to stimulating action, HT-induced thyrotroph destruction resulting in GD antibody formation, and treatment with LT4. Simultaneously elevated levels of both TSI and anti-TPO can occur, and therefore treatment and diagnosis should be based on thyroid function tests and clinical presentation. Patients with autoimmune thyroid disease require close monitoring, due to the potential risk of conversion from one clinical end of the spectrum to the other, and early recognition is important. Presentation: 6/1/2024

8640 Thyroid Orbitopathy in Pregnancy

Abstract Disclosure: Z. Maisonet -Feliciano: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. L. El Musa Penna: None. J. Segarra-Villafane: None. I.C. Arroyo: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. Thyroid orbitopathy, often associated with Graves' disease, is characterized by the inflammation and swelling of ocular tissues. Its occurrence or exacerbation during pregnancy is infrequent, primarily due to the immunosuppressive state inherent in pregnancy. In most instances, the immunosuppression associated with pregnancy leads to a reduction in TRAb levels, although they continue to be present in women who have an active form of the disease. The course and severity of ocular manifestation do not always correlate with thyroid hormone levels. Strict control of thyroid function is crucial in patients with thyroid eye disease. This report sheds light on the rare occurrence of thyroid orbitopathy during pregnancy, a condition that complicates treatment due to potential risks to both the mother and the child. In this case, a 35-year-old pregnant woman with no prior history of thyroid issues exhibited symptoms of hyperthyroidism in her first trimester, including unintended weight loss, anxiety, and tremors in the upper limbs. She also presented with ocular discomfort, diplopia, and eyelid lag. Thyroid tests confirmed Graves Disease, with a significant elevation in Thyroid Stimulating Immunoglobulin (TSI): 243 %, Free thyroxine (T4): 1.08 ng/dl and Triiodothyronine (T3): >1.89 units and decreased Thyroid Stimulation Hormone (TSH): 0.001 uIU/ml. Ophthalmic examination revealed mild Graves orbitopathy due to bilateral exophthalmos (measured by Hertel’s exophthalmometer) 21mm on both sides, Marginal reflex distance (MDR) 1: right eye 9 mm and left 7mm. MDR 2: right eye 6mm and left eye 7mm. Right upper eyelid retraction, lagophthalmos of the right eye, limitation in the upward movement of the left eye, and vertical diplopia on extreme gazes without signs of orbital compression. Considering her normal FT4 levels and the mild nature of her hyperthyroidism, the decision was made to prioritize the mother's treatment while minimizing fetal risk, thus opting not to initiate antithyroid medication but to closely monitor her thyroid function. Symptomatic management of her orbitopathy was provided including lubricating eye drops and an eye patch. Throughout the progression of her pregnancy, her TSI levels exhibited a decreasing trend while FT4 remained within normal limits. Following delivery, there was a notable improvement in her ocular symptoms, and her TSH started increasing up to normal values of 1.29 uIU/ml and FT4 remained in range. This report underscores the importance of recognizing uncommon presentations of autoimmune thyroid conditions, such as thyroid orbitopathy, during pregnancy. It emphasizes the complexities and necessary considerations in treating these cases. A collaborative approach involving endocrinology, ophthalmology, and obstetrics is essential to safeguard the health of both the mother and the fetus. Presentation: 6/1/2024

Prognostic factors for thyroid-stimulating immunoglobulin normalization in moderate-to-severe Graves’ orbitopathy: a 36-month longitudinal study

PurposeThe primary objective of this study was to identify predictive factors linked to the normalization of thyroid-stimulating immunoglobulin (TSI) levels in patients diagnosed with active, moderate-to-severe Graves’ orbitopathy (GO). The study also tracked the longitudinal changes in TSI levels over a 36-month period following treatment.MethodsThe study population consisted of individuals who were recently diagnosed with active, moderate-to-severe GO and received a 12-week course of intravenous methylprednisolone (IVMP) treatment. A subgroup of patients who did not respond to the initial treatment received an additional 20 Gy of radiation therapy (RTx). TSI levels were monitored at the time of diagnosis, after treatment, and subsequently every 6 months for 36 months. Normalization was defined as a TSI level below 140%. Patients were divdied into two groups with success and failure group depending on whether TSI became normal or not.ResultsOut of 83 patients, 36 (43.4%) achieved normalized TSI levels within two years post-IVMP treatment. Lower initial TSI levels (< 425%), absence of additional RTx, and early treatment initiation were associated with a higher likelihood of TSI normalization (P = 0.035, P = 0.028, P < 0.001, respectively). Notably, significant differences in TSI level reduction were observed from 18 months post-treatment between the two groups (P = 0.031). A TSI cutoff value of 413% was identified as predictive for normalization at 24 months (P = 0.002).ConclusionThis study is the first to identify key factors that influence normalization of TSI levels in moderate-to-severe Graves’ Orbitopathy. It highlights the importance of early treatment decisions, particularly for patients with initial TSI levels above 425%. Despite the treatment, less than half of the patients achieved TSI normalization within 24 months, underscoring the need for additional research to explore the relationship between TSI levels and the clinical manifestations of chronic GO.

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Thyroid stimulating immunoglobulin concentration is associated with disease activity and predicts response to treatment with intravenous methylprednisolone in patients with Graves' orbitopathy.

Thyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO. TSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.2 years old) and 25 healthy controls (5 male, 20 female; mean age 39.8 years old). Clinical characteristics and response to treatment were retrospectively retrieved from patient files. Higher sIL-2R levels were observed in GO patients compared to controls (p < 0.001). sIL-2R correlated with fT4 (r = 0.26), TSH (r = -0.40) and TSI (r = 0.21). TSI and sIL-2R concentrations were higher in patients with active compared to inactive GO (p < 0.001 and p < 0.05, respectively). Both TSI and sIL-2R correlated with total clinical activity score (CAS; r = 0.33 and r = 0.28, respectively) and with several individual CAS items. Cut-off levels for predicting active GO were 2.62 IU/L for TSI (AUC = 0.71, sensitivity 69%, specificity 69%) and 428 IU/mL for sIL-2R (AUC = 0.64, sensitivity 62%, specificity 62%). In multivariate testing higher TSI (p < 0.01), higher age (p < 0.001) and longer disease duration (p < 0.01) were associated with disease activity. TSI levels were higher in patients with a poor IVMP response (p = 0.048), while sIL-2R levels did not differ between responders and non-responders. TSI cut-off for predicting IVMP response was 19.4 IU/L (AUC = 0.69, sensitivity 50%, specificity 91%). In multivariate analysis TSI was the only independent predictor of response to IVMP (p < 0.05). High TSI levels are associated with active disease (cut-off 2.62 IU/L) and predict poor response to IVMP treatment (cut-off 19.4 IU/L) in GO. While sIL-2R correlates with disease activity, it is also related to thyroid function, making it less useful as an additional biomarker in GO.

Evaluation of hematologic inflammatory markers in Graves’ disease

Introduction: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) have been used as new inflammatory markers in certain autoimmune diseases to assess the severity of inflammation. The current study aimed to evaluate the changes in neutrophil and lymphocyte series in hyperthyroid patients and to investigate whether NLR, PLR, and SII may be markers of inflammation. Methods: This cross-sectional study was conducted with 207 Graves’ patients and 120 healthy controls between 2018-2022 years. Hematologic parameters, thyroid function tests, age and gender were recorded. The NLR, PLR and SII values of all subjects were calculated. Firstly, groups were composed as Graves' group and participants without thyroid disorder as control group. Secondly, Graves' patients composed as two groups before treatment and after antithyroid treatment. These groups were compared with each other in terms of descriptive data and hematological parameters. Results: The patient and control groups were similar in terms of gender (p=0.522) and age (p=0.051). Graves’ patients had a significantly lower NLR than the control group (p=0.004). There was no significant difference between the groups in terms of PLR (p=0.120) and SII (p=0.577). Patients’ baseline TSH-receptor antibodies (TRAb) levels had a significant positive correlation with fT3 (r:0.283, p&amp;lt;0.001), fT4 (r:0.252, p&amp;lt;0.001) and Thyroid stimulating immunoglobulin (TSI) (r:0.673, p&amp;lt;0.001). There was no significant correlation between TRAb and TSI levels, inflammatory markers, and hematological parameters. Conclusions: Graves’ patients had lower NLR compared to the control group. The patient and control groups did not have a significant difference with regard to PLR and SII. Thyroid autoantibody levels and inflammatory markers did not have a significant correlation. Keywords: Hyperthyroidism, inflammation, neutrophils, lymphocytes

Elevated serum thyroid stimulating immunoglobulin linked to failure of first-line intravenous methylprednisolone monotherapy in moderate-to-severe thyroid eye disease.

To assess factors associated with failure of intravenous methylprednisolone (IVMP) monotherapy as the first-line treatment for thyroid eye disease (TED) and to identify patients who might benefit from supplementing mycophenolate mofetil (MMF) to IVMP. Data for all patients with TED treated with IVMP according to the EUGOGO protocol in our center between 2016-2021 were retrospectively analysed. Forty-seven patients (mean age 51.32 ± 14 years, 27 females) were enrolled. The mean time from first reported symptoms to first IVMP treatment was 12.1 ± 5.59 months (range 0-120). The mean clinical activity score (CAS) before treatment and at a mean of 5 and 12.2 weeks after treatment initiation was 6.00, 2.96, and 1.81, respectively (P < 0.01). Twenty-one patients (44.68%) were recommended second-line treatment: nine due to no response or worsening of CAS, six due to partial response, four with good response but early relapse after completion of treatment, and one due to late relapse. Eighteen of those 21 patients received second-line treatment which included rituximab (n = 7), MMF (n = 6), a second course of IVMP (n = 4), and tocilizumab (n = 1). Serum thyroid-stimulating immunoglobulin (TSI) levels were higher in patients who received second-line treatment compared with patients who responded well to first-line IVMP monotherapy at presentation (2135% vs 1159%, P = 0.05) and after completion of first-line treatment (2201% vs. 986%, P = 0.043). TED patients requiring second-line treatment after failed IVMP monotherapy had higher baseline and post-first-line treatment serum TSI levels. Those with elevated TSI may benefit from dual therapy (IVMP and MMF) and require closer monitoring.

THU670 Serum TSI Concentration In Patients With Graves’ Disease Undergoing Maintenance-dose Of Antithyroid Drug (ATD) And Its Relationship With Disease Relapse After ATD Withdrawal

Abstract Disclosure: P.V. Nguyen: None. K.T. Nguyen: None. Background: Graves' disease (GD) is an autoimmune disorder in which thyroid-stimulating immunoglobulin (TSI) plays a key role in its pathogenesis. TSI assays have been recently optimized in their accuracy, and the procedure has also been simplified, which can potentially replace TRAb measured by conventional TSH-binding inhibitory immunoglobulins (TBII) assays in routine clinical practice. Objectives: Our objective was to study the serum TSI concentration in patients with Graves’ disease undergoing maintenance-dose ATD. We also aimed to assess the predictive value of TSI immunoassay, as well as the clinical signs and thyroid function tests in predicting Graves’ disease relapse following ATD discontinuation. Finally, follow-up would be continued to check for relapse or long term euthyroid status. Methods: Retrospective follow-up study of 352 patients with hyperthyroidism due to GD, treated at the endocrine outpatient clinic of Medic Medical Center, Ho Chi Minh City from January 2000 to April 2021. TSI was measured several times during the course of treatment when planning to stop the medication (at the discretion of the attending physician). ATD withdrawal would be considered when the patients achieved clinical euthyroidism with normal FT4 tests for at least 3 months with minimal dose of ATD. The decision to withdraw ATD was also based on TSI concentration, as well as the goiter’s characteristics and parenchymal vascularity observed via thyroid Doppler ultrasound. Results: The median TSI concentration of patients with GD undergoing maintenance-dose ATD was 1.45 IU/L (normal range &amp;lt;0.10 IU/L), and their thyroid function measured at the same time tended to be euthyroid in our study. TSI cut-off level at ATD withdrawal to predict the recurrence of GD was 1.31 IU/L which corresponded with the sensitivity, specificity, positive and negative predictive values of 63.64%, 78,79%, 50% and 86.67%, respectively. Multiple logistic regression analysis showed that the following factors were associated with an increased risk of relapse after the end of medical treatment: Graves' ophthalmopathy (GO), OR 3.69 (95% CI: 1.06-12.87; p=0.04), treatment duration less than 18 months, OR 7.77 (95% CI: 1.92-31.42; p&amp;lt;0.01), TSI level before ATD withdrawal ≥1.31 IU/L, OR 9.92 (95% CI: 2.77-35.42; p&amp;lt;0.01). Conclusion: At the time of ATD withdrawal, while normal FT4 levels were observed, high TSI levels were indicative of an ongoing immune process. These findings suggest that TSI measurements, in addition to clinical and ultrasound evaluations, may aid in the prediction of GD relapse after ATD discontinuation. In addition, GO, treatment duration of less than 18 months and TSI level before ATD withdrawal ≥1.31 IU/L were associated with an increased risk of relapse of GD after ATD discontinuation. Our study contributes to the expanding literature supporting the clinical utility of TSI assay in the management of GD. Presentation: Thursday, June 15, 2023

SAT462 TSI Versus TRAb In The Diagnosis Of Grave’s Disease

Abstract Disclosure: K. Ibrahim: None. K. Raju: None. M. Morkos: None. Objective: Improvement in the thyroid antibody titers can help in predicting the remission of Graves’ disease. We aimed to assess the level of elevation of the antibody titers, thyroid stimulating immunoglobulin (TSI) and thyroid receptor antibody (TRAb) in patients with Grave’s disease. Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with Graves’ disease at an academic outpatient endocrinology clinic from August 2019 to November 2022. TSI and TRAb were measured synchronously during the initial assessment of the patients, titers were compared against the upper limit of normal to assess their level of elevation. TSI was measured using Semi-Quantitative Chemiluminescent Immunoassay and TRAb using Quantitative Electrochemiluminescent Immunoassay. SPSS® (version 28) was used for statistical analysis, descriptive statistics were utilized and paired-sample t-test was used to compare TSI And TRAb ratios. Results: We identified 41 patients who presented for initial assessment of Graves’ disease, 31 (75.6%) were female, 23 (56.1%) Caucasian, and 16 (39.0%) African American. Mean age (± standard deviation) 46.3 ± 14.2 years. Mean TSI 8.3 ± 15.9 IU/L (ref &amp;lt;0.55), TSI ratio of elevation above the upper limit of normal was 11.1 ± 15.3, Mean TRAb 8.9 ± 9.4 (ref ≤1.75), TRAb ratio of elevation above the upper limit of normal was 5.1 ± 5.4. The correlation coefficient for both TSI and TRAb ratios was 0.92 (p &amp;lt;0.001). One patient had a normal TSI but elevated TRAb level and two patients had a normal TRAb level but elevated TSI levels. Conclusion: TSI was more highly elevated above its normal range than TRAb. TSI can be a reasonable initial antibody test for patients with Graves’ disease to establish a baseline. Presentation: Saturday, June 17, 2023

Thyrotropin Receptor Autoantibody Assessment in Thyroid Eye Disease: Does the Assay Type Matter?

Thyroid receptor antibodies can quantify thyroid eye disease activity, predict outcomes and aid timing of interventions. The type and generation of assay is frequently unspecified, complicating meta-analyses. To determine the clinical and biochemical relationships between a second-generation thyrotropin receptor-binding inhibition antibody (TRAb) immunoassay, detecting stimulatory and blocking antibodies, with the thyroid stimulating immunoglobulin (TSI) bridging immunoassay detecting the stimulatory component only. Retrospective review of 100 consecutive patients attending a regional specialist service. For each patient and visit, both a TRAb and TSI were performed, and a clinical activity score (CAS) recorded. A significant positive correlation between TRAb and TSI (rho = 0.828, p < 0.01) but a weaker correlation between the assays and CAS (TRAb: rho = 0.439, p < 0.01; TSI: r = 0.357, p < 0.01) were found. In 10% of the episodic data, patients had a TRAb level that was disproportionately high (39.41 ± 52.84 IU/L), compared to their TSI levels (9.53 ± 12.10 IU/L) with a higher-than-average CAS (2.47 ± 1.78; range, 0-5). Within 12 months of diagnosis, a significant positive correlation between CAS and TRAb (rho = 0.503, p < 0.01) as well as between CAS and TSI (rho = 0.329, p < 0.01) were found. In patients with a diagnosis over 12 months, the correlation with CAS for both TSI and TRAb were Spearman rank correlation coefficient of 0.347 (p < 0.01) and 0.327 (p < 0.01), respectively. TRAb and TSI correlate strongly and to a lesser extent with the CAS. For most patients, TRAb can be replaced with the more economical TSI. TRAb also correlates better with newly diagnosed, more active patients than TSI. In a subset of patients, blocking antibodies may play a significant pathogenic role, requiring different treatment and monitoring. Further studies are required to investigate this relationship.

Changes in Clinical Activity, Serum Autoantibody Levels, and Chorioretinal Vessels After Systemic Glucocorticoid Therapy in Thyroid Eye Disease.

The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment. This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12weeks after intravenous (IV) GC therapy initiation, and 2months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured. The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2months. The thyroid-stimulating hormone receptor antibody level decreased until 12weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78days. Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.

Factors related to steroid treatment responsiveness in thyroid eye disease patients and application of SHAP for feature analysis with XGBoost.

The primary treatment for active thyroid eye disease (TED) is immunosuppressive therapy with intravenous steroids. In this study, we attempted to predict responsiveness to steroid treatment in TED patients using eXtreme Gradient Boosting (XGBoost). Factors associated with steroid responsiveness were also statistically evaluated. Clinical characteristics and laboratory results of 89 patients with TED who received steroid treatment were retrospectively reviewed. XGBoost was used to explore responsiveness to steroid treatment, and the diagnostic performance was evaluated. Factors contributing to the model output were investigated using the SHapley Additive exPlanation (SHAP), and the treatment response was investigated statistically using SPSS software. The eXtra Gradient Boost model showed high performance, with an excellent accuracy of 0.861. Thyroid-stimulating hormone, thyroid-stimulating immunoglobulin (TSI), and low-density lipoprotein (LDL) cholesterol had the highest impact on the model. Multivariate logistic regression analysis showed that less extraocular muscle limitation and high TSI levels were associated with a high risk of poor intravenous methylprednisolone treatment response. As a result of analysis through SHAP, TSH, TSI, and LDL had the highest impact on the XGBoost model. TSI, extraocular muscle limitation, and LDL cholesterol levels may be useful in predicting steroid treatment response in patients with TED. In terms of machine learning, XGBoost showed relatively robust and reliable results for small datasets. The machine-learning model can assist in decision-making for further treatment of patients with TED.

Is there an association between endometriosis and thyroid autoimmunity?

It has been suggested that non-uterine endometrial implants can express thyroid-stimulating hormone receptors, thus inducing the formation of thyroid-stimulating immunoglobulin. We aimed to compare the autoantibody positivity in patients with and without endometriosis and to determine whether there is a difference in the incidence of thyroid diseases. This prospective observational study was conducted on 102 women who had been operated on for benign gynecological diseases. Cases enrolling in the study were divided into two groups: the study group with endometriosis (n=51) and the control group without endometriosis (n=51). The blood tests for thyroid-stimulating hormone, free thyroxine (fT4), thyroid-stimulating immunoglobulin, and anti-thyroid peroxidase antibody levels were checked. The mean thyroid-stimulating immunoglobulin level was found to be higher in the endometriosis group than in the control group. However, this difference was not statistically significant. No significant difference was detected between endometriosis and control groups in terms of anti-thyroid peroxidase antibody and thyroid-stimulating hormone levels. The mean fT4 value (0.97±0.13 ng/dL) of the endometriosis patients was found to be significantly lower than the control group (1.08±0.21 ng/dL) (p=0.002; p<0.05). The mean anti-thyroid peroxidase antibody value of cases with bilateral endometrioma (82.21±252.29 IU/mL) was significantly higher than cases with unilateral endometrioma (15.81±83.13 IU/mL) (p=0.028; p<0.05). There is a positive and significant relationship between the size of endometriosis and anti-thyroid peroxidase antibody values (p=0.011; p<0.05). This study points to an association between endometrioma diameter and anti-thyroid peroxidase antibody values which can be a stepping stone for new studies evaluating this hypothesis further.

Association of clinical course with thyroid-stimulating immunoglobulin in Graves' ophthalmopathy in Mongolians.

Graves' ophthalmopathy (GO) is a complex inflammatory condition affecting the orbit and is often associated with Graves' disease (GD). This study aims to determine the levels of thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone receptor autoantibody (TSHR-ab) in the serum of patients with GO, compare it with the GD, and determine whether there is a correlation with the clinical course of GO. The cross-sectional study included 82 patients with GO, 81 patients with GD, and 75 healthy subjects. The ocular manifestations of GO were identified and evaluated by the clinical activity score (CAS) and severity of GO using the European Group of Graves' Orbitopathy (EUGOGO). TSI and TSHR-ab levels in the serum of participants were determined with ELISA kits and correlated with clinical findings. A total of 238 participant's data were analyzed. There were 14 patients (17%) with unilateral GO. The most common ocular signs were eyelid retraction 68 (82.3%) and proptosis 61 (74.4%). The mean CAS score was 2.65±1.64 in GO patients and was higher in men than women (P = 0.008). The mean of TSI was 37.95±35.41 in GO, 14.16±15.67 in GD, and 4.33±2.94 in healthy controls (P<0.0001). The TSI was significantly higher in patients with GO than in those with GD (P<0.0001). There were no correlations between TSI and TSHR-ab levels and CAS scores. However, we observed a correlation between the TSI level and the severity of GO (P = 0.023). The area under the ROC curve (AUC) of TSI was 0.933 and selected 14.1 IU/ml was the optimal cutoff value (98.78% of sensitivity, 83.97% of specificity). Our study showed that TSI is significantly related to GO and the severity of GO. Therefore, TSI can be used as a predictor of severe GO to help in prognostication, follow-up and treatment planning.

ODP516 Subacute Thyroiditis due to SARS-CoV-2 Vaccine

Abstract Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a pandemic in 2019, causing systemic complications including endocrine system diseases. Subacute thyroiditis (SAT) of COVID-19 infection is believed to be due to direct virus entry into cells and cell destruction, cellular dysfunction due to inflammation and immune/antibody-mediated hormonal dysfunction. Here we present a case of SAT after the SARS-CoV-2 vaccine (Pfizer-BioNTech). Clinical Case A 39-year-old male healthcare worker presented with four weeks history of symptoms: fullness of the anterior neck, odynophagia, enlarged cervical lymph nodes, palpitations, anxiety and weight loss. Onset of symptoms was two days the second dose of Pfizer-BioNTech vaccine. There was no recent history of upper respiratory system infection or COVID-19 infection. Vital signs and physical exam findings were unavailable, as it was a telephone encounter. Initial workup was significant for a TSH of 0. 020 uIU/mL (n 0.45-5.330 uIU/mL), free T4 of 2.42 ng/mL (n 0.45-1.80 ng/mL) and total T3 225.4 pg/mL (n 87-179 pg/mL). There was no evidence of leukocytosis. Ultrasound of the thyroid gland was unremarkable for nodules or hyperemia. Autoimmune thyroid disease was ruled out with negative levels of thyroid stimulating immunoglobulin, thyroid receptor antibody and anti-microsomal antibody. Thyroid scintigraphy was significant for abnormally low uptake, consistent with SAT. Clinical and biochemical improvements (TSH 4.193 uIU/mL; free T4 0.98 ng/dL) were seen after 5 months. Conclusion Subacute thyroiditis (SAT) is an acute inflammatory disorder of the thyroid usually related to a viral infection. It was described in total of 27 patients of COVID-19 infection (3) . There are only a handful of cases related to COVID-19 vaccine and most of them are due to the inactivated vaccine (1,2) . To our knowledge, there are only three documented cases of subacute thyroiditis after receiving the Pfizer mRNA vaccine (1) . The pathophysiology in generating an autoimmune response is believed to be due to molecular mimicry and cross recognition between the coronavirus spike protein targeted with the mRNA vaccine and healthy thyroid cell antigens (1,2) . Clinicians should be alert and consider the possibility of SARS-CoV-2 vaccine as an etiology when evaluating patients for subacute thyroiditis.

PSAT321 Post-partum Thyroiditis Precipitated by SARS CoV-2 Infection-a Case Report

Abstract Introduction Postpartum thyroiditis is a form of destructive thyroiditis. It is thought to originate from an autoimmune mechanism that develops within one year of parturition. The condition results in inflammation of the thyroid resulting in damage to the thyroid follicles and release of previously stored thyroid hormone. There are only a handful of documented cases of postpartum thyroiditis associated with SARS CoV-2. Since the onset of COVID-19 a multitude of thyroid abnormalities have been associated with the virus. Case Summary A 33-year-old female, 5 months post-partum with a medical history significant for hypertension presents to the clinic for evaluation of hyperthyroidism. She tested positive for SARS-CoV-2 eleven days prior to delivering her child. Her pregnancy was only complicated by chronic hypertension. COVID-19 infection was symptomatic for mild respiratory symptoms. She had no history of hypo or hyperthyroidism prior to or during her pregnancy. At presentation, patient was largely asymptomatic with a physical exam significant only for sinus tachycardia. Laboratory tests done two weeks before her visit, were significant for a suppressed TSH &amp;lt;0.001 uIU/mL (reference range: 0.450- 4.50) and a mildly elevated Free T4: 1.84 NG/dL (reference range: 0.82-1.77) and T3: 139 NG/dL (reference range: 71-180). We repeated the tests and noted a recovering TSH of 0.110 uIU/mL; a low Free T4: 0.77 NG/dL and T3: 66 NG/dL. Thyroglobulin level was found to be elevated at 742.6 IU/mL (reference range 0.0-0.9). Thyroid Stimulating Immunoglobulin level was &amp;lt;0.10 IU/L (Normal- 0.00-0.55) and serum thyrotropin receptor Ab &amp;lt;1.10 IU/L (Normal- 0.00-1.75). Radioactive iodine uptake &amp; scan was deferred as patient was breast-feeding at the time. As our patient was asymptomatic, she was prescribed only propranolol for her tachycardia. Discussion Documented cases of post-partum thyroiditis associated with SARS-CoV-2 infection are far and few. Post-partum thyroiditis is characterized by an initial thyrotoxic phase followed by hypothyroid phase and then a recovery period. Most patients are only mildly symptomatic during the initial hyperthyroid phase. At the time of referral to our clinic, the patient was already entering a hypothyroid state. She was asymptomatic at the time and therefore treated with expectant management only. COVID-19 has been identified as a cause of subacute post-infectious thyroiditis. It is known to be associated with a hyperinflammatory state characterized by a cytokine storm. Elevation of these cytokines can contribute to thyroid dysfunction. Conclusion It is hard to say whether our patient's acute thyroiditis was secondary to postpartum thyroiditis, subacute thyroiditis secondary to COVID-19 infection, or a combination of both factors. However, regardless of etiology it is important to note a possible correlation of post-partum thyroiditis in the setting of a SARS-CoV-2 infection. It is necessary to identify all cases of COVID-19 infection that can be associated with thyroid dysfunction. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Treatment of corticosteroid-resistant Graves’ orbitopathy with tocilizumab: a single-centre prospective study

ABSTRACT Purpose To assess tocilizumab (TCZ) as an emergent treatment for corticosteroid-resistant active Graves’ orbitopathy (GO). Methods We conducted a single-centre prospective study. We assessed TCZ in patients with active corticosteroid-resistant GO. Each patient received intravenous TCZ every four weeks until symptom stabilization. Our primary outcome was GO activity evaluated by the clinical activity score (CAS). The secondary outcomes included variation in thyroid-stimulating immunoglobulin (TSI). Results We included ten patients. Three patients had compressive neuropathy with visual field impairment and vision loss. CAS improved significantly in 100% of the patients included in the analysis, with a decrease in the mean CAS of 4.5 ± 1.2 points (p = .003). There was a significant decrease in the TSI after therapy, from 21.7 ± 22.9 at baseline to 4.0 ± 3.3 (p = .006). A mean of three infusions was necessary to drastically decrease the TSI amount. The baseline mean before TCZ was 4.7 ± 1.2 and the final mean after TCZ IV infusion was 0.2 ± 0.4. Conclusions Our study showed the efficiency of TCZ in patients with GO resistant to corticosteroid therapy, as shown in previous studies. Our present work adds two important pieces of information: TCZ might be particularly useful for GO with compressive neuropathy and it is efficient regardless of initial TSI level. Considering the numerous advantages over steroids (high response rate and lower rate of adverse events), further randomized controlled trials should be conducted to assess the possible place of TCZ as a first-line treatment.

Clinical evaluation of an automated TSI bridge immunoassay in the diagnosis of Graves’ disease and its relationship to the degree of hyperthyroidism

BackgroundThe rapid and accurate detection of thyroid-stimulating hormone (TSH) receptor antibodies has always been an urgent need for the clinical diagnosis and management of Graves’ disease (GD). We aimed to evaluate the use of an automated thyroid-stimulating immunoglobulin (TSI) bridge immunoassay in the diagnosis of GD and to analyze the relationship between TSI and the degree of hyperthyroidism.MethodsA total of 227 new-onset GD patients, 29 Hashimoto thyroiditis, 43 non-autoimmune thyroid diseases and 37 euthyroid controls were consecutively recruited. All participants accepted the measurement of their serum thyroid function and thyroid-associated antibodies, including TSI being measured by an Immulite 2000 bridge immunoassay and TSH receptor autoantibodies (TRAb) being measured by a third-generation Roche electrochemiluminescence immunoassay. The quantitative consistency between the TSI and TRAb detection methods was analyzed by using Passing-Bablok regression and Bland–Altman plots. The diagnostic performance for GD was assessed by receiver operating characteristic (ROC) curve analysis.ResultsAmong 227 GD patients (174 females and 53 males, with a mean age of 39 years), the quantitative TSI was positively correlated with TRAb (r = 0.8099). According to the cut-off values proposed by the manufacturers (TSI: 0.55 IU/L, TRAb: 1.75 IU/L), the positive rates of TSI and TRAb in new-onset GD patients were 96.92% and 95.15%, respectively. Both TSI and TRAb levels positively correlated with FT4 levels (TSI: r = 0.243, TRAb: r = 0.317; all P < 0.001) and FT3 levels (TSI: r = 0.288, TRAb: r = 0.360; all P < 0.001) in new-onset GD patients. The ROC analysis showed that the optimal TSI cut-off value was 0.577 IU/L for GD diagnosis in this Chinese population, with a sensitivity of 96.92% and a specificity of 97.25%, respectively. The optimal TRAb cut-off value of was 1.38 IU/L, with a sensitivity of 96.92% and a specificity of 99.08%. There were no significant differences between the cut-off values obtained through the ROC analysis and those provided by the manufacturer for both TSI and TRAb when calculating their sensitivity and specificity in diagnosing GD. Among the 8 newly diagnosed GD cases with discordant qualitative antibody results, TSI was more likely than TRAb to match the clinical diagnosis of GD (6 TSI-positive vs. 2 TRAb-positive patients).ConclusionThe automated TSI bridge immunoassay was positively correlated with thyroxine levels in new-onset GD patients and was more likely to be consistent with the clinical diagnosis of GD than with that of TRAb. The positive Immulite 2000 TSI cut-off value of 0.577 IU/L for GD diagnosis in the Chinese population were close to the value recommended by the manufacturer.

Longitudinal association of thyroid-stimulating immunoglobulin levels with clinical characteristics in thyroid eye disease

ObjectivesThe clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the...