TSH Receptor Antibodies Research Articles

Comparison of two different TSH-receptor antibody assays: A clinical practice study

BackgroundGraves’ disease (GD) is caused by the production of TSH-receptor (TSHR) stimulating auto-antibodies. Over the years various TSHR-antibody (TRAb) detection assays have been developed. Most clinical laboratories use competitive TSH-binding inhibitory immunoglobulin (TBII) assays, which measure the total amount of stimulating and blocking auto-antibodies. Selective detection of TSHR stimulating auto-antibodies (TSI) was previously only possible with functional cell-based bioassays. However, more recently an automated bridge-based binding assay to more specifically measure TSI has become available. The aim of our study was to compare the third-generation automated competitive immunoassay (TBII) with the automated bridge immunoassay (TSI) in clinical practice in an academic thyroid expert center. MethodsA retrospective study in 356 patients with Graves’ disease, Graves orbitopathy (GO), and other (thyroid) disease treated in an academic thyroid center was performed. All samples were analyzed for TBII and TSI. For both assays, sensitivity, specificity, positive predictive value (PVV), negative predictive value (NPV) and diagnostic odds ratios were calculated using different cut-offs for negativity. ResultsUsing the provided cut-off, the overall sensitivity appeared similar between TBII and TSI, but TSI showed higher overall specificity, PPV, NPV and diagnostic odds ratio. Using two or three times the cut-off for negativity resulted in a decrease in sensitivity, but an increase in specificity and PPV, which was most pronounced for the TBII-assay. Analysis in a subgroup of newly diagnosed treatment naïve GD/GO patients also revealed overall favorable results for the TSI-assay. Increasing the cut-off for negativity resulted in increased specificity for both assays, with similar results using two or three times the cut-off. Most patients with concordant positive results for TBII and TSI suffered from GD or GD + GO (n = 110, 95.6 %), while patients negative for both TBII and TSI mostly suffered from other (thyroid) disease (n = 143, 77.3 %). From patients with positive TBII but negative TSI only 42.1 % had GD/GO (n = 16), whereas 57.9 % (n = 22) had other (thyroid) disease. In contrast, 88.9 % of patients with positive TSI but negative TBII had GD/GO (n = 16), whereas 11.1 % (n = 2) had other (thyroid) disease. ConclusionIn our academic thyroid center, the diagnostic performance of the TSI-assay outperformed the TBII-assay. Using a higher cut-off value for negativity can be helpful in assessing clinical relevance.

A Rare Case of Painless Destructive Thyroiditis Resulting in Thyroid Storm.

Thyroid storm is a life-threatening clinical condition that is usually triggered by untreated or interrupted treatment of Graves' disease, leading to the sudden onset of severe thyrotoxicosis, which requires an immediate diagnosis and treatment based on diagnostic criteria. Cases of thyroid storm caused by painless/painless subacute thyroiditis are very rare. We herein report an 85-year-old man with features of severe thyrotoxicosis caused by painless/painless subacute thyroiditis who had no uptake of 99mTcO4 and was negative for thyroid-stimulating hormone receptor antibodies. In thyroid storm patients in whom the findings are inconsistent with Graves' disease, careful follow-up and management are necessary, assuming the possibility of painless or painless subacute thyroiditis.

Clinical and immunological predictors of Graves' orbitopathy after radioiodine therapy of Graves' disease

Data on the effect of 131I on the course of Graves' orbitopathy (GO) are contradictory. A number of studies indicate a deterioration in the course of GO against the background of RAIT, in other studies such a connection has not been established. Cytokines that regulate inflammation could potentially be biomarkers for assessing GO activity and predicting the course of GO after RAIT. The purpose of this study was to evaluate the dynamics of eye symptoms and analyze immunological parameters: cytokine TGF-β1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, sIL-6R over time after RAIT, as possible predictors of GO activation. The study included 59 patients (118 orbits) with GD in the state of euthyroidism and subclinical hyperthyroidism and low active and inactive GO, aimed at conducting RAIT. Concentrations of cytokine TGF-β1, sTNFα-RI and sTNFα-R2, sIL-2R, sIL-6R, TSH receptor antibodies (rTSH-Ab), free thyroxine (FT4) and free triiodothyronine (FT3), -thyroid-stimulating hormone (TSH) in the blood serum were determined. Ultrasound examination of the thyroid gland, multispiral computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits was performed. The examination was carried out 3, 6, 12 months after the RAIT. The deterioration of the course of the GO (1-2 points according to CAS) was noted after 3 months. (32.5%) and to a lesser degree after 6 and 12 months (13.2% and 8.45%, respectively). Dynamics were not noted, approximately, in the same number of patients (40.5%, 41.5%, 45.8%, respectively). An improvement in the course of the GO was noted after 6 and 12 months (45.3, 45.8, respectively). After 3 and 6 months, the achievement of hypothyroidism and a significant increase in the level of rTSH-Ab were noted. In the analysis of cytokines and their receptors a significant decrease in the level of TGF-β1 was noted after 3, 6 and 12 months. There was also a significant decrease in sTNF-R1 and sIL-2R at 3 and 6 months. The level of sTNFα-R2 significantly decreased 3 months after RAIT. The level of sIL-6R has not changed significantly. After 3 months in patients with positive dynamics of image intensification, the level of TGF-β1 did not significantly change compared with the level before RAIT, in patients with worsening of the course of GO or without dynamics, the level of TGF-β1 significantly decreased. After 6 months, there was the same trend, not reaching statistical significance. The IgG4 level and the IgG4/IgG ratio increased to 6 and 12 months, which corresponded to an increase in diplopia index. The main limiting factor in the conduct of RAIT is the activity of the autoimmune process in the orbits. Since patients with inactive (CAS 0-2) or low activity (CAS 3-4) GO were referred for RAIT, there was no pronounced activation of GO after RAIT. There was a slight deterioration in the course of GO by only 1-2 points according to CAS after 3 months. (32.5%) and to a lesser degree after 6 months (13.2%). In the study, it was found that the main predictors of the deterioration of the course of GO after RAIT are uncompensated hypothyroidism, a high level of rTSH-Ab and a decrease in the level of cytokine TGF-β1.

Abstract 17455: Heart in Crisis: Graves’ Thyrotoxicosis-Induced Cardiomyopathy

Background: We present a case of a young healthy male who presented with signs and symptoms of congestive heart failure and was subsequently diagnosed with dilated cardiomyopathy secondary to an unknown history of Graves’ disease. Case Presentation: A 40-year-old male with no medical history presented to the hospital with scrotal and bilateral lower leg edema for 4 days with associated shortness of breath. Physical examination was significant for an irregularly irregular heart rhythm. Electrocardiogram showed atrial fibrillation with a rapid ventricular response (Image B). Initial laboratory findings were elevated NT-proBNP of 1,240 pg/mL (<125 pg/mL). Chest x-ray revealed significant cardiomegaly (Image A). Echocardiogram demonstrated an ejection fraction of 20% with a severely dilated bilateral atrium, left ventricle with severe diffuse hypokinesis of the left ventricle, and severe mitral regurgitation (Images C and D). Endocrine was consulted for abnormal thyroid function tests with TSH of <0.010 mU/L (0.27-4.2 mU/L), free T4 of 6.06 ng/dL (.93-1.70 ng/dL), T3 of 258 ng/dL (80-200 ng/dL), thyroid-stimulating immunoglobulin of 9.51 IU/L (0.00-.55 IU/L) and TSH receptor antibody 14.00 IU/L (0.00-1.75 IU/L). The patient was started on methimazole and metoprolol with close follow-up with cardiology and endocrinology. Discussion: Severe Cardiomyopathy in adult patients with hyperthyroidism is rare occurring in approximately 6% of patients with less than 1% developing dilated cardiomyopathy with impaired left ventricular systolic function. Although the mechanism of dilated cardiomyopathy is still being researched it has been suggested that prolonged uncontrolled hyperthyroidism and autoimmunity as the potential causes. Further studies are needed to develop optimal management studies as it has been shown that the management of thyrotoxicosis can reverse cardiovascular manifestations and prevent irreversible cardiomyopathy.

Abstract 17328: A Case of Reversible Severe Systolic Cardiomyopathy; Thinking Outside the Box

Introduction: Non-ischemic systolic cardiomyopathy is associated with significant morbidity and mortality. Prompt evaluation and timely removal of the potential insult may lead to reverse remodeling and recovery of the left ventricular (LV) systolic function. Case: A 39-year-old female with BMI 40 presented with dyspnea and bilateral lower extremity edema. Vital signs significant for mild tachycardia and hypertension. ECG showed sinus tachycardia. Physical exam revealed bibasilar crackles and 3+ pitting edema of the lower extremities. Laboratory significant for NTpro BNP 563 pg/dL and TSH <0.005 IU/mL with a free T4 of 2.73 ng/dL. Chest x-ray showed pulmonary vascular congestion. Echocardiogram showed severely reduced LV systolic function with ejection fraction (EF) of 27%, global LV hypokinesis and diastolic LV diameter of 6.85 cm. No significant atrial or ventricular arrhythmias noted on Telemetry. A CT angiography of the coronary arteries showed no evidence of calcification or obstructive coronary disease. Additional labs revealed severely elevated TSH receptor antibody and thyroid stimulating immunoglobulin. Diffuse thyroid enlargement noted on ultrasound. Patient was diagnosed with Grave’s disease (GD) with Burch-Wartofsky score of 30 indicating an impending thyroid storm. She was treated with Metoprolol and Methimazole. She underwent intravenous diuresis and was started on guideline-directed medical therapy for systolic cardiomyopathy. In follow-up after 6 months, her TSH had normalized. On repeat imaging, her LVEF improved to > 50% with diastolic LV diameter of 5.6 cm. Discussion: This patient was diagnosed with non-ischemic dilated systolic cardiomyopathy due to severe hyperthyroidism from GD. Thyrotoxicosis-induced systolic cardiomyopathy occurs in about 1% of patients with GD and is associated with increased morbidity and mortality. Excess thyroid hormones in thyrotoxicosis can affect multiple regulatory and structural genes of cardiac myocytes resulting in abnormal intracellular calcium regulation and impaired LV systolic and diastolic function. Our experience is consistent with literature demonstrating the importance of timely diagnosis and treatment of this reversible cause of systolic cardiomyopathy.

Effect of smoking status on TSH Receptor Antibody (TRAb) levels following treatment for Graves' disease

Effect of smoking status on TSH Receptor Antibody (TRAb) levels following treatment for Graves' disease

Cut-Off Value of Thyrotropin-Receptor Antibodies in Grave's Disease in Basrah.

The diagnosis of Grave's disease (GD) poses a challenge. Thyrotropin-receptor antibodies (TRAb) are the key diagnostic feature of GD, as the American and European Thyroid Associations suggested. This study aims to find a cut-off level of TRAb in GD in Basrah. This is a retrospective study that included 617 patients with hyperthyroidism (530 GD and 87 non-Grave's disease (NGD) (thyroiditis or subclinical hyperthyroidism)). The candidates were patients presenting with hyperthyroidism who were referred for TRAb assay, while patients with thyroid carcinoma or nodular thyroid disease, pregnant ladies, and patients who were treated were excluded. The manufacturer cut-off value of 1.75 IU/L had a sensitivity of 88.1%, specificity of 72.4%, positive predictive value (PPV) of 95.1%, and negative predictive value (NPV) of 50.0%. Our data analysis through receiver operating characteristic (ROC) statistics revealed that the optimum cut-off point with the highest total sensitivity and specificity was determined to be 3.95 IU/L, as it had a sensitivity of 76.9%, specificity of 98.8%, PPV of 99.7%, NPV of 41.3%. For a more accurate diagnosis of GD, the findings of the present study support the implementation of a higher TRAb cut-off value (3.95 IU/L) than that predefined by the manufacturer (1.75 IU/L).

Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves' disease.

The aim is to validate the third generation Thyrotropin receptor antibody (TRAb) assay for predicting neonatal thyroid dysfunction and adverse pregnancy outcomes in pregnant women with Graves' disease. This prospective cohort study was conducted in TRAb positive pregnant women with Graves' disease and their off springs. The primary outcome was to assess different forms of neonatal thyroid dysfunction in relation to maternal and neonatal TRAb levels. The secondary outcome was to predict adverse pregnancy outcomes by using maternal TRAb levels. Serum T3, FT4, TSH, TRAb levels were measured using electrochemiluminescence immunoassay. 51 pregnant women were included. Five women had adverse pregnancy outcomes, TRAb levels of > 19.06 IU/L (10.9 times the upper limit of normal (ULN)) predicted adverse pregnancy outcomes with 100% sensitivity and 93.5% specificity. Among the 46 successful live births, 13 (28.3%) had neonatal thyroid dysfunction. Out of 13 neonates, 7 (32%) had neonatal thyrotoxicosis, 4 (18%) had primary hypothyroidism, and 2 (9%) had central hypothyroidism. Third trimester maternal TRAb levels of > 7.99 IU/L (4.6 times the ULN)and day three neonatal TRAb levels of > 5.03 IU/L (2.9 times the ULN), predicted the neonatal thyrotoxicosis with 100% sensitivity and 97.4% specificity. Very high maternal third generation TRAb levels strongly predicted the adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnant women with Graves' disease. Neonatal thyroid function test along with the TRAb levels strongly correlated with different forms of neonatal thyroid dysfunction and is very useful in avoiding inadvertent treatment to neonates.

Hyperthyroidism: A Review.

Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

PREGNANCY OUTCOME IN WOMEN WITH GRAVES’ DISEASE

Background and Aims: Pregnancy complicated with poorly controlled thyrotoxicosis is associated with an increased risk of adverse pregnancy outcomes, and maternal complications. To study the clinical characteristics, feto-maternal outcomes in women with Graves’ disease (GD) during pregnancy. Methods: This was observational study on 98 patients with GD during pregnancy at the tertiary care hospital. GD was documented by Thyrotropin receptor antibody (TRAb). Patients were subjected to complete clinical work up and thyroid profile. The diagnosis of TAO was based on the criteria of Bartley and Gorman. 100 pregnant women with normal thyroid function were taken as control. Birth outcomes recorded were: route of delivery (vaginal or cesarean section), neonatal birth weight, spontaneous abortion, stillbirth, and small for gestational age (SGA). Maternal outcomes accessed were: gestational hypertension, gestational diabetes (GDM), preeclampsia, gestational age at delivery, preterm delivery, antepartum hemorrhage, and postpartum hemorrhage. Results: The mean age of the patients was 30.8±7.6 years as compared to 32.9±6.8 years in controls. Compared with the controls; the pregnant women with GD had significantly higher rates of small for gestational age (SGA) (23.5% vs. 12.0%; p: 0.034), preterm birth (22.4% vs. 12.0%; p: 0.049), preeclampsia (15.3% vs. 5.0%; p: 0.016) and cesarean section (82.7% vs.70.0%; p: 0.036). Maternal and neonatal outcomes in pregnant women with GD with controlled and uncontrolled thyrotoxicosis were not significantly different except for birth weight. Conclusion: GD was significantly associated with an increased risk of adverse pregnancy outcomes.

VASOSPATIC ANGINA IN GRAVES DISEASE

Category A Thyroid hormones play a key role in the growth and metabolism of almost all tissues. Any abnormal increase or decrease of these hormones can cause impairment in functioning of almost all organ systems. Hyperthyroidism has been associated with a number of cardiac manifestations including tachycardia, cardiac arrhythmia especially AF, cardiomyopathy, angina or even myocardial infarction. Here we present a case of a 38 year old female with no known comorbidities who presented to medicine casualty with complaints of recurrent episodes of typical angina lasting 15–20 min or more. Her vitals showed mildly elevated blood pressure of 150/90 mmHg and tachycardia. An ECG taken immediately showed ST segment depression in the anterolateral leads. Cardiac biomarkers were negative. A provisional diagnosis of acute coronary syndrome was made and treatment started. Echo was found to be normal. Patient continued to have recurrent episodes of angina. Coronary angiography was normal. On detailed evaluation patient gave a history of palpitation, loss of weight, diarrhoea and increased sweating in the last 3 months. Detailed physical examination revealed a painless neck swelling. Laboratory tests showed Hb – 12 g/dl, serum K – 4.1 mmol/dl, Ca – 9.2 mg/dl, LFT and RFT normal, fT3 – 22.9, fT4 – 64.2, TSH <0.01 suggestive of hyperthyroidism. On further evaluation she was found to be positive for TSH receptor antibody and was diagnosed with Grave’s disease. She was started on anti-thyroid drugs and propranolol. Nitrates were stopped after 6 months and patient remains asymptomatic on treatment. Conclusion: Hyperthyroidism may present in numerous ways and may even be life threatening. This case highlights the importance of checking the thyroid status of patients, especially in the younger age group, with no obvious cause or risk factors presenting with angina. They may not always have classical symptoms of hyperthyroidism. A delay in diagnosis can result in undue complications and unnecessary interventions. Most of these patients were found to lead a normal life with proper medications once diagnosed.

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<0.001), fT4 (r:0.252, p<0.001) and Thyroid stimulating immunoglobulin (TSI) (r:0.673, p<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

SAT460 Higher TSH Receptor Antibody At Diagnosis And Younger Age Predict Recurrence of Graves' Thyrotoxicosis After Thionamide Withdrawal At 10 Years

Abstract Disclosure: F.W. Gibb: None. N. Tun: None. Background: Anti-thyroid drug (ATD) therapy in Graves’ disease is generally accepted to be a safe and effective means of restoring euthyroidism. Treatment is typically administered for 12 to 18 months followed by cessation subject to certain conditions such as achieving euthyroidism on a low dose and, in some centers, exclusion of persistently elevated TSH receptor antibody (TRAb) levels. We and others have previously demonstrated the prognostic utility of TRAb at diagnosis and cessation of ATDs in predicting recurrence risk. However, very few studies have assessed recurrence risk in the long-term. Methods: Prospective observational study of thyroid status at 10 years in 231 people who completed a physician directed course of ATD for Graves’ disease (first episode). We also assessed clinical predictors of recurrence at 10 years post ATD-cessation. Results: Median age was 43 years (IQR 35 - 53) and 181/231 (78%) were female. 10 years after cessation of ATD 124/231 (53.7%) had experience a relapse of thyrotoxicosis. The following parameters were associated with recurrence at 10 years: 1. TRAb category at diagnosis: <5 IU/L (relapse 43.2%), 5 - 12 IU/L (relapse 50.0%) and >12 IU/L (relapse 71.9%) (p = 0.003). Median TRAb in those with relapse was 8.7IU/L (4.9 - 16.9) vs. 5.9 IU/L (4.1 - 9.9) in those in remission at 10 years (p = 0.002). 2. TRAb at cessation of ATD was 1.3 IU/L (<0.6 - 2.2) in relapse and 1.0IU/L (<0.6 - 1.4) in remission (p = 0.006). 3. Median age in those with relapse was 40 years (32 - 49) vs. 47 (39 - 56) in remission (p = 0.001). 4. Median fT4 at diagnosis was 33pM (26 - 42) in those with subsequent relapse vs. 30pM (24 - 36) in remission (p = 0.045) 5. Time to normalisation of fT4 was 2 months (1 - 2) in people with relapse vs. 1 month (1 - 2) in people in remission (p = 0.003). In logistic regression higher TRAb at cessation (p = 0.003) and younger age (p = 0.002) were independently associated with relapse at 10 years. Sex, smoking status and presence of ophthalmopathy did not influence recurrence risk. 73% of relapses occurred within 2 years and only 5% of relapses occurred between 5 and 10 years. At ten years, 16 patients (6.9%) had died (9 in remission and 7 after relapse), 45 were on long-term ATD (19.5%), 39 received radioiodine (16.9%), 13 had thyroidectomy (5.6%), 7 developed hypothyroidism (3.0%) and 111 were on no treatment (48.1%). Conclusions: Discussions with patients about risk of relapse should be individualised based on TRAb and age. In this cohort someone under 43 years with TRAb >12 IU/L at diagnosis had a 88% risk of relapse whilst someone older than 43 with TRAb <5 IU/L at diagnosis had a relapse rate of 38%. However, although the recurrence rate is lower in older individuals, the clinical risks of recurrent thyrotoxicosis are greater and may still support definitive therapy or long-term ATD use. Presentation: Saturday, June 17, 2023

THU668 Euthyroid Graves’ Ophthalmopathy: Case Series

Abstract Disclosure: S.S. Alfadl: None. A.A. Asiri: None. A.A. Jammah: None. O. Alsagheir: None. Introduction: Graves’ ophthalmopathy is an autoimmune disorder that affects the eyes, characterized by swelling, proptosis, lid lag, inflammation and eyelid retraction. A significant proportion of cases are associated with thyrotoxicosis and positive serum TSH receptor antibody tests. Case Description: We present a case series of euthyroid Graves’ ophthalmopathy in patients with a negative TSH receptor antibody. The first case is of a 37-year-old lady who was recently diagnosed with idiopathic intracranial hypertension due to history of recurrent headaches and was found on CT brain to have an incidental empty sella syndrome and findings highly suggestive of thyroid associated orbitopathy. A dedicated MRI orbit showed bilateral mild proptosis with bilateral medial and inferior recti thickening, sparing the tendinous insertion. The involved extraocular muscles show mild peripheral high T2 signals and minimal enhancement on post gadolinium images. The enlarged extraocular muscle demonstrates diffusion restriction with low Apparent Diffusion Coefficient (ADC) value. Clinically, the patient did not exhibit any symptoms of hyperthyroidism or hypothyroidism. She did not notice any changes in her eyes’ appearance, nor any changes in vision or double vision. On examination, she had mild proptosis, no restriction of extraocular movement or provoked double vision. Consequently, she was referred to Ophthalmology for further management. Investigations included a pituitary panel which did not reveal any abnormalities and a thyroid panel which revealed that she was biochemically euthyroid with a negative TSH receptor antibody test. The second case is of a 24-year-old male who is medically free and initially visited the ophthalmology clinic complaining of double vision, without any additional ophthalmic complaints. He was subsequently referred to our care to rule out thyroid eye disease. Clinically, the patient had no indications of thyroid dysfunction. Upon examination, he exhibited severe right eye proptosis with dystopia and early left eye proptosis. CT orbit showed swelling of the right-sided superior rectus, medial rectus, lateral rectus and left-sided superior rectus muscles. The left-sided superior rectus muscle was abutting the optic nerve. Nevertheless, all tendons were spared. Biochemically, he was euthyroid with unremarkable laboratory results. Conclusion: These findings provide insight into the clinical presentation of euthyroid Graves’ ophthalmopathy in patients without thyrotoxicosis or detectable circulating levels of TSH receptor antibodies. Thus, suggesting that thyroid ophthalmopathy might present earlier than Graves’ disease and even earlier than the presence of TSH receptor antibodies. We conclude that a high index of suspicion and proper follow up is recommended in similar patients for the development of Graves’s disease. Presentation: Thursday, June 15, 2023

FRI549 The See-Saw Theory - Hypothyroidism Due To Hashimoto's Thyroiditis Followed By Hyperthyroidism Due To Graves' Disease

Abstract Disclosure: P. Sharma: None. Introduction: Hashimoto's thyroiditis is an autoimmune disorder characterized by chronic inflammation of the thyroid gland that leads to hypothyroidism due to formation of autoantibodies against thyroid antigens such as thyroid peroxidase (TPO Ab). Graves' disease is caused by stimulating TSH-receptor antibodies (TRAb) that cause hypertrophy of the thyroid gland leading to hyperthyroidism. While the transformation of Graves' disease to Hashimoto's thyroiditis has been reported, flipping from Hashimoto's thyroiditis to Graves' disease is uncommon. Case Report: A 62 year old female with 20 year history of hypothyroidism secondary to Hashimoto's thyroiditis presented to establish care. She had run out of levothyroxine refills one year prior during COVID-19 pandemic restrictions. She had tachycardia, diarrhea, fatigue, tremors, hair loss, dysphagia, and weight gain. Thyroid panel testing showed hyperthyroidism with an undetectable TSH (normal range 0.45-4.5uIU/ml) and elevated free T4 (2.84, normal 0.82-1.77ng/ml). Patient denied recent infections, iodine intake or iodine contrast exposure. Repeat labs confirmed hyperthyroidism with undetectable TSH with elevated free T4 (3.17ng/ml). Antibody testing comfirmed hyperthyroidism secondary to Graves disease (TRAb 20.7, normal <1.75IU/L). Patient has been on methimazole with fluctuating response and is reviewing definitive therapy options. Discussion: We demonstrate the rare phenomenon of thyroid function transformation from long-standing inhibition to stimulation after 20 years. Hashimoto's thyroiditis is characterized by chronic inflammation due to autoantibodies against TPO, thyroglobulin and the TSH receptor with gradual gland destruction and hypothyroidism. Stimulating autoantibodies to the TSH receptor (thyroid stimulating immunoglobulin (TSIg), TRAb) in Graves' disease lead to hyperthyroidism from gland hypertrophy. The flip from underactivity to overactivity can be explained by recovery of the gland from Hashimoto's thyroiditis injury which gradually leads to an overt response to TSIg, causing a hyperfunctioning gland. An imbalance between the inhibitory and stimulating antibodies can also lead to this transformation. Age, pregnancy and immunomodulating drugs such as alemtuzumab are also thought to play a role. The recovery theory is unlikely in our patient with a 20 year history of Hashimoto's thyroiditis. We believe that she had a high inhibitory antibody titre initially and now has higher titre of stimulating antibodies later, leading to Graves' disease. Luckily, she ran out of levothyroxine otherwise the additive effect of levothyroxine and intrinsic gland activity could have led to worse symptoms. This case highlights that autoimmune hypothyroidism and hyperthyroidism are conditions in the same spectrum, rather than two distinct entities as previously thought. Presentation: Friday, June 16, 2023

FRI559 An Uncommon Association Of Two Common Etiologies Of Hyperthyroidism

Abstract Disclosure: C. Chew: None. Introduction: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. Association of these two diseases in patient presented with recurrent hyperthyroidism has rarely been reported. Case Report: A 35 years old women, with no known medical illness, was referred to Endocrine Clinic for painful anterior neck swelling associated with palpitation for 2 weeks. The symptoms were preceded by 3 days history of sore throat and mild fever She denied other symptoms of hyperthyroidism. Her last menses was 3 weeks prior. On physical examination, she was tachycardic with heart rate of 115 beats per minute. Her blood pressure was 135/90 mmHg and she was afebrile. There was a tender and diffusely enlarged goiter. However, there were no signs of thyroid eye disease and other signs of hyperthyroidism. Examinations of her throat, lung, abdomen, cardiovascular system and neurological system were unremarkable. There was also absence of lymphadenopathy. She denied family history of thyroid disease. Results of laboratory investigations were suggestive of hyperthyroidism secondary to subacute thyroiditis: Free T4 52 pmol/L (8-16), TSH <0.01 mIU/L (0.45-4.50), TRAb 0.8 IU/L (0-1.0) and ESR 108 mm/hr (1-10). The technetium scan showed mildly enlarged gland with decreased uptake of Tc-99m tracer suggestive of thyroiditis. She was treated with Ibuprofen and Propranolol, and her symptoms improved. At 6 weeks follow up, her thyroid function normalized with Free T4 of 13 pmol/L (8-16), TSH of 1.28 mIU/L (0.45-4.50). However, she complained of weight loss and palpitation at 6 months follow up. Examination revealed a small painless diffuse goiter and she was tachycardic with heart rate of 115 beats per minute. Thyroid function test confirmed recurrence of hyperthyroidism: free T4 45.8 pmol/L (8-16) and TSH <0.01 mIU/L (0.45-4.50). Elevated TSH receptor antibody (TRAb) level at 16.8 IU/L confirmed the diagnosis of Graves’ disease. Carbimazole was then started. Discussion: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. The incidence of association of these two diseases had been reported to be rare at 0.15% in patients with Graves’ disease and 0.76% in patients with subacute thyroiditis (1). The postulated mechanism of the association is that the release of thyroid antigens and corresponding activation of the immune system due to viral invasion of the thyroid gland in subacute thyroiditis may cause the subsequent Graves’ disease (1,2). Conclusion: Graves’ disease should be suspected in patient with persistent or recurrent hyperthyroidism after an episode of subacute thyroiditis although it is rare. Reference: 1. Nakano Y et al. Graves’ disease following subacute thyroiditis. Tohoku J. Exp. Med. 2011; 225:301-309. 2. Bartalena L et al. Graves’ disease occurring after subacute thyroiditis. Report of a case and review of the literature. Thyroid. 1996; 4:345-348. Presentation: Friday, June 16, 2023

SAT495 Persistent Euthyroid State in a Patient with Biochemical and Imaging Evidence of Graves' Disease

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. M. Joglekar: None. B. Fritz: None. S. Patel: None. V. Verma: None. R. Kant: None. INTRODUCTION: Elevated TSI antibody and/or diffuse uptake on radioactive Iodine-123 scan is diagnostic of Graves’ disease. Thyromegaly with increased blood flow on color doppler seen on thyroid USG can also aid in the diagnosis. Rare presence of positive TSI antibody without hyperthyroidism has been reported1. Rare co-existence of both Graves’ disease and Hashimoto’s thyroiditis in a patient causing a challenging clinical course has been reported2. Presence of a neutralizing or blocking antibody against the TSH receptor1 or a false positive TSI have been implicated in such rare cases. CLINICAL CASE: A 37-year-old Caucasian Female was seen at our endocrinology clinic for further evaluation of thyroid disorder. Patient initially experienced goiter during 1st pregnancy at age 18, followed by hypothyroidism during last pregnancy needing levothyroxine treatment. Due to goiter history, patient underwent work-up by her primary physician in 2021. Thyroid ultrasound (usg) showed bilateral hyperemia, heterogeneous echotexture, and 0.2 cm cystic nodule in the right upper lobe. Labs showed normal TSH 1.33 uIU/ml (0.3-4.0 uIU/ml), normal Free T4 0.99 ng/dl (0.8-1.8 ng/dl), normal total T3 140 ng/dl (71-180 ng/dl). Patient underwent further work-up by endocrinology in 2022. Thyroid ultrasound again revealed bilateral hyperemia with other similar findings. Labs showed normal TSH 2.02uUI/ml, normal free T4 0.93 ng/dl, normal total T3 138 ng/dl. Interestingly, TSI antibody and TPO antibody were significantly elevated at 66.70 IU/L (0.0-0.55 IU/L) and 517 IU/ml (0-34 IU/ml), respectively. Repeat labs in April 2022, again showed normal TSH 1.77 uIU/ml, normal free T4 0.90 ng/dl and normal free T3 2.94 (2.0-4.40 pg/ml). Thyroid uptake scan was not performed due to persistently normal TSH values. Patient denied the use of biotin supplementation. Patient continues to remain clinically and biochemically euthyroid without treatment. CONCLUSION: Our case supports the rare presence of TSI antibody without hyperthyroidism. Close monitoring is warranted due to possibility of future progression to overt hyperthyroidism. REFERENCE: 1. Alvin Mathew A, Papaly R, Maliakal A, et al.(November 10, 2021)Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi:10.7759/cureus.194482. Vipin Verma, MD, Mc Anto Antony, MD, PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach, Journal of the Endocrine Society, Volume 6, Issue Supplement_1, November-December 2022, Page A833, https://doi.org/10.1210/jendso/bvac150.1723 Presentation Date: Saturday, June 17, 2023

THU665 Unilateral Graves’ Disease In A Bilobar Thyroid Gland: Unusual Cause Of Hyperthyroidism

Abstract Disclosure: K.H. Alaybaa: None. O. Alhuzaim: None. Introduction: Graves' disease (GD) is an autoimmune condition that affects both thyroid gland lobes. GD patients with unilateral thyroid scan uptake are rare. These patients present with classic Graves' symptoms, occasionally with Graves' ophthalmopathy characteristics and increased thyroid hormones, and scintigraphic assessment reveals radiotracer uptake in only one lobe of the thyroid gland. Patient Findings: In this case, a 48-year-old female presented with symptoms and signs indicative of thyrotoxicosis. Lab results revealed that thyroid-stimulating hormone (TSH) was undetectable, while free thyroxine (T4) and free triiodothyronine (T3) were in the high-normal range. Positive results were observed for both thyroid-stimulating immunoglobulin and TSH receptor antibodies. Ultrasonography of the thyroid gland revealed an enlarged left lobe with heterogeneous echotexture and a hyperemic gland without any focal lesions, distinct nodules, or cysts. The NM TC-99M thyroid scintigraphy revealed enlarged and increased radioisotopes uptake in the left thyroid lobe and decreased uptake in the right thyroid lobe, with no hot or cold nodules. The calculated thyroid uptake is 4.5 percent (normal range: 0.5% to 3.5 percent). The most likely diagnosis was unilateral GD. The patient was administered carbimazole and within eight weeks had improved clinically and biochemically. Summary: This patient has thyrotoxicosis symptoms and positive autoantibodies. Tc99m uptake was increased in the left thyroid lobe and decreased in the right thyroid lobe. The left thyroid lobe was hypervascular and enlarged on ultrasonography, indicating the presence of unilateral GD. Unilateral GD is a rare disease with a poorly understood pathophysiology. Presentation: Thursday, June 15, 2023

THU240 A Study Of 21 Cases Of Graves Disease In Childhood Presenting At Our Hospital For The First Time

Abstract Disclosure: T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. M. Noordin: None. Although Graves disease is most common among women in their 20s and childhood-onset cases account for less than 5% of all cases of Graves disease, they account for the majority of hyperthyroidism in children. We report here a retrospective review of data on pediatric patients with Graves' disease who visited our hospital for the first time at the time of their initial examination. Methods We analyzed 21 pediatric patients with Graves disease who visited our hospital between November 2004 and January 2022. The electronic medical records of 21 patients were retrospectively reviewed for sex, age, height SD score, weight SD score, underlying disease, blood test results, and treatment initiation. Results There were 17 girls and 4 boys. The median age was 11 years and 5 months. Symptoms such as fever, feverishness, palpitations, weight loss, hyperactivity, and irritability were observed in 5 of the patients. Four patients had symptoms related to academic performance, such as low grades and poor concentration. Median physical findings were height SD score 0.62 (N=21), weight SD score 0.06 (N=21), and body mass index -4.4%. Two patients had bronchial asthma and atopic dermatitis, and one had myasthenia gravis and trisomy21 as underlying diseases. One patient was considered to have attention deficit hyperactivity disorder and was receiving antipsychotic medication. The median blood test values at the first visit were ALP 857 U/L (N=19), total cholesterol level 122 mg/dL (N=19), fT3 14.31 pg/mL (N=21), fT4 4.60 ng/dL (N=21), thyroid stimulating antibody 668 % (N=7), TSH receptor antibody 16.6 IU/L (N=20 TSH was less than sensitive in all cases. Nineteen patients received thiamazole. Fourteen patients received propranolol. Five patients received inorganic iodine. Five patients received inorganic iodine, starting at a median of 0.926 mg/kg/day of body weight. Discussion As with adults, females were more common. The symptoms were similar to those of attention deficit hyperactivity disorder, and thus warranted attention. Symptoms related to poor academic performance were also considered important. Anti-thyroglobulin antibodies and anti-TPO antibodies were also detected, suggesting that we should be careful about the possibility of the disease progressing to Hashimoto's disease. Presentation: Thursday, June 15, 2023

FRI548 A Case Of Periureteric Myxedema

Abstract Disclosure: J.M. Ferris: None. J. Merrimen: None. S.M. Kaiser: Advisory Board Member; Self; Amgen Inc. Speaker; Self; Amgen Inc. Background: Graves’ disease is the most common cause of hyperthyroidism. Classic extrathyroidal manifestations include Graves orbitopathy and pretibial myxedema (also known as thyroid dermopathy). Both involve cytokine-induced hyaluronic acid secretion by fibroblasts, likely related to TSH-receptor antibodies. Pretibial myxedema is now rare, but nearly always coexists with orbitopathy. It classically involves the shins, but has been described in other locations. Here we present a case of myxedema changes affecting the periureteric soft tissue of a patient with Graves’ disease. Case: A 46-year-old male was seen by endocrinology for symptomatic hyperthyroidism. His clinical presentation was consistent with Graves’ disease and the diagnosis was confirmed with a strongly positive TSH receptor antibody of 25 IU/L (normal <1 IU/L). He had findings of moderate thyroid eye disease and had bilateral skin changes suspicious for pretibial myxedema. The skin findings preceded his hyperthyroidism by a few years. Dermatology was consulted and a skin biopsy confirmed pretibial myxedema, which was treated with triamcinolone injections with good effect. His thyroid function normalized with methimazole. Coincidentally, while being treated for Graves’ disease he altruistically donated a kidney to a transplant recipient. During the nephrectomy, it was noted that part of the periureteric tissue appeared thickened and firm, and further dissection revealed a soft tissue, lipoma-like mass surrounding the ureter. A frozen section sent from the operating room was found to contain myxomatous adipose tissue with very little cellularity. The final pathology reported adipose tissue with myxoid degeneration and reactive lymphoid aggregates. The histomorphology was consistent with a reactive process and there was no evidence of malignancy. In the context of the patient’s history the findings were concluded to be related to his Graves’ disease. Discussion: While pretibial myxedema most commonly affects the shins, it has also been described at other dermatologic sites, often associated with areas of trauma. Our patient, who had biopsy proven thyroid dermopathy, was also found to have myxedema affecting the ureter. To our knowledge this is only the third reported case of ureteral myxedema, and the first in a kidney donor. The patient’s renal function before surgery was normal, and post-nephrectomy his eGFR is mildly decreased, but stable. His thyroid function remains normal on methimazole. Presentation: Friday, June 16, 2023