TSH Receptor Antibodies Research Articles

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

FRI480 Uncovering The Mystery Of Macro TSH

Abstract Disclosure: F. Anwar: None. Z.I. Saeed: None. Introduction: An isolated elevation in TSH level, while uncommon, may result in incorrect diagnosis and improper treatment. We present a case of suspected hypothyroidism that was later found to be caused by macroTSH in the blood. Clinical Case: A 21-year-old asymptomatic female was diagnosed with hypothyroidism and started on levothyroxine at age 16 when routine lab work revealed TSH of 34.2 MCU (0.550-4.780 MCU) and free T4 of 1.1 ng/dl (0.89-1.76 ng/dl). She denied any personal or family history of thyroid disorders in the past. Patient later reported symptoms including palpitations and weight loss leading to discontinuation of levothyroxine. Repeat lab work showed TSH of 0.112 MCU and free T4 of 1.71 ng/dl. After discontinuing levothyroxine, TSH levels were found in range of 89.26 MCU to 106 MCU (0.550-4.780 MCU). Free T4 levels remained normal, even when tested using dialysis method. Total T3 level also remained normal at 87 ng/dl (80-200 ng/dl). TPO antibodies were slightly elevated at 9.3 IU/mL (0.0-9.0 IU/ml), TSI and TSH receptor antibodies were negative. Patient's high TSH level, lack of symptoms, and normal free T4 levels prompted the use of different assays to test TSH. We contacted Mayo Clinic Lab for further testing. One assay (Roche Elecsys) showed TSH level of 90.8 mIU/L, but this result was not significantly changed when sample was incubated with a commercial heterophile antibody blocking reagent. Another assay (Beckman Coulter Access TSH) produced a significantly different but still elevated result of 43.1 mIU/L. For research purposes, the sample was further tested for macroTSH using polyethylene glycol (PEG) precipitation, which resulted in TSH level of 5.8 mIU/L which was reduced from 90.8 mIU/L (94% reduction). These results were higher than the mean +/- 2 standard deviations of the control group (range 0% to 65% reduction in TSH with PEG in controls). This suggested presence of macroTSH, although the assay's performance characteristics and reference ranges had not been established at the time of testing for this patient. Patient's TSH levels remain high and she was advised not to begin the medication unless circulating thyroid hormone levels are abnormal. Conclusion: Macro TSH is a combination of monomeric TSH and anti-TSH antibodies, similar to macro-prolactin. It is considered inactive and has an estimated prevalence of 0.6-1.6%. In a review of over 150 patients, more than 50% of documented thyroid interferences, including macro TSH, led to incorrect diagnosis and improper treatment. This case demonstrates the significance of identifying macro TSH to avoid misdiagnosis and inappropriate management of euthyroid patients with isolated TSH elevation. Presentation: Friday, June 16, 2023

SAT472 A Case of Contrast Induced Thyrotoxicosis in a Patient Newly Diagnosed with Hyperthyroidism

Abstract Disclosure: E. Askar: None. B. Reddy: None. Background: It is quite uncommon for thyrotoxicosis to manifest itself after the administration of iodinated contrast. Although the actual prevalence has not yet been identified, estimates showed that the prevalence in areas with iodine deficiency is 0.25 to 0.5% and 0.025% in non-iodine-deficient areas with higher risk in elderly patients. Clinical Case: A 68-year-old female presented to the emergency department for 2 weeks of intermittent substernal chest pain associated with diaphoresis. She was diagnosed with hyperthyroidism by an outside clinic approximately one week prior to her presentation and was prescribed methimazole but did not start it. Her physical examination was significant for mild exophthalmos. EKG showed ST depression in anterolateral leads. Laboratory data showed a troponin of 0.328 ng/ml (0.0.015-0.45) which trended up to 4.830 after 3 hours and TSH of <0.005 mIU/L (0.358-3.74), otherwise BMP and CBC were within normal limits. Patient was started on aspirin, statin and heparin infusion along with methimazole. Patient was transferred to tertiary hospital for urgent cardiac catheterization that showed 90 % stenosis of left anterior descending artery (LAD) and 95 % stenosis in distal right coronary artery (RCA). A successful drug eluting stent was deployed in LAD with a plan of staged PCI in RCA. An hour after the procedure, Patient complained of palpitations and diaphoresis. Laboratory findings at that time revealed Free T4 of 17.5 ng/dl (0.9-1.8), Free T3 of 12.3 pg/ml (1.8-4.6) with positive Thyroperoxidase antibody, TSI and TSH Receptor Antibody. Thyroid ultrasound revealed diffusely heterogeneous thyroid gland with increased vascularity, consistent with Graves’ disease. The patient was diagnosed with thyrotoxicosis secondary to contrast administration. She was treated with methimazole 20 mg TID, metoprolol tartrate 25mg BID and hydrocortisone 25 mg BID. Decision was made to postpone the second procedure until trending down of thyroid hormones and improvement of symptoms. A successful staged RCA PCI was performed eight days later and patient did not experience any complications despite exposure to the same dose of iodinated contrast. Conclusion: Rarely, hyperthyroid patients may experience chest discomfort and EKG abnormalities that are consistent with cardiac ischemia. This usually happens in older patients with known underlying coronary artery disease in response to the rise in cardiac contractility and strain caused by thyrotoxicosis. Our case did not have any history or risk factors of coronary artery disease other than hyperthyroidism. This case highlights how recognition of hyperthyroidism may alter management, because the use of some procedures or treatments may acutely exacerbate the condition of the patient. Presentation Date: Saturday, June 17, 2023

SAT579 Newly Diagnosed Graves' Disease With Complete Heart Block In Elderly Patient. A Case Report

Abstract Disclosure: M.M. Eid: None. T. Zahra: None. J. Vargas-Jerez: None. Introduction: Hypothyroidism is the most common thyroid disorder in elderly. The prevalence of hyperthyroidism in elderly is 0.5-3% and mainly caused by toxic thyroid nodules. Graves’ disease is an autoimmune disorder mediated by TSH receptor antibody (TSHR AB), presents commonly with hyperthyroidism in middle age female(1). Complete heart block in elderly can be due to conduction system fibrosis, Ischemic/structural heart diseases, medications, electrolyte disturbance and hypothyroidism(2). Case 72yo, Female with history of DM and HTN. Denied smoking, alcohol, drug and allergy. Irrelevant family history. Medications include amlodipine, metformin and atorvastatin. She was referred to endocrinology clinic for low TSH (was normal last year). Review of system was negative, denied tremor, palpitation, anxiety, weight loss, bowel movement/mood/sleep change, vision/swallowing problem. Physical examination: ABP150/80, Heart Rate(HR) 75/min. Mild lid lag, no exophthalmos. No tremor. Thyroid gland: diffusely enlarged non tender, no bruit. Normal cardiopulmonary and abdomen examination. Laboratory work up TSH less than 0.01 normal 0.2 to 4.20 uIU/ml , FT4 3.5 normal 0.9 to1.8 ng/dl, FT3 6 normal 2 to 4.4 pg/ml. Repeat lab confirmed TSH suppression and high FT4 ,FT3. TSHR antibody 7.66 normal less than 1.75 IU/L, Thyroid stimulating immunoglobulin 5.05 normal less than 0.5 IU/L ,HBA1C 6.6, Normal liver and kidney function tests and Complete blood count. She was diagnosed with Graves’ disease, kept on Methimazole 10mg/day. 2 weeks later, she presented to the ED after syncope at home. Initial EKG showed complete heart block HR 35/min and right bundle branch block (RBBB), ABP 110/65. Hours later EKG showed transient first degree heart block HR 75/min, RBBB and left axis deviation, then complete heart block with HR 30/min. Normal Troponin, potassium 4.2 mmol/L, sodium 141 mmol/L, calcium 9.2mg/dl, TSH 0.015 uIU/ml,FT4 3 ng/dl. Negative Anti-Lyme IgG and IgM. Normal Echocardiogram. She underwent uneventful Dual chamber pacemaker implantation with close endocrinology follow up. Conclusion: Graves’ Disease has variable presentations in elderly. Hyperthyroidism causes tachyarrhythmia due to the positive chronotropic effect of thyroid hormones. Bradyarrhythmia in our case is most likely due to conduction system fibrosis and could be related to the inhibitory effect of TSHR AB in elderly in contrary to the simulating effect in young patients. It is still rare to diagnose symptomatic bradyarrhythmia with uncontrolled hyperthyroidism(1).

THU661 Marine-Lenhart Syndrome: An Unusual Presentation Of Hyperthyroid Disease

Abstract Disclosure: B. Ji: None. O. Adeniran: None. L. Soni: None. Background: Marine-Lenhart syndrome, also known as nodular Graves’ disease, is defined as the coexistence of functioning thyroid nodules and Graves’ disease. It is a rare syndrome, with a prevalence of approximately 0.8-2.7%. The two diseases may coexist or present at different times [1]. Treatment options include high doses of antithyroid medications or radioactive iodine and thyroidectomy in selected cases [2]. Clinical Case: A 72-year-old female with a medical history of right-sided breast cancer treated with lumpectomy and radiation therapy in 2012 on anastrozole was referred for multinodular goiter (MNG) evaluation in 2018. She was clinically and biochemically euthyroid. Her thyroid ultrasound demonstrated two isoechoic right lobe nodules measuring 2.1cm and 1.3cm, respectively. An isoechoic rounded isthmus nodule measures 2.1cm. Three isoechoic nodules in the left lobe measuring 2.6cm, 2.2cm, and 1.7cm. She underwent fine needle aspiration (FNA) of two nodules in 2019, and both demonstrated benign follicular nodules with Bethesda II classification. At a follow-up visit in 2021, she reported unintentional weight loss but denied any other symptoms of hyperthyroidism, including heat intolerance, palpitation, tremor, or diarrhea. Physical examination was significant for exophthalmos, lid retraction, and diffusely enlarged thyroid with non-tenderness to palpation. Thyroid function tests revealed subclinical hyperthyroidism with TSH of <0.01uIU/mL (0.27-4.2uIU/ml) and FT4 of 1.5ng/dL(0.9-1.8ng/mL). Thyroid stimulating immunoglobulin (TSI) was 3.98IU/L (0.00-0.55IU/L), and TSH receptor antibody was 7.64 IU/L (0.00-1.75 IU/L). She was started on low-dose methimazole therapy. Thyroid uptake scan showed markedly elevated radioactive iodine uptake with 63.46% in 24 hours and focal nodular regions of increased uptake of the bilateral thyroid lobes compatible with toxic multinodular goiter. Repeated thyroid ultrasound in 2022 revealed stable-sized nodules with at least two new sub-centimeter nodules in both lobes. The patient was also seen by ophthalmology and plans to start teprotumumab treatment. At her most recent follow-up visit in January 2023, she has been continued on methimazole 2.5mg daily. Conclusion: The criteria for diagnosing Marine-Lenhart syndrome have not been well established. The possibility of Marine-Lenhart syndrome should be considered in hyperthyroid patients with positive antibodies and nodular goiter. In this case, she was initially asymptomatic with an enlarged multinodular goiter; three years later, she developed subclinical hyperthyroidism due to Graves’ disease and toxic multinodular goiter. Her symptom and thyroid function are well-controlled with low-dose methimazole. Presentation: Thursday, June 15, 2023

FRI499 The Importance Of Identifying Atypical Presentation Of Thyroid Storm

Abstract Disclosure: D.H. Sacoto: None. C.A. Villavicencio: None. A. Franco-Akel, MD: None. R. Belokovskaya: None. Thyroid storm is a rare and life-threatening syndrome. Despite treatment and supportive measures, it has an estimated mortality around 8–25%. Identifying atypical clinical presentation such as psychosis is crucial since prompt diagnosis and treatment is paramount for survival. We present an unusual case of psychosis as the manifesting symptom of thyroid storm.A 54-year-old female with a history of major depressive disorder, hypertension, and Graves’ disease presented to the ED with a 3-day history of bizarre behavior noted by the family. At the time of examination, the patient had pressured and circumferential speech, flight of ideas, labile mood, and paranoid ideations. On further questioning, patient reported palpitations and lack of sleep on days previous to presentation. Vital signs revealed hypertension (182/101 mmHg), tachycardia (176 beat per minute), tachypnea, and a temperature of 99.6 °F. Warm skin, fine tremors, and patellar hyperreflexia were noted on physical examination. Subsequent studies showed a suppressed TSH (<0.01uIU/mL), an elevated T3 (227ng/dL) and free T4 (2.1ng/dL). TSH receptor antibody was found positive. Patient’s clinical presentation combined with a Burch-Wartovsky scale of 55 stablished the diagnosis. Further history was notable for non-adherence to methimazole. Iodine-131 was administered. Further treatment with prednisone, propranolol, and cholestyramine was started. Patient showed subsequent clinical improvement. Thyroid storm is a rare complication of hyperthyroidism. It is commonly precipitated by infection, surgery, or medication non-adherence. Atypical presentation of thyroid storm can be disguised as psychiatric condition or substance abuse disorder. These manifestations can be the result of a generalized hypermetabolism generated by an increase in NA+/K+ ATPAse activity, raising the basal metabolism, resulting in thermogenesis. In addition, upregulation of beta-adrenergic receptors lead to increased central nervous system sympathetic response. This results in a catecholamine surge which may manifest as psychosis, mania, or coma. Being aware of atypical presentation in thyroid storm such as active psychosis is key in early diagnosis and prompt management. Presentation: Friday, June 16, 2023