TSH Receptor Antibodies Research Articles

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

FRI484 Assessment Of Early-trimester Maternal Thyroid Function And Iodine Nutritional Status Of Pregnant Women In Northern Taiwan

Abstract Disclosure: G. Su: None. C. Yeh: None. C. Yang: None. C. Hwu: None. H. Chen: None. F. Wang: None. C. Huang: None. Background: The American Thyroid Association (ATA) has proposed to lower the early-trimester upper limit of the TSH reference interval to become 0.5 mIU/L less than the non-pregnant value. The local-regional reference intervals in Taiwan is unknown. The aim of the study is to evaluate the early-trimester thyroid function and iodine nutritional status of pregnant women in Taiwan. Methods: Women aged ≥20 years-old and in gestation 8 to 15 weeks were recruited in Taipei Veterans General Hospital from March 2019 to July 2022. Thyroid function and antibodies, including TSH, free T4, free T3, total T4, total T3, anti-thyroglobulin antibody (aTG) and anti-thyroidperoxidase antibody (aTPO), TSH receptor antibody, were measured. The gestation-specific thyroid function reference range was derived from the 2.5th and 97.5th percentiles of the studied women. Random spot urine sample was collected and urinary iodine concentration was checked by inductively coupled plasma mass spectrometry. A simple food frequency questionnaire was also completed. Results: A total of 211 women were enrolled and the derived early-trimester upper limit of serum TSH (median: 0.92 [0.007-3.08] uIU/mL) was lower than the value provided by the manufacturer (0.27-4.2 uIU/mL), while the upper limit of free T4 (median: 1.28 [0.93-2.15] ng/dL) and free T3 (3.00 [2.30-5.10]ng/dL) were both higher than the non-pregnant value (0.93-1.7 ng/dL and 2.0-4.4 ng/dL, respectively). The range of total T4 (median: 9.90 [6.39-15.36] ng/dL) and total T3 (median: 136 [89.50-223.20] ng/dL) in the studied women were similar to the non-pregnant range (5.1-14.1 ng/dL and 80-200 ng/dL, respectively). The positivity rate of aTG & aTPO were 8.6%. Two patients with mild Graves’ disease and three patients with subclinical hypothyroidism were incidentally detected and treated. The positive predictive value for detecting thyroid dysfunction using the non-pregnant reference interval was only 15.9% because subclinical hyperthyroidism (18.2%, n=37) would be over-diagnosed and subclinical hypothyroidism (1.0%, n=2) would be under-diagnosed. The overall median UIC was 160.9 μg/L, indicating a sufficient iodine status. Dairy products were the most commonly consumed iodine-containing food type with 71.8% of the pregnant women ingesting dairy products ≥3 days/week. The median intake frequency for seaweed, fish, and seafood were one day per week. Approximately 34.0% of the women took multivitamin every day, but 58.4% of the women never took multivitamin. Conclusion: Our results indicate that the iodine nutritional status in the early trimester of pregnancy is adequate and that the upper limit of serum TSH was approximately 1.12 uIU/mL lower than the upper limit provided by the manufacturer. Gestation-specific thyroid function reference intervals are needed for correct diagnosis of thyroid dysfunction in pregnancy. Presentation: Friday, June 16, 2023

FRI512 Thyrotoxic Periodic Paralysis With Extreme Hypokalemia Precipitated By Acute Alcohol Intoxication In A Patient With Graves’ Disease

Abstract Disclosure: J. Batra: None. A.R. Ankireddypalli: None. J. Kaur: None. Introduction: Thyrotoxic periodic paralysis (TPP) is a muscle and electrolyte disorder, mostly seen in the setting of hyperthyroidism. It is characterized by reversible painless muscle weakness and hypokalemia. Prevalence is highest in East Asian populations, approximately 2%, and 0.1-0.2% in other populations. Males are much more likely to be affected. Common provoking factors include exercise, fasting, and changes in diet. Clinical case: A 29-year-old male of East Asian ethnicity presented to the hospital with the complaint of multiple bouts of inability to lift his extremities for 1 day. He also complained of generalized weakness. He did not have any changes in his mental status and was fully oriented at the time of the presentation. No breathing difficulty was reported. He had been drinking the night before with his friends and drank 1 L of vodka. His past medical history was significant for hyperthyroidism secondary to Graves’ disease, which was diagnosed a year ago. He had been prescribed methimazole but had not been adherent to the medication. The basic metabolic panel revealed undetectable serum potassium of <1.5 (3.4 to 5.3 mmol/L). The rest of the electrolytes and renal function were unremarkable. TSH was suppressed at <0.01 (0.3 to 4.20 uIU/L) and free T4 levels were significantly elevated at 7.77 (0.9 to 1.70 ng/dL). The thyrotropin receptor antibody was 33 (0.00 to 1.75 IU/L). EKG showed sinus tachycardia with nonspecific T-wave abnormalities. Thyroid ultrasound showed diffusely heterogenous parenchyma with diffusely increased blood flow throughout the thyroid on doppler. Echocardiogram showed a normal ejection fraction of 55-60% with mild concentric left ventricular wall thickening consistent with left ventricular hypertrophy. He was initially treated with intravenous potassium replacement and high doses of propylthiouracil, hydrocortisone, and propranolol, leading to the resolution of his symptoms. He was discharged on methimazole and propranolol therapies. Learning points: • Patients with Graves’ disease are routinely counseled against tobacco use to avoid worsening of orbitopathy. Hyperthyroid patients should also be counseled regarding avoidance or moderation of alcohol intake to avoid this rare but potentially life-threatening complication of thyrotoxic periodic paralysis. • The incidence of TPP is significantly higher in the East Asian populations, especially among males (8.7-13%). Counseling regarding provoking factors, the importance of adherence to medications, and the maintenance of euthyroidism to avoid TPP is essential. Presentation: Friday, June 16, 2023

FRI503 HCG-induced And Autoimmune Hyperthyroidism In A Male Patient With HCG Secreting Germ Cell Tumor

Abstract Disclosure: A.H. Mohamed: None. M. Basina: None. Background: While Graves’ disease is the most common cause of hyperthyroidism, other rare causes include HCG secreting germ cell tumors. We describe a hyperthyroidism case with metastatic HCG secreting germ tumor and Graves’ disease. Case: 34 years old smoker male presented in 2016 with weakness and hypokalemia 2.7 mmol/L with concerns of paroxysmal periodic paralysis and was found to have hyperthyroidism consistent with Graves’ disease per work up (suppressed TSH <0.01- uIU/ml (ref 0.27-4.2 uIU/ml), elevated FT4 4.08 ng/dl (ref 0.93-1.7 ng/dl), elevated Free T3 15.0 (ref 2.3 - 4.0 pg/ml), and (thyroid stimulating immunoglobulin (TSI) 354 (ref 0 - 139 %). He was started on methimazole 20 mg that he did not use and lost follow up. In May 2022, he presented with expressive aphasia and seizures along with 4 months of right scrotal swelling, generalized lymphadenopathy, and hemoptysis episodes. He had intermittent palpitations, 30 Ibs weight loss and eye bulging. On exam he was tachycardic 120 bpm, enlarged thyroid, brisk reflexes and mild tremors. His eye exam was significant for stare, lid lag, proptosis and bilateral lid edema. His labs were remarkable for suppressed TSH <0.01 uIU/ml, FT4 >7.7 ng/dl , Total T3 394 ng/dl (80 - 200 ng/dl)Thyrotropin receptor antibodies (TRAb) 29 IU/L (ref 0-1.75 IU/L), TSI 4.8 (ref <1.3 index), Thyroglobulin Ab 5.8 IU/ml (ref <4IU/ml), TPO-Ab >900 (ref <9.0) and HCG >1,000,000 (ref <2mIU/ml). Thyroid US showed diffuse heterogeneous enlargement of the thyroid with increased vascularity and without a discrete well-defined nodule. His lymphadenopathy work revealed high grade stage III C non-seminomatous mixed germ tumors (60% teratoma and 40% choriocarcinoma) with metastasis to brain, lungs, liver, spine, iliac and sacral bones. He was started on methimazole (MMI) 20 mg TID, propranolol 40 mg TID, dexamethasone 2 mg q6hrs and chemotherapy. His thyroid labs improved in 3 days to FT4 2.83 ng/dl and TT3 93 ng/dl while TSH and HCG were unchanged. He was discharged on MMI 25 mg daily. Over 3 months, he subsequently underwent right orchiectomy, cyber knife radiation of the brain metastatic lesions and 4 chemotherapy cycles. His HCG levels fluctuated (1,000,000->3980-> 120,181) as well thyroid function test (TSH <0.01-> 5.1->0.01 uIU/ml, FT4 1.02->0.65->5.7 ng/dl and TSI 6.4 ). He required multiple methimazole adjustments. Discussion: Co-occurrence of HCG secreting germ tumors and Graves’ hyperthyroidism is rare. HCG can bind TSH receptors and in high levels has thyrotropic effects. The interplay between HCG thyrotropic effects and thyroid autoimmunity can be challenging and use of both binding and functional bioassays maybe helpful. Close thyroid function monitoring and frequent adjustment of thioamides are needed as patients undergo treatment of the primary HCG source as well as long term follow up. Presentation: Friday, June 16, 2023

FRI561 The Thyroid Trifecta

Abstract Disclosure: P. Kachhadia: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. Introduction: Autoimmune Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) may co-exist or may occur alternatingly, known in many case reports as Graves’s Alternans. Hyperfunctioning (Toxic, hot) thyroid nodules (TN) may also co-exist with GD, a rare condition called Marine-Lenhart syndrome. However, the co-existence of HT, GD and TN is perceivably rarer. Case Presentation: The patient is a 45 year old female with a prior history of HT for 20 years, who presented to the clinic with symptoms of minimal eye pain, tremors, fatigue, diarrhea and anxiety. She was not on thyroid replacement, with normal thyroid function tests (TFTs). Physical exam showed bilateral proptosis, a moderate goiter, hand tremors, mild anxiety and tachycardia. Labs showed high TPO (3995.0 IU/mL, n <18 IU/mL), Thyrotropin receptor antibody (5.25 IU/L, n<1.75 IU/L), and Thyroid-stimulating immunoglobulins (1.8 TSI index, n<1.3 TSI index) with low-normal TSH of 0.42 uIU/mL (0.35-4.01 uIU/mL) , mid-range free triiodothyronine (FT3) at 3.6 pg/mL (2.8-4.4 pg/mL) and normal free thyroxine (FT4) at 0.80 NG/dL (0.61-1.37 NG/dL). Thyroid US showed a 2.4 cm left lobe inferior nodule classified as TI-RADS 3. Fine needle aspiration of this nodule was benign. Radioactive Iodine-123 Uptake Scan showed a hot nodule in the left inferior lobe and with visible uptake in the rest of the gland (uptake was mid-normal). She was started on methimazole 5mg once daily and propranolol 10mg BID with improvement in her symptoms. Subsequent TFTs showed stable T4 and T3 and normalization of TSH to 1.78 uIU/mL (0.35-4.01 uIU/mL). Discussion: Marine-Lenhart syndrome was described in 1911 by surgeons David Marine and Carl Lenhart. Graves’ Alternans has been described in the literature, with variable time separation. Though thyroid nodules occur in up to 35% of those with GD, only 1-4.1% are deemed functional nodules. Nuclear medicine imaging via Tc-99m pertechnetate or I-123 iodine at diagnosis of GD generally shows such nodules as cold nodules lacking uptake, while the rest of the gland has diffuse uptake. However, with normalization of TSH through treatment, these cold nodules may alternate uptake and present as hot nodules. Conclusion: In conclusion, this case presents the co-existence of HT, GD and HN, a term we are calling “Thyroid Trifecta”. It is imperative that HNs should be identified if RAI treatment is planned in such patients. Literature review portrays cases in which if thyrotoxicosis persists post RAI treatment for GD, careful examination and repeat RAIU may show a hot nodule consistent with Marine-Lenhart Syndrome. These patients may benefit instead from thyroidectomy. In the case of our patient, definitive treatment options have been discussed and she has been referred for thyroidectomy due to the presence of the TN. RAI ablation will be avoided in view of mild but active thyroid eye disease. Presentation: Friday, June 16, 2023

SAT476 A Case of Thyroid Hemiagenesis

Abstract Disclosure: P. Kachhadia: None. S. Khan: None. S. Aldasouqi: None. A. Abu Limon: None. Introduction: Thyroid hemiagenesis is congenitally rare, in which one side of the thyroid does not develop. Hemiagenesis is more common with an absent left thyroid lobe, at a 4:1 ratio. Though prevalence is sited at 0.05%, actual incidence of hemiagenesis amongst the population is unknown as most patients are euthyroid and asymptomatic. We present a case of a patient who was referred to our clinic for unilateral thyroid enlargement on physical exam. Thyroid Ultrasound (US) was done which showed an absent left thyroid lobe along with enlarged right thyroid lobe and hypervascularity. There was also an incidental thyroid nodule noted on US. Case Presentation: Patient is a 38 year old female who presented to the clinic 4 years prior for enlarged thyroid nodule noted on ultrasound. With symptoms of dysphagia and a visibly enlarged gland, an US with labs was prompted by her primary physician. US showed absent left thyroid lobe and right lobe enlargement with hypervascularity and incidental subcentimeter nodule. Clinically and biochemically, the patient was euthyroid. Singular right lobe was verified on clinic real time ultrasound and on NM uptake scan. The 24 hour uptake was at 30.5%, with the upper limit of normal being 30%. With increased uptake and hypervascularity, thyroid stimulating immunoglobulin and thyrotropin receptor antibodies were checked and were not detected. It was thought that the right thyroid gland enlargement and hypervascularity were compensatory due to the left hemiagenesis. The thyroid nodule was monitored, and within 3 years of original imaging, it enlarged to 0.98 x 0.59 x 0.39 cm, with TI-RADS 5 assessment per ACR criteria. Patient chose to undergo thyroid biopsy which showed Bethesda III, Follicular Lesion of Undetermined Significance (FLUS). Microscopy showed follicular cells arranged in microfollicles and crowded groups with round, enlarged, irregular nuclei and overlapping nucleoli. Intranuclear chromatin clearing and intranuclear grooves are present. Background is hemorrhagic with minimal colloid. Molecular Thyroseq testing was at 5-10% chance of malignancy or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Genetic markers were only positive for copy number alterations. Discussion: Thyroid Hemiagenesis, though rare, has been associated with other thyroid pathologies such as hypothyroidism, hyperthyroidism and thyroid malignancies. Genetic studies have not found a common background within cases reported. As these patients are more likely to incur additional thyroid pathologies, questions still remain as to the clinical management and outcome of such patients. Due to concerning cytological features for PTC, the patient was offered right thyroidectomy and will be looking to make a decision in the near future. Presentation Date: Saturday, June 17, 2023

FRI553 ICI-induced Thyroid Ophthalmopathy With De Novo Graves’ Disease

Abstract Disclosure: S.I. Moctezuma: None. J. Perlman: None. J.S. Mammen: None. Background: Immune checkpoint inhibitors frequently target the thyroid gland. However, immune checkpoint inhibitor (ICI)-induced Graves’ disease (GD) is rare. To our knowledge, there are no reported cases of thyroid eye disease after immune checkpoint inhibitor therapy in patients with newly positive anti-thyroid antibodies. Clinical Case: An 81-year-old man developed thyroiditis within three weeks of a single dose of ipilimumab/nivolumab for the treatment of metastatic cholangiocarcinoma. ICI therapy was discontinued for cardiotoxicity. He presented one year later with onset of periorbital edema, pain with downgaze, redness, irritation and progressive proptosis with diplopia. He did not have a prior history of thyroid disease. Thyroid function tests before the start of ICI therapy revealed euthyroidism [TSH 2.982 uIU/mL (0.55 - 4.78)]. Symptoms of palpitations, weight loss, and hyper-defecation that characterized his initial presentation with thyroiditis were absent at the time of onset of eye disease. At presentation of thyrotoxicosis his TSH was <0.01 uIU/mL, free T4 3.6 ng/dL (0.89 - 1.76) total T3 190 ng/dL (60-180) Thyroid-peroxidase autoantibodies (TPOAb) and thyroid-stimulating immunoglobulin (TSI) were negative. When his visual symptoms appeared, TPOAb remained negative while a repeat TSI antibody was positive [0.64 IU/L (0.00 - 0.55)]. Thyroid ultrasound at the time of thyroiditis revealed a heterogeneous gland without discrete nodules and a normal vascular flow. Most cases of ICI-induced GD have been reported at the start of therapy, particularly in the first 6 weeks, although thyrotoxicosis has been described to occur as late as 224 days after starting PD-1 inhibitor. GD is more frequently reported with combination anti-CTLA-4 and anti-PD-1 therapy. Patients with thyroid ICI-induced adverse events experience either isolated hypothyroidism or thyroiditis spontaneously evolving towards hypothyroidism. However, ICI-induced GD is more likely to have a relapsing-remitting disease. In 2021, Peiffert et al. described the antibody profile for 243 patients with ICI-induced thyrotoxicosis. In this case series, 5 patients developed thyrotoxicosis with positive thyrotropin-receptor antibodies (TRAb). Only 2 patients had a typical clinical presentation of GD. TSI antibodies were not reported. Furthermore, none of the patients with positive TRAb had Graves’ ophthalmopathy. Conclusion: Our case demonstrates the acquisition of auto-antibodies capable of mediating Graves’ disease, and raises the possibility that thyroid eye disease-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy. These symptoms developed as late as one year after initiation of therapy. As with sporadic cases, this can occur in the absence of clinically significant hyperthyroidism. Presentation: Friday, June 16, 2023