Thyroid-stimulating Immunoglobulin Research Articles

Tocilizumabuse for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort.

To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.

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

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

Graves Disease - A Comprehensive Review

Graves Disease (GD) is an inflammatory disorder that often results in hyperthyroidism. GD is particularly prone to affecting women, African Americans, individuals with pre-existing autoimmune conditions, and first-degree relatives of those with GD. GD presents through a breakdown of immune tolerance against thyroid antigens. This occurs through a multifactorial autoimmune dysfunction of environmental and mainly genetic contribution. Hereditary predisposition accounts for 79% of the GD risk and increases susceptibility to dysfunction by environmental risk factors such as smoking, vitamin D deficiency, and stressful life events. GD is caused by a disruption of the thyroid gland on a molecular level. The disease is characterized by an overstimulation of the thyroid gland causing hyperthyroidism. This issue is caused by thyroid-stimulating immunoglobulin (TSI) synthesized by B cells. These immunoglobulins bind to the TSH receptors on the thyroid gland, activating it and producing an abundance of the thyroid hormones, levothyroxine (T4) and triiodothyronine (T3). The clinical presentation of GD encompasses a diverse array of signs and symptoms, from common manifestations such as palpitations, weight reduction, and exophthalmos, to less conventional presentations like cardiac complications and cholestatic hepatic injury. There are many methods of diagnosis that are used for GD including the gold standard, which tests for TSI and antibodies against the TSH receptor. Other methods include radioactive iodine uptake and CT scans that test for thyroid enlargement and are used to substitute radioactive iodine uptake tests for pregnant women. The three classical treatments for GD are antithyroid drugs, radioiodine treatment, and thyroidectomy. Additional treatments include corticosteroids which are used to decrease exophthalmos. Beta-adrenergic blockers are used for tachycardia, palpitations, and also blocking the peripheral conversion of T4 to T3. Immunotherapies, such as Mycophenolate mofetil and Azathioprine show promise as potential treatments are currently being investigated. This comprehensive review provides an up-to-date compact analysis of literature pertinent to the epidemiology, etiology, risk factors, genetics, pathophysiology, classifications, clinical presentation, diagnosis, and treatments of GD.

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

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

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

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

Evaluation of hematologic inflammatory markers in Graves’ disease

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

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

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

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

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

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

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

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 &amp;lt;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 &amp;lt;0.01 uIU/ml, FT4 &amp;gt;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 &amp;lt;1.3 index), Thyroglobulin Ab 5.8 IU/ml (ref &amp;lt;4IU/ml), TPO-Ab &amp;gt;900 (ref &amp;lt;9.0) and HCG &amp;gt;1,000,000 (ref &amp;lt;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-&amp;gt;3980-&amp;gt; 120,181) as well thyroid function test (TSH &amp;lt;0.01-&amp;gt; 5.1-&amp;gt;0.01 uIU/ml, FT4 1.02-&amp;gt;0.65-&amp;gt;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

FRI554 Pretibial Myxedema Associated With Hashimoto Thyroiditis Treated With Teprotumumab

Abstract Disclosure: E.M. Niedzialkowska: None. B. Ajaz: None. A. Pokharel: None. Introduction: Pretibial myxedema (PTM) is a localized thyroid-associated dermopathy characterized by local thickening of the skin of the lower extremities. It mostly develops after the onset of thyroid eye disease (TED). Majority of the cases are associated with Graves disease (GD) but infrequently it can occur in Hashimoto thyroiditis (HT) in the presence of thyroid stimulating immunoglobulins (TSIs). Orbital fibroblasts and the pretibial dermis share antigenic sites that underlie autoimmune thyroid disease. IGF-1 has been reported to potentiate the effects of TSH and TSI on TSHR signaling and fibroblast proliferation. Teprotumumab, a novel monoclonal antibody that blocks IGF-1R receptors, is registered for TED treatment. It is plausible it also improves outcomes in PTM through the same mechanism. Clinical case: 52 year old female reported to our Endocrinology clinic with proptosis and myxedema. The patient was diagnosed with hypothyroidism at the age of 21 and was on substitutional dose of levothyroxine, 125 mcg daily. She developed TED 7 years prior with bilateral exophthalmos with medial rectus muscle infiltration. She underwent 5 decompression surgeries and steroid courses due to concern for optic nerve compression. 4 years prior to the visit she developed bilateral, erythematous pitting edema of the lower extremities with involvement of the pretibial areas, ankles and toes and underwent excess left toe callus excision. Despite multiple courses of intralesional steroid injections and topical ammonium lactate use the patient reported persistent edema, pruritus, and restriction of motion. Laboratory results were significant for TSH of 1.73 uIU/mL (n 0.40 - 4.50 uIU/mL), TRAB &amp;gt;40 IU/L (0.00 - 1.75 IU/L), TSI 4.95 (n &amp;lt;0.10 IU/L), TPO antibody &amp;lt;=35 IU/mL, free ft3 2.5 pg/ml (1.7 - 3.7 pg/mL), free ft4 1.0 (0.7 - 1.5 ng/dL). The patient underwent thyroidectomy with pathology results consistent with Hashimoto thyroiditis (thyroiditis with thyroid follicles, Hurthle cell change, marked lymphoid and fibroadipose tissue). Following the procedure she experienced PTM and TED flare up. Subsequent orbital decompression and orbital steroid injections provided minimal improvement. The patient was started on Teprotumumab (8 infusions every 3 weeks) with marked improvement of orbitopathy (CAS reduction from 6/10 to 1/10) and significant reduction of lower extremity edema and rash. Conclusion: We present the case of Hashimoto thyroiditis associated with TED with PTM successfully treated with Teprotumumab. In TED, TSI binds to IGF-1R creating a complex that promotes orbital inflammation. Teprotumumab is believed to degrade antibody-receptor complex and downregulate fibroblast activation and glycosaminoglycans deposition. We postulate the same process may occur in dermal fibroblasts in the light of PTM improvement after teprotumumab treatment. Presentation: Friday, June 16, 2023

SAT481 Metastatic Choriocarcinoma, A Rare Cause of hCG-Mediated Hyperthyroidism

Abstract Disclosure: S. Jain: None. M. Crabtree: None. C. Houston: None. Background: Structural homology between human chorionic gonadotropin (hCG) and thyrotropin stimulating hormone (TSH) allows high levels of hCG to exert thyrotropic effects via TSH receptors. Although hCG-mediated hyperthyroidism is most frequently encountered in the context of pregnancy, it also occurs rarely as a paraneoplastic syndrome. We present a case of hCG-mediated hyperthyroidism due to metastatic choriocarcinoma in a postmenopausal woman. Case Presentation: A previously healthy 59-year-old woman was evaluated for shortness of breath and found to have multiple lung nodules concerning for metastatic malignancy. Further imaging demonstrated an enlarged heterogeneous uterus with an enlarged endometrial cavity. Endometrial biopsy revealed poorly differentiated carcinoma with some areas of possible squamous differentiation. Subspecialty cytopathology review was requested. One week after biopsy, the patient was brought to the emergency department with acute hypoxic respiratory failure following a seizure. She was found to be febrile, tachycardic, hypertensive, and minimally responsive. Head CT revealed a left frontal brain mass with surrounding vasogenic edema, concerning for metastasis. Laboratory evaluation revealed TSH of 0.03 mIU/L (normal 0.35-4.94) and free T4 of 2.30 ng/dL (normal 0.70-1.48). Thyroid stimulating immunoglobulin was negative. Beta-hCG was found to be significantly elevated at 982,093 mIU/mL after 1:100 dilution. She was started on treatment with propranolol, dexamethasone, and chemotherapy with etoposide and cisplatin. Meanwhile, cytopathology review identified scattered cells with features of choriocarcinoma and positive hCG immunostaining, felt to represent a diagnosis of poorly differentiated choriocarcinoma. After one cycle of chemotherapy, the patient’s beta-hCG decreased to 477,668 mIU/mL and free T4 decreased to 1.05 ng/dL. Due to progressive worsening of her clinical status, she was transitioned to palliative care and passed away on hospital day 14. Discussion: Hyperthyroidism mediated by hCG is most often seen in patients with hyperemesis gravidarum, gestational transient thyrotoxicosis, or gestational trophoblastic disease. Our case underscores the importance of considering hCG-mediated hyperthyroidism outside the context of pregnancy. Rare paraneoplastic sources of hCG include choriocarcinoma, seminoma, and other germ cell tumors. Hyperthyroidism in these cases is usually subclinical or mild, but instances of thyroid storm have been reported with metastatic disease. Beta blockers, glucocorticoids, and thionamides can be used as temporizing measures, but definitive therapy requires treatment of the causative malignancy. Presentation Date: Saturday, June 17, 2023

SAT465 Spectral Doppler Ultrasound in Thyrotoxicosis, a Valuable Bedside Tool

Abstract Disclosure: M. Morkos: None. K. Raju: None. K. Ibrahim: None. Objective: To assess the utility of spectral Doppler ultrasound as a bedside tool in the differentiation of various etiologies of thyrotoxicosis Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with thyrotoxicosis at an academic outpatient endocrinology clinic from August 2019 to November 2022. The peak systolic velocities (PSV) were measured using spectral Doppler ultrasound at the superior and inferior thyroid arteries bilaterally. PSV ≥40 cm/sec in at least a single thyroid artery was considered a specific cut-off for Graves’ disease and PSV of peri-nodular artery ≥ 25 cm/sec was considered a specific cut-off for toxic adenoma. Thyroid antibodies (thyroid stimulating immunoglobulin and thyroid receptor antibody) and occasionally thyroid scan were used to confirm the diagnosis. Descriptive statistics, Chi square, and t-test were utilized to describe and compare data. Results: We identified 73 patients who presented for evaluation and management of thyrotoxicosis, mean age ± standard deviation 45.2 ± 16.4 years, 54 (74.0%) were female, 49 (67.1%) Caucasian, 23 (31.5%) African American, and one (1.4%) was Asian. The confirmed diagnoses were 48 (65.8%) Graves’ disease, 13 (17.8%) thyroiditis, 4 (5.5%) toxic adenoma, 4 (5.5%) amiodarone-induced thyroiditis type 2, 1 (1.4%) toxic multinodular goiter, 1 (1.4%) had a normal repeat thyroid function testing, and 2 (2.7%) were unconfirmed. Diagnosis based on the initial assessment including the spectral Doppler was accurate in 65 (89.0%) of the patients and it was conclusive and confirmatory during the initial encounter in 55 (75.3%) of the patients before additional testing. Thyroid scan was obtained in 9 (12.3%) patients. Incorrectly diagnosed patients included Graves’ disease, thyroiditis, toxic adenoma, and unconfirmed diagnoses, two patients each, a total of eight patients. Conclusion: Spectral Doppler ultrasound can be an effective bedside tool in the clinical assessment of thyrotoxicosis. Presentation Date: Saturday, June 17, 2023

FRI568 Hashimoto’s Thyroiditis With Negative Antibodies In Association With Common Variable Immunodeficiency

Abstract Disclosure: I.C. Ebrahim: None. K.F. Brown: None. N.O. Vietor: None. T.D. Hoang: None. M.K. Shakir: None. Introduction: Common variable immunodeficiency (CVID) is associated with several autoimmune manifestations including Hashimoto’s thyroiditis (HT). We report a 47-year-old male with CVID and HT with negative thyroid antibodies (Abs). Case Report: A 47-year-old male, while undergoing coronary calcium scan in 2021, was found to have scattered lung nodules. Follow-up Ct scans showed interval increase in size of lung nodules and a PET scan confirmed bilateral lung nodules which demonstrated hypermetabolic activity and scattered hypermetabolic lymph nodes, suggesting infectious or inflammatory processes. PET scan also revealed thyromegaly with diffusely increased uptake, suggesting thyroiditis. Serum immunoglobulins were measured: IgA &amp;lt; 5 mg/dL (normal 70-400), IgG 334 mg/dL (normal 700-1600), and IgM &amp;lt; 25 mg/dL (normal 40-230). Serum immunoglobulins levels from depository serum samples collected in 2005 also showed similarly low values. CBC was normal, excluding any bone marrow disorders. There was no family history of immunodeficiency or thyroid disorders. On review of systems patients did not have any symptoms of hypothyroidism. Exam: thyroid 50-gms diffusely enlarged with no palpable nodules; heart and lung exam was normal. Laboratory tests including comprehensive metabolic panel, serum complement CH 50, leukemia/lymphoma panel, T/B - lymphocyte/Natkiller, CRP were all normal. Thyroid functions: TSH 5.6 mc1U/mL (0.27-4.2), Free T4 1.20 ng/dL (0.93-1.71), TPO Ab &amp;lt; 9 IU/mL (0-34), TG Ab &amp;lt; 1.0 1U/mL (0.0-0.9), thyrotropin receptor Ab &amp;lt; 0.3 IU/L (&amp;lt;1.0), thyroid stimulating immunoglobulin &amp;lt; 0.10 1U/L (0.06-0.55). Serum thyroid Ab levels from depository samples collected in 2005 also showed normal values. FNA of thyroid showed atypical lymphoid infiltrates and an excision biopsy of the thyroid isthmus confirmed lymphocytic thyroiditis. A PET avid right inguinal lymph node biopsy showed a reactive lymph node. Additional lab evaluation also showed low post vaccination pneumococcal titers. With pan-hypoglobulinemia and low vaccine response, a diagnosis of CVID was made. Patient preferred watchful waiting than iv immunoglobulin therapy. Additionally, the patient has HT with negative thyroid Abs and although patient had mild subclinical hypothyroidism patient elected no treatment. Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency in adults. Autoimmune manifestations occur in 22% of CVID patients and these include autoimmune cytopenia, pernicious anemia, rheumatoid arthritis, vitiligo, and/or HT. Interestingly, our patient did not manifest any thyroid Abs thus it may be postulated that thyroid follicles destruction in HT is mediated predominantly by thyroid-specific B and T cells rather than by thyroid antibodies. Presentation: Friday, June 16, 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 &amp;lt;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

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).

SAT473 First Case Of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Hyperthyroidism

Abstract Disclosure: A.M. Gonzalez Gil: None. M.A. Ruiz Santillan: None. H. Quadri: None. B.K. Force: None. R. Gaba: None. Background: Diffuse thyroid lipomatosis (DTL) is an exceedingly rare entity of unknown etiology which can be associated with amyloidosis. It generally presents with euthyroidism but very few cases with hyperthyroidism have been reported. Clinical Case: A 64-year-old woman from Pakistan with a several-year history of a non-tender goiter presented to the emergency department with an upper respiratory and gastrointestinal viral syndrome in the context of several weeks of progressively worsening fatigue. She also reported unintentional weight loss over several years. She denied other hyperthyroid or compressive symptoms. Her exam was notable for resting sinus tachycardia and an approximately 100 gm painless goiter. Laboratory evaluation was notable for a markedly elevated creatinine with nephrotic range proteinuria. She was declared to have end stage renal disease (ESRD) and hemodialysis was initiated. She was also found to have a suppressed TSH (&amp;lt;0.01 uIU/mL, NR=0.45-5.33) and elevated FT4 (2.17 ng/dl, NR=0.64-1.42). Total T3 was low (42 ng/dl, NR=87-178), which was attributed to hypoalbuminemia and altered peripheral thyroid hormone metabolism with underlying ESRD. Further evaluation revealed elevated ESR, CRP and thyroglobulin levels (625.9 ng/mL, NR=1.5-38.5), while thyroid stimulating immunoglobulin, thyroid receptor antibodies and thyroid peroxidase antibodies were undetectable. A thyroid ultrasound revealed an enlarged fatty thyroid consistent with DTL. A radioactive iodine uptake scan revealed normal 24-hour uptake (14.1%, NR=7-32%) in a slightly heterogeneous thyroid with no aberrant functioning thyroid tissue. She was started on atenolol, with significant improvement in her tachycardia, but her FT4 continued to increase. Methimazole was initiated. Dose uptitration and administration after dialysis resulted in near-normalization of FT4 levels. She subsequently underwent renal and thyroid biopsies, both of which showed apple green birefringence under polarized light with Congo Red stain, indicating amyloidosis. Core thyroid biopsy additionally showed benign adipose tissue with entrapped thyroid follicles, confirming concomitant DTL. Although other authors have found thyroid amyloid deposits in DTL, and yet others have reported hyperthyroidism in DTL without amyloidosis, this is the first reported case of hyperthyroidism in a patient with DTL with amyloid deposits. Interestingly, chronic hypoxia in amyloid goiters has been hypothesized to cause fibroblast-to-adipocyte metaplasia leading to DTL. We speculate that excess thyroid hormone release could also be mediated by follicular cells’ response to hypoxia induced by amyloid and fatty infiltration of the thyroid. Conclusion: To the best of our knowledge, this is the first reported case of diffuse thyroid lipomatosis with amyloid deposits to be associated with concurrent hyperthyroidism. Presentation Date: Saturday, June 17, 2023

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 &amp;lt;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

SAT490 Graves’ Disease In Remission Aggravated By Himalayan Salt Consumption

Abstract Disclosure: M.K. Shakir: None. K.F. Brown: None. J.S. Hatfield: None. N.O. Vietor: None. T.D. Hoang: None. Introduction: In iodine-replete countries, iodine-induced thyrotoxicosis may occasionally develop after ingestion or therapy with high doses of iodine. Recently, Himalayan salt has become very popular to bridge iodine deficiency, control hypothyroidism, and improve thyroid function. We report a patient with a history of treated Graves’ disease (GD) who developed acute thyrotoxicosis following the use of Himalayan salt. Case report: A 58-year-old woman presented with symptoms of heat intolerance, and unexpected 18-lbs weight loss over 3 months. Physical examination: HR 108 bpm, BP 110/70 mm Hg, normal eye examination, thyroid 45 gms, diffusely enlarged. Examinations of the heart, lungs and abdomen were normal. Lab tests: TSH 0.01 IU/mL, free T4 3.8 ng/dL, T3 308 pg/dL, thyrotropin receptor Ab 4.2 IU/L (&amp;lt;1.0), and thyroid stimulating immunoglobulin 1.89 1U/L (0.06-0.55). The I131 uptake was 60% at 4 hours and the thyroid scan revealed diffuse homogenous uptake confirming GD. She was treated with methimazole (MMI) for 2 years and remission was achieved. MMI was stopped and she remained euthyroid. Twelve months later, she developed hyperthyroid symptoms with a 15-lb weight loss, palpitations, and anxiety. Examination confirmed a 50-gram diffuse goiter and other physical findings consistent with hyperthyroidism. She admitted that she had been taking Himalayan salt (approximately 10 grams daily) in place of regular salt for the past 6 months. Lab tests confirmed recurrent GD: TSH &amp;lt;0.01 IU/mL, FT4 4.1 ng/dL, total T3 278 pg/dL, and I131 uptake was 55% at 24 hours. A 24-hours urine iodine was 898 mcg (normal 100-199) and plasma iodine level was 484 mcg/L (normal 52-109). A diagnosis of iodine-induced recurrence of GD was made, and she was treated with MMI and low iodine diet. After 3 months, she improved significantly and was able to discontinue the MMI by 6 months. A follow- up urine iodine was 189 mcg/L with a plasma iodine level of 78 mcg/L. Subsequently she remained euthyroid for an additional 18 months of follow-up without any treatment. Conclusion: The recommended daily dietary allowance for iodine in adults is 150mcg. Himalayan rock salt may provide a rich source of iodine and consumption of large amounts can lead to iodine excess. However, the available studies do not provide the iodine content in commercially available Himalayan salt preparations. Although the Himalayan salt is advertised to have beneficial effects in patients with thyroid disorders, this food supplement may have deleterious effects in susceptible patients who do not have iodine deficiency, have GD, or are at risk for thyrotoxicosis. Indeed, Himalayan salt use exacerbated GD in our patient, as evidenced by iodine overdose during acute exacerbation and resolution of GD with iodine normalization and low dose MMI. We recommend that patients with thyroid disorders be educated regarding Himalayan salt use. Presentation Date: Saturday, June 17, 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