Thyroid Uptake Research Articles

Effect of methimazole withdrawl period on the I-131 uptake estimation using Tc-99m thyroid scanning in Graves' disease.

The effect of methimazole withdrawl period (MWP) on the estimation of 24 hour-radioiodine thyroid uptake (131IU24h) from 99mTc-pertechnetate thyroid uptake (99mTcTU) remains unclear for patients with Graves disease (GD) . This study aims to investigate the feasibility and reliability of 99mTcTU-based 131IU24h estimation with different MWPs. We enrolled 116 GD patients scheduled for 131I therapy at our hospital between April 2022 and April 2023. Based on MWP, the patients were categorized: standard (no methimazole or MWP>1 month), MWP1 (MWP≤1 week), MWP2 (MWP>1 week to ≤2 weeks) and MWP3 groups (MWP>2 weeks to <1 month). Fisher's exact test, one-way ANOVA or Kruskal-Wallis test were used to compare variables. Fitted curves of 99mTcTU20min versus 131IU24h were plotted for the standard group. Linear relationships and Bland-Altman plots were used to illustrate the relationship and consistency between estimated and measured 131IU24h. 131IU24h was higher in MWP1 group compared to MWP2 (70.22±7.95% vs 61.92±9.84%, P = 0.001), and thyroid masswas greater in MWP1 group (36.15±22.38g) versus MWP3 (21.25±11.90g, P = 0.005). The relationship between131IU24h and 99mTcTU20min in the standard group is described by the algorithm: estimated 131IU24h=11.3ln (99mTcTU20min)+39.4 (R2=0.62). Based on it, the correlation between estimated and measured 131IU24h was weak in MWP1 and MWP2 groups (both P>0.05) but strong in MWP3 (r=0.66, P=0.002). Additionally, the agreement between estimated and measured 131IU24h was highest in the MWP3 group (95% CI, -15.86 to 15.52%), compared to the MWP1and MWP2 groups. Estimated 131IU24h based on 99mTcTU is not suitable for GD patients with MWP less than 2 weeks at our institution, necessitating further prospective multi-center studies for validation.

Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves' Hyperthyroidism with Potassium Iodide.

Graves' hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal 123I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves' disease (GD) with a large goiter (>40 g), 131I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Usefulness and limitations of various detector systems for estimation of 131I thyroid activity following an RN event

Following a radiological or nuclear (RN) event, rapid measurement of131I in members of the public is of utmost importance, and much equipment is needed for a high throughput. In this study, three gamma cameras (GCs), two thyroid uptake meters (TUMs) and one whole-body counter (WBC) were calibrated for activity measurements of131I in the thyroid. Minimum detectable activity was derived for the GCs, the TUMs and the WBC giving that a committed effective dose (CED) in the interval 2.0-85μSv, 13-700μSv and 0.52-6.4μSv, and thyroid absorbed doses in the interval 0.075-2.1 mGy, 0.48-17 mGy, and 0.020-0.15 mGy, respectively, can be assessed for children, adolescents, and adults. These numbers are based on 10 min measurement, performed at 1, 3 and 7 d after intake, and the CED includes intake by ingestion and inhalation of aerosols Type F, with an activity median aerodynamic diameter of 1μm. For a fractional signal loss of 63% due to dead time, a CED up to 2.0, 84 and 3.6 Sv and thyroid absorbed dose up to 47 Gy, 2000 Gy and 88 Gy for the three systems, respectively, can be assessed for children and intake by ingestion as a worst-case scenario in terms of CED, measured 7 d after intake. This study demonstrates the potential and limitations of using equipment readily available at larger hospitals for estimation of131I content in thyroid, which could increase the measurement capability following an RN event.

7045 A Rare Case of Lyme-Associated Thyroiditis in an Otherwise Healthy Patient

Abstract Disclosure: M. Windham: None. S.K. Majumdar: None. Introduction: Lyme disease, a common tick-borne illness, causes multiorgan inflammation and dysfunction. It commonly affects the musculoskeletal, neurologic, cardiovascular, and integumentary systems. The endocrine system is rarely involved. We report a case of Lyme-associated thyroiditis in an otherwise healthy 41-year-old man. Case: A 41-year-old man with a history of hypertension, gastroesophageal reflux and a known BRCA2 mutation presented to the emergency department due to one week of frequent palpitations, fatigue, dyspnea on exertion, and dry cough. Laboratory testing revealed thyrotoxicosis with an undetectable TSH (n 0.270—4.200 µIU/mL), FT4 of 7.04 ng/dL (n 0.80—1.70 ng/dL), and TT3 of 253 ng/dL (n 92.0—224 ng/dL). He denied any recent illnesses or pain in his thyroid. Further work up revealed negative TSI and TPO but did show an elevated high sensitivity CRP of 4.3 mg/L (n &amp;lt;1.0 mg/L) and a sedimentation rate of 33 mm/hr (n 0—20 mm/hr). A thyroid uptake and scan showed markedly decreased uptake suggestive of thyroiditis. The patient was started on a prednisone taper with improvement in his TFTs. At his follow up visit approximately one month later, he reported increasing stiffness in his bilateral jaw and continuing palpitations with movement despite near normalization in his FT4 and TT3, suggestive of possible underlying cardiac conduction defects. He did not recall a tick bite but lived in an area with endemic Lyme disease. Lyme antibodies were sent and returned with a positive Lyme IgG and an indeterminate Lyme IgM, which would be consistent with an active Lyme disease infection at the time of his initial presentation. Treatment for Lyme disease was prescribed. Conclusion: Between 1991 and 2021, the incidence of Lyme disease in the United States doubled due to the combined effects of climate change, increasing host species populations, and human encroachment on animal habitats. People who live in areas with endemic Lyme disease, such as the Northeast and upper Midwest regions of the United States, are at risk even if they do not recall a specific exposure. Although Lyme thyroiditis is extremely rare, its incidence is expected to increase as the overall incidence of Lyme disease increases. Therefore, it is important to consider Lyme disease in the differential when a patient from an endemic area presents with unexplained thyroiditis. Presentation: 6/2/2024

6414 Refractory Hyperthyroidism Following COVID-19 Infection

Abstract Disclosure: A.T. Wahba: None. A.A. Shibli-Rahhal: None. A 40-year-old man presented with 2 weeks of palpitations, weight loss, decreased appetite and malaise. The symptoms were preceded by neck pain for 1-2 weeks that improved spontaneously. He was in atrial fibrillation at 126 bpm, but otherwise clinically stable. He had a mildly tender enlarged thyroid with no palpable nodules, and the rest of his exam was negative. A chest CT with IV contrast ruled out pulmonary embolism. His TSH was &amp;lt; 0.01 µIU/mL (N:0.27-4.20), free T4 &amp;gt; 7.77 ng/dL (N: 0.80-1.80) and free T3 of 29.7 (N: 2.6-4.4 pg/ml), obtained prior to contrast administration. TSI antibody was negative and thyroid ultrasound showed diffuse enlargement with heterogeneous echotexture and reduced vascularity on doppler images. Thyroid uptake and scan could not be obtained due to iodinated contrast exposure. The patient’s medical history was notable for nonischemic cardiomyopathy (EF 50%), cardiac arrest with implantable cardiac defibrillator, and paroxysmal atrial fibrillation. He was previously treated with amiodarone for 2 years, and it was stopped 2 months before presentation. Other relevant medical problems included subclinical hypothyroidism diagnosed within the previous year and an uncomplicated acute COVID-19 infection 1 month prior to presentation.Given his cardiac history and high Burch-Wartofsky score, he received PTU 200 mg Q4h, hydrocortisone 100mg Q8h and propranolol for 3 days. As his FT3 level declined to 9.8 pg/ml, he was transitioned to methimazole 40 mg daily, propranolol and prednisone 40 mg daily and discharged with outpatient follow up. The atrial fibrillation worsened again 1 week later, and his FT3 increased to 20.2 with a FT4 &amp;gt; 7.77. He was put back on PTU 200 mg TID, prednisone and propranolol were continued and cholestyramine 2g BID was added. 1 week later, his FT4 and FT3 were unchanged. The tests were performed using a different assay and the results were consistent. Two sessions of plasma exchange (PLEX) did not yield a significant response, so thyroidectomy was eventually performed. Pathology showed morphologic findings consistent with type 2 amiodarone-induced thyrotoxicosis. While pathology showed amiodarone-induced changes, the patient’s hyperthyroidism occurred after a COVID-19 infection and was associated with neck pain, pointing to severe viral thyroiditis. De novo thyroid hormone production has been reported following COVID-19 infection, but the minimal improvement in thyroid hormone levels with thionamide therapy suggests that de novo secretion had little contribution to this patient’s hyperthyroidism. Presentation: 6/3/2024

6537 Recurrent Graves Thyrotoxicosis After Prolonged Radioiodine-Induced Hypothyroidism

Abstract Disclosure: H.K. Deveaux: None. A. Gundeti: None. K. Mitrollari: None. A.P. Calimag: None. T. Yasmeen: None. Radioactive iodine (I-131) ablation (RAI) is one of the effective therapies for Graves’ disease (GD). Successful treatment is indicated by sustained, irreversible hypothyroidism requiring lifelong replacement for which recurrence of disease rarely develops. Recurrent hyperthyroidism is a rare development without apparent predisposition. Here, we describe a case of recurrent thyrotoxicosis after 36 years of RAI.70-year-old female PMH atrial fibrillation (AFib) on apixaban s/p cardioversion, HTN, HFpEF, Pulmonary HTN, and Graves’ Disease s/p RAI ablation 36 years ago with RAI-induced hypothyroidism. The patient was initially on levothyroxine for post-ablative hypothyroidism and stopped taking levothyroxine around 2019. NM scintigraphy done in 2019 showed an abnormal I-123 thyroid uptake and scan with the five-hour radioiodine thyroid uptake showed mildly hyperthyroid. On the thyroid scan, there is a note of a prominent pyramidal lobe with some thyroid gland asymmetry. In 2022, the patient was admitted for new-onset AFib and was noted to have subclinical hyperthyroidism with TSH 0.157, fT4 1.4, TrAb&amp;gt;40, and TSI 34.8. The patient was started on methimazole, which she stopped one month later. During this admission, the patient presented secondary to a mechanical fall and was found to be in AFib with a rapid ventricular rate. Her labs were significant for TSH&amp;lt;0.008 fT4 4.2, TrAb &amp;gt;40. Methimazole was restarted with maximal doses of diltiazem and metoprolol for rate control. Thyroid ultrasound demonstrated an enlarged, heterogeneous thyroid gland with increased vascularity and multiple bilateral TR3 thyroid nodules.Hyperthyroidism affects approximately 1.2% of the population. GD involves autoantibodies activating the thyrotropin receptor, increasing synthesis and release of thyroid hormone and is for 50-60% of cases with a 5-to-10-fold preference for females. RAI ablation is preferred, being inexpensive, with a cure rate approaching 100%. The incidence of transient hypothyroidism post-RAI varies from 9-17%. Retrospective studies have observed hyperthyroidism within the first 12 months post-RAI; however, some cases have seen a resurgence as late as 22 years later. Recurrent hyperthyroidism is an uncommon occurrence with various postulated aetiologies, such as inadequate dosing/incomplete ablation with residual cells remaining viable and regenerating in the setting of increased TSIiv, Marine-Lenhart syndrome (MLS), or an unclear mechanism associated with autoimmunity in the presence of TSI. Hyperthyroidism rarely recurs in GD after successful post-ablative treatment with RAI. Our case, while an uncommon presentation and underlying aetiology yet to be determined, illustrates the importance of continued surveillance, even after successful treatment.‌ Presentation: 6/3/2024

8592 Parathyroid Carcinoma: A Rare Cause of Primary Hyperparathyroidism

Abstract Disclosure: S.E. Koshy: None. C.F. Mulcahy: None. P.S. Kothari: None. E.M. Jacobi: None. T.D. Cubb: None. Introduction: Parathyroid carcinoma (PC) is a rare malignancy that accounts for &amp;lt;1% of cases of primary hyperparathyroidism (PHPT). Patients often present with symptoms of hypercalcemia, serum calcium (Ca) &amp;gt;14 mg/dL, large tumor size, and a very high parathyroid hormone (PTH) level. We report a case of an asymptomatic patient with incidentally found hypercalcemia consistent with PHPT who was ultimately diagnosed with PC. Clinical Case: A 31yo male was found to have elevated serum Ca of 12.7 mg/dL (8.6-10.3 mg/dL) on labs obtained during routine physical exam. He had no known significant medical or family history and notably had no laboratory evaluation within the prior 10 years. He denied constipation, polyuria, confusion, depression, bone pain, and history of fractures or nephrolithiasis. Workup showed an inappropriately elevated PTH of 505 pg/mL (16-77 pg/mL). Neck ultrasound demonstrated a left inferior 3.9 cm complex thyroid nodule. Sestamibi scan confirmed increased uptake in the inferior left thyroid. Left neck exploration was performed. Intraoperatively, a 3.7 cm left parathyroid mass weighing 13.0 grams was encountered and excised in an en bloc fashion. The left superior parathyroid gland was evaluated and found to be normal. Intraoperative PTH level decreased from 529 pg/mL to 48 pg/mL 10 minutes after excision. Left hemithyroidectomy was not performed. Surgical pathology revealed PC with lymphovascular invasion, suspected capsular invasion, and negative margins. Immunohistochemical staining showed a Ki67 proliferation index up to 5% and complete loss of nuclear staining for parafibromin. Next generation sequencing demonstrated a somatic CDC73 p.L8fs mutation, tumor mutational burden 4.7m/MB, and stable microsatellite instability. Germline testing was negative for a CDC73 mutation. Postoperative staging did not demonstrate evidence of metastatic disease in the neck or chest. Serum Ca remained within normal limits. After multidisciplinary discussion, no further surgical intervention was recommended and plan was for ongoing biochemical and imaging surveillance. Conclusion: Though rare, PC should be considered as a cause of PHPT. The primary treatment is complete surgical resection. Unfortunately, there is a high rate of recurrence, &amp;gt;50%, with most occurring 2-5 years after initial surgery with a median overall survival of 14 years. Thus, long-term surveillance is of utmost importance. Treatment of recurrent disease is surgical resection when feasible as well as medical management of hypercalcemia. Further research is needed to better understand the role of targeted systemic therapy in addition to immunotherapy. PC is most commonly sporadic but can be hereditary, thus genetic evaluation is recommended. Given its rarity and complexity, PC is best managed in a multidisciplinary setting. Presentation: 6/1/2024

8592 Parathyroid Carcinoma: A Rare Cause of Primary Hyperparathyroidism

Abstract Disclosure: S.E. Koshy: None. C.F. Mulcahy: None. P.S. Kothari: None. E.M. Jacobi: None. T.D. Cubb: None. Introduction: Parathyroid carcinoma (PC) is a rare malignancy that accounts for &amp;lt;1% of cases of primary hyperparathyroidism (PHPT). Patients often present with symptoms of hypercalcemia, serum calcium (Ca) &amp;gt;14 mg/dL, large tumor size, and a very high parathyroid hormone (PTH) level. We report a case of an asymptomatic patient with incidentally found hypercalcemia consistent with PHPT who was ultimately diagnosed with PC. Clinical Case: A 31yo male was found to have elevated serum Ca of 12.7 mg/dL (8.6-10.3 mg/dL) on labs obtained during routine physical exam. He had no known significant medical or family history and notably had no laboratory evaluation within the prior 10 years. He denied constipation, polyuria, confusion, depression, bone pain, and history of fractures or nephrolithiasis. Workup showed an inappropriately elevated PTH of 505 pg/mL (16-77 pg/mL). Neck ultrasound demonstrated a left inferior 3.9 cm complex thyroid nodule. Sestamibi scan confirmed increased uptake in the inferior left thyroid. Left neck exploration was performed. Intraoperatively, a 3.7 cm left parathyroid mass weighing 13.0 grams was encountered and excised in an en bloc fashion. The left superior parathyroid gland was evaluated and found to be normal. Intraoperative PTH level decreased from 529 pg/mL to 48 pg/mL 10 minutes after excision. Left hemithyroidectomy was not performed. Surgical pathology revealed PC with lymphovascular invasion, suspected capsular invasion, and negative margins. Immunohistochemical staining showed a Ki67 proliferation index up to 5% and complete loss of nuclear staining for parafibromin. Next generation sequencing demonstrated a somatic CDC73 p.L8fs mutation, tumor mutational burden 4.7m/MB, and stable microsatellite instability. Germline testing was negative for a CDC73 mutation. Postoperative staging did not demonstrate evidence of metastatic disease in the neck or chest. Serum Ca remained within normal limits. After multidisciplinary discussion, no further surgical intervention was recommended and plan was for ongoing biochemical and imaging surveillance. Conclusion: Though rare, PC should be considered as a cause of PHPT. The primary treatment is complete surgical resection. Unfortunately, there is a high rate of recurrence, &amp;gt;50%, with most occurring 2-5 years after initial surgery with a median overall survival of 14 years. Thus, long-term surveillance is of utmost importance. Treatment of recurrent disease is surgical resection when feasible as well as medical management of hypercalcemia. Further research is needed to better understand the role of targeted systemic therapy in addition to immunotherapy. PC is most commonly sporadic but can be hereditary, thus genetic evaluation is recommended. Given its rarity and complexity, PC is best managed in a multidisciplinary setting. Presentation: 6/1/2024

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

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

6770 Graves’ disease induced by COVID-19 infection in a 49 year old male

Abstract Disclosure: N. Al-hosainat: None. A. Al Najada: None. T. Salar: None. S. Iqbal: None. K. Abdel Gadir: None. Introduction: Graves’ disease is an autoimmune disease causing hyperthyroidism, characterized by elevated thyrotropin-receptor antibodies. COVID-19 infection has been increasingly reported as a trigger of thyroid illness including Graves’ disease. We present a unique case of 49-year-old patient who was diagnosed with Graves’ disease after COVID-19 infection. Case description: A 49-year-old male patient with history of prediabetes presented with complaints of tremor, fatigue, generalized itching, and unintentional weight loss (30 Ibs in 6 months). He had COVID-19 infection 3 months prior. The remainder of review of systems was negative. No family history of thyroid disease. On exam, the patient had sinus tachycardia with otherwise normal vital signs. Diffuse thyromegaly was noted along with an intermittent fine tremor of the extremities. Blood work was notable for low TSH &amp;lt;0.01 uIU/mL, elevated free T4 (3.4 ng/dL), free T3 (17.6ng/dL), and TSH receptor antibody (12 IU/L). Thyroid ultrasound showed mild goiter with 2 nodules, one of which was TIRADS 4 and 1.5cm. This nodule was biopsied and found to be benign. Radioactive iodine uptake scan revealed homogeneous diffuse increased thyroid uptake. The diagnosis of Graves’ disease was made, and the patient was started on propranolol and methimazole with significant improvement of his symptoms and his laboratory tests normalizing. Discussion: Graves' disease is an autoimmune disease, characterized by hyperthyroidism, goiter, occasional orbitopathy and dermopathy. Caused by antibodies against thyroid-stimulating hormone receptors which stimulate thyroid hormone secretion and thyroid growth. Treatment is aimed to decrease thyroid hormone synthesis by either a Thionamide, radioiodine ablation, or surgery. Remission rates with antithyroid drugs average under 40 percent after one to two years of treatment and could exceed 80 percent after 5 to 10 years of treatment. COVID-19 is a multi-system disease, caused by SARS-CoV-2 virus, transmitted by large droplets and small particle aerosols, was declared a pandemic in 2020 and affected millions of people worldwide. There is emerging data showing the association of COVID-19 with various thyroid diseases including thyroiditis and relapse of known Graves' disease after the infection. We present a case of newly diagnosed Graves’ disease after COVID-19 infection in a patient with no personal or family history of such disease which raises the concern of autoimmune pathway activation induced by the infection. The onset of Graves’ disease after COVID-19 infection does not depend on the presence of pre-existing thyroid pathology and in this case responded well to antithyroid medication. Conclusion: COVID-19 can lead to the development of a range of medical illnesses. In patients who develop symptoms of thyrotoxicosis, Graves’ disease should be suspected, investigated, and treated appropriately Presentation: 6/3/2024

7618 Thyroid Nodules, Normal Thyroid Levels, and Chronic Anxiety: A Case for Sub-Clinical Toxic Multinodular Goiter

Abstract Disclosure: C.M. Barrera: None. Introduction: Chronic anxiety and panic disorders, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), are the most common psychiatric conditions. Hyperthyroidism is a known cause of both chronic anxiety and panic disorder. Case 1: A 36-year-old overweight Latin female is referred for evaluation of multiple thyroid nodules. The thyroid ultrasound was heterogeneous, with multiple bilateral nodules. In her history, the patient has chronic anxiety with panic attacks resulting in frequent emergency room visits. The TSH and T4 levels were TSH 0.59 mIU/L (0.40-4.5) and T4 10.7 mcg/dL (5.1-11.9). An I[1]23- Thyroid Scan showed a hot nodule with mild suppression and an uptake of 31.8% (The top limit is 35%). The patient started methimazole 2.5 mg daily, and after two months, her chronic anxiety and panic attacks resolved. Post-methimazole TSH rose to 1.18 mIU/L, and T4 10.0 mcg/dL and she has weaned off anxiety medications. Case 2: A 49-year-old overweight Latin female is referred for increased thyroid nodules. She complained of six months of tachycardia and anxiety. The TSH and T4 levels were TSH of 0.828 mIU/L (0.40-4.5) and T4 of 7.9 mcg/dl (4.5-12.0). An I[1]23-Thyroid Scan showed no dominant hot or cold nodules, with an uptake of 36.4% (The top limit is 35%, within normal error limits). She started methimazole 5 mg daily, resolving her tachycardia and anxiety within five weeks. Post-methimazole TSH was 1.64 mIU/L (0.45-4.5), and T4 6.7 mcg/dL (4.5-12.0). Case 3: A 60-year-old overweight Latin female is referred for evaluation of multiple thyroid nodules of ten years. She complained of chronic anxiety and panic attacks for two years. The TSH and T4 were normal at TSH 0.36 mIU/L (0.35- 5.50) and T4 9.7 mcg/dL (4.5-10.9). The thyroid ultrasound showed multiple bilateral nodules. An I[1]23-Thyroid Scan showed a suspected hot nodule without appreciable suppression and an uptake of 33% (The top limit is 35%). The patient started methimazole 5 mg daily. After eight weeks, she reported the resolution of most of her chronic anxiety with post-methimazole TSH 2.39 mIU/L and T4 7.1 mcg/dL (4.5-12.0). Discussion: The normal range of TSH, typically from 0.4-4.5 mIU/L, is calculated by measuring the TSH levels among a normal population. The group range then determines the laboratory reference range. This contrasts with individual values, which have a narrower range, suggesting that each person has a unique thyroid level. This suggests that TSH levels at the extremum, associated with hyperfunctioning nodules contributing to a rise in uptake, may not be normal for that patient and may explain the anxiety and other symptoms. Learning Points: Evolving multiple autonomous thyroid nodules lowers TSH levels while raising thyroid uptake. Symptoms of chronic anxiety and panic attacks can predate abnormal thyroid levels and resolve with low-dose methimazole. Presentation: 6/1/2024

6771 New onset Graves’ Disease in a Patient with Hashimoto's Thyroiditis and Positive Thyroid Peroxidase Autoantibodies. Case Report

Abstract Disclosure: M.M. Eid: None. J.L. Zapater: None. Introduction: Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) are the most common thyroid autoimmune disorders. Transition of GD to HT is common, but transition of HT to GD is rare. Case: A 55 year old, female with depression, HTN and fibromyalgia. She was referred for evaluation of chronic fatigue and reduction in functional capacity. Five years earlier, she had also been evaluated for fatigue. Labs at that time: TSH 3.80 µIU/ml (0.35-3.74 µIU/ml), free T4 0.8 ng/dl (0.76-1.46 ng/dl), thyroid peroxidase antibody (anti-TPO) 605.6 U/ml (0-60 U/ml), and anti-thyroglobulin antibody (anti-TG) 37.2 U/ml (0-60 U/ml). Subclinical hypothyroidism was diagnosed, but no levothyroxine was initiated. Her TSH was found to be normal in 2019 and 2021. At the current clinical encounter, other than fatigue she denies weight/voice change, tremor, palpitation, anxiety, recent flu like illness or radiation exposure, neck swelling/pain, heat intolerance, or difficulty swallowing. Her daily medications are amlodipine 10mg and duloxetine 20mg. She had menopause 2 years ago. She has no known allergy. She has a brother with rheumatoid arthritis. She denies smoking or alcohol consumption. On exam, vital signs are normal, and BMI is 28.1. There is diffuse, firm thyromegaly without a palpable nodule. There is no cervical lymphadenopathy, tremor, neck tenderness, exophthalmos, or lid lag. Creatinine, liver enzymes are normal but hemoglobin is 9gm/dl. Anti-tissue transglutaminase and anti-gliadin antibodies were negative. Her thyroid labs were: TSH &amp;lt;0.008 uIU/ml, free T4 1.06ng/dl, free T3 4.07 pg/ml (2.3-4.2 pg/ml), total T3 1.74 ng/ml (0.60-1.81 ng/ml), anti-TPO antibody 12,414 U/ml, anti-TG antibody 22 U/ml, thyrotropin receptor antibody (TRAB) 15.24 IU/L (0-1.75 IU/L), and thyroid stimulating immunoglobulin (TSI) 331% (&amp;lt;130%). Thyroid uptake scan showed 49% iodine-131 uptake in symmetric and homogenous uptake, and no hot or cold nodules. GD was diagnosed, methimazole 5mg daily was initiated. Conclusion: Our case had subclinical HT with positive anti-TPO antibodies 5 years preceding the onset of GD. Causes of autoimmune conversion are not well understood. Viral infection or radiation exposure in genetic susceptible patients have been assumed as triggers (1). The blocking and stimulating action of TRAB on TSH receptors is considered as a possible mechanism of switching between hypothyroidism and hyperthyroidism. Clinical and biochemical evaluation for possible conversion to GD in patients with HT is recommended (2).

7235 Papillary Thyroid Carcinoma in a Hyperfunctioning Thyroid Nodule

Abstract Disclosure: J. Yang: None. P.V. Nadkarni: None. Background: The prevalence of malignancy in a hyperfunctioning or hot thyroid nodule is considered to be low. According to the 2015 American Thyroid Association Guidelines, no cytologic evaluation is routinely recommended for hyperfunctioning nodules since they are rarely associated with malignancy (1). We present a case of a 71-year-old female with a hot nodule containing papillary thyroid cancer. Clinical Case: A 71-year-old female with Type 1 diabetes mellitus and coronary artery disease on dual antiplatelet therapy was found to have a 1.5 cm firm, non-tender right-sided thyroid nodule on a routine physical exam. Laboratory tests demonstrated low TSH &amp;lt;0.01 (normal 0.36 - 3.74 m[IU]/L) and FT4 level elevated at 1.62 (normal 0.76 -1.46 ng/dL). She noticed palpitations and started on low dose Methimazole. Thyroid ultrasound results showed a 2.1 x 2.0 x 2.0 cm right inferior lobe thyroid nodule. This thyroid nodule appeared mixed cystic and solid, hypoechoic, not taller than wide, with ill-defined margins and peripheral calcifications (ACR TI-RADS risk category: TR4). Nuclear medicine thyroid uptake scan demonstrated focally increased activity in the right lower pole corresponding with her right inferior thyroid nodule seen on ultrasound. Remainder of the gland appeared suppressed. She was recommended for ultrasound-guided fine needle aspiration biopsy of her right inferior thyroid nodule, given concerning characteristics on ultrasound findings despite results consistent with a hot nodule. Timing of her antiplatelet therapy was coordinated with her cardiologist, and her biopsy procedure scheduled after she stopped dual antiplatelet therapy. Her FNA results showed clusters of follicular cells with nuclear and architectural atypia, suspicious for papillary thyroid carcinoma. She underwent right thyroid lobectomy. Surgical pathology revealed 2 foci of papillary thyroid carcinoma, follicular variant (2.0 cm, 0.1 cm) and confined to the thyroid. All regional lymph nodes were negative for tumor. Methimazole was discontinued post-operatively, and she started Levothyroxine suppression therapy. Discussion: We present a rare association of papillary thyroid carcinoma presenting as a hot thyroid nodule. Though uncommon, detection of a hyperfunctioning thyroid nodule does not exclude the possibility of thyroid carcinoma and warrants careful evaluation. Clinicians should retain a high index of suspicion particularly when ultrasonography demonstrates findings suspicious for malignancy and consider additional evaluation with fine needle aspiration. Reference: (1) Haugen BR, Alexander EK, Bible KC et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. Presentation: 6/2/2024

7699 Unanticipated Harmony: PD-L1 Inhibitor Treatment for Urothelial Cancer Resolving Graves' Disease in a Patient - A Case of Immune Modulation Surprises

Abstract Disclosure: K. Tiwari: None. C.A. Resta: None. Introduction: Programmed death ligand 1(PD-L1) inhibitors constitute a class of immune checkpoint inhibitors (ICI) employed in treating various cancers. Thyroid-related immune-related adverse events (irAEs), such as hypothyroidism, are found to be in 3.9% of patients with PD L1 treatments. This case explores a unique scenario where a patient with pre-existing Graves' disease, undergoing PD-L1 inhibitor therapy for cancer, experienced an unexpected sequence of events leading to the default treatment of Graves' disease and subsequent progression to hypothyroidism. Case Presentation: A 59-year-old male, who had been effectively managed on methimazole for Graves' disease over two years and had chosen not to pursue definitive therapy for the condition, presented with tremors and a bilaterally enlarged thyroid gland during treatment for urothelial carcinoma. Laboratory findings included a TSH of 0.03 mIU/L (nl 0.40-4.50 mIU/L), fT4 of 3.4 ng/dL (nl 0.8-1.8 ng/dl), and tT3 of 284ng/dl (nl 76-181 ng/dl). The patient had recently started treatment with Avelumab, a PD-L1 inhibitor, as maintenance therapy following 4 cycles of gemcitabine/cisplatin cycles. Concerned about worsening Graves' disease, the methimazole dose was increased, and follow-up labs were performed after three weeks. These results showed low-normal fT4 of 0.8 ng/dL, TSH of 1.01 mIU/L(N), and low T3 of 58 ng/dL. TSI was mildly elevated at 168%. Due to rapidly changing thyroid function tests and suspicion of thyroiditis, methimazole was stopped. A PET scan a week later indicated diffuse thyroid uptake consistent with thyroiditis. Repeat labs 10 days later revealed a TSH of 67.36 mIU/L(H) and fT4 of 0.4 ng/dL(L), indicative of overt primary hypothyroidism. The patient exhibited symptoms including fatigue, constipation, and cold intolerance. The patient was initiated on levothyroxine therapy to address overt primary hypothyroidism, likely secondary to destructive thyroiditis from ICI. Discussion: Thyroid irAEs are typically incidentally discovered during routine monitoring of ICI treatment. It includes thyrotoxicosis, subclinical hypothyroidism, and overt hypothyroidism. These events commonly occur in patients lacking pre-existing thyroid conditions. In contrast, our patient, with a history of Graves' disease, experienced resolution of Graves' disease following treatment with PD-L1 inhibitor use with subsequent progression to hypothyroidism. Conclusion: This case emphasizes the importance of recognizing atypical presentations of thyroid irAEs in individuals with pre-existing thyroid disorders undergoing ICI treatment. Presentation: 6/3/2024

5039 Chronic Painful Hashimoto's Thyroiditis

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

7081 A Spotlight on Marine Lenhart Syndrome

Abstract Disclosure: R. Alshantti: None. A.M. San Hernandez: None. J. Wu: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Marine-Lenhart Syndrome is a rare condition with a prevalence of 0.8-4.1% of cases with Graves’ disease. It is defined by the coexistence of Graves’ disease and autonomously functioning thyroid nodule(s). It is an under-recognized cause of hyperthyroidism. A limited number of cases have been reported in the literature. We report an interesting case of Marine-Lenhart Syndrome characterized by the presence of elevated thyroid stimulating immunoglobulins (TSI) and an autonomous right thyroid nodule. Case Description: A 37-year-old man with a history of hyperthyroidism from Graves’ disease and a right thyroid nodule was referred to endocrinology clinic. He was diagnosed with hyperthyroidism in 2015 at an outside facility. He had elevated thyroid stimulating immunoglobulins (TSI) and a 2.9 cm right thyroid nodule which was biopsied and had benign cytopathology. Hyperthyroidism was treated with methimazole (MMI) but without subsequent remission of Graves’ disease. He ran out of MMI and re-presented with symptomatic hyperthyroidism with fatigue, tremors, and hyperdefecation. There was no ocular involvement or thyroid compressive symptoms. Biochemical work up was consistent with uncontrolled hyperthyroidism (suppressed TSH 0.01 uIU/mL [Ref range: 0.45-5.33], and elevated FT4 2.58 ng/dl [Ref range: 0.70-2.20], elevated free T3 8.7 pg/ml [Ref range: 2.5-3.9], and mildly elevated TSI 0.72 IU/L [Ref range: 0.54 or less]. MMI was therefore reinitiated. Thyroid Uptake scan demonstrated an increased focal 24-hour Iodine-131 uptake of 57% in the right lobe with suppression of the left lobe. Thyroid ultrasound support the finding of large right thyroid nodule (2.3 x 2.4 x 3.9 cm) with diffuse heterogeneous thyroid. The presence of TSI, lack of control of hyperthyroidism for more than 2 years of treatment, and presence of a functioning thyroid nodule raise the suspicion of Marine-Lenhart Syndrome. Indeed, the findings of an autonomously functioning right thyroid nodule with concomitant Graves’ disease establish the diagnosis of Marine-Lenhart Syndrome. The option of RAI ablation vs total thyroidectomy was discussed with the patient. The patient opted for thyroidectomy. Conclusion: Based on studies, approximately 35% of patients with Graves’ disease have thyroid nodule(s) and only 2.7% are functioning adenomas. The combination of positive TSI or TrAb and functioning thyroid nodules has been termed Marine-Lenhart syndrome. The syndrome was named after David Marine and Carl Lenhart who initially described it in 1911. Unlike Graves’ disease, patients with Marine-Lenhart Syndrome have a lower remission rate with thioamides, require definitive treatment with RAI ablation at a high dose or total thyroidectomy, and may easily be misdiagnosed by many endocrinologists. Presentation: 6/2/2024

8477 Medullary Thyroid Carcinoma Masquerading as a Cold Nodule in a Patient With Graves' Disease

Abstract Disclosure: T. Umashree: None. K.J. Farooqui: None. A. Mithal: None. Background: Only a handful of cases of MTC have been reported in the setting of Graves’ disease. Clinical Case: A 38 year old lady presented with symptoms of significant weight loss and palpitations for past six months. Thyromegaly was present, with non tender left lobe enlargement of about 3x3 cm. On further probing it was found that her father had been operated for thyroid cancer 22 years ago, the type of which patient was not aware of. TFTs reflected a thyroxtoxic state (TSH -&amp;lt;0.01mIU/mL [0.34-5.6] FT4 - 3.38 ng/dL [0.58-1.64] FT3 - 8.46 pg/mL [2.6-4.2]) and TRAb was positive (8.74 IU/L [&amp;lt;1.22]). USG neck revealed a hypoechoic lesion of 18x18x13 mm in left lobe thyroid with internal calcifications, with multiple bilateral non-significant lymph nodes. Technetium99 (Tc99) scan showed an enlarged left lobe, with diffuse thyroid uptake at 20 minutes of 4%, and a well-defined photopenic area in left lobe, corresponding to the nodule seen on USG. FNAC of the nodule was suggestive of Hürthle cell neoplasm and patient underwent left hemithyroidectomy. Surprisingly, HPE was consistent with medullary thyroid cancer. Serum calcitonin was raised at 148 pg/mL (N&amp;lt;4.8 for females) and plasma free metanephrines and normetanephrine were normal. F-18 DOPA PET CT showed uptake in residual right lobe of thyroid only, no other abnormal uptake was seen. She underwent completion thyroidectomy with central compartment clearance and is now under regular follow up. Genetic analysis showed RET gene mutation of Cys634Ser, which is heterozygous for MTC. Cold nodules in Graves’ disease should be viewed with suspicion, and while PTC and FTC have been reported more commonly, MTC is extremely rare in this setting. A calcitonin washout of the FNAC may have prevented this patient from undergoing two surgeries. Moreover, Hürthle cell change can also occur in C-cells of the thyroid, not just the follicular cells. Lastly, given the history of thyroid cancer in her father, index of suspicion of MTC should have been higher in this patient. Conclusion: Cold nodules in Graves’ Disease may be malignant, and should always be examined by FNAC. Though MTC is rare, it is not unknown in Grave’s disease. Presentation: 6/3/2024

8507 Misdiagnosis of Graves’ and RAI Treatment in Patient with THRB Gene Mutation

Abstract Disclosure: E. McBride: None. R. Kennedy: None. A.N. Davis: None. S.J. Healy: None. Introduction: Resistance to thyroid hormone (RTH) is an inherited condition in which there is decreased tissue responsiveness to thyroid hormone. Occasionally patients with this condition can be misdiagnosed with hyperthyroidism.Clinical case: A 35 yo female was referred to our clinic for evaluation of postablative hypothyroidism. 6 years prior, the patient was evaluated by endocrinology at our city’s army hospital. The patient had abnormal TFTs during HTN workup but was otherwise asymptomatic. Family history included goiter in paternal aunt and grandmother (s/p thyroidectomy). Labs showed TSH 0.370 mIU/L (0.3-3); FT4 2.01, repeat 1.96 ng/dl (0.6-1.6); FT3 6.10 pg/ml (2.3-4.4); T4 16.2 mcg/dl (4.5-12); alpha subunit 0.32ng/ml; TBG 31 mcg/ml (13-39). On exam patient had thyromegaly. Thyroid US showed normal gland with length 5.6 cm. Subsequent labs showed negative thyroglobulin ab, antithyroid microsomal ab, TBII, and TSI. Resistance to thyroid hormone (RTH) was suspected. Pt underwent RTH mutation analysis. Result was heterozygous for c.715T&amp;gt;A (pTrp239Arg) in exon 7 of the THRB gene, described as variant of unknown significance. Treatment was not recommended. Patient desired pregnancy and was evaluated by our hospital’s MFM clinic for preconception counseling. Per notes, patient had another child who tested negative for the gene.Patient then moved out of state, and 1 year later she underwent ablation for presumed diagnosis of Graves’ disease. The records from that hospital are not available. Patient later moved back to our city and was evaluated in clinic. At that visit, weight was 44 kg and patient was on 200 mcg LT4 daily. Pt endorsed cold intolerance, mood swings, brain fog, some hair loss. Recent thyroid US showed diminutive thyroid, and outside labs showed TSH 7.288, TPO ab &amp;lt;4. Our labs showed TSH 8.6 and FT4 2.05. Pt was still interested in becoming pregnant. She did not recall the prior genetic testing or diagnosis of RTH, and believed that she had Graves’. Patient did not return for follow up visit and later moved out of state.Conclusions: Patient’s labs showed elevated T4 and T3 with normal TSH. Genetic testing revealed a mutation in THRB gene. The normal codon is TGG coding for tryptophan and mutation in this patient is AGG coding for arginine. Other mutations in this same codon result in reduced T3 binding affinity.This patient was later was misdiagnosed as having Graves’ at an outside hospital, presumably due to labs and increased thyroid uptake. Patient underwent unnecessary RAI treatment. It is common for these patients to require higher than expected doses of thyroid hormone.This case illustrates the importance of obtaining outside records and correlating thyroid function tests with imaging studies. It is a reminder that not all cases of increased thyroid uptake are due to Graves’. Management of thyroid hormone can be challenging in patients with RTH who have undergone ablation. Presentation: 6/3/2024

8161 A Rare Case of Malignant Melanoma Metastatic to the Thyroid Gland

Abstract Disclosure: J. Ferri-Guerra: None. O. Abdulhussein: None. E. Kasper-Guerra: None. G. Madrigal Loria: None. L. El Hage: None. 69 yo female presented with neck swelling in 2014. TSH was normal. Thyroid ultrasound showed multiple nodules with a right 2.9 x 2.3 x 2.1 cm that was cold on subsequent thyroid uptake scan. FNA of the right nodule in 08/2014 showed malignant cells with spindle cell pattern thought to be medullary thyroid cancer. She was scheduled for total thyroidectomy but presented with small bowl obstruction prior to her surgery and was diagnosed with metastatic melanoma (BRAF +). Initial PET scan showed a 4.1 x 2.8 x 2.8 cm hypermetabolic right thyroid lobe lesion in addition to other multiple hypermetabolic lesions consistent with known melanoma. The thyroid FNA specimen correlated with the small bowel excision specimen and showed similar features diagnosing metastatic melanoma to the thyroid gland.She was started on ipilimumab with subsequent scan in 04/2015 showing increase in right thyroid mass size to 5.4 x 4.2 x 9 cm with mixed results of other metastatic locations. She was switched to pembrolizumab and later dobrafenib/trametinib in 05/2015. Imaging thereafter showing significant improvement including a decrease in the right thyroid nodule size to 1.6 cm x 2.5 cm x 2.4 cm with no hypermetabolic activity on further PET scans. Repeat thyroid ultrasound in 2021 showed multiple nodules with a 2.2 x 1.5 x 1 cm nodule in the right. Repeat FNA of the right nodule was benign. Last imaging in 2023 showed stable nodules. Conclusion: metastasis to thyroid gland from malignant melanoma is a rare finding and should be considered in rapidly growing thyroid nodules. These lesions can be treated with targeted therapy that can spare affected individuals surgery. Presentation: 6/1/2024

8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?

Abstract Disclosure: K.S. Hill: None. R. Osman: None. Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use. Presentation: 6/3/2024