Radioactive Iodine Ablation Research Articles

Prevalence and Risk Factors of Heart Failure in Patients Diagnosed with Hyperthyroidism: A Systematic Review and Meta-analysis.

Objectives: Hyperthyroidism has a significant impact on the cardiovascular system, causing thyrotoxic cardiomyopathy, which is characterized by atrial fibrillation, left ventricular hypertrophy and diastolic dysfunction, and may lead to heart failure. This study aimed to investigate the prevalence and associated risk factors for heart failure in patients with hyperthyroidism. Methods: A systematic literature search was conducted on PubMed, SCOPUS and Ovid SP up until April 2023. Pooled prevalence and pooled odds ratio for risk factors were calculated using the generic inverse variance method. Results: Studies involving 30,889 patients were included in this meta-analysis. The overall prevalence of heart failure in patients with hyperthyroidism was 8% (95% confidence interval [CI]: 6-11%). Further analyses revealed that the prevalence of heart failure in patients who underwent treatment with radioactive iodine ablation, antithyroid medication and thyroidectomy was 8% (95% CI: -1 to 16%), 6% (95% CI: 2 to 11%) and 4% (95% CI: -2 to 10%), respectively. The risk factors of heart failure in hyperthyroidism include atrial fibrillation, chronic kidney disease, anaemia, hypertension, history of stroke or transient ischaemic attack, history of coronary artery disease and diabetes mellitus. Conclusion: Heart failure occurs in 8% of patients with hyperthyroidism, with the most common risk factor being atrial fibrillation.

Association of Radioactive Iodine Administration With Outcome Among Patients With Low-Risk Differentiated Thyroid Cancer: A Real-World Data Analysis.

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC. We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted. Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06-1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease. Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

6688 Clinical Presentation and Management of Highly Differentiated Follicular Carcinoma Arising from Struma Ovarii with DICER1 Mutation: A Case Report

Abstract Disclosure: S.M. Seav: None. J. Shah: None. C. Dosiou: None. Background: Struma ovarii (SO) is a rare type of ovarian teratoma comprised of > 50% thyroid tissue. Extra-ovarian spread of SO, called peritoneal strumosis, was previously considered benign given the lack of histological malignant features. The 2020 WHO Classification of Female Genital Tumors has reclassified this as highly differentiated follicular carcinoma arising from struma ovarii (HDFCO), highlighting its low-grade malignant potential.[1] We report a case of HDFCO with extensive peritoneal disease and discuss its management. Clinical Case: A 38-year-old female presented to her OBGYN for irregular menses. Pelvic MRI showed an 8 cm right ovarian mass. Right salpingo-oopherectomy and pelvic peritoneal biopsies revealed well-differentiated thyroid tissue. Thyroid ultrasound demonstrated a multinodular goiter with ATA high risk nodules; 4 of 5 biopsied with benign results. Her thyroglobulin (Tg) was 170 ng/mL (normal 2 – 35 ng/ml). No further intervention was recommended. Two years later she was referred to our clinic. CT of abdomen/pelvis showed multifocal residual disease. We recommended more aggressive management, given the diagnosis of HDFCO. All visible disease was resected in a diagnostic laparoscopy with pelvic and omental biopsies. Pathology showed well-differentiated thyroid tissue. Molecular testing for the FGFR4 mutation associated with HDFCO was negative, but there was a DICER1 mutation c.5428 G>T of undetermined significance. DICER1 mutations are associated with thyroid cancers2. A total thyroidectomy and radioactive iodine ablation (RAI) were recommended. Thyroid pathology was benign. Tg was 9 ng/mL one month post-op. MRI six months post-laparoscopy revealed only one 6 mm omental lesion. Withdrawal I-123 whole body scan (WBS) showed multiple peritoneal implants. Tg was 214 ng/mL and TSH was 72 ulU/mL. The patient was treated with 157 mCi of oral I-131. Given the extensive peritoneal disease, she received prophylactic oral dexamethasone for 2 weeks after RAI to decrease the risk of peritoneal inflammation and bowel obstruction potentially mediated by local inflammation from radiation-related tissue injury. Her Tg three months post-RAI was 4 ng/mL. The surveillance plan is to alternate between RAI WBS and MRI abdomen/pelvis every 6 months. Conclusions: Peritoneal strumosis, previously considered benign, has recently been reclassified as HFDCO, an extremely rare low-grade malignancy with no standardized treatment. We report the first case of extensive HFDCO with a DICER1 mutation. Given the significant peritoneal involvement, our case was treated with total thyroidectomy, surgical excision of all implants, RAI, and prophylactic steroids post-RAI. Further research into the prognostic factors and optimal treatment of HFDCO is needed. Reference: [1]Giovanopoulou et al. Curr Oncol. 2022; 29(12): 9105-9116. 2Sauer et al. Head Neck Pathol. 2022; 16(1): 190–199. Presentation: 6/1/2024

7854 Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection

Abstract Disclosure: K.T. Lim: None. O.C. Dampil: None. Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection Introduction: Thyroid dermopathy (TD) represents an unusual extrathyroidal presentation of Graves' disease (GD), impacting about 0.5–4% of patients. RAI treatment for hyperthyroidism is known to progress Graves' ophthalmopathy. RAI-induced TD exacerbation, however, is rare in literature. Here, we present a case of worsening TD and ophthalmopathy in a Filipino patient with GD who underwent definitive therapy for persistent hyperthyroidism. Clinical Case: A 44-year-old man with GD had bilateral lower extremity indurated, mildly erythematous plaques for 4 years. Hyperthyroidism persisted despite methimazole compliance, so he underwent RAI ablation two years earlier, total thyroidectomy a year later, and has been on levothyroxine since. Despite definitive treatment, his extrathyroidal symptoms worsened. A punch biopsy of the skin lesions revealed upper and mid-lower dermis mucin deposition, with occasional spindle-shaped and stellate fibroblasts, and mast cells. These histopathologic findings were consistent with pretibial myxedema. We assessed his thyroid function and found he was euthyroid with normal TSH (3.1 μIU/mL; reference range 0.27-4.20) and an elevated TRAb (35.73 IU/L; reference range <1.75). Physical examination revealed thickened skin, cobblestone-like plaques, and non-pitting edema on the pretibial, ankle, and pedal areas. A 3.5-cm-diameter, circumscribed, orange-peel-textured, indurated plaque covered his left ankle. Fluocinolone acetonide 0.025% w/w ointment was initiated. After 3 weeks, his cutaneous symptoms improved by 35%, albeit his left ankle circumscribed plaque improved marginally. Triamcinolone acetonide 40 mg/mL was injected into this and other nodular lesions at 4mg (0.1 mL) per 1-cm-diameter circular region. Each dose was equally dispersed by multipoint intradermal injections using a 1 mL syringe with a 0.5”x 25G needle. A week after intralesional triamcinolone injection and continuous topical steroid application on the non-nodular lesions, a 70% improvement in cutaneous manifestations was observed (from baseline) with the plaques becoming thinner and softer. After three weekly intradermal steroid injections, the circumscribed plaque had flattened (with residual hyperpigmentation), and the other plaques and nonpitting edema dissipated. Conclusion: Our experience with this patient highlights a paradoxical TD exacerbation following RAI ablation and definitive surgery for persistent hyperthyroidism in GD. It also reveals that weekly administration of multiple subcutaneous injections of a long-acting glucocorticoid alleviates lesions where topical ointment does not. Presentation: 6/1/2024

6925 A Rare Case of Metastatic Papillary Thyroid Carcinoma Confined to Cervical Lymph Node with No Identifiable Primary Tumor In The Thyroid Gland. A Diagnostic Conundrum

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Papillary thyroid carcinoma (PTC) is the most common treatable thyroid cancer (TC) with very good prognosis. Metastatic PTC either in the lymph node LN or extra-nodal with no primary thyroid lesion identified is a rare phenomenon referred to as occult thyroid carcinoma (OTC). Despite its rarity, it is reported and constitute a diagnostic conundrum. herein we present a case of metastatic PTC identified in cervical lymph nodes (LN) without a primary tumor in the thyroid gland confirmed with surgical pathology. Case Presentation: A 43-year-old female with history of post-ablative hypothyroidism after treatment of toxic nodular goiter for 10 years, with no family history of thyroid cancer presented with incidentally found left 1.8 Heterogeneous hypoechoic solid nodule with lobulated borders and internal calcifications along with left-sided 0.8 LN without normal fatty hilum on Ultrasound Head and Neck. Fine needle aspiration of the left thyroid nodule and suspicious LN revealed PTC in the left LN though the thyroid nodule sample was non-diagnostic. CT of head and neck showed partially calcified thyroid nodule, Hyperattenuating 8 mm left III LN without fatty hilum, and 9 mm left II calcified LN. Patient underwent total thyroidectomy, central neck, and left lateral neck dissection. Surgical pathology showed no malignancy in thyroid gland or central LNs and 1 out 5 LN of the left neck dissection showed PTC with tumor grading of pT0 pN1b pMNA. patient underwent whole-body thyrogen-stimulated thyroid scan which showed iodine avid tissue in the thyroid bed followed by high-dose I-131 radioactive iodine ablation (RAI). Discussion: OTC refers to impalpable incidental TC less than 10 mm per the WHO. Boucek et al classify OTC into four categories, recently a fifth category was added, in which metastasis is confirmed either in regional LN or distant metastasis though thyroid tissue is confirmed to be benign per pathology and imaging evaluation, our patient falls in the fifth category. Hypothesis of this phenomenon is not well understood, one suggested explanation is missed diagnosis due to not enough sample or if lesion is less than 3 mm. another hypothesis is tumor spontaneous regression, or regression secondary to treatment that was inadequate to treat the systemic process of the tumor, which we believe our patient fits in this hypothesis, given that she underwent RAI ablation many years ago. Tumor regression is very rare and reported to be 1 in 140,000 cases. Another theory suggests that PTC can arise in ectopic thyroid tissue. This case is to shed light on a rare clinical and pathological entity to avoid missed diagnoses. Prognosis depends on the extent of metastasis, with favorable one when it is limited to regional LN and worse with distant metastasis. More cases reports are warranted to help guide further management of such cases due to the lack of available guidance in use of RAI surveillance and ablation. Presentation: 6/1/2024

6955 A Rare Case of Rapidly Enlarging High Grade Follicular-Derived Carcinoma in a Young Patient - Formerly Known as Insular Thyroid Carcinoma with good response to Radioactive iodine ablation- A New Name, Same Aggressive Features

Abstract Disclosure: R. Abdelmasih: None. N. Prasad: None. N. Shah: None. Introduction: Follicular-derived thyroid carcinomas, formerly known as insular thyroid carcinomas, are an albeit rare but highly lethal thyroid carcinoma subtype with an incidence of 1-10% worldwide. It is known for its aggressive nature and comprises the majority of deaths from non-anaplastic follicular thyroid cancers. Case Presentation: A 30-year-old male presented with 2-year history of progressively enlarging painless right neck mass. Physical exam revealed 6x3 cm right well-circumscribed mobile mass not displacing the trachea. Head and neck CT showed 6.5 cm right thyroid mass with level 2A lymph node. Neck Ultrasound showed a 6.4 cm right thyroid nodule. Fine needle aspiration of the mass showed atypia of undetermined significance. Patient returned to clinic 1 year later with progressively enlarging right neck mass, now associated with dysphagia measuring 10 cm in physical exam deviating the trachea to the left. Repeat CT H&N showed 10 cm right thyroid mass with moderate tracheal deviation and US showed 11 cm right heterogenous thyroid mass with regular margins and negative LNs. Patient underwent right thyroid lobectomy with surgical pathology showed 11.4 cm tumor with vascular invasion and no extrathyroidal extension. Pathology showed high grade follicular-derived Thyroid Carcinoma. Patient underwent completion thyroidectomy with benign pathology followed by radioactive iodine ablation 107.8 mCi I131 with successful targeting of residual thyroid tissue and no evidence of iodine avid distant metastasis. Patient has been followed closely for 2 years now with regular US, thyroglobulin level with recurrence. Discussion: Insular thyroid carcinomas are aggressive malignancies predominantly seen in females within the age of 55-65 though cases of young patients and children have been reported. Patients often present with enlarging goiter, dysphagia, and dyspnea however, metastatic disease to lymph nodes, lung and bone has also been reported as primary presentation in 20% of cases. Per literature review, recurrence and mortality rates have very wide range of 36-83% and 9-75% respectively which could be explained by a variety of prognostic factors including Patient age, tumor size, Macroscopic evident extrathyroidal extension, distant metastasis, or tumor necrosis. Often times insular thyroid carcinomas are mistaken for anaplastic carcinoma and thus fine needle aspiration is a helpful diagnostic tool to differentiate insular carcinoma. Pathology typically demonstrates well-defined insulae of thyroglobulin-filled follicles, necrotic foci, and high random mitotic activity. Treatment includes total thyroidectomy followed by high-dose radiotherapy. We Present this case to shed light on such a rare aggressive entity that requires early detection, belligerent management, and close follow-up for promising outcomes. Presentation: 6/3/2024

8465 Diagnostic Conundrum: The Mystery of Metastatic Papillary Thyroid Cancer with Persistently Elusive Thyroglobulin

Abstract Disclosure: P. Vemparala: None. M. Bollineni: None. Introduction- Among endocrine malignancies, differentiated thyroid cancers account for the majority with most of them boasting a favorable prognosis. Thyroglobulin, a pivotal biochemical marker, aids in detecting recurrence or persistent disease when combined with neck ultrasound, I-131 scintigraphy, and FDG PET scans. Anti-thyroglobulin antibodies, found in a quarter of cases, can falsely lower serum thyroglobulin levels in immunometric assays. Our intriguing case features a patient with metastatic papillary thyroid cancer, yet thyroglobulin levels persistently eluded detection. CASE PRESENTATION- A 33-year-old female presented initially to an outside facility with neck swelling, leading to a diagnosis of a 4 x 3 cm papillary thyroid cancer (PTC) in the right lobe and a 0.5 x 0.5 cm focus of PTC in the left lobe, accompanied by capsular extension, malignant cells in the left lobe margin, and lymphovascular invasion. After total thyroidectomy and lymph node exploration, radioactive iodine scan detected disease in right-sided lymph nodes, treated subsequently with radioactive iodine ablation. Two years later, she presented to our clinic with neck swelling, voice changes, and fatigue. Thyroglobulin level was measured which returned at <0.1 ng/ml, however thyroglobulin antibodies were elevated at 292 IU/ml, albeit decreased from a value of 431.5 IU/ml at initial diagnosis. Elevated thyroglobulin antibodies complicated interpretation, prompting liquid chromatography-mass spectrometry (LC-MS) for accurate measurement of thyroglobulin, which returned at <0.5 ng/ml. Ultrasound indicated metastatic disease in right cervical lymph nodes, confirmed by fine needle aspiration. In-office ultrasound-guided FNA of additional nodes validated metastasis. Modified radical neck dissection revealed metastatic PTC in 7 out of 34 lymph nodes. Surprisingly, thyroglobulin levels remained <0.5 ng/ml, pre- and post-operatively. Referred for radioactive iodine ablation, her complex journey underscored the challenges in monitoring thyroid cancer recurrence or persistent disease with thyroglobulin levels even by methods such as mass spectrometry. Conclusion- Key learnings from this case highlight the importance of cognizance in utilizing thyroglobulin levels to guide adjuvant therapy decisions and for postoperative monitoring in high risk patients, as low levels do not rule out recurrence or persistence. Anti-thyroglobulin antibodies pose challenges, necessitating techniques like LC-MS. Finally, recognizing “nonsecretor” thyroid cancers, an aggressive subgroup with poorer prognosis, is vital as they often present with low or undetectable thyroglobulin levels. Presentation: 6/2/2024

9398 Early Identification of Impending Thyroid Storm Leading to Improved Thyrotoxic Induce Cardiomyopathy

Abstract Disclosure: D.H. Sacoto: None. D. Patel: None. A. De Rosairo: None. K. Madani: None. B. Singh: None. A. Bonilla Campos: None. R. Belokovskaya: None. F. Alberto A.: None. Introduction: Heart failure can be the leading presentation in 6% of thyroid storm cases and is the leading cause of death, particularly in elderly patients. However, its importance lies in symptom control and heart function reversibility once the euthyroid state is achieved. We present a caseof thyroid storm-induced atrial fibrillation (Afib) leading to severe systolic dysfunction. Case: A 61-year-old female with a history of Graves’ disease (GD) presented to the ED with two months of palpitations and one week of shortness of breath. There were bibasilar lung crackles, irregular heart rhythm, pedal edema, and thyromegaly at the examination. EKG was consistent with Afib with rapid ventricular response (123-135 beats per minute); She was tachypneic (respiratory rate: 40 per minute) and hypoxemic (87% O2 saturation), which required bilevel positive airway pressure. Otherwise, hemodynamically stable (BP: 127/106 mmHg). Laboratories showed negative troponin T (<0.010 ng/mL, n <0.01 ng/mL). However, elevation of Pro-B-type natriuretic peptide (6000 pg/mL, n <125 pg/mL), an x-ray displaying bibasilar pleural effusions and an echocardiogram demonstrating a severely reduced ejection fraction (EF) (21%, n 50-70%), myocardial perfusion scan was normal. Thyroid evaluation showed a suppressed TSH (<0.01 uIU/mL, n 0.27-4.20 uIU/mL) with elevated free T4 (5.8 ng/dL, n 0.9-1.8 ng/dL), free T3 (202 ng/dL, n 2.0-4.4 ng/dL), and TSI (8.25 IU/L, n 0-0.55 IU/L). A thyroid ultrasound revealed increased vascular flow on the left thyroid lobe. A Burh-Schakowsky score of 45 points was consistent with impending thyroid storm. She was started on methimazole, cholestyramine, and propranolol. Three months follow-up, she was asymptomatic, TSH normalized (4.12 uIU/mL), and mild improvement of cardiac EF 25%. Discussion: A thyroid storm in the setting of GD often presents after precipitating factors such as surgery, infection, or, as in our case, anti-thyroid medication non-compliance. Increased thyroid hormone levels upregulate cardiac β receptors, enhancing sensitivity to sympathetic innervation. These can shorten the refractory period of cardiomyocytes, leading to tachyarrhythmias, with Afib occurring in 20% of patients. Chronic tachycardia finally impairs left ventricle function, with heart failure as an outcome. A high index of suspicion and the ability of early diagnosis of impending thyroid storm is critical since the first laboratory confirmation is often delayed, and second, either anti-thyroid medication, radioactive iodine ablation or thyroidectomy, in addition to non-selective beta-blockers, can reverse cardiac dysfunction and lead to clinical improvement as early as 12 -Twenty-four hours of medical treatment. In our case, the early diagnosis and treatment of thyroid storm, in addition to the rate control prevented a deadly outcome and contributed to the improvement of heart failure. Presentation: 6/1/2024

8675 Dosing of Radioactive Iodine for Papillary Thyroid Cancer in Advanced Chronic Kidney Disease

Abstract Disclosure: C. Cheatham: None. D. Beckman: None. INTRO Radioactive Iodine (RAI) ablation is an important treatment for patients diagnosed with papillary thyroid carcinoma. Most studies completed on RAI in renal dysfunction were focused on End Stage Renal Disease (ESRD) patients on dialysis to establish protocols on timing of dialysis to allow desired clinical response to RAI without increased risks and minimizing exposure of dialysis staff to radiation dose. The ideal RAI dosing and monitoring of patients with advanced chronic kidney disease (CKD) stage 4 or 5 not requiring dialysis has not been systematically reviewed. CASE 26 year-old female with CKD stage 4/5 secondary to chronic hydronephrosis from vesicoureteral reflux with baseline eGFR 15-20 mL/min/1.73 m2 was diagnosed with papillary thyroid cancer. She underwent total thyroidectomy with central and left lateral neck dissection, resulting in pathologic stage I, pT2 N1b M0 disease, high risk for recurrence according to the 2015 American Thyroid Association guidelines due to 17 positive lymph nodes from left level II-IV and VI, multiple with extranodal extension, as well as 1 vessel angioinvasion. She was referred for adjuvant RAI ablation after withdrawal from thyroid hormone. Decision was made to proceed with a 50% dose reduction and close monitoring of radioactivity clearance as an inpatient given decrease of eGFR to 10-12 mL/min/1.73 m2. She was cleared for discharge 4 days after RAI dose of 74.8mCi when activity level dropped to <2mR/hr. Post-ablation whole body scan showed activity in the thyroid bed and parasternal notch without evidence of metastatic disease. Post-treatment non-stimulated thyroglobulin 6 weeks later was 0.4 ng/mL down from 269.7 ng/mL. DISCUSSION Given RAI is predominately renally cleared, decreased renal function affects clearance rates and associated exposure to radiation. Risks with decreased RAI clearance include bone marrow toxicity and prolonged isolation requirements. In a 2017 retrospective review, patients with eGFR <30 mL/min/1.73 m2 had delayed clearance leading to a mean proportional reduction of exposure rate at 48 hours of -67.2% compared to -94.3% in healthy controls. While protocols exist for patients on hemodialysis, no such protocols have been established for patients with advanced CKD not requiring dialysis. For this patient, after multidisciplinary discussion with nuclear medicine, health physics, and nephrology in setting of further eGFR reduction during hormone withdrawal, decision was made to reduce the intended dose by 50% with inpatient monitoring and backup to dialyze if no significant decrease in radiation activity level was seen or if she were to progress to anuric or oliguric renal failure. This case highlights the need for established protocols and long-term studies to evaluate risk and treatment response in relation to dosing of RAI in this population, but a 50% dose reduction appears to be effective without adverse event. Presentation: 6/2/2024

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 <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: < 0.55), thyroglobulin antibody of 351 IU/ml (< 0.9) and anti-TPO Ab >600 IU/ml (ref< 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

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>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<0.008 fT4 4.2, TrAb >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

8534 Comorbid Autoimmune Thyroid Disease in a Parent-Child Pair with Resistance to Thyroid Hormone Beta

Abstract Disclosure: A.H. Smith: None. E. Grethen: None. Resistance to Thyroid Hormone Beta (RTHβ) is an inherited disorder caused by mutations in the gene encoding the thyroid hormone receptor beta protein, resulting in decreased binding affinity to triiodothyronine in certain tissues. An asymptomatic individual with RTHβ may demonstrate abnormalities in serologic evaluation of thyroid hormone markers. When other thyroid pathologies present with RTHβ, however, the diagnosis and management can quickly become complex. Below we discuss two cases, a parent-child pair, with different presentations of presumably the same RTHβ gene. Patient 1 is a 61-year-old male with a history of autoimmune thyroiditis several years ago, presenting for continuation of care; he has had levothyroxine doses gradually uptitrated to over 3 mcg/kg to normalize TSH despite persistently high free T4 levels. He also has a family history notable for six out of seven siblings with autoimmune thyroid disease. Patient 2 is a 44-year-old male who was evaluated for hypothyroidism and difficulty with levothyroxine titration. Prior to consultation, he underwent radioactive iodine ablation for presumed Grave’s disease, followed by total thyroidectomy due to persistent symptoms. Post-operatively, he required high doses of levothyroxine to maintain normal TSH levels; however T4 and T3 levels remained high. Both patients confirmed proper levothyroxine supplementation. Further analysis of both patients demonstrated mildly elevated TBG and normal alpha subunit. Patient 2 pursued genetic testing while patient 1 declined, revealing a heterozygous R320S mutation in the TR-beta protein. Further testing and genetic counseling were offered to other family members. Propranolol and levothyroxine supplementation were titrated accordingly; triiodothyronine administration was attempted but did not alleviate symptoms. These two cases demonstrate the increased risk of autoimmune thyroid disorders in patients with RTHβ and the unique challenges they pose in accurate diagnosis. Autoimmune thyroiditis in RTHβ, with goiter, elevated T4 and elevated T3 levels, can be easily confused with Grave’s disease, especially when TSH is suppressed during active thyroiditis. Timely diagnosis can aid in targeted management of sequelae, prevent ineffective treatments for comorbid conditions which may mimic other diseases, and provide anticipatory/preventive guidance for family members to help with screening. Presentation: 6/1/2024

5118 When Thyroid Gland Is Not Made Of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

5118 When Thyroid Gland is Not Made of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

12387 Late New-onset Graves' Orbitopathy: 14 Years Post-radioactive Iodine Treatment Of Graves' Disease: Case Report

Abstract Disclosure: F.F. Altaleb: None. K. Alaybaa: None. N. Aljohani: None. Introduction: Graves' orbitopathy (GO) is an autoimmune condition affecting the orbit and retro-ocular tissues, often accompanied by hyperthyroidism associated with Graves' disease, but it is rarely observed in euthyroid or hypothyroid individuals. Radioactive iodine (RAI) therapy for Graves' disease and smoking are recognized risk factors for GO development and progression. Individuals who smoke and undergo RAI treatment are significantly more likely to experience ocular lesions and worsening of GO compared to non-smokers. The exacerbation of GO post RAI therapy is attributed to elevated levels of TSH receptor antibodies, which may persist for up to a year post-treatment. Our case presents a rare occurrence of severe new-onset GO manifesting 14 years after achieving prolonged euthyroid status and successful RAI treatment for Graves' disease, accompanied by persistent TSH receptor antibody positivity that is unlikely to be suppressed by long term levothyroxine therapy. Clinical case: A 55-year-old male who’s a smoker and previously diagnosed with Grave’s hyperthyroidism, received treatment with RAI ablation therapy 14 years ago. At the time of diagnosis, there were no symptoms or signs of GO, and no history of thyroid eye disease was detected. Following the RAI treatment, he developed hypothyroidism and was promptly started on a daily dosage of 100 mcg of levothyroxine.Upon ocular examination: Visual acuity: 20/30 in both eyes. Significant restriction in extraocular muscle movements, with reported diplopia and pain. Bilateral lid retraction, proptosis, right conjunctival chemosis, and injection of the bulbar conjunctiva and caruncle, as well as lagophthalmos, were evident. No relative afferent pupillary defect observed. Color vision: 3/15 in the right eye, 15/15 in the left eye. Intraocular pressure: 22 mmHg (right eye), 16 mmHg (left eye). Optic discs unremarkable. Proptosis measurements: 26 mm (right eye), 23 mm (left eye). Ophthalmopathy clinical activity score: 7.Our laboratory analysis indicated normal thyroid function test However, the TSH receptor antibody and TPO antibody returned positive.We initiated treatment with IV methylprednisolone at a dosage of 500 Mg weekly for a duration of 4 weeks. Additionally, we introduced local measures, along with selenium supplementation. Within a week of initiating treatment, the conjunctival chemosis resolved, and there was improvement in ocular movement, resulting in mild to moderate restriction in all directions of gaze. Conclusion: This case illustrates the unexpected development of GO in a patient who had been euthyroid and effectively cured of Grave's disease for a span of 14 years following RAI treatment. The presence of TSH receptor antibodies, which are likely unresponsive to suppression by levothyroxine, as well as smoking cigarette might have contributed to the late new onset of the disease. Presentation: 6/3/2024

8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n< 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases. Presentation: 6/3/2024

The Definition of Recurrence of Differentiated Thyroid Cancer: A Systematic Review of the Literature.

Background: Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories. Methods: This study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In December 2023, a systematic literature search in MEDLINE and EMBASE was performed for studies reporting on the recurrence of DTC, from January 2018 to December 2023. Studies that did not provide a definition were excluded. Primary outcome was the definition of recurrence of DTC. Secondary outcome was whether studies differentiated between recurrence and persistent disease. Two independent investigators screened the titles and abstracts, followed by full-text assessment and data extraction. The study protocol was registered in PROSPERO, CRD42021291753. Results: In total, 1450 studies were identified. Seventy studies met the inclusion criteria, including 69 retrospective studies and 1 randomised controlled trial (RCT). Median number of patients in the included studies was 438 (range 25-2297). In total, 17 studies (24.3%) reported on lobectomy, 4 studies (5.7%) on total thyroidectomy without RAI, and 49 studies (70.0%) with RAI. All studies defined recurrence using one or a combination of four diagnostic modalities cytology/pathology, imaging studies, thyroglobulin (-antibodies), and a predetermined minimum tumor-free time span. The most common definition of recurrence following lobectomy was cytology/pathology-proven recurrence (47.1% of this subgroup), following total thyroidectomy with RAI was cytology/pathology-proven recurrence and/or anomalies detected on imaging studies (22.4% of this subgroup). No consistent definition was found following total thyroidectomy without RAI. Nine studies (12.9%) differentiated between recurrence and persistent disease. Conclusion: Our main finding is that there is no universally accepted definition for recurrence of DTC in the current studies across any of the treatment categories. The findings of this study will provide the basis for a future, international Delphi-based proposal to establish a universally accepted definition of recurrence of DTC. A uniform definition could facilitate global discussion and enhance the assessment of treatment outcomes regarding recurrence of DTC.

Cost Effectiveness of Definitive Treatment Strategies for Autonomously Functioning Thyroid Nodules.

Autonomously functioning thyroid nodules (AFTN) can be treated with antithyroid drugs, radioactive iodine (RAI), thyroid lobectomy or radiofrequency ablation (RFA). Although surgery is most definitive, some patients require lifelong hormone supplementation. RFA avoids this sequela, but its efficacy depends on nodule size. This study aims to compare the relative cost-effectiveness of RAI, RFA and lobectomy for treatment of AFTNs. A Markov analysis model was created to simulate clinical outcomes, costs and utilities for three AFTN treatments: (1) thyroid lobectomy, (2) RAI, and (3) RFA. This mathematical model was created using published literature and modeling. Transition probabilities, utilities and costs were extracted from published literature, Medicare, and RedBook. The willingness to pay threshold was set to $100,000 per quality-adjusted life year. The model simulated 2-year outcomes, reflecting RFA literature. Sensitivity analyses were conducted to account for uncertainty in model variables. In the base model, RAI dominated both lobectomy and RFA, with lower estimated cost ($2000 vs. $9452 and $10,087) and higher cumulative utility (1.89 vs. 1.82 and 1.78 quality-adjusted life years). One-way sensitivity analyses demonstrated that relative cost-effectiveness between surgery and RFA was driven by the probability of euthyroidism after RFA and hypothyroidism after lobectomy. RFA becomes more cost-effective than surgery if the rate of euthyroidism after ablation is higher than 69% (baseline 54%). Based on published data, RAI is most cost-effective in treating most AFTN. Surgery is more cost-effective than RFA in most scenarios, but RFA may be more resource-efficient for smaller nodules with a high likelihood of complete treatment.

Health-related quality of life and radioiodine therapy in thyroid cancer patients: a before-and-after study.

Thyroid cancers are on the rise, but the associated vital prognosis and long-term survival rates are very good. Therefore, treated patients' quality of life and psychological well-being are important considerations. The treatment usually involves surgery and radioactive iodine (radioiodine) ablation. This study aims to investigate potential effects of radioiodine ablation therapy on health-related quality of life, anxiety and depression symptoms, and nutritional status at 6 months post-therapy. This study included 136 patients diagnosed with thyroid cancer. Absorbed doses to the salivary glands were estimated from dosimeters worn by patients. Patient health-related quality of life, psychological status and nutritional status were assessed before and 6 months after therapy using standardized questionnaires (including SF-36, Hospital Anxiety and Depression (HAD) scale). Statistical analyses included random-effects logistic and linear regressions adjusted for potential confounders. While no significant association was found between radioiodine exposure and anxiety or depression symptoms, or nutritional status, a significant increase in the SF-36 role physical sub- score was observed in relation with the salivary gland dose (β= 6.54, 95%CI 2.71;10.36 for a 1-Gy increase). The findings suggest an improved physical health-related quality of life, namely reduced pain and functional impairment, 6 months after radioiodine therapy in thyroid cancer patients. No significant association was found between radioiodine exposure and mental health-related quality of life, anxiety or depression scores nor nutritional status. This study does not provide any evidence that radioiodine therapy has a potentially adverse effect on patient health-related quality of life.

Cervical Lymphadenitis Tuberculosis Coexistent with Metastatic Papillary Thyroid Carcinoma.

Malignant lesions and tuberculosis coexisting at the same anatomical site in a patient are extremely uncommon. We present a case of a 53-year-old female with cervical lymphadenitis tuberculosis combined with metastatic papillary thyroid carcinoma. Thyroidectomy was performed on the patient with central and lateral neck dissection. The patient received anti-tuberculosis medication and radioactive iodine ablation. No recurrence was observed during a 2-year follow-up period.