Thyroid Uptake Research Articles

FRI557 Don’t Forget The Incidental Thyroid Nodule In Graves’ Disease. A Case of Marine-Lenhart Syndrome

Abstract Disclosure: K.N. Andino-Lebrón: None. A. Martinó-Morales: None. J.M. Colón-Castellano: None. Marine-Lenhart syndrome (MLS) was initially described by Charkes in 1972 as he observed patients with Graves’ disease (GD) and incidental functioning thyroid nodules. He named the disease Marine-Lenhart syndrome based on a paper published by Marine and Lenhart in 1911. MLS is a variant of GD now described as the coexistence of GD and autonomous functional thyroid nodules (AFTN); thus, patients present with thyrotoxicosis due to GD and AFTN. MLS is very rare, and prevalence is estimated to be around 0.8%-2.7%. Here, we present a case of MLS in a 79-year-old female. A 79-year-old Hispanic woman with history of breast metaplasia s/p chemoprevention with tamoxifen for 5 years, atrial premature contractions on metoprolol, among other medical conditions was referred to Endocrinology clinics by her primary care physician (PCP) because of abnormal thyroid function tests and ultrasound. She reported feeling anxious with associated palpitations, she denied weight loss. Physical examination was remarkable for regular rate and rhythm, no goiter, no palpable nodules, no proptosis, and deep tendon reflexes +1. Laboratory testing revealed a suppressed TSH of 0.224 uIU/mL, normal free T4 at 1.17 ng/dL, normal total T3 at 142.5 ng/dL, and positive thyroid stimulating immunoglobulins at 345%. Thyroid ultrasound showed a normal size gland with multiple complex nodules. In the right lobe there was a mixed cystic and solid nodule, measuring 1.48x1.21x1.71cm, wider than tall, with internal vascularity and punctate calcifications. In the left lobe there was an isoechoic and solid nodule measuring 0.7x0.5x0.7cm, wider than tall, without calcifications. Thyroid uptake scan with SPECT-CT demonstrated a focus of increased tracer uptake on the upper pole of the right thyroid lobe that corresponds to the one found on CT scan and a diminished and nonuniform uptake of the tracer in the reminders of the thyroid gland. The 24-hour radioactive iodine uptake was 17.5%. Diagnosis of MLS was made, and the patient was started on methimazole 5mg daily, which she has been tolerating well. Follow up laboratories show a biochemically euthyroid state. Marine-Lenhart syndrome is a rare entity of Graves’ disease which is currently defined as GD and accompanying functioning nodule(s). To establish the diagnosis, it is important the evaluation with scintigraphy and autoimmune testing. Multiple treatment options are available and patients with GD should be evaluated for the presence of thyroid nodules and their functional status to achieve optimal therapy. Patients with GD have a chance of remission when treated with antithyroid drugs. Due to the pathophysiology of AFTN, patients with MLS (concurrent GD and AFTN) have lower remission rates with antithyroid drugs and may require definitive management therapy with radioactive iodine or surgery. Presentation: Friday, June 16, 2023

SAT452 Efficacy Of I-131 Treatment Dosage For Hyperthyroidism With Current Institution Formula

Abstract Disclosure: S. Salam: None. N. Nso: None. M. Nassar: None. R. Kondaveeti: None. S. chings: None. -131 (radioactive iodine) therapy effectively targets overactivity of the thyroid gland; however, literature provides conflicting outcomes regarding dosage optimization of I-131 for patients with hyperthyroidism and associated clinical complications. This retrospective study aimed to validate the therapeutic efficacy of an empirically derived I-131 institution formula in resolving hyperthyroidism by establishing a euthyroid or a hypothyroid state. Methods: This retrospective chart review was undertaken for 89 adult patients (>18 years) who received I-131 therapy from 2016 to 2020 at H&H/Queens, New York. The I-131 dose range was determined in accordance with their thyroid gland weight and thyroid uptake percentages; however, the follow-up assessment was performed for the duration of 6 months. The primary endpoint (i.e., treatment success) was defined by the interim development of a euthyroid state, or hypothyroidism, or subclinical/questionable/suspected hypothyroidism, or questionable euthyroid state. The secondary endpoints included the frequency of repeat RAI doses and post-ablation thyroid function tests (TFTs). Results: The univariate and multivariate analysis of patient data indicated an 83% I-131 treatment success rate defined by the achievement of a euthyroid state and hypothyroidism in 6.7% and 70.8% of patients along with the attainment of questionable euthyroid status, questionable hypothyroidism, subclinical hypothyroidism, and suspected hypothyroidism in 1.1%, 1.1%, 2.2%, and 1.1% of patients, respectively. In addition, a low number (i.e., 9%) of patients with hyperthyroidism required repeat I-131 treatment dosages to achieve a hypothyroid or euthyroid state. The results indicated a clinically significant impact of I-131 treatment dosages on post-ablation TSH, T3, and FT4 levels. Conclusion: The results of this study testified to the therapeutic efficacy of the current institution formula for I-131 treatment dosages in treating hyperthyroidism. In addition, 83% treatment success and a low retreatment requirement strengthened current evidence favoring the optimization of RAI therapy for hyperthyroidism. Presentation: Saturday, June 17, 2023

FRI569 A Therapeutic Dilemma: Spontaneous Oscillating Graves' Disease And Hypothyroidism

Abstract Disclosure: D. Suravajjala: None. J. Case: None. S. Kolli: None. V. Eranki: None. Spontaneous recurrent conversions between hyperthyroidism and hypothyroidism in Graves’ disease (GD) is very rare. We present a case of GD with spontaneous oscillation since diagnosis. From our review, less than 10 cases have been reported in the literature with alternating hyper and hypothyroidism. The patient is a 68-year-old female diagnosed with GD 4 years back with TSH <0.01 (0.4 - 4.5 uIU/mL) and TSI 25.70 (0.00-0.5 IU/L). She denied viral illness, radiation exposure, Lithium or Amiodarone use. Ultrasound thyroid was consistent with GD. Thyroid uptake scan was also consistent with GD. Eventually, Methimazole (MMI) 10 mg daily was initiated. About five months after MMI treatment, she was found to be hypothyroid with TSH 9.030 (0.4-4.5 uIU/mL) and FT4 0.99 (0.9-2.2 ng/dl) which led to discontinuation of MMI. 2 months later, she was clinically hyperthyroid with TSH 0.026, FT4 2.93 (0.9-2.2 ng/dl), TSI 9.59 (0-0.55 IU/L). MMI 5 mg daily was resumed, and as she preferred medical management, other treatment options for GD were not considered. Six months after low dose MMI, patient again reverted to hypothyroidism with TSH 21.420, FT4 0.82. MMI 5 mg was changed to every other day. After 8 months, she was found to be clinically and biochemically hypothyroid with TSH 147, FT4 0.41 (0.9-2.2 ng/dl), TSI 7.98 (0-0.55 IU/L). With the suspicion that she had burnt out GD, she was started on Levothyroxine (LT4) 100 mcg daily. Two months after LT4 initiation, she became clinically hyperthyroid with TSH 0.010 (0.4-4.5 uIU/mL) and FT4 1.91 (0.9-2.2 ng/dl). When trial of LT4 dose reduction failed to alleviate patient hyperthyroid symptoms, it was discontinued and MMI was resumed at 2.5 mg qd. Within 3 months she reverted to hypothyroidism. HAMA interference was as well ruled out. Although the patient's thyroid function ranged spontaneously from hyperthyroidism to hypothyroidism, she was still reluctant for definitive treatment options for GD, including RAI ablation and total thyroidectomy. As GD patients may have definitive treatment early, spontaneous conversion between hyperthyroidism and hypothyroidism is usually not seen in GD and most episodes usually occur several years after discontinuation of antithyroid drugs. It is known that both TSH receptor stimulating antibodies (TSAb) and TSH receptor blocking antibodies (TBAb) can be produced at the same time. The presence of hyper or hypothyroidism may depend on the equilibrium between stimulating and blocking antibodies. Switching of TSH receptor antibodies between stimulation and blockage is uncommon. Diagnosis demands careful clinical and biochemical assessments. Alternatively, the case may be easily mistaken for excessive thyroid suppression or replacement. This condition is difficult to manage, and definitive treatment options could be considered with I-131 ablation, thyroidectomy, or pharmacological treatment (block and replace). Presentation: Friday, June 16, 2023

THU665 Unilateral Graves’ Disease In A Bilobar Thyroid Gland: Unusual Cause Of Hyperthyroidism

Abstract Disclosure: K.H. Alaybaa: None. O. Alhuzaim: None. Introduction: Graves' disease (GD) is an autoimmune condition that affects both thyroid gland lobes. GD patients with unilateral thyroid scan uptake are rare. These patients present with classic Graves' symptoms, occasionally with Graves' ophthalmopathy characteristics and increased thyroid hormones, and scintigraphic assessment reveals radiotracer uptake in only one lobe of the thyroid gland. Patient Findings: In this case, a 48-year-old female presented with symptoms and signs indicative of thyrotoxicosis. Lab results revealed that thyroid-stimulating hormone (TSH) was undetectable, while free thyroxine (T4) and free triiodothyronine (T3) were in the high-normal range. Positive results were observed for both thyroid-stimulating immunoglobulin and TSH receptor antibodies. Ultrasonography of the thyroid gland revealed an enlarged left lobe with heterogeneous echotexture and a hyperemic gland without any focal lesions, distinct nodules, or cysts. The NM TC-99M thyroid scintigraphy revealed enlarged and increased radioisotopes uptake in the left thyroid lobe and decreased uptake in the right thyroid lobe, with no hot or cold nodules. The calculated thyroid uptake is 4.5 percent (normal range: 0.5% to 3.5 percent). The most likely diagnosis was unilateral GD. The patient was administered carbimazole and within eight weeks had improved clinically and biochemically. Summary: This patient has thyrotoxicosis symptoms and positive autoantibodies. Tc99m uptake was increased in the left thyroid lobe and decreased in the right thyroid lobe. The left thyroid lobe was hypervascular and enlarged on ultrasonography, indicating the presence of unilateral GD. Unilateral GD is a rare disease with a poorly understood pathophysiology. Presentation: Thursday, June 15, 2023

SAT495 Persistent Euthyroid State in a Patient with Biochemical and Imaging Evidence of Graves' Disease

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. M. Joglekar: None. B. Fritz: None. S. Patel: None. V. Verma: None. R. Kant: None. INTRODUCTION: Elevated TSI antibody and/or diffuse uptake on radioactive Iodine-123 scan is diagnostic of Graves’ disease. Thyromegaly with increased blood flow on color doppler seen on thyroid USG can also aid in the diagnosis. Rare presence of positive TSI antibody without hyperthyroidism has been reported1. Rare co-existence of both Graves’ disease and Hashimoto’s thyroiditis in a patient causing a challenging clinical course has been reported2. Presence of a neutralizing or blocking antibody against the TSH receptor1 or a false positive TSI have been implicated in such rare cases. CLINICAL CASE: A 37-year-old Caucasian Female was seen at our endocrinology clinic for further evaluation of thyroid disorder. Patient initially experienced goiter during 1st pregnancy at age 18, followed by hypothyroidism during last pregnancy needing levothyroxine treatment. Due to goiter history, patient underwent work-up by her primary physician in 2021. Thyroid ultrasound (usg) showed bilateral hyperemia, heterogeneous echotexture, and 0.2 cm cystic nodule in the right upper lobe. Labs showed normal TSH 1.33 uIU/ml (0.3-4.0 uIU/ml), normal Free T4 0.99 ng/dl (0.8-1.8 ng/dl), normal total T3 140 ng/dl (71-180 ng/dl). Patient underwent further work-up by endocrinology in 2022. Thyroid ultrasound again revealed bilateral hyperemia with other similar findings. Labs showed normal TSH 2.02uUI/ml, normal free T4 0.93 ng/dl, normal total T3 138 ng/dl. Interestingly, TSI antibody and TPO antibody were significantly elevated at 66.70 IU/L (0.0-0.55 IU/L) and 517 IU/ml (0-34 IU/ml), respectively. Repeat labs in April 2022, again showed normal TSH 1.77 uIU/ml, normal free T4 0.90 ng/dl and normal free T3 2.94 (2.0-4.40 pg/ml). Thyroid uptake scan was not performed due to persistently normal TSH values. Patient denied the use of biotin supplementation. Patient continues to remain clinically and biochemically euthyroid without treatment. CONCLUSION: Our case supports the rare presence of TSI antibody without hyperthyroidism. Close monitoring is warranted due to possibility of future progression to overt hyperthyroidism. REFERENCE: 1. Alvin Mathew A, Papaly R, Maliakal A, et al.(November 10, 2021)Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi:10.7759/cureus.194482. Vipin Verma, MD, Mc Anto Antony, MD, PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach, Journal of the Endocrine Society, Volume 6, Issue Supplement_1, November-December 2022, Page A833, https://doi.org/10.1210/jendso/bvac150.1723 Presentation Date: Saturday, June 17, 2023

FRI466 Toxic Retrosternal Goiter Following SARS-CoV-2 Vaccination

Abstract Disclosure: J. Schipper: None. Z. Abdul Sater: None. Since the outbreak of the SARS-CoV-2 pandemic, there have been reports of autoimmune thyroid diseases related to COVID inflection and SARS-CoV-2 vaccination. We report a case of SARS-CoV-2 mRNA vaccination (mCoVvax)-induced Graves with retrosternal extension. A 21-year-old Hispanic male with no previous history of thyroid illness presented with a 4-month history of tachycardia, tremors, agitation, unintentional weight loss, night sweats, low-grade fever, and orthopnea that developed 62 days after receiving the first dose of mCoVvax. His physical examination was significant for sinus tachycardia, hypertension, a resting tremor, brisk deep tendon reflexes, and diffuse nonpruritic maculopapular rash. His thyroid gland was diffusely enlarged with an unpalpable lower margin and positive Pemberton sign. TSH was undetectable with elevated Free T4 and Total T3 [11.0 (NL 0.8-1.8 ng/dL) and 800 (76-181 ng/dL), respectively]. Thyroid-stimulating immunoglobulin (TSI) was 337% (NL<140%), and thyroid peroxidase antibody was 653 IU/mL (NL < 9 IU/mL). Thyroid ultrasound showed a diffusely enlarged thyroid gland with diffusely increased thyroid uptake on technetium thyroid scan (95% and 85% uptake after 6 and 24 hrs, respectively), consistent with Graves’ disease. CT scan of the neck and chest confirmed retrosternal Goiter without tracheal deviation. He was treated with high-dose of Methimazole, Atenolol, and Prednisone. A literature search revealed five cases of Graves’ disease after mCOVvax, all of which did not have a retrosternal extension of the thyroid. Our case represents a rare complication of mCoVvax. Clinicians should consider retrosternal goiter in patients with thyrotoxicosis and orthopnea after mCoVvax exposure. Presentation: Friday, June 16, 2023

SAT483 Role of Cholestyramine in Refractory Amiodarone-induced Thyrotoxicosis

Abstract Disclosure: H. Zhao: None. J. Leung: None. Role of Cholestyramine in Refractory Amiodarone-Induced Thyrotoxicosis. Background: Amiodarone-induced thyrotoxicosis (AIT) is divided into type 1 (AIT1; treated with thioamides) and type 2 (AIT2; treated with glucocorticoids). Combined therapy is utilized in mixed or indefinite forms. When medical treatment is unsuccessful, radioiodine ablation or thyroidectomy are considered. Clinical Case: A 76-year-old gentleman, with a history of atrial fibrillation treated with amiodarone, presented with recurrent atrial fibrillation refractory to cardioversion. Investigations revealed TSH <0.01, FT4 58.1 (ref 10.0-20.0 pmol/L), FT3 16.0 (ref 3.5-6.5 pmol/L), TPO negative and TRAB negative. As thyroid ultrasound revealed absence of focal nodules or hypervascularity and technetium pertechnetate scan demonstrated no thyroid activity, AIT2 was suspected. Prednisone was initiated and amiodarone discontinued. Due to minimal response after a month, a mixed type was suggested and methimazole added. Despite intensification of the antithyroid regimen, FT4 increased to 59.5. Methimazole was discontinued for radioiodine ablation assessment. Given low thyroid uptake (<3%), ablation was deemed unlikely beneficial. After patient refused thyroidectomy, cholestyramine was initiated, resulting in significant improvement, with FT4 declining from 46.0 to 29.0 in 2 weeks. Euthyroidism was achieved after 2 months of cholestyramine treatment and medications were stopped. At 6 months post presentation, he developed amiodarone-related hypothyroidism and began levothyroxine. Conclusion: Previous reports propose that cholestyramine, an ion exchange resin, interrupts enterohepatic circulation of thyroid hormone and demonstrated the use of cholestyramine in refractory Grave’s hyperthyroidism. This is one of the first few reports demonstrating the possible role of cholestyramine in AIT refractory to first line medical therapy. Presentation Date: Saturday, June 17, 2023

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

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

FRI464 Subacute Thyroiditis Related To COVID-19 Vaccines- A Case Series

Abstract Disclosure: H. Mejia: None. S.A. Gillis Funderburk: None. S.R. Thomas: None. Background: Subacute thyroiditis (SAT) has been reported following SARS-COV-2 viral infection, as well as in recipients of the mRNA vaccines for SARS-COV-2. Patients present with palpitations, tremors and weight loss as well as low grade fevers and a tender thyroid. It is a self-limited condition that typically follows a triphasic course that may include thyrotoxicosis, hypothyroidism and return to normal thyroid function. Clinical features and sonographic findings can provide a specific diagnosis, and a radioactive iodine uptake study is often not required. Report: In 2021, 123 patients were referred to our outpatient service for evaluation of thyrotoxicosis. Among them, we identified 9 women without history of thyroid disease who presented with clinical findings of SAT with thyrotoxicosis. Patients with history of thyroid dysfunction and thyroid nodules were excluded. The symptoms began between 4-27 days after the first or second dose of either the Pfizer Bio-NTech or the Moderna COVID-19 mRNA vaccine. All tested negative for TSI and had no nodules on ultrasound. 2 patients had thyroid uptake scans which confirmed thyroiditis. All 9 patients improved with symptomatic treatment and thyroid functions normalized with time. Discussion: Since the mRNA vaccines for SARS-COV-2 became nationally available, several adverse reactions have been reported including SAT. The mechanism for post-vaccination SAT or thyroid dysfunction remains unknown. Transmembrane protease serine-2 (TMPRSS-2) and ACE-2 receptors allow the SARS-CoV-2 to enter human cells. ACE-2 and TMPRSS-2 are expressed in thyroid follicular cells, and their expression is higher than in lung cells, especially in women. These situations may explain why SARS-CoV-2 causes SAT in women more frequently. Inactive virus vaccines contain many proteins belonging to the pathogen virus and similar antigenic parts. The increased affinity of the SARS-CoV-2 towards the thyroid suggests that inactive vaccine may also affect the thyroid tissue. In the past, SAT has been reported after an inactive virus vaccine- seasonal influenza vaccine, H1N1 vaccine and hepatitis B vaccine. In addition, the COVID-19 vaccine contains aluminum hydroxide as an adjuvant. Autoimmune inflammatory syndrome induced by adjuvants (ASIA syndrome) was previously reported following various vaccines. A recent article describes a patient with COVID-19 vaccine related ASIA syndrome and SAT. In some cases, elevated proinflammatory markers and cytokines after receiving the vaccine may play a major role, as it can stimulate a significant response from our immune system. Hence, SAT should be included as a possible side effect of receiving these vaccines. Conclusion: Our case series highlights a possible relationship between the COVID-19 mRNA vaccines and subacute thyroiditis which has been previously underreported or not recognized by healthcare providers. Presentation: Friday, June 16, 2023

SAT533 The Case of an Ectopic Thyroid Twin

Abstract Disclosure: A. Abu Limon: None. S.A. Aldasouqi: Consulting Fee; Self; Abbott Laboratories. P. Kachhadia: None. S. Khan: None. Introduction: Ectopic thyroid tissue is a rare but known developmental abnormality during the descent of the thyroid tissue from the floor of the foregut to its final location Infront of the trachea. The most frequent ectopic locations are the base of the tongue and anywhere along the course of the thyroglossal duct. It is very rare to have an ectopic thyroid tissue located in the mediastinum. It’s even more rare when the patient still has an almost normal thyroid gland in its usual location in the neck, and both are sizable and functional. Case Presentation: We are reporting the case of a 38-Year-old African American Female, who was involved in a car accident with non-critical injuries to her neck and chest area. She underwent a contrasted CT scan of her neck and chest that showed an anterior mediastinal mass towards the right at the level of the great vessels and arch, right paratracheal location overall measuring 6.0 x 4.6 x 4.5 cm. She was seen by Cardiothoracic surgery group and underwent Mediastinoscopy that confirmed a large firm to hard mass just inferior to the innominate artery was firmly adherent to the trachea as well as surrounding structures. Multiple biopsies showed thyroid tissue with focal mild chronic inflammation, benign. No atypia or malignancy is noted. Then, she was referred to our clinic for further evaluation. When interviewed, the patient denies any compressive symptoms (Shortness of breath, palpitations, chest pain or dysphagia). The patient has no personal or family history of thyroid disorders, including no thyroid cancer history. She has no Goiter on exam and no Pemberton sign is elicited. Laboratory work up was unremarkable including normal thyroid functions. Neck Ultrasound confirmed presence of a thyroid gland in its expected location, with Right Lobe Measurement: 5.04 x 1.70 x 1.47 cm Vol: 6.02 ml and Left Lobe Measurement: 3.94 x 1.25 x 1.21 cm Vol: 2.87 ml. We were keen to explore this matter further and ordered a thyroid uptake scan with 0.97 uCi iodine-123, that showed a 24-hour normal uptake of 27.4% at the thyroid bed and a separate substernal and RT paratracheal location uptake. Discussion: This patient has supplementary ectopic thyroid tissue in her mediastinum along with a normal thyroid gland in her neck. From the literature review and search, This is a very rare occurrence. The discussion with the patient is about the specific concern of the malignant potential of this ectopic thyroid and if surgical intervention is needed. The probability of cancer on ectopic thyroid tissue is less than 1% and when it occurs papillary carcinoma is the most common histology. Our patient has benign biopsy results and no signs nor symptoms related to this ectopic thyroid gland. The final decision is to not undergo surgery, but rather, a follow up with CT scan in 6 months. Presentation Date: Saturday, June 17, 2023

SAT508 Siblings With Heterozygous DICER1 c.322C>T, pGln108* Variant: A Novel Genetic Variant for DICER1 Syndrome

Abstract Disclosure: N.L. Yamashita: None. J. Austin: Consulting Fee; Self; Ascendis, Vertice. Research Investigator; Self; IBSA Pharmaceuticals. Background: Several genetic variants are implicated in DICER1 syndrome - a neoplasm predisposition syndrome with a spectrum of presentations with both benign and malignant tumors. DICER1 c.322C>T, pGln108* variant is a new mutation that was found in this case of two siblings presenting with thyroid cancers. Clinical case: Sibling A is a 10-year-old female who presented to the emergency department (ED) with a rapidly progressing right neck mass. She underwent fine needle aspiration (FNA) that returned as Follicular Lesion of Undetermined Significance (FLUS), Bethesda III. Subsequently, she had a right lobectomy, and pathology results revealed multiple follicular adenomatous nodules with focal papillary hyperplasia. Approximately one year later, she re-presented with a new left sided neck swelling with ultrasound revealing three new nodules. She underwent left lobectomy and pathology showed follicular variant papillary thyroid carcinoma (FVPTC). She was started on levothyroxine replacement daily. Her surveillance regimen included I-123 thyroid uptake scans which showed uptake in the neck. Her TSH-stimulated thyroglobulin was as high as 4.3 ng/mL with negative thyroglobulin antibody titer. She did not receive radioactive iodine ablation (RAI). Since then, routine thyroglobulin levels have remained low and neck ultrasounds have been reassuring. She is currently 19 years old. Approximately three years after Sibling A’s second lobectomy, her sister, Sibling B, presented as an 11-year-old female to the ED with neck swelling. Thyroid ultrasound showed multiple solid and cystic nodules on both right and left thyroid lobes. FNA returned with Bethesda Category IV (suspicious for follicular neoplasm) on the left lower nodule and Bethesda II (benign follicular nodule) on other nodules. She underwent total thyroidectomy and was found to have follicular thyroid carcinoma (FTC). TSH-stimulated thyroglobulin was as high as 8.9 ng/mL. Her surveillance thyroid scan showed uptake in the right thyroidectomy bed and 1.6 cm nodule was found on ultrasound. FNA of this lesion was benign with stable repeat thyroid scans with downtrending TSH-stimulated thyroglobulin. This patient is currently 15 years old. Soon after the Sibling B was diagnosed with FTC, the decision was made to pursue genetic analysis. Both siblings underwent mutation analysis which were both positive for heterozygous DICER1 c.322C>T, pGln108* variant.Conclusion: This case introduces a novel variant to DICER1 syndrome: DICER1 c.322C>T, pGln108* variant. Without a family history of multinodular goiter (MNG), thyroid cancers, or other associated tumors to this syndrome, these siblings had unusual presentations of a germline DICER1 syndrome variant. This case highlights the expressive variability in DICER1 syndrome and this variant may be of consideration when children present without other predisposing tumors. Presentation Date: Saturday, June 17, 2023

Evaluation of Pendrin Expression Using Nuclear Imaging Modalities and Immunohistochemistry in Animal Thyroid Cancer Model.

The impaired ability of thyroid cancer (TC) cells to uptake and concentrate iodine represents a major therapeutic challenge in malignant TC management. This has been reported probably due to reduced or loss of expression of pendrin in thyroid tumors. In view of this, we evaluated the pendrin expression in the chemically induced (using N-bis[2-hydroxypropyl] nitrosamine [DHPN]) TC model in Wistar rats. Uptake in the thyroid gland was evaluated by positron emission tomography with computed tomography (PET-CT) and scintigraphy imaging. Further histopathology (HP) and immunohistochemistry (IHC) were performed for confirming malignancy. The altered uptake in the thyroid gland was observed by PET-CT and scintigraphy imaging. Significant pathological changes in the thyroid were observed using 2-deoxy-2-(fluorine-18) fluoro-D-glucose PET-CT, technetium-99m pertechnetate imaging, and reduced iodine-131 uptake (n = 4) in DHPN-induced animals compared to control indicative of thyroid cell proliferation. In treated groups, tissue HP revealed hyperplastic follicular to papillary cell proliferation with variable mitotic activity. The malignant nature of the tissue and variable uptake of the tracer were further reconfirmed by IHC. IHC revealed reduced pendrin expression in malignant thyroid tissue. Hence, nuclear imaging techniques can be of aid in the early identification and evaluation of cellular changes during the early development of tumor models in laboratory animals. In conclusion, our study reveals that pendrin expression plays a vital role in thyroid uptake, and its reduction was observed in TC in a chemically induced TC model.

Effects of somatostatin analogs on uptake of radiolabeled somatostatin analogs on imaging: a systematic review and meta-analysis.

The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients. The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 vs. 7.62±2.12, P=0.001) and spleen (25.74±7.14 vs. 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique. Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.

Quantitative analysis of 99mTc-pertechnetate thyroid uptake with a large-field CZT gamma camera: feasibility and comparison between SPECT/CT and planar acquisitions

PurposeThe main objective of this study was to evaluate the ability of a large field Cadmium Zinc Telluride (CZT) camera to estimate thyroid uptake (TU) on single photon emission computed tomography (SPECT) images with and without attenuation correction (Tomo-AC and Tomo-NoAC) compared with Planar acquisition in a series of 23 consecutive patients. The secondary objective was to determine radiation doses for the tracer administration and for the additional Computed Tomography (CT) scan.MethodsCross-calibration factors were determined using a thyroid phantom, for Planar, Tomo-AC and Tomo-NoAC images. Then Planar and SPECT/CT acquisitions centered on the thyroid were performed on 5 anthropomorphic phantoms with activity ranging from 0.4 to 10 MBq, and 23 patients after administration of 79.2 ± 3.7 MBq of [99mTc]-pertechnetate. We estimated the absolute thyroid activity (AThA) for the anthropomorphic phantoms and the TU for the patients. Radiation dose was also determined using International Commission on Radiological Protection (ICRP) reports and VirtualDoseTMCT software.ResultsCross-calibration factors were 66.2 ± 4.9, 60.7 ± 0.7 and 26.5 ± 0.3 counts/(MBq s), respectively, for Planar, Tomo-AC and Tomo-NoAC images. Theoretical and estimated AThA for Planar, Tomo-AC and Tomo-NoAC images were statistically highly correlated (r < 0.99; P < 10–4) and the average of the relative percentage difference between theoretical and estimated AThA were (8.6 ± 17.8), (− 1.3 ± 5.2) and (12.8 ± 5.7) %, respectively. Comparisons between TU based on different pairs of images (Planar vs Tomo-AC, Planar vs Tomo-NoAC and Tomo-AC vs Tomo-NoAC) showed statistically significant correlation (r = 0.972, 0.961 and 0.935, respectively; P < 10–3). Effective and thyroid absorbed doses were, respectively (0.34CT + 0.95NM) mSv, and (3.88CT + 1.74NM) mGy.ConclusionAThA estimation using Planar and SPECT/CT acquisitions on a new generation of CZT large-field cameras is feasible. In addition, TU on SPECT/CT was as accurate as conventional planar acquisition, but the CT induced additional thyroid exposure.Trial registration Name of the registry: Thyroid Uptake Quantification on a New Generation of Gamma Camera (QUANTHYC). Trial number: NCT05049551. Registered September 20, 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05049551?cntry=MC&draw=2&rank=4.

Exploring the prevalence and causes of normal Tc 99m thyroid uptake in thyrotoxic patients A retrospective study at a regional hospital of nuclear medicine in Oman

This study focuses on assessing the prevalence of normal Technetium-99m (Tc-99m) Thyroid uptake scans among thyrotoxic patients at a specific medical facility in Oman, named "Royal hospital-nuclear medicine department". Thyrotoxicosis is a condition characterized by high levels of thyroid hormones in the body which is usually reflects as a high uptake in Tc-99m Thyroid Pertechnetate uptake scan. However, in some cases the scan shows normal thyroid activity which may lead to misdiagnosis or delayed treatment.

The Role of [99mTc]Tc-Sestamibi in Functional Imaging of the Iodine-Loaded Thyroid Gland.

Due to high iodine loading from iodinated contrast media, the thyroid uptake of common radiopharmaceuticals ([99mTc]NaTcO4 and [123I]NaI) can be influenced up to 2 mo after administration. In such cases, and generally when differential diagnosis between productive and destructive thyrotoxicosis is necessary, [99mTc]Tc-sestamibi scintigraphy could be an option. This case highlights the role of [99mTc]Tc-sestamibi in the evaluation of thyrotoxicosis in a patient with a blocked thyroid gland as a result of stable iodine saturation.

Prevalence and significance of extracardiac uptake on pyrophosphate imaging in the SCAN-MP study: the first 379 cases.

Technetium-labeled bone-avid radiotracers can be used to diagnose transthyretin cardiac amyloidosis (ATTR-CA). Extracardiac uptake of technetium pyrophosphate (Tc-99m PYP) in this context has not been extensively explored and its significance is not well characterized. We assessed extracardiac Tc-99m PYP uptake in individuals undergoing nuclear scintigraphy and the extent of clinically actionable findings. The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study utilizes Tc-99m PYP imaging to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥60 years old with heart failure. We characterized the distribution of extracardiac uptake, including stratification of findings by timing of scan (1 hour vs 3 hours after Tc-99m PYP administration) and noted any additional testing in these subjects. Of 379 participants, 195 (51%) were male, 306 (81%) Black race, and 120 (32%) Hispanic ethnicity; mean age was 73 years. Extracardiac Tc-99m PYP uptake was found in 42 subjects (11.1%): 21 with renal uptake only, 14 with bone uptake only, 4 with both renal and bone uptake, 2 with breast uptake, and 1 with thyroid uptake. Extracardiac uptake was more common in subjects with Tc-99m PYP scans at 1 hour (23.8%) than at 3 hours (6.2%). Overall, four individuals (1.1%) had clinically actionable findings. Extracardiac Tc-99m PYP uptake manifested in about 1 in 9 SCAN-MP subjects but was clinically actionable in only 1.1% of cases.

Abstract #1406483: Thyroid Hormone Resistance Diagnostic and Therapeutic Challenges

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH). We present the challenges in diagnosing and treating a 24-year-old male who presented with a mixed picture of hypothyroidism and hyperthyroidism with elevated TSH, upper normal free T4, and elevated free T3 and was found to have a mutation in the THRβ gene. A 24-year-old male was referred for a second opinion of post-ablative hypothyroidism with elevated TSH, elevated free T3, and suspicion of pituitary microadenoma. He complained of fatigue, weight gain, tremors heat cold intolerance. Family history is Graves’ disease in his mother's status post partial thyroidectomy due to a salivary tumor. Initially, in 2020, he was diagnosed with negative antibody Grave’s disease. Labs were TSH 0.86 mIU/L, free T4 1.99 ng/dl (0.89-1.76), and free T3 4.66 pg/ml (2.3-4.2). A thyroid ultrasound showed mild thyromegaly. A thyroid uptake scan showed 24-hour thyroid uptake of 36.7%. Thyroid antibodies including thyroglobulin, TPO, thyroid receptor, and thyroid stimulating immunoglobulin were negative. He was treated with radioactive iodine ablation (I-131). Afterward, His TSH increased gradually along with free T3. Free T4 was normal. The patient remained symptomatic, and he was not on any thyroid replacement therapy. A repeat thyroid uptake scan showed an increase uptake of 36% at 24 hrs. During our evaluation, a repeat TSH 54.05 mIU/l, free T4 1.3 ng/dl, free T3 4.3 pg/ml, and T3 by equilibrium dialysis 4.0. A repeat magnetic resonance imaging of the head showed no definitive focal enhancing lesion. Pituitary axis hormones were normal, and the alpha subunit was 0.73 (high); however, the alpha-glycoprotein subunit /TSH molar ratio 0.135 sex hormone binding globulin 5.8 nmol/l (low), macro TSH was not detected. These findings raised suspicion for THRB mutation; hence genetic studies were obtained. PCR amplification of THRB gene exons 10, 9, and 8, followed by gene sequencing, showed a heterozygous missense mutation C >G located at exon 10. The mutation caused a change in thyroid hormone receptor beta protein amino acid 453 proline to an alanine, P453A Initially, he was started on levothyroxine 25 mg PO daily but soon after, it was stopped due to palpitations; a beta blocker was started along with liothyronine 5 mg every other day and levothyroxine 50 mg every other day. The patient tolerated the regimen with significant improvement in his symptoms. RTH is rather uncommon; it is important to be able to recognize the syndrome to avoid unnecessary invasive treatment. There is no specific therapy currently available to fully correct the TRβ defect. The goal of treatment is based on the patient's symptoms and clinical picture instead of aiming to normalize thyroid hormone levels. Thyroidectomy and radioactive iodine ablation result in lifelong levothyroxine replacement therapy and RTHβ persistently high serum TSH. Levothyroxine therapy is challenging, and supraphysiologic doses are often needed to maintain serum TSH in the lowest tolerable level.

Abstract #1399287: New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves’ Disease Post-Radioactive Iodine Treatment

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves’ Disease (GD) even after treatment with radioactive iodine (RAI). In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.

Abstract #1403045: Thyroiditis Post COVID-19 mRNA Booster Dose Vaccination

SARS-CoV-2 vaccines have been associated with thyroid dysfunction including thyroiditis and Graves' disease. We report a patient who developed thyrotoxicosis secondary to thyroiditis after COVID-19 mRNA booster dose vaccination. A 74-year-old man with no known personal or family history of thyroid disorders went to his primary care physician with symptoms of palpitations. Of note, he had the first booster (third dose) of the Pfizer/BioNTech vaccine about 1 week before. He did not recall any similar symptoms after the first two doses of the same vaccine. There were no other symptoms of thyrotoxicosis such as hand tremors, weight loss or mood change. There was no family history of thyroid disorders. He was not on any medications such as amiodarone and was not taking any herbal supplements. He did not have any symptoms of upper respiratory tract infection. There was no neck pain. Physical examination was unremarkable with no goiter or thyroid eye manifestations. Thyroid function: free T4 elevated at 46.7 pmol/L (11.5-22.7) and TSH suppressed at 0.01 mIU/L (0.5-4.5). Thyroid stimulating immunoglobulin was positive at 200% (50-179). He was initially started on carbimazole 15mg daily. However, the patient became rapidly hypothyroid despite dose reduction and subsequent discontinuation of carbimazole with free T4 of 8 pmol/L and TSH of 36.4 mIU/L. An ultrasound of the thyroid gland showed vascularity with no discrete nodules. No thyroid uptake scan was done. The diagnosis was revised to thyroiditis post vaccination. Hypothyroidism persisted despite discontinuation of carbimazole before recovery 8 months later. Patient was well and did not require any thyroxine supplementation. It is postulated that COVID-19 vaccines triggered thyroiditis via an autoimmune inflammatory syndrome caused by the vaccine adjuvants. A high index of suspicion is necessary and a thyroid uptake scan may be useful in making the diagnosis. Thyroiditis is a self-limiting condition and recognising it is important as no specific thyroid treatment is necessary in most patients. Patients should not be deterred from subsequent vaccination as COVID-19 infection has higher mortality risk than thyroiditis.