bluuebunny/crossref_metadata_2025 huggingface dataset:
THU668 Euthyroid Graves’ Ophthalmopathy: Case Series
Authors: Saleh Alfadl Sultan , Ahmed Asiri Alanood , Ali Jammah Anwar , Alsagheir Osamah
Published: October 2023

Disclosure: S.S. Alfadl: None. A.A. Asiri: None. A.A. Jammah: None. O. Alsagheir: None.

Introduction: Graves’ ophthalmopathy is an autoimmune disorder that affects the eyes, characterized by swelling, proptosis, lid lag, inflammation and eyelid retraction. A significant proportion of cases are associated with thyrotoxicosis and positive serum TSH receptor antibody tests. Case Description: We present a case series of euthyroid Graves’ ophthalmopathy in patients with a negative TSH receptor antibody. The first case is of a 37-year-old lady who was recently diagnosed with idiopathic intracranial hypertension due to history of recurrent headaches and was found on CT brain to have an incidental empty sella syndrome and findings highly suggestive of thyroid associated orbitopathy. A dedicated MRI orbit showed bilateral mild proptosis with bilateral medial and inferior recti thickening, sparing the tendinous insertion. The involved extraocular muscles show mild peripheral high T2 signals and minimal enhancement on post gadolinium images. The enlarged extraocular muscle demonstrates diffusion restriction with low Apparent Diffusion Coefficient (ADC) value. Clinically, the patient did not exhibit any symptoms of hyperthyroidism or hypothyroidism. She did not notice any changes in her eyes’ appearance, nor any changes in vision or double vision. On examination, she had mild proptosis, no restriction of extraocular movement or provoked double vision. Consequently, she was referred to Ophthalmology for further management. Investigations included a pituitary panel which did not reveal any abnormalities and a thyroid panel which revealed that she was biochemically euthyroid with a negative TSH receptor antibody test. The second case is of a 24-year-old male who is medically free and initially visited the ophthalmology clinic complaining of double vision, without any additional ophthalmic complaints. He was subsequently referred to our care to rule out thyroid eye disease. Clinically, the patient had no indications of thyroid dysfunction. Upon examination, he exhibited severe right eye proptosis with dystopia and early left eye proptosis. CT orbit showed swelling of the right-sided superior rectus, medial rectus, lateral rectus and left-sided superior rectus muscles. The left-sided superior rectus muscle was abutting the optic nerve. Nevertheless, all tendons were spared. Biochemically, he was euthyroid with unremarkable laboratory results. Conclusion: These findings provide insight into the clinical presentation of euthyroid Graves’ ophthalmopathy in patients without thyrotoxicosis or detectable circulating levels of TSH receptor antibodies. Thus, suggesting that thyroid ophthalmopathy might present earlier than Graves’ disease and even earlier than the presence of TSH receptor antibodies. We conclude that a high index of suspicion and proper follow up is recommended in similar patients for the development of Graves’s disease.

Presentation: Thursday, June 15, 2023
THU671 Genes Encoding Adaptive Immune Receptor Repertoire Might Be Associated With The Risk Of Graves’ Disease And Antithyroid Drug-induced Agranulocytosis
Authors: Jui Huang Chun , Yang Shun-Jie , Lai Sheng-Kai , Chen Harn-Shen , Chen Pei-Lung
Published: October 2023

Disclosure: C. Huang: None. S. Yang: None. S. Lai: None. H. Chen: None. P. Chen: None.

Graves' disease (GD) is an autoimmune disorder characterized by the immune system attacking the thyroid gland cells, leading to hyperthyroidism. One serious adverse effect that can occur in GD patients receiving antithyroid drugs, such as thionamides, is antithyroid drug-induced agranulocytosis (TiA), which affects 0.1% to 0.4% of patients. While previous research has shown that specific human leukocyte antigen (HLA) genes/alleles are associated with GD or TiA, the role of the genes encoding adaptive immune receptor repertoire (gAIRR), including the B cell receptor and T cell receptor genes, in GD or TiA has not been explored. This study aims to investigate whether gAIRR has a genetic association with GD or TiA. We enrolled 128 GD patients, 19 TiA patients, and 104 controls, and conducted gAIRR genotyping using gAIRR Suite, a probe capture-based targeted sequencing and analysis platform. Our results identified several gAIRR alleles that were more prevalent in GD cases than in controls, including IGLV1-41*02N (a novel allele with the sequence closest to IGLV1-41*02, 20.3% in GD patients vs. 7.7% in controls, p=0.008), IGHV1-69*04N (12.5% vs. 3.8%, p=0.02), TRGV4*01 (46.9% vs. 31.7%, p=0.022), and several other alleles (such as TRBV6-6*03, IGKV1/OR22-5*01N, TRVB12-2*01N, TRAV8-4*01N, IGHV3-71*02, IGHV2-70*04N, etc.) We also found several gAIRR alleles that were less prevalent in GD cases than in controls, including IGLV5-45*03N, IGLV2-14*04, IGLV(V)-66*01, IGLV3-13*01N, TRBV20/OR9-2*02N, TRBD2*01, TRAV6*02, among others. Regarding the TiA cohort (compared to GD patients without TiA), some gAIRR alleles showed frequencies difference, but did not reach statistical significance. Overall, our findings provide supporting evidence that gAIRR genes/alleles might be associated with the development of GD or TiA. Future studies with larger sample sizes are necessary. Furthermore, a joint analysis of HLA and gAIRR genotypes might provide valuable insight into the pathogenesis of GD and TiA.

Presentation: Thursday, June 15, 2023
THU673 Unusual Metastasis Of Differentiated Thyroid Carcinoma
Authors: Aiad Mina , Aluko Oluwatomisin A , Bhatt Bankim
Published: October 2023

Disclosure: M. Aiad: None. O.A. Aluko: None. B. Bhatt: None.

Background: Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid malignancy. Distant metastasis of PTC are rare and usually occur in the bones, lungs, and lymph nodes of the neck. Retinal and skin metastases are extremely rare. We present a case of PTC with metastasis to the distal extremity with sites including retina, skin and breasts. Clinical Case: A 40-year-old Caucasian female with a past medical history of papillary thyroid cancer at age 16 status post total thyroidectomy followed by two radioactive iodine treatments, who is incidentally found to have recurrent metastatic disease to lungs, retina, subcutaneous soft tissue and bones. After having an accident, trauma CT revealed pulmonary nodules and around the time patient started to notice subcutaneous lumps on the chest and gradually worsening blurry vision indicating further imaging as well as ophthalmological evaluation. The biopsy of the right lower lung nodules showed metastatic differentiated follicular variant papillary thyroid cancer, positive for RET mutation. TSH was appropriately suppressed at 0.128uIU/mL on levothyroxine 100 mcg daily, with elevated thyroglobulin level 47ng/mL and antibody 1.7IU/mL. The molecular testing was positive for RET gene mutation; thus she started targeted therapy with selpercatinib 120 mg twice daily. Shortly after starting therapy, she presented to the ER with complaints of headaches and refractory nausea. Imaging done showed evidence of intracranial metastases, bilateral intraocular lesions in the posterior globe as well as intraventricular hemorrhage. She received IV steroids, selpercatinib was held due to the possibility of exacerbating intraventricular hemorrhage. Following multidisciplinary discussion between neuro-oncology and radiation oncology, she started stereotactic radiotherapy (SRT) to choroidal plexus lesions with a plan to restart systemic therapy once SRT is completed. Conclusion: The epidemiological aspects of thyroid metastases in rare sites are likely unknown and could significantly impact patient management. Most cases of uncommon metastasis have been reported after several years of diagnosis such as in our patient who developed multiple metastasis to rare sites including skin, retina, breast and choroid plexus.

Presentation: Thursday, June 15, 2023
FRI461 Two-years Course Of Subacute Thyroiditis After COVID-19 Vaccination: A Case Report
Authors: Yoshida Sumiko
Published: October 2023

Disclosure: S. Yoshida: None.

COVID-19 has been reported to cause subacute thyroiditis. Furthermore, the literature includes cases of COVID-19 vaccine-related subacute thyroiditis, but few reports describe the long-term course of vaccine-induced subacute thyroiditis. Herein, we report the case of a 47-year-old woman with no medical history who developed subacute thyroiditis after mRNA COVID-19 vaccination and was followed up for 2 years. Her fever persisted after the second dose of the COVID-19 vaccine, and she became aware of left anterior neck pain 8 days later. There were no infectious disease symptoms or signs in the patient’s history or at a recent physical examination. All thyroid autoantibodies were negative. On ultrasound, the thyroid gland was diffusely enlarged, and internal echogenicity was diffusely hypoechoic, coarse, and color Doppler blood flow signals were decreased without confinement to the pain area. She was diagnosed with subacute thyroiditis with tender thyroid swelling, thyrotoxicosis, and an inflammatory reaction. It was suspected that there was a causal link between the onset of subacute thyroiditis and COVID-19 mRNA vaccination because it developed immediately after vaccination and there were no other obvious causes. She was started on prednisolone, and her symptoms improved rapidly, leading to hypothyroidism 1 month later. The swelling of the thyroid gland improved rapidly, and it became atrophic several months after the onset of subacute thyroiditis. She never received any additional vaccinations. Two years after the onset, there was no recurrence of subacute thyroiditis, thyroid atrophy persisted, and the patient required levothyroxine supplementation (100 µg/day). Subacute thyroiditis generally has a good prognosis and rarely leads to permanent hypothyroidism. Subacute thyroiditis due to vaccination may follow a different course than that due to typical viral infection, and we need to examine its long-term prognosis.

Presentation: Friday, June 16, 2023
FRI462 Incidence Of Graves Hyperthyroidism Before And After The Implementation Of COVID-19 mRNA Vaccination
Authors: Oliveira Pinto Jessica , Yvonne Roth Mara , Hoofnagle Andrew N , Failor Richard A , Susan Tylee Tracy , Endo Mayumi
Published: October 2023

Disclosure: J.O. Pinto: None. M.Y. Roth: None. A.N. Hoofnagle: None. R.A. Failor: None. T.S. Tylee: None. M. Endo: None.

Background: There have been several case reports of post COVID-19 vaccination early-onset Graves’ disease (PVGD) and their distinct clinical features documented. The purpose of this study was to investigate whether the incidence of Graves’ disease (GD) increased after the administration of the COVID-19 vaccine or after COVID-19 infection. Methods: This is a single academic center retrospective study. This study compared the incidence of new-onset GD during two separate time periods. Periods were defined as December 2017-October 2019 and December 2020-October 2022 to assess for differences in new-onset GD before and after COVID-19 vaccine administration. PVGD was defined as laboratory-confirmed hyperthyroidism and GD within 4 weeks of vaccination/infection or reporting of symptoms of thyrotoxicosis within 4 weeks of vaccination/infection and laboratory evidence within 3 months. Results: There was a total of 803 patients in the pre-vaccination period that carried the diagnosis of GD, 131 (16.4%) of which were new diagnoses. There was a total of 901 patients in the post-vaccination period that carried the diagnosis of GD, 138 (15.3%) of which were new. There was no statistically significant difference in the incidence of new onset GD between the pre- and post-vaccination groups (p=0.52). Twenty-four (17.4%) out of the 138 newly diagnosed patients in the post-COVID group met criteria for PVGD. There was a higher median free T4 (3.9 vs 2.5; p=0.05), higher TRAb titer (7.5 vs 6.9; p=0.94), and higher TSI titer (3.61 vs 3.60, p=0.82) in the PVGD group when compared to the control although none were statistically significant. There was no statistically significant difference in age, gender, race, or vaccine type. Twenty patients (87%) from the PVGD group were started on methimazole and all cases achieved a euthyroid state with a relatively low median methimazole dose of 12.5 mg. Hyperthyroidism resolved spontaneously in three patients (13%) without any anti-thyroid medication. Conclusion: This study did not demonstrate statistically significant evidence that COVID-19 vaccines increase the incidence of GD. In addition, all patients with PVGD had a good clinical response and achieved a euthyroid state at follow-up. This evidence may be beneficial in reassuring patients on vaccine administration.

Presentation: Friday, June 16, 2023
FRI465 Thyroid Incidentalomas In Hospitalized Patients With COVID-19: A Single-Center Retrospective Analysis
Authors: Jantarapootirat Methus , Sriphrapradang Chutintorn , Traiwanatham Sirinapa , Boonsomsuk Woranan , Sungkanuparph Somnuek , Hirunpat Pornrujee
Published: October 2023

Disclosure: M. Jantarapootirat: None. C. Sriphrapradang: None. S. Traiwanatham: None. W. Boonsomsuk: None. S. Sungkanuparph: None. P. Hirunpat: None.

Context: During the COVID-19 pandemic, both people with underlying diseases and previously healthy people had been infected with SARS-CoV-2. In our institute, most hospitalized patients underwent chest computed tomography (CT) to evaluate pulmonary involvement and complication of COVID-19. There is currently limited data regarding thyroid incidentalomas in healthy people. Objective: We aim to investigate the prevalence and predictors of thyroid incidentalomas among hospitalized patients with COVID-19. Methods: A single-center retrospective study included hospitalized patients aged ≥ 15 years with COVID-19 who underwent chest CT during April 2020 and October 2021. Thyroid incidentalomas were reviewed and identified by an experienced radiologist. Logistic regression analysis was used to determine predictors for thyroid incidentalomas. Results: Of 1,326 patients (mean age 49.4 years and 55.3% female) that were included, the prevalence of thyroid incidentalomas was 20.2%. Patients with thyroid incidentalomas were older (59.6 years vs 46.8 years, p <0.001) and had a higher proportion of females (63.4% vs 53.2%, p=0.003) than those without incidentalomas. On multivariate analysis, only female gender (OR 1.56; 95%CI, 1.17-2.07) and older age (OR 1.04; 95%CI, 1.03-1.05) were significantly associated with thyroid incidentalomas. Conclusion: In COVID-19 patients, the prevalence of thyroid incidentalomas identified on chest CT was higher (20.2%) compared with previous studies in the general population (<1% to 16.8%). The female gender and older age were independent factors associated with thyroid incidentalomas. The higher prevalence of thyroid incidentalomas among COVID-19 patients needs further studies to explore the association between thyroid nodules and SARS-CoV-2 infection.

Presentation: Friday, June 16, 2023
FRI473 Central Hypothyroidism Following Neonatal Graves Presentation
Authors: Metzinger Emily , Halpin Kelsee
Published: October 2023

Disclosure: E. Metzinger: None. K. Halpin: None.

Background: Neonatal Graves’ disease is a rare disorder of neonatal autoimmune hyperthyroidism secondary to the transplacental passage of thyroid-stimulating hormone receptor antibodies. Although neonatal Graves’ disease is transient, it is associated with cardiac dysfunction, intrauterine growth restriction, prematurity, craniosynostosis, and developmental delay and can be life-threatening. Additionally, infants with neonatal Graves’ disease can rarely present with primary or central hypothyroidism later in infancy or childhood. This is suspected to be due to the disruption in the hypothalamic-pituitary-thyroid axis or development of the thyroid gland. Clinical Case: Here we describe a case of neonatal Graves’ disease that has been complicated by persistent central hypothyroidism requiring levothyroxine treatment. This was a preterm infant with tachycardia, biventricular heart failure, and hepatomegaly who was transferred to a higher level of care NICU for cardiac and respiratory failure. Pregnancy was complicated by history of maternal Graves’ disease status post radioiodine ablation. Maternal TRAB and thyroid levels were unavailable. Initial thyroid studies on DOL 1 were notable for suppressed TSH of <0.02mcIU/mL, elevated free T4 6.9ng/dL, and elevated total T4 >24.9mcg/dL. Total T3 was normal at 161ng/dL (50-452ng/dL) on DOL 2, and TSI was elevated at 4.8 (TSI Index, normal </= 1.3) on DOL 3. For neonatal thyrotoxicosis, the infant was treated with methimazole, potassium iodide (KI), propranolol, and hydrocortisone. Hydrocortisone was discontinued as the infant clinically improved, and KI was discontinued after 1 week. TFTs were closely followed during admission and methimazole dosing was adjusted as needed. He was discharged from the NICU on DOL 19 on methimazole and propranolol with close outpatient lab monitoring and follow-up. Propranolol was discontinued by 1.5 months of life, and methimazole was discontinued by 2 months of life as TFTs normalized. TSI was negative by four months of life. TSH remained low with decreasing free T4 levels. Ultimately, he was started on levothyroxine at 8.5mcg/kg/day at 2.5 months of age for central hypothyroidism. At that time, TSH was 0.06mcICU/mL and FT4 was 0.7ng/dL. TSH remained low through the first 14 months of treatment with normal free T4 levels on levothyroxine. He has been continued on levothyroxine (average 20mcg/day). Conclusion: This case highlights the severity of neonatal Graves’ disease and the possibility of the subsequent development and persistence of central hypothyroidism following neonatal Graves’ diagnosis despite the resolution of hyperthyroidism and normalization of TSI antibody. Due to the risk of the development of hypothyroidism, it may be worthwhile to continue to trend TSH and FT4 to ensure that the infant has not developed hypothyroidism.

Presentation: Friday, June 16, 2023
FRI493 Immune Checkpoint Inhibitors: Effects On Thyroid Nodular Disease
Authors: Maria Bignoli Daniela Laura , Kalara Niketa , Manzano Alex J
Published: October 2023

Disclosure: D.L. Bignoli: None. N. Kalara: None. A.J. Manzano: None.

Introduction: Immune checkpoint inhibitors (ICI) are more recent pharmacologic agents used to treat malignancies, linked to immune related adverse events (irAEs) especially involving the thyroid. Classically, a transient silent thyroiditis occurs followed by hypothyroidism, however the effects on multinodular goiter are not fully recognized. We report a patient with poorly differentiated colon adenocarcinoma, treated with Pembrolizumab and Ipilimumab with significant improvement in the size of her thyroid nodules. Pembrolizumab is a monoclonal antibody directed against PD-1 receptors and Ipilimumab is an anti-CTLA-4 antibody; combination therapy has a higher incidence of irAEs compared with monotherapy (54% versus 24%). Clinical Case: 71-year-old female with a history of nontoxic benign multinodular goiter and Hashimoto’s hypothyroidism began ICI therapy as adjunctive treatment for poorly differentiated colon adenocarcinoma with MSH 2 mutation. She was euthyroid on same dose of levothyroxine for years however developed subclinical hyperthyroidism after starting immunotherapy; reporting anxiety, palpitations, tremors, and anterior neck fullness. TSH then was 0.02 mIU/mL (reference range 0.40-4.50 mIU/mL), free T4 1 ug/dl (reference range 0.9-1.7 ng/dl), and T3 122 ng/dl (reference range 100-200 ng/dl) with positive TPO antibodies. Levothyroxine was stopped and her symptoms subsequently self-resolved at follow-up 4 weeks later. Ultrasonography (US) performed in 2018 prior to starting ICI revealed: left lobe 1.3 x 2.5 x 4.66 cm, right lobe 1.3 x1.4 x 4.6 cm, isthmus 0.7 cm. There were multiple nodules: 0.4 x 0.9 x 0.7 cm, 0.3 x 0.3 x 0.4 cm nodule at right lobe, and 0.9 x 2 x 2.1 cm over right isthmus. The left lobe had four nodules: 0.4 x 0.5 x 0.8 cm, 0.4 x 0.5 x 0.9 cm, 0.8 x 0.8 x 1.36 cm, and 1 x 1.1 x 1.5 cm. Repeat ultrasonography after immunotherapy in October 2022 revealed substantial decrease in thyroid size, and the previously reported isthmus nodule was no longer visualized. The left thyroid lobe measured 0.5 x 1.1 x 3.3 cm, the right lobe 0.92 x 0.6 x 3.4 cm, and isthmus measured 0.2 cm. The right lobe nodule measured 0.40 x 0.33 x 0.86 cm and the left lobe nodule 0.34 x 0.24 x 0.50 cm. TSH was 1.150 mIU/mL, free T4 1.61 ug/dl, T3 96 ng/dl; evidencing a drastic improvement of her multinodular goiter due to ICI therapy. Conclusion: To the best of the author’s knowledge at this point in time, this is one of the few cases demonstrating effects of ICI therapy on nontoxic multinodular goiter. As described, there was a significant change in size and a previously biopsied isthmus nodule was not seen on her last ultrasound. Although irAEs are well established, there is limited literature regarding changes in anatomy and thyroid nodule architecture.

Presentation: Friday, June 16, 2023
FRI189 Alcohol-induced Non-neoplastic Hypercortisolism: Report Of Eight Cases And Review Of The Literature
Authors: Surani Asif , Carroll Ty Brian , Javorsky Bradley Richard , Raff Hershel , Findling James W
Published: October 2023

Disclosure: A. Surani: None. T.B. Carroll: Consulting Fee; Self; Corcept Therapeutics. Research Investigator; Self; Corcept Therapeutics, Recordati. B.R. Javorsky: Consulting Fee; Self; Clarus. Research Investigator; Self; Recordati, Amryt Pharma. H. Raff: Consulting Fee; Self; Cerium Pharmaceuticals, Corcept Therapeutics. Research Investigator; Self; Cerium Pharmaceuticals. J.W. Findling: Consulting Fee; Self; Corcept Therapeutics, Recordati. Research Investigator; Self; Recordati.

Alcohol intake stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Alcohol-induced hypercortisolism (AIH) is an underrecognized clinical phenomenon thought to be of hypothalamic etiology. Patients with alcohol use disorder may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] thus obscuring its diagnosis. We addressed this issue using newer, more accurate biochemical testing for the diagnosis of CS. We evaluated eight patients with AIH referred for possible CS (six for inferior petrosal sinus sampling, one with persistent CS after removal of an adrenal adenoma, and one for pituitary surgery). All patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval (RI) confirming a centrally mediated mechanism. All eight patients had abnormal low-dose dexamethasone suppression test (DST) [post DST serum cortisol 2.2-19.1 mcg/dL (RI<1.8)] and increased late-night salivary cortisol [8.2-71.0 nmol/L (RI<3.2)]. Only one patient had increased urine cortisol excretion. In contrast to patients with pituitary CS, the 5 patients tested had blunted or absent ACTH and cortisol responses to dDAVP. Two patients had adrenal nodules and one patient had abnormal pituitary imaging. Most patients initially underreported their alcohol consumption and one patient denied alcohol use. A marked elevation of blood phosphatidylethanol (PEth) was required in one patient to confirm excessive alcohol use. All the patients had significant elevations of liver function tests (LFTs) with AST>ALT. Review of the literature discovered 37 reported cases of AIH. These cases also had clinical and many biochemical findings that were similar to neoplastic hypercortisolism. Conclusion: AIH is an under-appreciated potentially reversible cause of non-neoplastic hypercortisolism that may be indistinguishable from neoplastic ACTH-dependent CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption may further confound the diagnosis. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP may be helpful in distinguishing AIH from neoplastic hypercortisolism. Measurement of PEth helps to confirm an alcohol use disorder.

Presentation: Friday, June 16, 2023
FRI494 Ischemic Stroke After Radioactive Iodine Therapy In Graves Disease
Authors: Rave Talia , Giunta Judy
Published: October 2023

Disclosure: T. Rave: None. J. Giunta: None.

Hyperthyroidism is defined as excess thyroid hormone, most commonly due to Graves Disease. Thiomides are first line therapy, however more definitive options are radioactive iodine (RAI) or thyroidectomy. RAI enters thyroid follicular cells and destroys the thyroid tissue with beta ray emissions. Patients with Graves disease, toxic multinodular goiter, and thyroid cancer can benefit from RAI, but it is contraindicated in pregnancy, breast feeding, and severely uncontrolled thyrotoxicosis. Early side effects are pancytopenia, thyrotoxicosis, and later complications are bone marrow suppression and cancer. There are several reports of cerebral vascular accidents (CVA) after RAI therapy, however, there is limited research demonstrating whether CVA is a direct consequence of RAI or secondary to thyrotoxicosis. This case describes a possible RAI-induced CVA. A 60-year-old female with a past medical history of type 2 Diabetes Mellitus, hypertension, obesity, and Graves disease presented with altered mental status and gait instability for 1 day. She received RAI therapy 1 day prior to symptom onset for uncontrolled Graves disease. She was previously on Methimazole and PTU, however, both were discontinued due to an intolerable rash. As a result, she was maintained on a beta blocker prior to RAI. On presentation, she was afebrile, normotensive with a heart rate of 79. She was oriented only to person and place and had an unbalanced gait. Her Burch-Wartofsky score was 30, which was concerning for thyrotoxicosis. Her TSH was undetectable and EKG showed normal sinus rhythm. She was placed on atenolol, PTU and hydrocortisone. Her CT head was negative for acute disease, however, her MRI brain diagnosed an acute ischemic stroke. During admission, she had episodes of atrial fibrillation with rapid ventricular response. This patient presented with thyrotoxicosis after RAI therapy complicated by a CVA. It is important to note that on presentation she was reliably taking a beta blocker outpatient and her EKG was normal sinus rhythm making atrial fibrillation a less likely culprit of her CVA. Research has found that hyperthyroidism alone can lead to a prothrombotic state, however, additional literature reports that both hyperthyroid and euthyroid patients have an increased risk of CVA following RAI. Whether a CVA is secondary to thyrotoxicosis or a direct effect of RAI, this potentially life-threatening complication should be discussed with patients prior to treatment.

Presentation: Friday, June 16, 2023
FRI521 Low FT3 And Decline In FT3 Levels Are Associated With Mortality; A Big-data Study
Authors: Strich David M , Israel Ariel , Joseph Gillis David
Published: October 2023

Disclosure: D.M. Strich: None. A. Israel: None. D.J. Gillis: None.

Importance : If low free triiodothyronine levels could detect people at risk for early mortality, this could be helpful in focusing preventive medicine efforts on those who are in most need. Objectives: Thyroid hormone levels characteristic of "euthyroid sick syndrome" are seen in acute illness. Lower levels of free tri-iodothyronine and free thyroxine are seen with increasing age. We aimed, adjusting for normal age-associated decline of these hormones, to determine whether thyroid hormone levels could predict long-term survival. Design & Setting: This is a "big-data" study based on thyroid function tests from samples taken between 2008-2014. Data were crossed with electronic health records for morbidity and national death registry for mortality. Excluded: age below 18 years or above 95 years, taking thyroid or anti-thyroid drugs. We converted each measurement to an Age and Gender Adjusted Percentile (AGAP). We assessed survival according to ranges of initial AGAPs of Free Triiodothyronine (FT3), Free Thyroxine (FT4), and Thyrotropin (TSH) up to 8 years prior to death for two subgroups: "not healthy" - subjects with at least one of five chronic conditions registered in their electronic health chart; "healthy" - all others. The hazard ratio for death of various AGAPs was defined for the entire cohort and the subgroups separately. Results: Thyroid function tests were taken from 365,965 patients. 258,695 remained after exclusion criteria: 151,868 "not healthy" and 106,827 "healthy". After a median follow-up of 6.8 years, 5,865 /151,868 (10.4%) of the "not healthy" had died and 2,504/106,827 (2.3%) of "healthy" participants. The lowest 5th percentile initial FT3 AGAPs survival compared to the 95th percentile was for "not healthy" hazard ratio 5.71 (CI - 5.23 to 6.26, p<0.001), for "healthy" - hazard ratio was 3.92 (CI - 3.06 to 5.02, p<0.001)). Eight year survival associated with decline in FT3 AGAPs for 34,129 individuals was lowest for those with greater that 50%, decline: 86% of "not healthy" subjects and 95.5% of "healthy" subjects with such a decline survived 8 years. Conclusion and relevance: Lower age-adjusted values of FT3 were associated with decreased survival. This marker may potentially be used for focusing patients with expected reduced survival.

Presentation: Friday, June 16, 2023
FRI529 Hypothyroidism And Systemic Lupus Erythematosus: A Nationwide Analysis
Authors: Sami Faria , Ahmed Sami Shahzad , Razok Almurtada , Ayub Tooba , Olafimihan Ayobami
Published: October 2023

Disclosure: F. Sami: None. S. Sami: None. A. Razok: None. T. Ayub: None. A. Olafimihan: None.

Background: Hypothyroidism is the most common thyroid disease in Systemic Lupus Erythematosus (SLE) and more prevalent in SLE than the general population. Our aim is to study the prevalence, epidemiology and likelihood of hypothyroidism with SLE as well as impact on outcomes and healthcare burden. Methods: The National Inpatient Database from 2016-2019 was used to extract patient populations. Data was stratified to reflect national estimates. Adult patients with principal diagnosis of SLE and hypothyroidism as a primary or secondary diagnosis were identified. Epidemiology was compared. We analyzed mortality rates, hospital charges (THC) and length of stay (LOS). Secondary outcomes included sepsis, congestive heart failure (CHF), renal and respiratory failure, stroke and myocardial infarction (MI). Statistical analysis was performed with STATA17. Univariate and multivariate regression analyses adjusted for confounders. Results: Among 721,090 adult SLE patients, 17.64% had hypothyroidism. In SLE-hypothyroid group, there were more females (93.46% vs 87.35%, odds ratio 2.01) and whites ( 65.82%vs 33.53%, OR 2.37). The mean age was higher (59.95 SD 15.56 vs 50.91 SD 16.94, P-value 0.000) with significantly more patients in 60-80 years group (44.64% vs 28.56%) and less in 18-40 year age group (1.68% vs 29.01%). African-Americans and Hispanics were significantly less in hypothyroid group with OR 0.34 and 0.87 respectively. Charlson comorbidity Index was ssignificantly high (3.2 vs 2.97). Hypothyroidism was significantly more among higher socioeconomic class of SLE patients (20.62% vs 16.7%) and less prevalent among the low socioeconomic class (28.88% vs 35.36%) based on annual income. There was no significant rise in mortality when adjusted for confounders (1.93% vs 1.97%, P-value 0.702), mean length of stay (5.41 vs 5.46, P-value 0.284), or total hospital charges ($63372 vs 64065, P-value 0.273) between two groups. There was a significantly higher prevalence of MI (3.21% vs 2.9%, P-value 0.01,OR 1.11) and CHF (5.94% vs 5%, P-value 0.00,OR 1.2). Prevalence of sepsis (8.92% vs 8.77%, P-value 0.449), renal failure (37.94% vs 37.79%), respiratory failure (37.63% vs 37.84%) and stroke (0.88% vs 0.93%,) was comparable with no significant difference. Odds ratio for hypothyroidism in SLE was 1.5, p-value 0.000. Conclusion: SLE patients with hypothyroidism are more females, Caucasians, of higher mean age, between 60-80 years of age, and from higher socioeconomic status. There is no effect on mortality, LOS and THC, rate of sepsis, stroke, renal and respiratory failure with hypothyroidism. There is a significantly higher risk of MI and CHF. SLE patients have 1.5 times increased risk of developing hypothyroidism. This emphasizes screening at-risk individuals when suspicion arises, for timely diagnoses and improving outcomes.

Presentation: Friday, June 16, 2023
FRI531 IgG4 Related Mass -forming Thyroid Disease: Two Case Reports
Authors: Sarah Braham Rim , Droumaguet Céline , Vitellius Manuel , Tran-van-nhieu Jeanne , Béquignon Emilie , Desgranges Pascal , Limal Nicolas , Mahevas Matthieu , Godeau Bertrand
Published: October 2023

Disclosure: R.S. Braham: None. C. Droumaguet: None. M. Vitellius: None. J. Tran-van-nhieu: None. E. Béquignon: None. P. Desgranges: None. N. Limal: None. M. Mahevas: None. B. Godeau: None.

IgG4 thyroiditis is an invasive fibrotic process involving the thyroid in a systemic disease. It is a rare inflammatory autoimmune disease with insidious presentation and nonspecific symptoms.We describe two unusual cases of mass forming IgG4 thyroiditis that were diagnosed recently in our department. The first case is about a 42-year-old woman who has a history of Hashimoto thyroiditis with hypothyroidism presenting with a rapid goiter growth, neck pain, dysphagia and hoarseness. A lymphoma was suspected. Ultrasonography shows heterogeneous hypoechoic lesions that may infiltrate the perithyroid muscles. Fine-needle aspiration (FNA) was suspicious of IgG4 infiltrative disease which was confirmed by microbiopsy. Only the thyroid was hypermetabolic on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) Scan. No improvement under corticosteroid treatment and Rituximab. Surgery was planified to relieve pressure symptoms. The thyroid surgery was very difficult because of the extensive fibrosis and only a biopsy was performed, confirming the diagnosis and excluding malignancy. The second case is about a 68-year-old woman with a history of hypertension and Graves disease presented with a neck right mass that was suspected to be a paraganglioma, hypermetabolic on FDG PET scan with no other localisation. This mass was surrounding the right primitive carotid artery, associated with thrombi of the internal jugular vein. FNA and microbiopsy found a fibrotic non specific tissue. Thyroidectomy and surgical biopsy of the neck mass were performed with histopathology confirming IgG4 disease on the thyroid gland with fibrosis. There were no hypocalcemia in the two cases and no other localisation. IgG4 related mass-forming thyroiditis is an extremely rare disease. It is now a recognizable pattern of IgG4 thyroiditis, and has as differential diagnosis Hashimoto’s thyroiditis, Graves disease and thyroidal carcinoma.We will discuss through these cases the different clinical presentation of this rare disease, the diagnostic tools, the treatment and the long term follow up.

Presentation: Friday, June 16, 2023
FRI533 A Novel Cre-loxP Based Mouse Model For Graves' Disease
Authors: Kim Daham , Bao Yaru , Jeong Kang Min , Hee Cho Yoon , Kim Youngsook , Hwang Yoon-a , Ryong Ku Cheol , Jig Lee Eun
Published: October 2023

Disclosure: D. Kim: None. Y. Bao: None. M. Kang: None. Y. Cho: None. Y. Kim: None. Y. Hwang: None. C. Ku: None. E. Lee: None.

Objectives: Over years, various approaches have been used to model human Graves’ disease in mice, including transfected fibroblasts, and plasmid or adenoviral immunizations with the extracellular A subunit of the human thyrotropin receptor (hTSHRa). However, these models require a lot of effort for multiple dosing over several months and the results are very heterogeneous, limiting their use as a platform for the development of new therapeutics. Thus, we developed a novel Cre-loxP based mouse model for Graves' disease. Methods: To overcome the limitation of existing animal models, we made ESC-derived KI mouse expressing hTSHRa that will act as an antigen in a conditional manner by inserting the CAG-loxP-STOP-loxP-hTSHRa cassette into the mouse Rosa26 locus. TAT-Cre, a recombinant cell-permeant fusion cre-recombinase protein, was used for site-specific recombination to avoid leaky expression which may induce immune tolerance. Various concentrations of TAT-Cre were tested to avoid neutralization and produce adequate hyperthyroidism. Serum TSHR Ab and T4 levels were measured. Immunohistochemical examinations of the thyroid gland and orbits were performed. Results: Treatment with TAT-Cre within the range of 250-750U produced the most efficient TSHR Ab and significantly increased T4. Four weeks after TAT-Cre 500U administration, TSHR Ab levels were already significantly produced in all mice and T4 levels started to increase. At 8 and 12 weeks, TSHR Ab levels were produced at a very high levels in all mice and T4 levels were increased to a very high levels in over 80% of mice. After 3 months, MRI images did not show any significant protrusion. However, there was an enlargement in the volume of the orbital muscles. We also found thyroid enlargement and hypertrophy, orbital macrophage infiltration and fibrosis in Immunohistochemical examinations. Conclusions: A new mouse model for Graves' disease was successfully established by using the Cre-loxP system. After being optimized for orbitopathy induction, this model can be used as a platform for the development of novel therapeutics.

Presentation: Friday, June 16, 2023
FRI546 VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor In Development For Thyroid Eye Disease (TED): Pharmacodynamic Responses In Healthy Volunteers And Patients With Active TED
Authors: Foster Kelly , Dickinson Brent A , Summerfelt Rochelle M , She Angela , Bedian Vahe , Katz Barrett
Published: October 2023

Disclosure: K. Foster: Employee; Self; Viridian Therapeutics Inc. B.A. Dickinson: Employee; Self; Viridian Therapeutics Inc. R.M. Summerfelt: Employee; Self; Viridian Therapeutics Inc. A. She: Employee; Self; Viridian Therapeutics Inc. V. Bedian: Employee; Self; Viridian Therapeutics Inc. B. Katz: Employee; Self; Viridian Therapeutics Inc.

Introduction: VRDN-001, a full antagonist antibody to IGF-1 receptor (IGF-1R), is in development for the treatment of thyroid eye disease (TED). Clinical and preclinical evidence demonstrate IGF-1R antagonism reduces the inflammation and proptosis that occur in TED. We provide pharmacodynamic (PD) results in healthy volunteers and TED patients from our ongoing phase 1/2/3 clinical trial (NCT05176639) evaluating VRDN-001. Methods: Healthy volunteers (HVs) and patients with active, moderate-to-severe TED were randomized 3:1 to receive 2 intravenous infusions 3 weeks apart (i.e., at week 0 and week 3) of either VRDN-001 (at 3-20 mg/kg) or placebo. PD parameters (IGF-1 serum levels) were assessed through 7 weeks. Results: Thirteen HVs received either placebo (n=3) or VRDN-001, 3 mg/kg (n=3), 10 mg/kg (n=3), or 20 mg/kg (n=4). Additionally, 16 TED patients received either placebo (n=4), 10 mg/kg of VRDN-001 (n=6), or 20 mg/kg of VRDN-001 (n=6). Baseline characteristics were similar across all TED cohorts. All VRDN-001 doses (3-20 mg/kg) elicited rapid, sustained, and similar increases in IGF-1 serum levels, a biomarker for target engagement and IGF-1R inhibition. In HVs receiving VRDN-001 (n=10), IGF-1 serum levels increased within a day of the first infusion for all doses, reaching 4-6-fold above baseline; levels continued to increase after the second infusion, ultimately reaching 4-9-fold above baseline. In TED patients receiving VRDN-001 (n=12), IGF-1 serum levels increased for both doses 2-6-fold above baseline after the first infusion, and further increased after the second infusion, ultimately reaching levels 4-9-fold above baseline. No increases in IGF-1 serum levels occurred for placebo. Conclusions: Two infusions of VRDN-001 in healthy volunteers as well as TED patients elicited rapid and sustained increases in IGF-1 serum levels that were similar across groups, indicating maximal target engagement at all doses tested. Results from an additional ongoing cohort of 3 mg/kg in TED patients will further inform optimal VRDN-001 dosing and potential treatment regimens to balance efficacy and safety and minimize treatment burden in TED.

Presentation: Friday, June 16, 2023
FRI195 Tuberculosis and Adrenal Glands: The Great Forgotten
Authors: Vina Isabel , Sánchez Raquel , Fernández Ivonne C , Vázquez Clotilde
Published: October 2023

Disclosure: I. Vina: None. R. Sánchez: None. I.C. Fernández: None. C. Vázquez: None.

Background: Tuberculous adrenalitis is an extremely rare cause of Addison disease in developed countries. Since more than 80% of the primary adrenal insufficiency cases in the developed world are caused by autoimmune disease, tuberculous adrenalitis often go unnoticed. The aim of this case report is to remember that, even if it is not frequent, TB cannot be overlooked as a cause of longstanding primary adrenal insufficiency, even without evidence of pulmonary or extra glandular TB disease. Herein, we reported a case of bilateral tuberculous adrenalitis, wherein the patient initially presented with gastrointestinal symptoms, hyperpigmentation, bilateral adrenal masses, and no evidence of extra-adrenal tuberculosis. Case report: A 57-year-old woman from Madrid with no medical relevant history, was admitted to our hospital with 4 months of evolution of asthenia, weight loss (-8kg) and nausea that in recent days has been accompanied by fever and anorexia. He also refers progressive hyperpigmentation for the past 3 years. Denies recent travel abroad. On physical examination hypotension (80/53 mmHg) and generalized hyperpigmentation predominantly in the oral mucosa stand out. Blood test: Glu: 41 mg/dL, Na+: 122 mmol/L, K+: 4.8 mmol/L, ACTH: 922 pg/mL, Cortisol: 4.63 ug/dL, Anti-Hydroxylase Ab and Anti-Adrenal glands Ab: negative

A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands with small bilateral calcifications (12-18mm). TB QuantiFERON test: positive. She was initially treated with saline serum and intravenous hydrocortisone causing her symptoms to improve significantly in a few days and was subsequently discharged on hydrocortisone and fludrocortisone and proper treatment for TB Adrenalitis and follow-up in outpatient clinics. Conclusions: Although not frequent, infectious causes should always be kept in mind, such as the etiology of adrenal insufficiency in a patient with long-term compatible symptoms, even though it is a developed country, given world globalization, which makes infectious diseases highly transmissible between countries and continents.

Presentation: Friday, June 16, 2023
SAT450 High Diagnostic Yield Of NGS Analysis In Congenital Hypothyroidism With Thyorid Dyshormongenesis
Authors: Joo Eunyoung , Kim Sujin , Lee Ji-Eun
Published: October 2023

Disclosure: E. Joo: None. S. Kim: None. J. Lee: None.

Introduction: Congenital hypothyroidism is the most common neonatal metabolic disorder and detected at a rate of 1 in 3000 to 4000 live births. 10-15 % of congenital hypothyroidism is caused by thyroid dyshormonogenesis. And Its clinical manifestations are individually different. Thus, to evaluate exact causes and predict clinical course for congenital thyroid dyshormonogenesis and establish precise strategies for treatment, we conduct Next-Generation Sequencing (NGS) to patients who diagnosed congenital hypothyroidism with normal thyroid gland and analysis the results. Methods: We conducted NGS to 31 patients patients who were diagnosed congenital hypothyroidism with normal contour of thyroid gland in ultrasonography from Jan. 2018 to April. 2022 in a single university hospital. We also analyzed their thyroid function test results, dose of levothyroxine and clinical manifestations. Result: Among the 31 patients, 25patients were detected from NGS. 4patients have oligogenic mutations. 7 DUOX2 variants were detected in 7 patients (22.6%), 3 DUOXA2 variants were detected in 4 patients (12.9%), 4 TSHR variants were detected in 7 patients (22.6%) 5 TG variants were detected in 4 patients (12.9%), 2 GLIS3 variants in 2 patients (6.5%), 1 TPO variants in 1 patient, 1 THRB variants in 1 patient, 1 NKX2-1 variants in 1 patient, 1 TRH variants in 1 patient, 1 SLC5A5 variants in 1 patient. The patients with GLIS3 stop levothyroxine at 3years old and have remission. The patients with DUOX2 variants and DUOXA2 variants showed low remission rate. DUOXA2 variants has high association with goiter. None of the patients with TSHR c.1349G>A mutation to stop medicine. But patients with other mutation of TSHR stop levothyroxine at 3 years old and have remission. None of the patients with TG variants showed remission. The patients with GLIS3 have remission at 3 years old. Conclusions: We cautiously recommend that using the NGS to strategize treatment plan for CH based on the clinical manifestations and genetic analysis of the family members of the index patients.

Presentation: Saturday, June 17, 2023
SAT451 High-throughput Measurement Procedure Of Free Thyroid Hormones In Serum Based On Equilibrium Dialysis ID-LC/MS/MS
Authors: Zhang Li , Ribera Ashley , D'Zio Zachary , Doty Alex , Sugahara Otoe , Ying Tse Chui , Danilenko Uliana , Vesper Hubert W
Published: October 2023

Disclosure: L. Zhang: None. A. Ribera: None. Z. D'Zio: None. A. Doty: None. O. Sugahara: None. C. Tse: None. U. Danilenko: None. H.W. Vesper: None.

A Reliable and accurate measurement of serum free thyroxine (FT4) is critical for diagnosis and treatment of thyroid disorders. Immunoassays (IAs) are most popularly used for FT4 measurements in-patient care. However, there are concerns about the accuracy of FT4 IAs. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for standardization of routine FT4 IAs. FT4 RMP is highly accurate and precise, while it is labor-intensive and time-consuming which is not intended for routine clinical application. In the current study, we aim to develop a high-throughput FT4 method based on ED ID-LC/MS/MS that can be traceable to the RMP. FT4 in dialysate was isolated from protein-bound T4 in serum by using a commercially available micro-ED plate after 18-hours ED. The 13C6 labeled T4 was spiked into collected dialysate as an internal standard. FT4 in dialysate was extracted by using 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS. The certified primary reference material was used to for assay calibration. T4, T3, reverse triiodothyronine (rT3), and other interferences in the dialysate were resolved on a C18 UPLC column within 4 min. The linear range of the routine FT4 assay covered 1-100 pg/mL. The assay sensitivity allowed detection of 0.3 pg/mL FT4 in serum, which is sufficient for FT4 measurement covering clinically relevant ranges including hypothyroid patient samples. Method comparison showed good agreement between our high-throughput method and RMP in Deming regression analysis with slope close to 1, while there was significant bias of IA from RMP. The intra and inter-day CV% of the assay was 6.96 and 3.38 %, respectively. The use of a micro-ED plate together with automation system could improve the throughput of the procedure. The accuracy, precision, and sensitivity of our method are suitable for the high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. The traceability of the described FT4 method to RMP can support the standardized FT4 measurements in patient care.

Presentation: Saturday, June 17, 2023