bluuebunny/crossref_metadata_2025 huggingface dataset:
9189 Medullary Thyroid Cancer Due To A Novel Ret Oncogene Mutation In A Patient On Glp-1 Receptor Agonist
Authors: Lamar K , John D , Faour O , Meda N , Kinaan M
Published: October 2024

Disclosure: K. Lamar: None. D. John: None. O. Faour: None. N. Meda: None. M. Kinaan: None.

Introduction: Mutations in the RET oncogene have been associated with increased risk of endocrine neoplasia and Medullary Thyroid Cancer (MTC). We report the case of a patient who has a (c.3281G>A) RET mutation, previously reported as a variant of uncertain significance. Case: A 51-year-old lady presented to our endocrine clinic for routine management of hypothyroidism, type 2 diabetes mellitus, and obesity. She had been on liraglutide, metformin, glipizide, and basal insulin for several years with good diabetes management. She had also been on levothyroxine for more than 10 years. On physical examination, a right thyroid lobe nodule was palpated. We performed a neck ultrasound which revealed a solid, isoechoic nodule measuring (1.23 x 1.42 x 2.00 cm) with no calcifications. Fine needle aspiration was consistent with MTC. She denied family history of thyroid cancer. She was advised to stop liraglutide immediately given risk of MTC with GLP-1 receptor agonist use. Preoperative calcitonin and CEA were markedly high at 935 pg/mL and 60.3 ng/mL, respectively. Fortunately, Gallium Ga-68 dotatate PET CT showed no signs of metastatic disease. The patient underwent a total thyroidectomy with bilateral central and lateral neck dissection. No cervical metastases were noted on lymph node dissection. Genetic tumor testing demonstrated a mutation in the RET oncogene (c.3281G>A), which was previously reported as a variant with unknown significance. Screening for hyperparathyroidism and pheochromocytoma was normal. Postoperative calcitonin and CEA were <2.0 pg/mL and 3.2 ng/mL respectively. The patient continues MTC surveillance under the care of a multidisciplinary team. Discussion: Our case is the first case in literature that identifies the RET oncogene (c.3281G>A) mutation as a pathogenic variant associated with MTC. It also emphasizes the need for close monitoring for thyroid nodules in patients on GLP-1 receptor agonists and pre-existing thyroid disease, through a comprehensive physical examination and neck ultrasound if needed.

Presentation: 6/2/2024
7768 Hereditary Phaeochromocytoma/Paraganglioma And Aortopathy In A Patient With Known Macroprolactinoma: A Series Of Incidental Findings
Authors: Kelly Jessica R , Soule Steve , Jane Hunt Penelope
Published: October 2024

Disclosure: J.R. Kelly: None. S. Soule: None. P.J. Hunt: None.

Background: The three P association (3PAs) describes the combination of pituitary adenoma and phaeochromocytoma/paraganglioma. Recent case series describe a range of underlying genetic causes, including SDH mutations. We describe a patient with a macroprolactinoma and their subsequent incidental diagnoses of phaeochromocytoma and paraganglioma, with a pathogenic SDHA mutation. Clinical Case: A 58-year-old man had previously received a combination of medical therapy with cabergoline and transsphenoidal debulking surgery for a histologically confirmed macroprolactinoma. Due to a small risk of valvulopathy associated with cumulative doses of cabergoline, screening echocardiogram was requested after seven years of treatment. This showed a calcified bicuspid aortic valve and severe dilatation of the ascending aorta at 58mm. Prior to surgical repair, CT aorta was requested, which showed an incidental left adrenal lesion. Formal adrenal imaging and functional assessment confirmed a 50mm phaeochromocytoma, with a right para-aortic paraganglioma subsequently revealed on Ga-68 DOTATATE-PET scan. He described symptoms of catecholamine excess, with episodic palpitations, chest pain, and increasing anxiety over the previous year, on a background of hypertension. Hereditary phaeochromocytoma/paraganglioma gene panel revealed a pathogenic mutation in SDHA (c.1663+1G>T) – a splicing variant, likely resulting in nonsense decay. Screening was recommended for his three children. He initiated alpha blockade with doxazosin, then beta blockade with metoprolol, prior to open adrenalectomy and excision of paraganglioma. Histology confirmed a left phaeochromocytoma (Ki67 0.1%, PASS score 8, no vascular or capsular invasion) and a paraganglioma. Post-operative plasma normetanephrine normalised (406 pmol/L, pre-operative 6776 pmol/L, normal <1200 pmol/L) and the patient described resolution of symptoms. He subsequently underwent tissue aortic valve replacement and Bentall’s procedure. Histology showed severe atherosclerosis with diffuse medial degeneration of the aorta. Repeat Ga-68 DOTATATE-PET seven months later showed no evidence of residual or recurrent disease. Ongoing management includes cabergoline, annual plasma metanephrine measurement, and intermittent MRI of pituitary and base of skull to coccyx. Conclusion: Macroprolactinomas are relatively common, with only a small proportion associated with underlying genetic abnormalities. This case describes a patient with 3PAs, initially presenting with a macroprolactinoma, with incidental detection of phaeochromocytoma and paraganglioma and subsequent identification of a pathogenic SDHA mutation. In the context of a calcified bicuspid aortic valve and severe aortic dilatation, pre-operative alpha blockade allowed successful surgical management of both potentially life-threatening conditions.

Presentation: 6/3/2024
8477 Medullary Thyroid Carcinoma Masquerading as a Cold Nodule in a Patient With Graves' Disease
Authors: Umashree T , Farooqui K J , Mithal A
Published: October 2024

Disclosure: T. Umashree: None. K.J. Farooqui: None. A. Mithal: None.

Background: Only a handful of cases of MTC have been reported in the setting of Graves’ disease. Clinical Case: A 38 year old lady presented with symptoms of significant weight loss and palpitations for past six months. Thyromegaly was present, with non tender left lobe enlargement of about 3x3 cm. On further probing it was found that her father had been operated for thyroid cancer 22 years ago, the type of which patient was not aware of. TFTs reflected a thyroxtoxic state (TSH -<0.01mIU/mL [0.34-5.6] FT4 - 3.38 ng/dL [0.58-1.64] FT3 - 8.46 pg/mL [2.6-4.2]) and TRAb was positive (8.74 IU/L [<1.22]). USG neck revealed a hypoechoic lesion of 18x18x13 mm in left lobe thyroid with internal calcifications, with multiple bilateral non-significant lymph nodes. Technetium99 (Tc99) scan showed an enlarged left lobe, with diffuse thyroid uptake at 20 minutes of 4%, and a well-defined photopenic area in left lobe, corresponding to the nodule seen on USG. FNAC of the nodule was suggestive of Hürthle cell neoplasm and patient underwent left hemithyroidectomy. Surprisingly, HPE was consistent with medullary thyroid cancer. Serum calcitonin was raised at 148 pg/mL (N<4.8 for females) and plasma free metanephrines and normetanephrine were normal. F-18 DOPA PET CT showed uptake in residual right lobe of thyroid only, no other abnormal uptake was seen. She underwent completion thyroidectomy with central compartment clearance and is now under regular follow up. Genetic analysis showed RET gene mutation of Cys634Ser, which is heterozygous for MTC. Cold nodules in Graves’ disease should be viewed with suspicion, and while PTC and FTC have been reported more commonly, MTC is extremely rare in this setting. A calcitonin washout of the FNAC may have prevented this patient from undergoing two surgeries. Moreover, Hürthle cell change can also occur in C-cells of the thyroid, not just the follicular cells. Lastly, given the history of thyroid cancer in her father, index of suspicion of MTC should have been higher in this patient. Conclusion: Cold nodules in Graves’ Disease may be malignant, and should always be examined by FNAC. Though MTC is rare, it is not unknown in Grave’s disease.

Presentation: 6/3/2024
8759 Mild Iodine Deficiency During Pregnancy Impairs Hypothalamus-Pituitary-Thyroid Function Programing of the Adult Male Offspring
Authors: Oliveira Mikaeli , Tavares Evelyn , Henrique Guilherme , Anthony Pinto João , Serrano-Nascimento Caroline
Published: October 2024

Disclosure: M. Oliveira: None. E. Tavares: None. G. Henrique: None. J. Pinto: None. C. Serrano-Nascimento: None.

Introduction: Iodine plays a crucial role in the biosynthesis of thyroid hormones and is essential for proper thyroid embryonic development. While severe iodine deficiency during pregnancy and lactation has well-documented deleterious effects, the consequences of mild iodine deficiency (MID) remain not fully understood. MID during pregnancy is a reality in numerous countries, even in regions with seemingly adequate iodine supply in the diet. Previous studies have highlighted the adverse impact of MID on neurological development in offspring, but comprehensive data on thyroid function, particularly in progeny at different developmental stages, are lacking. This study aimed to investigate the repercussions of MID during pregnancy on the programming of thyroid dysfunctions during adulthood. Methods: Female CD1 mice were subjected to iodine-deficient animal chow and iodine-supplemented water, either at normal (NI; 0.2 mg/L) or mild iodine deficiency (MID; 0.8 mg/L) levels during pregnancy. Gene and protein expression in the hypothalamus, pituitary, and thyroid of adult male offspring animals (PND90) were evaluated using qPCR and Western blotting. Additionally, this study explored MID-induced programming of offspring thyroid gene expression through epigenetic mechanisms. Results: Maternal MID exposure led to increased gene and protein expression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) in the hypothalamus and pituitary of the offspring animals. Thyroid protein and gene expression of sodium iodide symporter (NIS), TSH receptor (TSHR), thyroid peroxidase (TPO), thyroglobulin (TG), paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and monocarboxylate transporter 8 (MCT8) were elevated in the offspring of MID-exposed animals. Epigenetic mechanisms appeared to contribute to the augmented thyroid gene expression in MID-exposed animals, with decreased DNA methyltransferase expression and reduced thyroid DNA global methylation. Additionally, histone 3 hypomethylation and increased acetylation of histones 3 and 4 were observed. Conclusion: The study suggests that MID exposure during pregnancy can be as harmful as severe iodine deficiency in programming the hypothalamus-pituitary-thyroid (HPT) axis, leading to HPT dysfunction during adult life. Consequently, our data suggest that monitoring iodine intake throughout pregnancy is crucial to prevent the occurrence of thyroid disorders in offspring during adulthood.

Presentation: 6/1/2024
8307 Molecularly Targeted Therapy in Oncogene-Driven Human Thyroid Cancer Cell Models: Assay Selection and Response Assessment
Authors: Yang Adeline T , Laetsch Theodore W , Franco Aime T
Published: October 2024

Disclosure: A.T. Yang: None. T.W. Laetsch: Consulting Fee; Self; Cellectis, Deciphera, GentiBio, Jazz Pharmaceuticals, Jumo Health, MassiveBio, Novartis Pharmaceuticals, Pyramid Biosciences, Y-mAbs Therapeutics, Advanced Microbubbles, AI Therapeutics, Bayer, Inc.. A.T. Franco: None.

Background: The most common types of pediatric thyroid cancer (TC) demonstrate kinase-activating genomic alterations that are clinically inhibitor responsive – however, optimal integration of molecular therapy into practice remains uncertain. Human TC cell models can facilitate evaluation of combination therapies. However, prior studies vary from using traditional cell counts to newer reaction-based assays; we assessed whether a linear relationship between cell count and alternative assays exist for human TC cell models. Methods: Standardized curves for Cell TiterGlo (CTG; measures total ATP using luciferase-based luminescence) and NucBlue (DAPI; binds to DNA with nuclear fluorescence) were generated using TC cells seeded at escalating concentrations (5k to 300k cells/well). A linear equation was fitted to the CTG data and used to estimate cell count. DAPI counts were obtained with EVOS automation. Human TC cell lines TPC1 (RET fusion) / CUTC5 (BRAF V600E) were seeded at low (1.5k/2k) and high (3k/4k) cells per well, exposed for 3 days to 0-256 nM selpercatinib (RET inhibitor) or 0-192 nM dabrafenib (BRAF inhibitor), respectively, and response was measured using CTG and DAPI. All were measured in triplicate. Results: Standardized curves of CTG and DAPI demonstrated a 9-23% difference between known and measured cell counts. CTG was accurate within 20k-40k cells/well; DAPI showed linearity within 10k-80k cells/well. TC cells exhibited different IC50 depending on the assay and seeding concentration. Prior studies for selpercatinib and dabrafenib reported in vitro IC50 of 0.4-67 nM and 0.5-6 nM, respectively. In this study, IC50 for CTG/DAPI were closer at higher cell counts: TPC1 was 6.1 / 8.2 nM respectively; CUTC5 was 10.6 / 5.1 nM. Wells seeded at lower counts demonstrated larger inter-assay difference: IC50 for TPC1 was 10.1 / 5.9 nM respectively; CUTC5 was 38.4 / 5.9 nM. Conclusion: IC50 values varied by cell seeding concentrations and assay used, with a two to six fold difference at lower seeding and loss of linearity between luminescence measurements and cell count. This variability complicates evaluating the concordance among data from different laboratories, and in vitro and clinical response. Alternative assays intended to assess viability of inhibitor-exposed human TC cell models may require additional evaluation to ensure measured values demonstrate the expected relationship to the intended measure (ie cell number) and ultimately clinical outcome.

Presentation: 6/3/2024
6668 Myxedema Coma and Takotsubo Cardiomyopathy
Authors: Skariah Annie M , Jain Sumeet
Published: October 2024

Disclosure: A.M. Skariah: None. S. Jain: None.

Background: Takotsubo cardiomyopathy (TCM) also know as broken heart syndrome is a transient decrease in systolic cardiac function in the absence of obstructive CAD. TCM is likely related to hyperadrenergic conditions leading to increased cardiac sensitivity to catecholamine surge leading to cardiomyopathy. TCM is more associated with hyperthyroidism. Case presentation: Patient is an 84-year-old female with PMH of celiac disease,hypertension,prediabetes, and atrial fibrillation s/p cardioversion, on amiodarone. She was brought to the ER after having an unwitnessed fall. She was hypotensive 76/56 mm of Hg, hypothermic 35.5 degree C, HR 90 beats/min; labs significant for hyponatremia, macrocytic anemia, TSH 65.47uIU/ml, FT4 <0.4 ng/dl and mild QTC prolongation of 469ms. Family mentioned history of constipation, progressive weakness, poor oral intake, memory problems and cold sensitivity for a couple of months. Started on 1 pressor, 3 units of PRBC and 2 liters of IVF; BP improved; labs and history suggestive of myxedema coma with myxedema coma Popoveniuc score 85 suggestive of high suspicion for myxedema coma.She had TSH 50.39 uIU/ml and FT4 of 0.4 ng/dl for her memory issues workup 2 months prior to presentation but was not started on medication. Upon admission, started stress dose steroids followed by IV levothyroxine 100 mcg. Not started on LT3 given her old age and atrial fibrillation history. Received additional dose of LT4 100 mcg within few hours. TFT improved with TSH 35 uIU/ml and FT4 1 ng/dl after 2 doses. Later same day, shock worsened, and patient was on 3 pressors along with stress dose of steroids. Cardiology was consulted; recommended an Echocardiogram.Echo was done on day 2; EF 55-60 % with severe hypokinesis of apical myocardium consistent with TCM. Normal echocardiogram studies 4 months ago.Started on weight-based regimen of LT4 75 mcg IV on day 3 and switched to 100 mcg oral when patient tolerated pills.Patient was down to 2 pressors on day 3 and gradually off pressors by day 6. Repeat TFT -showed improvement TSH 12 uIU/ml and FT4 0.7 ng/dl—day 5. Eventually her mentation improved and was discharged on oral LT4. Conclusion: TCM is rare complication of treatment of myxedema coma. Our patient developed shock requiring 1 pressor which unexpectedly worsened to 3 pressors requirement after initial LT4 treatment. High doses of LT4 and LT3 which is part of myxedema coma treatment sensitizes myocardial tissue to catecholamines by increasing expression of beta adrenoreceptors in cardiac myocytes with subsequent ionotropic and chronotropic effects. This may contribute to cardiac stunning and TCM. It’s beneficial to evaluate patients with myxedema coma who develop worsening cardiac status after initiation of high dose of thyroid hormone replacement for TCM.

Presentation: 6/2/2024
8089 Myxedema Coma Presenting with Reversible Cardiomyopathy and Acute Renal Failure
Authors: Mubashir A , Sajid F , Sattar M
Published: October 2024

Disclosure: A. Mubashir: None. F. Sajid: None. M. Sattar: None.

Myxedema Coma is a life-threatening complication of hypothyroidism and often presents with multi-organ failure. However, reversible cardiomyopathy and acute renal failure are rare. Here, we present a case of iatrogenic hypothyroidism leading to myxedema coma with reversible organ failure. Case Presentation: A 58-year-old male with a past medical history of iatrogenic hypothyroidism after total thyroidectomy for follicular thyroid cancer, noncompliant with levothyroxine for the past three years, was brought to the hospital due to worsening mental status, low energy, and cold extremities for three days. On admission, vital signs were within normal limits. Laboratory studies revealed Random Glucose 113 (74-200 mg/dl), Na 134 (135-149 mmol/l), TSH: 217 (0.39-4.08 MCIU/ml), Free T4 <0.25 (0.58-1.64 ng/dl), Free T3 1.01 (2.53-3.87 pg/ml), BUN 53.3 (7-21 mg/dl), Creatinine 4.9 (0.5-1.3mg/dl). Urinalysis was positive for protein of 300 mg/dl (negative). Urine studies showed hematuria, total protein/cr 3.18 (<0.10), with increased total protein of 60/24 hours (0-12 mg/dl), suggesting glomerular etiology. Additionally, Bence Jones protein and monoclonal band were negative, interpreted as mild glomerular proteinuria. FeNa >2%, Urine sodium of >40 (20-40mmol/l) suggest acute tubular necrosis. EKG showed normal sinus rhythm with low voltage. To rule out diastolic dysfunction, an echocardiogram was performed, which revealed depressed systolic function with an ejection fraction of 31-35% and a large pericardial effusion with echocardiographic features of tamponade. He also had global cardiomyopathy with akinesis, especially in the inferior segments. He was treated with IV levothyroxine. Repeat imaging in one month showed an increase in ejection fraction to 55% with moderate-sized pericardial effusion and no echocardiographic features of tamponade. Global cardiomyopathy had also resolved. However, left ventricular systolic function was borderline, with delayed diastolic expansion of the right ventricle. Repeat creatinine was 2mg/dl. The patient’s condition greatly improved, and he was discharged with follow-up with endocrinology, nephrology, and cardiology. Discussion: In the available literature, diastolic dysfunction is associated with severe hypothyroidism. However, reversible global cardiomyopathy with decreased systolic function is rare. The pathogenesis of this myopathy is not well understood. Similarly, known mechanisms of renal injury in hypothyroidism include renal hypoperfusion, rhabdomyolysis, decreased kidney-to-body weight ratio, truncated tubular mass, and altered glomerular architecture. While the need to perform a renal biopsy or the use of goal-directed therapy for dilated cardiomyopathy remains questionable in such cases, reversible complications of severe hypothyroidism should be investigated in patients with suspected myxedema.

Presentation: 6/2/2024
12393 Myxedema Presenting With Impending Cardiac Tamponade : A Case Report
Authors: Hoskote Abhinav , Gupta Vishal , Seidenberg Jacob
Published: October 2024

Disclosure: A. Hoskote: None. V. Gupta: None. J. Seidenberg: None.

The widespread availability of thyroid stimulating hormone (TSH) assays, routine screening and affordable replacement therapy has resulted in decreased prevalence of complications of untreated hypothyroidism. “Myxedema heart” is a rare syndrome that results in bradycardia, cardiomyopathy and pericardial effusion. We present a rare case of cardiac tamponade due to myxedema in a patient with unidentified hypothyroidism. A 49-year-old male was brought to the ER by his family for several weeks of cognitive slowing, weakness and inappropriate behavior involving defecating on himself eating old food and barricading in his room. The patient denied past medical or psychiatric history, medication use or recent physician evaluation. On exam he had macroglossia, was disheveled, forgetful but alert with slow speech, ataxia and muscle wasting. He was afebrile and hemodynamically stable. EKG showed sinus bradycardia. Labs were notable for sodium 133, hemoglobin 8.8g/dL and TSH was incidentally >100U. Levothyroxine was begun. The next day, he was noted to have increased lethargy, bradycardia and hypoglycemia and was transferred to the intensive care unit with concern for myxedema coma. Free T4 was <0.3 ng/dL (0.6-1.6) and free T3 was 1.6pg/mL (2.5-3.9). An echocardiogram revealed a large circumferential pericardial effusion with right atrial and ventricular collapse with tamponade. Treatment with 5 mcg liothyronine, intravenous levothyroxine and stress dose hydrocortisone was begun. A pericardial drain was placed, draining 980mL of sanguineous fluid. After clamping trials, the drain was removed 48 hours later. Labs revealed thyroglobulin <0.1ng/mL (1.6-50), thyroid peroxidase (TPO) antibody 574 IU/mL (<9), thyroglobulin antibody >2500 (<4) and thyroid ultrasound showed a normal sized thyroid gland with heterogenous echogenicity confirming a diagnosis of Hashimoto’s thyroiditis. Serial echocardiograms during the admission and a follow-up two months later showed a stable posterior effusion with no recurrence of the anterior pericardial effusion. Gradually mentation, hemodynamics and electrolyte derangements improved, and he was discharged on oral levothyroxine. TSH values showed sequential improvement to 48U in 15 days and to 11U in 2 months. Myxedema is a manifestation of severe hypothyroidism. The pericardium, a collagen-rich structure, is susceptible to myxedematous infiltration, leading to pericardial effusion. While small pericardial effusions are common with chronic hypothyroidism, a large pericardial effusion with tamponade is a rare life-threatening complication that requires prompt recognition and management. Clinicians must promptly identify myxedema and replace thyroid hormone to prevent progression of pericardial effusion to tamponade, maintaining especially high suspicion in those at risk of poor access to healthcare or inadequate health literacy.

Presentation: 6/3/2024
12337 Nivolumab Induced Secondary Adrenal Insufficiency And Hypothyroidism In A Patient With Graves’ Disease: A Case Report
Authors: Sajid Fatima , Kaur Jasveen , Zatsepina Alina , Khan Muzammil , Resta Christine A
Published: October 2024

Disclosure: F. Sajid: None. J. Kaur: None. A. Zatsepina: None. M. Khan: None. C.A. Resta: None.

Introduction: We present a case of a patient with Graves’ disease who developed concurrent secondary adrenal insufficiency (SAI) and primary hypothyroidism while undergoing treatment with nivolumab for non-small cell lung cancer (NSCLC). This case sheds light on the immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy. Case Presentation: A 63-year-old woman with a history of Graves’ disease and NSCLC undergoing neoadjuvant chemoimmunotherapy was admitted with hyponatremia. She was diagnosed with Graves’ disease a year before and was treated with methimazole (MMI). When she was diagnosed with Graves’ disease, her TSI was 1.64 IU/L (<0.55). Before starting nivolumab, TSH had normalized at 0.5 MCIU/mL on MMI therapy. She started nivolumab 3 months before admission. One month after starting nivolumab, her TSH was <0.01. By the time she was admitted, she had severe hypothyroidism and SAI with sodium 116 mmol/L (135-149), TSH 40.34 mIU/mL (0.39-4.08), free T4 <0.25 ng/dL (0.8-1.8), TSI 21.2 IU/L (0.00-0.55) Total Cortisol 0.4 ug/dL (6.7-27.6), AM Cortisol 0.6 ug/dL, ACTH <1.5 pg/mL (7.2-63.3), LH 75.5 IU/L (7.7-58.5), and FSH 179 IU/L (25.8-134.8). MMI was discontinued due to hypothyroidism. She was started on replacement therapy with levothyroxine and hydrocortisone. Subsequent sodium levels normalized. Discussion: Nivolumab has emerged as a promising immunotherapy for NSCLC. Our patient developed irAEs following nivolumab treatment. Notably, this case represents only the third documented case to our knowledge of both primary hypothyroidism and secondary adrenal insufficiency occurring post-nivolumab treatment. Workup for our patient revealed two irAE’s. She developed primary hypothyroidism and isolated ACTH deficiency with other pituitary function remaining normal. The pattern of thyroid profile over time was consistent with thyroiditis due to ICI therapy. TSI increased, ruling out remission from Graves’ disease. Even after discontinuing methimazole, she remained hypothyroid. Hence, in this case, ICI effectively acted as definitive therapy for her Graves’ disease. Conclusion: This case sheds light on the intricate interplay between nivolumab therapy, pre-existing autoimmune conditions such as Graves’ Disease, and the emergence of irAEs. This case underscores the importance of vigilant monitoring of serum sodium levels, and thyroid and pituitary function tests in patients undergoing immunotherapy.

Presentation: 6/1/2024
9365 Now You See Me: The Case Of The Ectopic Thyroid
Authors: Isabelle Suarez Solangel , Majumdar Sachin K
Published: October 2024

Disclosure: S.I. Suarez: None. S.K. Majumdar: None.

Introduction: Lingual thyroid refers to ectopic thyroid tissue located at the base of the tongue or within the thyroglossal tract secondary to failed descent to its usual site (1). Ninety percent of ectopic thyroid glands are found at the base of the tongue and can occur in 1 in every 100,000 patients (2, 3). Clinical presentations commonly relate to obstruction of the oropharynx, and patients may experience dysphagia or throat fullness/discomfort (1). We present a case of lingual thyroid presenting as dysphagia and progressive hypothyroidism. Case: A 38-year-old woman with a history of HLD and hypothyroidism was referred for evaluation of ectopic thyroid tissue. She presented to her provider for concerns of dysphagia, neck swelling, and excessive hair thinning/loss. She had a recent increase in levothyroxine dose from 112 to 125 mcg after a TSH of 20.4 (0.27 to 4.2 uIU/mL). Repeat tests showed a TSH of 29.4 and a free T4 level of 0.79 (0.8 to 1.7 ng/dL). She denied use of thyrotoxic medications, any radiation or surgeries to head or neck, personal or family history of autoimmune disorders. Thyroid was nonpalpable on exam. A thyroid US 5 years prior showed a 15 x 5 x 5 mm right lobe and 12 x 8 x 5 mm left lobe. CT scan of soft tissue of neck with contrast showed a 14 x 13 x 15 mm hyperintense nodular lesion midline along the anterior glossoepiglottic fold at the foramen cecum, with an 8 x 11 x 8 mm hyperintense nodular lesion at midline abutting the anterior body of the hyoid bone, and no thyroid tissue in the expected thyroid bed, findings consistent with ectopic thyroid tissue along the expected thyroglossal duct. Furthermore, an I-123 scan with SPECT confirmed the ectopic thyroid tissue. What was thought to be thyroid lobes on previous thyroid US was likely paratracheal fat. Levothyroxine was increased to 137 mcg per day with improvement at 2 months (TSH 10.4, Free T4 0.91). Adjusting levothyroxine replacement was the primary intervention, given that elevated TSH may result in hypertrophy of lingual thyroid tissue resulting in dysphagia, particularly if there is no mass or suspicion of cancer on imaging. Conclusion Hypothyroidism presenting with dysphagia in the absence of goiter, previous thyroid surgery, or detectable thyroid tissue should warrant consideration of ectopic thyroid tissue and initial therapy should be directed towards normalizing TSH in conjunction with excluding malignant causes. References: 1. Randolph, G. W., & Kamani D. V. (2023). Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid. UpToDate. Retrieved February 13, 2024, from 2. Patil, Y. S., Rajashekhar R. P. (2015). Lingual Thyroid: A Case Series of Six Lingual Thyroid with Incidence and Different Treatment Modalities. International Journal of Head and Neck Surgery (IJHNS). 10.5005/jp-journals-10001-1234. 3. Kumar, L. K., Kurien, N. M. (2015). Lingual Thyroid. Annals of Maxillofacial Surgery. DOI: 10.4103/2231-0746.161103

Presentation: 6/1/2024
8096 Optimization of Radiation Safety Release Instructions After Iodine-131 Treatment for Differentiated Thyroid Cancers
Authors: Smith A H , Greist T
Published: October 2024

Disclosure: A.H. Smith: None. T. Greist: None.

Introduction: Iodine-131 (I-131) is a common therapy for treatment of differentiated thyroid cancers (DTC); however its radioactivity poses a risk to public health. There is wide inter-facility variation in release instructions to minimize incident exposure to other individuals. Isolation measures to reduce gamma exposure may pose harm to an individual's mental or physical health, especially in new parents or patients who require caregivers. Most studies estimating incident exposure utilize cumulative dosimetry to estimate duration of safety release instructions, but this relies on expert assumptions of the clearance of I-131, which is altered in patients who have had their thyroid removed. Measuring real-time longitudinal gamma exposure would optimize recommendations to balance the radiation safety risks with the risks associated with isolation. Objective: Quantify real-time longitudinal incident gamma radiation exposure to others from patients with DTC status post thyroidectomy treated with I-131. Methods: Patients were asked to measure exposure rates at a distance of one meter three times a day for fourteen days, using a portable ion chamber at their homes. Exposure rates over time were used to form an exponential decay model and to estimate the time after which cumulative exposure is below a reasonably low threshold. Results: 32 patients were included in the study. The average effective half-life was 15.8 hours. Exposure readings over time were best fit with an exponential decay model using one decay rate, rather than a model that uses separate extrathyroidal and thyroidal decay rates. Among patients administered less than 114 mCi, cumulative gamma exposure is less than 100 mR after 24 hours of isolation. Between 114 and 163 mCi, cumulative gamma exposure is less than 100 mR after 48 hours of isolation. Conclusion: Cumulative gamma radiation exposure at one meter was found to be low enough to consider re-evaluating isolation protocols and safety release instructions for long-term distancing in patients status post thyroidectomy treated with I-131.

Presentation: 6/1/2024
7824 Orbital Lymphoma masquerading as Thyroid Eye Disease
Authors: Ganawa S , Joseph S , Anshuman C , Luciane L D , Sajid A , Anne C , Dhage S
Published: October 2024

Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report.

Presentation: 6/3/2024
12570 Papillary Thyroid Carcinoma Found In A Malignant Struma Ovarii
Authors: Arunachalam Amar , Iyer Priyanka
Published: October 2024

Disclosure: A. Arunachalam: None. P. Iyer: None.

Struma ovarii is a monodermal teratoma primarily composed of mature thyroid tissue.[1] Depending on histologic findings, struma ovarii can be classified as benign or malignant. Among malignant struma ovarii, papillary type is the most common.2Women with struma ovarii can present with pelvic pain and less frequently ascites. Clinical features of hyperthyroidism can occur.[3] We present a 66 year old female of Chinese descent status post hysterectomy and left oophorectomy in 9/2021, prior right oophorectomy in 1985 with pathology consistent with a teratoma as per patient, who presented after being lost to follow-up. Her pathology of her left ovary showed diffuse thyroid tissue with focal areas consistent with papillary thyroid carcinoma. Her initial diagnosis was found in the setting of abdominal pain. She had a transvaginal ultrasound with a 16.9 x 13.1 x 8.9 cm cystic mass. Patient was lost to follow-up .She denied any symptoms of hyper or hypothyroidism. On biochemical evaluation, TSH 1.45 mcunit/ml, FT4 0.91 ng/dl, Thyroblobulin 4.21 ng/ml, Thyroglobulin Antibody undetectable. Thyroid ultrasound was significant for a 0.5 left thyroid isthmus nodule which was benign after FNA biopsy. CT chest, abdomen, pelvis without any evidence of distant metastasis. Decision was made to monitor with repeat thyroid ultrasound and biochemical evaluation in one year because no evidence of concerning lesions in the thyroid for PTC or evidence of distant metastasis. The frequency of struma ovarii among ovarian teratomas is less than 3% which makes this case rare. The most common sites of metastasis of a malignant struma ovarii include abdominal cavity, liver, lungs, brain and bone.[4] In certain cases, thyroid tissue found in struma ovarii can secrete T3 and T4.[5] Our patient had no abnormalities on imaging of the thyroid with normal thyroid function tests. We recommended monitoring of the thyroid gland to assess for malignant transformation. Mainstay of treatment is hysterectomy and bilateral salpingo-oophorectomy for postmenopausal women and unilateral salpingo-oophorectomy or cystectomy for women in the reproductive age. For metastatic struma ovarii, thyroidectomy and adjuvant treatment with radioactive iodine can be considered.[6]The risk of recurrence is lower based on size, location and histopathological features of the tumor. One study proprosed following unilateral salipingo-oophorectomy in patients with low risk of recurrence, TSH suppression at 0.1 to 0.5 mIU/L..[7] Considering the findings for our patient who presents years after hysterectomy and left oophorectomy in 2021 with normal thyroid gland on ultrasound and appropriate thyroid function tests, we recommended no additional complementary treatment with monitoring of labs and imaging in one year. This patient currently shows no evidence of metastatic disease or high risk of recurrence but long term monitoring remains a mainstay of the management.

Presentation: 6/2/2024
8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent
Authors: Aponte Velez Alexandra , Mangual Garcia Michelle Marie
Published: October 2024

Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None.

Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children.

Presentation: 6/2/2024
12231 PAPP-A As A Potential Target In Thyroid Eye Disease
Authors: Conover Cheryl A , Bale Laurie K , Hamadi Dana , Stan Marius
Published: October 2024

Disclosure: C.A. Conover: None. L.K. Bale: None. D. Hamadi: None. M. Stan: ; Tourmaline, Genentech, Third Rock Ventures, ArgenX, Septerna, OrthoDi. ; Horizon, Immunovant, Lassen, Sling.

Background: Proptosis in Thyroid Eye Disease (TED) can result in facial disfigurement and visual dysfunction. Studies revealed an interaction between thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-I receptor (IGF-IR) that is essential in promoting TED pathogenesis. Treatment with Insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects. PAPP-A is metalloprotease that can increase pericellular IGF bioavailability through specific cleavage of inhibitory IGF binding proteins, in particular IGFBP-4. We propose that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitory antibodies attenuates IGF-IR signaling in TED with fewer side effects. Methods: Informed consent was obtained from TED patients undergoing surgery in Mayo Clinic operating suites in Rochester, MN. Retro-orbital tissue was collected from 19 TED patients and 2 control subjects for fibroblast isolation and culture and was performed in a sterile tissue culture facility. TED and control fibroblasts were treated with pro-inflammatory cytokines, and flow separation of CD34- and CD34+ orbital fibroblasts was done, the latter representing infiltrating fibrocytes into the orbit in TED. Main outcome measured were PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status and associated PAPP-A and IGF-IR expression. Results: Primary cultured cells showed that PAPP-A is expressed in orbital fibroblasts from TED patients but not in control subject fibroblasts and were markedly increased by pro-inflammatory cytokines stimulation. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A’s proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from TED patients. CD34+ orbital fibroblasts represent 80% of cells in culture from TED patients, and approximately 70% of these cells were accountable for PAPP-A and IGF-IR expression. Conclusion: These results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis.

Presentation: 6/2/2024
7502 Patient Suffering from Laryngeal Edema in the Setting of Hypothyroidism
Authors: Seidenberg J , Prabhu P , Ansari M
Published: October 2024

Disclosure: J. Seidenberg: None. P. Prabhu: None. M. Ansari: None.

Hypothyroidism can present with many different symptoms including dry skin, weight gain, and lethargy, with severe presentations being altered mental status, bradycardia, hypotension, and myxedema coma. Rarely, hypothyroidism can present with isolated laryngeal myxedema with few cases being noted. Myxedema is defined as swelling and thickening of the skin, and airway compromise secondary to myxedema is a potentially life-threatening presentation. In this case report, the patient is a 41-year-old female with PMH of hypothyroidism, homelessness, alcohol use, and morbid obesity who presented to the ED for nausea, vomiting, abdominal pain, and throat swelling. The swelling had been present for several months and acutely worsened with voice changes on the day prior to presentation. She noted poor compliance with Levothyroxine for several months. On exam, she was found to have hoarseness, difficulty swallowing, drooling, and tenderness in anterior neck. She was admitted to ICU for airway protection observation. On her blood work, she was found to have an undetectable T4, TSH > 100 (0.45-4.5 UI/mL), and CT neck and abdomen negative for alternative causes of swelling. Laryngoscopy showing normal larynx. The patient had a Popoveniuc myxedema score of 35 with no electrolyte abnormalities. She was given racemic epinephrine with minimal effect and IV Levothyroxine 200 mcg. After 3 days of IV Levothyroxine 84 mcg and high dose Decadron, she had improvement in throat swelling and breathing. She was later discharged with Synthroid and a 5-day Decadron course. Myxedema is a potentially life-threatening presentation of hypothyroidism. Patients who have untreated hypothyroidism can have chronic myxedema with acute worsening of symptoms that put them at risk of airway compromise, even with an initially low diagnostic score. Patients should be screened on admission when they present with unknown cause of airway compromise for hypothyroidism and treated with empiric high dose levothyroxine IV followed by daily IV levothyroxine until symptom improvement and daily TSH and T3/T4 improvement. Treatment with both high dose steroids and racemic epinephrine should be initiated before diagnosis due to feasible alternative or additional causes of airway obstruction.

Presentation: 6/3/2024
6417 Phase 1 Healthy Volunteer Data Supports Phase 2 Study of LASN01 in Thyroid Eye Disease (TED) - Actively Enrolling
Authors: Takamura T , Dimaano C , Jun T , Swaney J , King D , Fardis M
Published: October 2024

Disclosure: T. Takamura: Employee; Self; Lassen Therapeutics. C. Dimaano: Employee; Self; Lassen Therapeutics. T. Jun: Employee; Self; Lassen Therapeutics. J. Swaney: Employee; Self; Lassen Therapeutics. D. King: Employee; Self; Lassen Therapeutics. M. Fardis: Employee; Self; Lassen Therapeutics.

Interleukin-11 (IL-11) is a key effector of fibro-inflammatory disease processes in multiple organs. IL-11 is elevated in both orbital fibroblasts and serum of thyroid eye disease (TED) patients and stimulates hyaluronic acid (HA) production from TED patient-derived orbital fibroblasts (OF). LASN01 inhibits a number of signals which are known to be associated with TED including hyaluronic acid elevation and procollagen. In patient-derived orbital fibroblasts IGF-1 and IL-11 induced HA release, as well as TGFβ stimulated procollagen production were inhibited by LASN01. LASN01 is a highly specific, fully human monoclonal antibody that binds to IL-11R with high affinity and inhibits IL-11 signaling. A randomized, placebo controlled (3:1) Phase 1 trial was conducted in healthy volunteers to assess safety, pharmacokinetics (PK) and target engagement with single and multiple ascending doses (SAD and MAD) of intravenous LASN01 in healthy volunteers. Fifty-eight volunteers were dosed in 5 single dose cohorts (25-1200 mg) and 2 multiple dose cohorts (600-1200 mg). Sixty-one treatment emergent adverse events (TEAEs) were reported by 35 subjects, which included no serious or severe adverse events. The most common AEs were headaches (13) and light headedness/dizziness (5). Data from healthy volunteers in the Phase 1 SAD/MAD Phase 1 trial show favorable safety and predictable and linear PK and dose-dependent target engagement. The half-life in the 1200 mg cohort was approximately 11 days. This data supports monthly dosing in the Phase 2 study. A proof-of-concept, global, randomized, double-masked Phase 2 trial is actively enrolling. Patients with diagnosed Graves’ disease and active, moderate to severe thyroid eye disease (TED), within 12 months of start of symptoms and with a Clinical Activity Score (CAS) ≥ 3, will be randomized to 3 treatment arms (high and low dose LASN01 and placebo) and will be treated Q4 weeks for 12 weeks with a follow-up period of 12 weeks. The primary endpoint is the percentage of patients with response in proptosis (≥2mm) on active treatments vs. placebo. Secondary endpoints include degree of proptosis reduction, assessment of diplopia, lid retraction, and extraocular movements. Orbital MRIs will be collected to assess proptosis and extraocular muscles. LASN01 is the only agent being developed for TED which offers the possibility of addressing the fibro-inflammatory pathology of TED.

Presentation: 6/3/2024