bluuebunny/crossref_metadata_2025_split huggingface dataset:
9381 Hypothyroidism Unmasked: A Rare Culprit Of Cardiac Tamponade
Authors: Shaykh Natalie , Agrawal Avni , Patel Niyati , Patel Falguni , Tripathi Vanshika , Rai Oshin , Reddy Pramod 
Published: October 2024

Abstract
Disclosure: N. Shaykh: None. A. Agrawal: None. N. Patel: None. F. Patel: None. V. Tripathi: None. O. Rai: None. P. Reddy: None.
While pericardial disease may manifest in severe cases of hypothyroidism, occurrences of cardiac tamponade are uncommon. A 37-year-old female 19 weeks into her pregnancy with past medical history significant for Graves’ disease status post RAIU at age 15 and untreated hypothyroidism due to medication non-compliance required admission to the hospital for medical management of miscarriage. Labs were notable for TSH 61.6 MIU/L (0.270- 4.200 MIU/L) and thyroxine level 0.1 ng/dL (0.80 - 1.70 ng/dL) with a thyroid peroxidase antibody within normal range. Thyroid ultrasound was unremarkable. Clinically, the patient did not appear to be in myxedema coma and remained hemodynamically stable. Patient was started on levothyroxine 150 mcg daily with specific intake instructions as to not impede absorption. Her course was further complicated by new-onset chest pain with unremarkable ischemic workup. Transthoracic echocardiogram, however, showed a moderate pericardial effusion with right ventricular collapse suggestive of tamponade physiology likely related to her severe hypothyroid state. Patient was started on intravenous fluids and transferred to the cardiac ICU for monitoring. She underwent pericardiocentesis with 500 mL of serous fluid extraction. Fluid studies were not suggestive of infection or a rheumatologic cause. The decision was later made for a pericardial window due to fluid re-accumulation with drain in place for three days. Repeat thyroxine levels uptrended to 0.7 ng/dL, and serial echocardiograms showed pericardial effusion reduced in size with no hemodynamic compromise present. Patient was cleared for discharge with plans for repeat echocardiogram in two months and close outpatient follow-up. The presence of pericardial effusion in hypothyroidism seems to correlate with the severity of the condition. While research indicates a low occurrence rate of pericardial effusions in hypothyroidism, ranging from 3-6%, clinicians should maintain a heightened awareness based on the comprehensive clinical assessment, as cardiac tamponade poses a significant risk regardless of the size of the effusion. Management typically involves urgent pericardiocentesis and administration of thyroxine hormone replacement therapy. Patil VC, Patil HV, Agrawal V, Patil S. Cardiac tamponade in a patient with primary hypothyroidism. Indian J Endocrinol Metab. 2011 Jul;15(Suppl 2):S144-6. doi: 10.4103/2230-8210.83358. PMID: 21966654; PMCID: PMC3169864.
Presentation: 6/1/2024
7929 Immediate Read Telecytopathology Improves Diagnostic Rates Without Altering Indeterminate Rates for Thyroid Nodule Biopsy
Authors: Lanik Wyatt E , Fingeret Abbey , Rose Blake , Kotwal Anupam , Yuil-Valdes Ana , Patel Anery , Goldner Whitney 
Published: October 2024

Abstract
Disclosure: W.E. Lanik: None. A. Fingeret: None. B. Rose: None. A. Kotwal: None. A. Yuil-Valdes: None. A. Patel: None. W.S. Goldner: None.
Introduction: Ultrasound-guided fine-needle aspiration (FNA) is the preferred biopsy method for evaluation of thyroid nodules. Non-diagnostic and indeterminate biopsies impact patient care and healthcare cost. Rapid on-site evaluation (ROSE) seeks to alleviate this burden and involves evaluation of thyroid material at the time of biopsy. ROSE improves FNA adequacy rates. In our retrospective study, we sought to determine if the adaption of ROSE + telecytopathology (ROSE/T) increased diagnostic biopsies and reduced rates of Bethesda III and IV. Methods: A retrospective analysis of 3,310 ultrasound-guided thyroid FNAs including no ROSE, ROSE, or ROSE/T from 2018 to 2022 was performed. When utilizing ROSE, thyroid biopsy specimens were assessed using conventional microscopy and interpreted by a cytotechnologist while ROSE/T utilized a synchronous audiovisual communication with a remote cytopathologist. Biopsy results were reported using the Bethesda classification system for reporting thyroid cytology. Non-diagnostic vs diagnostic rates and indeterminate rates (Bethesda III and IV) vs Bethesda II, V, and VI were analyzed. Results: Of the 3,310 cases, 275 (8.31%) were Bethesda I. There were 2,242 (67.73%) Bethesda II, 394 (11.90%) Bethesda III, 208 (6.28%) Bethesda IV, 80 (2.42%) Bethesda V, and 111 (3.35%) Bethesda VI. Distribution of cases was 314 (9.49%) without ROSE, 1,570 (47.43%) ROSE, and 1,426 (43.08%) ROSE/T. Non-diagnostic rates without ROSE were significantly higher at 43 (13.69%) vs ROSE and ROSE/T (p=0.0008), while no difference in diagnostic rates was observed between ROSE 129 (8.22%) and ROSE/T 103 (7.22%) (p=0.012). Indeterminate rates were 49 (18.08%) without ROSE, 262 (18.18%) with ROSE, and 291 (22.0%) with ROSE/T. Overall diagnostic FNAs significantly increased over time (p=0.0063), however there was no trend detected in indeterminate biopsies over time (p=0.1176). Discussion: Both types of ROSE allow for immediate feedback to the practitioner leading to further passes and increased diagnostic rates. The trend of diagnostic biopsies represents the increasing adoption of ROSE/T over time. Indeterminate rates were higher with ROSE/T, despite no increase in the indeterminate trend over time. These findings could represent the influence of academic dialogue between physicians at the time of biopsy promoting a personalized approach to each biopsy to improve diagnostic accuracy.
Presentation: 6/1/2024
6580 Inhibition of IGF-1 Receptor Signaling and Ocular Fibroblast Cell Growth by VRDN-001 vs Teprotumumab
Authors: Newell Rachel , Nguyen Tricia , Bedian Vahe 
Published: October 2024

Abstract
Disclosure: R. Newell: Employee; Self; Viridian Therapeutics. Stock Owner; Self; Viridian Therapeutics. T. Nguyen: Employee; Self; Viridian Therapeutics. Stock Owner; Self; Viridian Therapeutics. V. Bedian: Employee; Self; Viridian Therapeutics. Stock Owner; Self; Viridian Therapeutics.
Introduction: Clinical data have shown that IGF-1 receptor (IGF-1R) antagonism reduces the inflammation and proptosis that occur in thyroid eye disease (TED), while preclinical data have shown that VRDN-001 provides more complete inhibition of IGF-1R autophosphorylation and downstream phosphorylation of AKT than teprotumumab. Here we assess the extent to which these antibodies inhibit another distal end point of IGF-1R signaling—phosphorylation of ERK, part of the mitogen-activated protein kinase (MAPK) pathway, and ocular fibroblast growth. Methods: Antagonist characteristics were determined by assessing dose-responses of 1) inhibition of biotinylated IGF-1 binding to IGF-1R-expressing FreeStyle™ 293-F cells using flow cytometry, 2) inhibition of IGF-1-mediated ERK phosphorylation in primary human ocular choroid fibroblasts (HOCF), and 3) inhibition of IGF-1-mediated cell growth measured by a) ATP released from metabolically active cells and b) imaging data in HOCF cells. Results: Over the dose ranges tested, VRDN-001 inhibited both the binding of biotinylated IGF-1 to cells and IGF-1-mediated MAPK activation to a greater extent than teprotumumab. At concentrations ≥30 nM, VRDN-001 provided near-complete inhibition of ERK phosphorylation vs partial inhibition by teprotumumab. Further, VRDN-001 inhibited IGF-1-mediated cell growth, a downstream functional effect of the MAPK pathway, more fully than teprotumumab. Conclusion: Prior in vitro research showed that compared with teprotumumab, VRDN-001 provided more complete inhibition of IGF-1R autophosphorylation and AKT phosphorylation (PI3K signaling pathway). The current research extends these findings by showing that VRDN-001 also provides more complete inhibition of IGF-1-mediated ERK phosphorylation (MAPK signaling pathway activation) and fibroblast cell growth. While teprotumumab and VRDN-001 share a similar mechanism of action, their binding properties are distinct, which may explain the differences in ligand blocking, antagonism of signaling, and inhibition of functional activity. Ongoing Phase 3 clinical trials will assess the clinical efficacy and safety of VRDN-001 in patients with active and chronic TED.
Presentation: 6/1/2024
6404 Iodide Metabolism Anomalies in Patients with Thyroid Cancer; A Case Series
Authors: Uwaifo G I 
Published: October 2024

Abstract
Disclosure: G.I. Uwaifo: None.
Thyroid cancer is often treatable and often involves iodine ablation therapy. Iodine based imaging and/or therapy can be complicated in patients with abnormal iodide metabolism. We present two patients with thyroid cancer and disparate abnormal iodide metabolism. Case 1 is a 35 yr old Caucasian lady with papillary thyroid cancer (PTC) stage 1 with no metastases. After total thyroidectomy and prior to I-131 remnant ablation she had a contrast Chest CT for shortness of breath. A month after serum iodine was elevated (545 Ug/L; 40—92). 24 hr urine iodine levels was also elevated; (2,300Ug/day; 150-500). She denied dietary intake of iodine rich foods. Ablation was postponed and she commenced a strict “zero” iodine diet. Despite this and despite having no further contrast imaging serum and urinary iodine remain elevated for nearly 3 yrs. Further history indicated episodes of sensitivity to several medications and Cytochrome P450 genetic profiling revealed two polymorphisms of CYP P450 2C19 and 2D6 associated with slow drug metabolizer phenotype. 34 months after her Chest CT with serum iodine of 127Ug/L and 24 hr Urine iodine of 652 she had radio iodine-ablation (RIA) with 130Mci of I-131. She had post treatment dysgeusia and parotitis. She remains on a low iodine diet and is presumably cured. Case 2 is a 66 yr old Caucasian man referred for second opinion regarding therapeutic options for known metastatic PTC with metastases to thoracic spine and lungs. He was diagnosed with follicular variant PTC 7 yrs ago. He had total thyroidectomy and repeated RIAs with a total accumulated dose of ∼ 850Mci and last RIA 3 yrs ago. His latest two whole body I-131 scans were -ve despite elevated thyroglobulins and metastatic disease. He was unable to tolerate sorefanib. He is on thyroid hormone repletion and quarterly denosumab. Contrast PET-CT scan a week prior showed extensive metastatic disease and thyroglobulins in the 300—650 ng/ml range. Work up for repeat whole body I-131 scan revealed curiously that serum iodine was 46 Ug/L (40-92) despite his recent contrast study and this was confirmed on two repeats. 24 hr urine iodine was reduced; 87 ug/day (150-500) and he had a typical diet with no excess intake of goitrogens. Based on history of often needing significantly higher doses of medications like opioids, anesthetics and sedatives cytochrome P450 genetic profile obtained showed two polymorphisms (of CYP P450 2C-19 and CVPs 3A4 +3A5) associated with fast metabolizer phenotype. Given his unusually rapid iodine clearance the utility of any further iodine based imaging and/or therapy was deemed dubious. His current management continues without change. We present two patients with extremes of iodine metabolic processing that had clinical management significance. Careful evaluation of ambient iodine status of patients is an important part of the preparation of thyroid cancer patients for iodine based imaging and/or therapy.
Presentation: 6/1/2024
8454 Iron deficiency as a cause of euthyroid syndrome
Authors: Samburskaya Olga V , Kalinchenko Svetlana , Vorslov Leonid 
Published: October 2024

Abstract
Disclosure: O.V. Samburskaya: None. S. Kalinchenko: None. L. Vorslov: None.
Annotation: The prevalence of euthyroid pathology syndrome is increasing, and the cause of its occurrence remains unknown, despite the decrease in the quality of life of these patients, there is no treatment for this pathology. One of the reasons may be iron deficiency, which not only reduces the activity of thyroid enzymes, but also disrupts the feedback between a decrease in triiodothyronine and the level of thyroid-stimulating hormone (TSH). Materials and methods: There are 6 patients under observation, aged from 25 to 55 years, average age 38.4±12.67 years, gender distribution: 4 women 67% and 2 men 33%, who are undergoing treatment to compensate for iron deficiency and simultaneously control thyroid function. The analysis of iron deficiency is performed according to blood test parameters: total blood count, total serum iron binding capacity, transferrin, ferritin, serum iron. The function of the thyroid gland is determined by blood test parameters: T4 free, T3 free, TSH.The received data. According to the results of the data obtained, latent iron deficiency was found in all 6 patients. All patients have a decrease in thyroid hormone levels: T3 free 3.87±0.45 pmol/l (reference range 3.69-8.46 pmol/L) and T4 free 14.17±1.23 pmol/L (reference range 12.3-22.8 pmol/L) is closer to the lower limit of normal, but TSH is also closer to the lower limit of the norm is 1.46±0.33 µm/ml (reference range 0.70-5.9 µm/ml). Discussion: The existing iron deficiency leads to the development of chronic hypoxia, which leads to a violation of the functioning of many endocrine glands, including a violation of the work of thyroid enzymes: thyroid peroxidase and deiodinases, with a decrease in the synthesis of thyroid hormones (T4 and T3), and according to the feedback principle, an decrease in the level of thyroxine and triiodothyronine is expected raising the level of TSH. However, with chronic hypoxia, iron deficiency, hypoxic dysfunction develops not only of the peripheral endocrine glands, but also hypoxic hypothalamic-pituitary dysfunction, which leads to an inadequate response of the pituitary gland, i.e. the absence of an increase in TSH in response to a decrease in thyroid hormones. Conclusion: All patients with euthyroid syndrome need to evaluate the biochemical parameters of the body's iron supply, and the elimination of deficiency of which may be the necessary treatment for patients with euthyroid pathology.
Presentation: 6/2/2024
7982 Is there a Connection between Alpha Thalassemia and Thyroid Disorders
Authors: Akhter Wajeeha , Taqi Vian , Gilden Janice L 
Published: October 2024

Abstract
Disclosure: W. Akhter: None. V. Taqi: None. J.L. Gilden: None.
IntroductionA number of case reports suggest an association between thalassemia and autoimmune diseases through specific mutations and molecular pathways. An example is thyroid disease in thalassemia patients. Due to factors such as age, ethnicity and treatment protocol differences, the frequency of hypothyroidism in thalassemia patients is a wide range of 4 to 29% based on free T4 and TSH levels. Subclinical hypothyroidism is more common in thalassemia patients as compared to overt hypothyroidism. 90% of morbidity and mortality in B-Thalassemia patients is attributed to iron overload, anemia and hypoxia. Understanding this possible mechanism helps guide treatment and monitoring. Case PresentationWe present the case of a 26-year-old African American with Haitian ethnicity female, who upon routine testing was found to have a very high TSH level of 79.084 uIU/ml (nl=0.550-4.780 uIU/ml) for which 125 mcg of Levothyroxine was started, and then she was referred to the endocrine clinic. Past history was notable for sickle cell trait and alpha thalassemia trait. Patient stated that at age 12, she developed fatigue and low energy and was found to have hyperthyroidism which was treated with RAI ablation. After that, no follow up or lab tests were done until recently. The patient denied symptoms of hypo or hyperthyroidism or enlargement of the thyroid gland. She denied any family history of thyroid disorders. After presenting to the endocrine clinic a few days later, she was diagnosed with postprocedural hypothyroidism and the same dose of levothyroxine was continued. Physical exam was unremarkable and no thyromegaly was appreciated on exam. Labs were notable for decreased Hemoglobin of 11.4 g/dL (nl=12-16 g/dL) and CMP was unremarkable except low glucose of 65 mg/dL (nl=70-99 mg/dL). The patient’s most recent labs after 8 weeks of taking Levothyroxine were notable for TSH of 14.65 uIU/ml (nl=0.550-4.780 uIU/ml) and free T4 of 1 ng/dL (nl= 0.89-1.76 ng/dL) and the patient admitted to having still no thyroid symptoms and a little more energy. ConclusionEndocrinopathies are common complications of thalassemia with hypothyroidism being the second most common endocrine disorder in thalassemia patients after hypogonadism, reported in 5.6-17% of patients. In thalassemia patients, endocrine disorders have to be managed as early as possible. Therefore, it is recommended that an endocrine evaluation be carried out in thalassemia patients at a young age.Monitoring for glucose homeostasis, hypothyroidism and hypoparathyroidism is also warranted. Physicians caring for thalassemia patients should perform routine screening for and treat thyroid dysfunction appropriately. Reference: De Sanctis V, Soliman AT, Canatan, et al.. Thyroid Disorders in Homozygous β-Thalassemia: Mediterr J Hematol Infect Dis. 2019 May 1;11(1):e2019029. doi: 10.4084/MJHID.2019.029. PMID: 31205633; PMCID: PMC6548211.
Presentation: 6/2/2024
12387 Late New-onset Graves' Orbitopathy: 14 Years Post-radioactive Iodine Treatment Of Graves' Disease: Case Report
Authors: Altaleb F F , Alaybaa K , Aljohani N 
Published: October 2024

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

Abstract
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&gt;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&gt;A), which was previously reported as a variant with unknown significance. Screening for hyperparathyroidism and pheochromocytoma was normal. Postoperative calcitonin and CEA were &lt;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&gt;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