bluuebunny/crossref_metadata_2025 huggingface dataset:
7450 Geographic Hotspots Of Adrenocortical Carcinoma (ACC) In Colorado
Authors: Holmstoen Tessa B , Volino Lucy K , Molina Kuna Elizabeth , Banerjee Tapahsama , Fishbein Lauren , Kiseljak-Vassiliades Katja , Wierman Margaret E
Published: October 2024

Disclosure: T.B. Holmstoen: None. L.K. Volino: None. T. Banerjee: None. L. Fishbein: None. K. Kiseljak-Vassiliades: None. M.E. Wierman: None.

Background: Adrenocortical carcinoma (ACC) is an under-investigated endocrine malignancy, with a reported annual incidence in the United States of 0.5-2 cases per million. The genetic profiles of ACC patients exhibit great heterogeneity, and 40% of cases have an unknown driver. We have observed an increase of ACC cases originating from western Colorado – a place of lower population, greater elevation, and focus on farming as well as oil and mining-related activities. Given this observation, we hypothesized there may be environmental factors associated with higher ACC incidence in western CO. Methods: We employed a population-based retrospective cohort study to analyze the characteristics of consecutive patients with ACC from Colorado who were seen in our multidisciplinary Adrenal Tumor Program between 2012 and 2023. Data collection included patient’s sex, age, date of diagnosis, and ZIP code of residence. Colorado population data were collected from the 2020 CO Census records. To classify location as western or eastern CO, patient ZIP codes were grouped into their appropriate counties, 21 of which are defined as western CO by the state demography office. The remaining 43 counties were considered to be eastern CO. ZIP code data were also collected from consecutive patients with pheochromocytoma or paraganglioma (PPGL) from Colorado, and these cases were classified as western or eastern CO using the same methods as described above. Chi-square tests were performed for the statistical comparison of population proportions. Results: Between 2012 and 2023, there were 62 incident cases of ACC in the state of Colorado. Given that the state population is 5.7 million, this equates to an average annual incidence of about 0.81 cases per million. Out of the 62 Colorado cases, 38 (61.2%) were female and 24 (38.7%) were male. The average age of diagnosis was 48.9 years. Of interest, the average annual incidence of ACC was increased at 1.44 per million in western CO and only 0.76 per million in eastern CO (p=0.024). The same analysis for 163 PPGL cases yielded no such difference, with an annual incidence of 3.2 cases per million in western CO, and 3.57 cases per million in eastern CO (p=0.7884). Conclusion: The overall clinical demographics and annual incidence of ACC in our Colorado cohort are similar to reported literature. However, the incidence of ACC in western CO is about twice as high as in eastern CO. Since this geographic dichotomy is not also observed in PPGL cases, these data suggest that environmental or other factors may play a role in ACC development. These data warrant further investigation of risk factors that predispose to ACC.

Presentation: 6/3/2024
8771 Evolving Landscape of Thyroid Cancer Attributable to High Body Mass Index in 38 OECD Countries (1990-2019): A Comprehensive Global Assessment
Authors: Adedara V , Chinthapalli M , Parisapogu A , Potluri G , Markandu K , Maddineni K , Desai H
Published: October 2024

Disclosure: V. Adedara: None. M. Chinthapalli: None. A. Parisapogu: None. G. Potluri: None. K. Markandu: None. K. Maddineni: None. H. Desai: None.

Introduction: Thyroid cancer (TC) is an increasingly pressing health issue worldwide, particularly within the Organisation for Economic Co-operation and Development (OECD) countries, which account for 36.57% of all global TC cases. This study focuses on the impact of high Body Mass Index (h-BMI), paralleling rising obesity rates, on the burden of TC across 38 OECD countries. Method: Employing the Global Burden of Disease framework, we analyzed the trends in deaths, Disability Adjusted Life Years (DALYs), and Years Lived with Disabilities (YLDs) attributable to TC attributable to h-BMI, considering variables such as age, sex, year, and location over the past three decades. Results: Our findings show a significant increase in the total number of TC deaths attributable to h-BMI, rising from 873 (95%UI: 422-1471) in 1990 to 1646 (95%UI: 819-2703) in 2019. Similarly, DALYs escalated from 22041 (95%UI: 10576-37075) in 1990 to 39485 (95%UI: 19952-63534) in 2019, with YLDs increasing from 2360 (95%UI: 1082-4179) to 6170 (95%UI: 3036-10416). The age-standardized rate (ASR) showed an annual percentage change (APC) in the death rate of 5% (95%UI: -0.07-20%), and a 10% increase (95%UI: 2-10) in DALYs rate over three decades. The United States reported the highest number of deaths at 449 (95%UI: 233-703) in 2019. Regarding ASR, Iceland had the highest death rate of 0.16 per 100,000, followed by Mexico (0.13), Estonia (0.11), and Latvia (0.11). Males exhibited a higher APC in deaths (131% vs. 60%) and DALYs (112% vs. 52%) compared to females over the last three decades. Additionally, an increase in deaths was observed with advancing age, with the highest DALYs noted in the 75-79 year age group. Conclusion: To effectively address the rising thyroid cancer rates linked to high BMI, a unified approach is essential: public health policies must focus on obesity prevention, clinicians should integrate BMI management in thyroid cancer care, collaboration between policymakers and healthcare providers needs strengthening, and public awareness about the risks of high BMI must be increased to promote early screening and lifestyle changes.

Presentation: 6/3/2024
8742 Exploring the Clinical Landscape of Papillary Thyroid Microcarcinoma with Lymph Node Metastasis: A Single-Institution Case Series and Implications for Treatment Decisions
Authors: Manas F N U , Nakdali Rama , Almajali Dina Aljbour , Bhan Arti , Simon Rebecca
Published: October 2024

Disclosure: F. Manas: None. R. Nakdali: None. D. Aljbour Almajali: None. A. Bhan: None. R. Simon: None.

Introduction: Papillary thyroid microcarcinomas (PTMC) refer to papillary thyroid carcinomas with primary tumor size ≤ 1cm. Characterized by their indolent nature, PTMCs boast a mortality rate of less than 1%. Loco-regional spread occurs in approximately 2-6% of cases, while distant metastasis is observed in about 1-2%. Notably, the rate of recurrence after lymph node (LN) metastasis can reach up to 20%. The optimal management of PTMC remains controversial with some studies suggesting no discernible difference in clinical outcomes between patients undergoing active surveillance and those opting for surgical removal. There is limited research on thyroid cancer oncogenes that can predict the progression of PTMC outside of the thyroid gland. We report the clinical outcomes of a series of patients with PTMC who presented with LN metastasis at our institution.Case Series: We describe five patients diagnosed with papillary thyroid microcarcinoma with LN metastasis. All patients presented with a neck mass and evaluation by fine needle aspiration (FNA), showed papillary thyroid cancer. The tumor sizes ranged from 0.15 cm to 1 cm and all cases had extensive LN involvement, with sizes ranging from 0.7 to 4.5 cm. All patients received adjuvant RAI according to ATA guidelines. Molecular testing was not available for any of these patients.Discussion: Our case series offers valuable insight into the clinical outcomes of individuals with PTMC who underwent total thyroidectomy with LN dissection. We postulate that there are two separate groups of patients with PTMC. One group with indolent disease, which lends itself to careful follow-up, even without surgery, and the other group with aggressive disease at presentation. The challenge lies in the correct classification of the patient at baseline so that therapy is tailored to the type of cancer. We need better predictors of disease severity so that patients can be risk-stratified appropriately. The absence of clear guidelines regarding the optimal extent of surgery for PTMC adds complexity to treatment decisions. Nevertheless, our case series sheds light on the infrequent occurrence of PTMC with LN metastasis. It is noteworthy that despite the absence of a mutational profile for these patients, consistent with prior small-scale studies, no genetic alterations have been identified as reliable predictors of LN metastasis in PTMC. Our findings underscore the imperative for further investigative studies to enhance our ability to predict more aggressive cases of PTMC. By addressing the gap in knowledge, future research endeavors may contribute to the refinement of treatment strategies for individuals with PTMC.

Presentation: 6/1/2024
8713 Fluctuating Graves' Disease: A Rare Complication of Alemtuzumab
Authors: Tran Brandon , Woodfield David A , Poudyal Dinesh , Majety Priyanka
Published: October 2024

Disclosure: B. Tran: None. D.A. Woodfield: None. D. Poudyal: None. P. Majety: None.

Background: Alemtuzumab is a monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis. Its principal adverse effect is the development of autoimmunity. Thyroid autoimmunity is most common occurring in about 17% to 34%, with Graves’ disease (GD) comprising 60% to 70% of these cases. Alternating hypothyroidism and hyperthyroidism occur rarely in GD. Thyrotropin Receptor Binding Antibodies (TRAb) are functionally heterogeneous and can coexist in the same individual. They can be either stimulating, blocking, or neutral. Spontaneous switch between hypo- and hyperthyroidism, which can be bidirectional, occurs rarely and is thought to be due to a shift in the ratio between blocking and stimulating TRAbs. Clinical Case: A 42-year-old black woman with multiple sclerosis was treated with Alemtuzumab between 2019-2020, before which she was noted to have normal thyroid function tests. In 2022, she presented with hypothyroid symptoms and anterior neck pain with a Thyroid Stimulating Hormone (TSH) of 34.6 (0.35-4.94 uIU/mL) and elevated Thyroid-peroxidase (TPO) antibodies of 76 (0-34 IU/mL). She was started on levothyroxine 175 mcg. Over the next six months, her TSH gradually decreased and eventually became undetectable. Although the levothyroxine dose was gradually tapered, followed by complete cessation, she remained hyperthyroid, both clinically and biochemically. She had symptoms of palpitations, tremors, diaphoresis and a 20 lb weight loss. Additional workup was notable for elevated Thyroid-stimulating Immunoglobulin (TSI) at 19.3 (0-0.55 IU/L) and TRAb at 20 (0-1.75 IU/L). A radioactive iodine uptake scan showed increased and uniform tracer uptake of 72%, confirming GD. She was initially treated with methimazole (MMI) 20mg daily with rapid improvement. MMI was quickly tapered to 2.5mg daily within 2 months and while on this dose, her TSH rose to 58.2 necessitating cessation of MMI. Conclusion: This case illustrates the importance of continued monitoring for autoimmune thyroid complications, in patients receiving Alemtuzumab for multiple sclerosis, even after cessation of treatment. In patients presenting with hypothyroidism, both TPO and TRAb should be checked. Patients with TRAb-positive hypothyroidism should be closely monitored for potential fluctuation in disease course.

Presentation: 6/1/2024
9188 Hashitoxicosis To Graves': A Case Of Fluctuating Thyroid Autoimmunity Induced By The Covid Vaccine
Authors: Lamar K , Meda N , Straughan J , John D , Suryanarayanan S K
Published: October 2024

Disclosure: K. Lamar: None. N. Meda: None. J. Straughan: None. D. John: None. S.K. Suryanarayanan: None.

Introduction: Thyroid antibodies are essential for identifying autoimmune thyroid disease. In Graves' disease thyroid stimulating immunoglobulin (TSI) is crucial to diagnosing, guiding treatment, and determining prognosis for ophthalmopathy; thyroid peroxidase (TPO) antibody is likewise crucial in the diagnosis of Hashimoto’s Thyroiditis. Conversion between these two diseases is extremely rare. Case: The patient is a 60-year-old female with a medical history of hypertension, asthma, T2NxM0 low grade gastrointestinal stromal tumor (GIST), and hyperaldosteronism who was referred to the endocrine clinic for “thyroid disorders'' with symptoms including weight gain and palpitations. Her labs showed thyroid stimulating hormone (TSH) <0.01mIU/L, free Triiodothyronine (fT3) 6.5ng/mL, free Thyroxine (fT4) 1.6ng/dL, TPO antibodies 46IU/mL, negative TSI antibodies 102%, and a negative Thyroglobulin antibody (Tg Ab) <1IU/mL. A slightly enlarged thyroid was noted on ultrasound. Radioactive iodine uptake (RAI) was normal with 15% uptake at 6 hours and 25% at 24 hours. These findings led to the diagnosis of Hashimoto thyrotoxicosis. She started methimazole 10mg and atenolol 50mg. One year later, she received the Pfizer mRNA COVID-19 vaccine and had her GIST tumor resected. She then began switching between hyper-, hypo-, and euthyroid states with multiple titrations of her Methimazole dose. Repeat testing demonstrated a positive TPO 41 IU/mL, negative Tg Ab <1, positive TSI 294%, and positive RAI with 47% uptake at 6 hours and 61% at 24 hours, consistent with Graves’ disease. It was found that even minor titration by 2.5mg in her Methimazole led to profound changes in her thyroid laboratory values and symptoms. She underwent total thyroidectomy and was started on levothyroxine with significant improvement. Discussion: This patient initially presented with antibodies as well as low uptake on the radio-iodine scan indicating her state of hyperthyroidism was due to Hashitoxicosis, but then later these tests were repeated and were more indicative of Grave’s disease. This was possibly due to immune challenges in the patient, assay inter-variability of thyroid autoantibodies, or an effect of the patient receiving the COVID vaccine. The phenomenon of TSI antibodies converting from negative to positive has not been well documented previously. The goal of this case was to report an interesting conversion of Grave’s disease identifying antibodies and the importance of evaluating underlying immune challenges which could play a role in altering clinical disease.

Presentation: 6/1/2024
8112 Hyalinizing Trabecular Tumor of the Thyroid in a Patient with Familial Adenomatous Polyposis
Authors: Kelly C , O’Donnell B M
Published: October 2024

Disclosure: C. Kelly: None. B.M. O'Donnell: None.

A 33 year old female presented to the Endocrinology clinic for evaluation of a 1.4 cm thyroid nodule. She has a relevant past medical history of Familial Adenomatous Polyposis (FAP). She was diagnosed with FAP in her early 20s after she had developed hematochezia. When she underwent her first endoscopy she reports there “were hundreds of polyps” as well as multiple stomach ulcers/polyps. In 2012 she underwent a total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Then in August 2023 the patient underwent a Whipple procedure due to the discovery of duodenal polyps on endoscopy that demonstrated low grade dysplasia. On pathology the duodenal adenoma was significant for adenocarcinoma invading the lamina propria, no lymphovascular invasion, negative margins, and 0/20 involved lymph nodes. No chemotherapy indicated per Medical Oncology. Thyroid ultrasound was performed as a screening assessment, and given the presence of a nodule she was referred to Endocrinology. On repeat ultrasound approximately 1 year after her initial ultrasound, the nodules measured 15.5. mm x 15.9 mm x 16.9 mm; increased in size from 14 mm x 14 mm x 12 mm. Due to the increase in size and the nodule characteristics of hypoechogenecity and taller-than-wide shape we recommended the patient undergo fine needle aspiration (FNA) biopsy of the nodule. Cytology from the FNA was notable for Papillary Thyroid Carcinoma. In December 2023 the patient underwent a total thyroidectomy, and pathology showed bilateral foci of hyalinizing trabecular tumor. Hyalinizing trabecular tumors (HTT) of the thyroid are follicular neoplasms with benign behavior. On sonographic imaging they tend to present as round to oval hypoechoic, well-defined lesions. On cytology these lesions can be mistaken for papillary thyroid carcinoma (PTC), medullary thyroid carcinoma, non-invasive follicular thyroid neoplasm with papillary like features, paraganglioma, and follicular neoplasm. The incidence of HTT varies but is approximately 1.5% of benign thyroid tumors. While FAP has been linked to thyroid tumors, in 70-90% of cases the pathology is consistent with cribriform-morular variant of PTC (CMV-PTC). CMV-PTC is in and of itself a rare variant accounting for less than 1% of all PTCs in the general population. Historically, the lifetime risk of thyroid cancer development in FAP patients is 2%, but this number has been climbing recently with a prevalence as high as 12% in patients screened with ultrasonography. It is important that this patient’s case be added to the body of medical literature as HTT is not currently known to be associated with FAP, but as more lesions are found with increased ultrasound surveillance, it may be an emerging extraintestinal manifestation of the disease.

Presentation: 6/1/2024
8259 Hypercalcemia as an Unusual Presentation of Hyperthyroidism
Authors: Mohammadrezaei F , Mubashir A , Chen K
Published: October 2024

Disclosure: F. Mohammadrezaei: None. A. Mubashir: None. K. Chen: None.

Background: Asymptomatic Non-Parathyroid dependent hypercalcemia can occur in 20% of patients with hyperthyroidism [1]. It is uncommon for hyperthyroidism to present with hypercalcemia, and it is rare for calcium levels to exceed 12 mg/dl [2]. Case Presentation: A 65-year-old man was referred to Endocrinology for hypercalcemia with complaint of poor appetite and gradual 10–15-pound weight loss over the past year. Patient was under the care of a rheumatologist for joint pain who noted his calcium levels to be elevated at 12.1 mg/dl (8.2-10.1). Further investigation into hypercalcemia revealed an alkaline phosphatase level of 129 IU/L (36-112), 25OH Vitamin D level of 60.6 NG/ML (30-100), ACE level of 79.8 U/L (9-67), PTH of 18 PG/ML (15-65) and PTHrP levels < 2.0 pmol/L (< 2.0). A CT scan of the chest, abdomen, and pelvis was performed due to hypercalcemia and mildly elevated ACE level and did not reveal any evidence of sarcoidosis; however, it showed enlargement of the thymus. On our initial examination, his vital signs were within normal range and physical examination revealed fine tremors in his upper extremities. On further evaluation, his thyroid function tests (TFTs) showed suppressed TSH < 0.005 MICU/ML (0.39-4.08) and elevated FT4 7.34 NG/DL (0.58-1.64) and patient was initiated on methimazole and propranolol. Thyroid Stimulating Immunoglobulin (TSI) was positive 1.96 IU/L (0.00-0.55) consistent with Graves' disease. Thyroid ultrasound revealed a heterogeneous thyroid with multiple nodules and radioactive iodine uptake and scan displayed multiple "hot and cold" areas consistent with a multinodular goiter (MNG) and elevated uptake of 78% at 24 hours (10-30%). Subsequent fine-needle aspiration (FNA) findings were benign. Following initiation of treatment for hyperthyroidism and normalization of FT4, the patient's unintentional weight loss improved with weight regain and more notably, hypercalcemia resolved, as indicated by calcium levels of 10 and 9.5 at 3 months and 1 year respectively, supporting the diagnosis of hyperthyroidism-related hypercalcemia. Conclusion: The key takeaway from this case is the identification of hypercalcemia as a potential complication of hyperthyroidism, though the precise mechanism remains unclear. It may be related to the stimulation of bone turnover by thyroid hormones. Further studies are needed to uncover the exact underlying pathophysiological mechanism. References: (1) Baxter JD, Bondy PK: Hypercalcemia of thyrotoxicosis. Ann Intern Med. 1966, 65:429-42. 10.7326/0003- 4819-65-3-429. (2) Khan H, Nawaz M, Schofield J, Soran H. Severe hypercalcaemia secondary to relapsed Graves' disease. BMJ Case Rep. 2021 Jan 18;14(1): e238898.

Presentation: 6/1/2024
7276 Hypothyroid Patients With Gastric Diseases In Treatment With Liquid L-T4: An Observational Study
Authors: Fallahi Poupak , Ragusa Francesca , Patrizio Armando , Mazzi Valeria , Botrini Chiara , Elia Giusy , Balestri Eugenia , Barozzi Emilio , Rugani Licia , Palmisano Elena , Cosenza Maria Carla , Varricchi Gilda , Ulisse Salvatore , Benvenga Salvatore , Ferrari Silvia Martina , Antonelli Alessandro
Published: October 2024

Disclosure: P. Fallahi: None. F. Ragusa: None. A. Patrizio: None. V. Mazzi: None. C. Botrini: None. G. Elia: None. E. Balestri: None. E. Barozzi: None. L. Rugani: None. E. Palmisano: None. M. Cosenza: None. G. Varricchi: None. S. Ulisse: None. S. Benvenga: None. S. Ferrari: None. A. Antonelli: None.

We have conducted an observational and retrospective study, by enrolling patients with hypothyroidism and gastric diseases in treatment with liquid L-T4 (L-LT4) or tablet L-T4 (T-LT4). The aim of the study was to compare the stability of TSH in these patients. Eighty-four patients were in treatment with L-LT4, and 120 patients with T-LT4; all of them assumed L-T4 30 minutes before breakfast. The patients were affected by different types of gastric disease: a) in T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) in L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). In the T-LT4 group 66% of the patients were chronically treated with PPI, against 51% in the L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the two groups (p>0.05). The mean L-T4 dosage in the T-LT4 group at the basal evaluation was 1.22+/-0.27 μg/kg/die, in the L-LT4 group was 1.36+/-0.22 μg/kg/die (p>0.05). At the basal evaluation the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 36%, whereas in the L-LT4 group was of 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the patients were re-evaluated with an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of patients with a TSH>3.5 μIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 26%, and of 13% in the L-LT4 group (p<0.05). At the third re-evaluation, the prevalence of patients with TSH>3.5 μIU/mL in the T-LT4 group was 19%, and of 9% in the L-LT4 group (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 18%, and of 5% in the L-LT4 group (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. These data highlight a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up, by using a liquid L-T4 formulation therapy with respect to a tablet L-T4.

Presentation: 6/3/2024
6910 Hypothyroidism Induced by a TSH Receptor Peptide -Implications for Thyroid Autoimmunity
Authors: Xiang Pingping , Latif Rauf , Morshed Syed A , Davies Terry F
Published: October 2024

Disclosure: P. xiang: None. R. Latif: None. S.A. Morshed: None. T.F. Davies: None.

The “Neutral” thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro and also when administered in vivo. For example, during these earlier studies we developed a mouse monoclonal antibody (MC1) specific for a peptide (aa 322-340) in the hinge region (MC1 - Mab) which was able to induce thyroid cell stress and apoptosis. In order to examine the effect of in vivo generated N-TSHR-Abs we immunized Balb/c mice with the same hinge region peptide and examined their thyroid function over the subsequent 18 weeks. We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular cell apoptosis, thyroglobulin release, induction of thyroglobulin antibodies and hypothyroidism with increased TSH levels. These data add further evidence to the complexity of the immune response to the TSHR and indicate that the simple presence of stimulating type TSHR antibodies is not the entire story of Graves’ disease.

Presentation: 6/3/2024
5052 Hypothyroidism Management with Roux en Y Gastric Bypass
Authors: Vallabh Sean Nikunj , Swavely Jessica , Kattamanchi Adithya
Published: October 2024

Disclosure: S.N. Vallabh: None. J. Swavely: None. A. Kattamanchi: None.

Background: Roux en Y Gastric Bypass surgery has been shown to cause effective weight loss in individuals who qualify for the procedure. However, drug absorption is reduced in certain medications post-bariatric surgery. There is consistent evidence for diminished absorption in cyclosporine, thyroxine, phenytoin, and rifampin. No current literature found an association between levothyroxine liquid form and increased absorption status-post bariatric surgery. However, there are studies showing increased liquid absorption of levothyroxine in patients with suboptimal thyroid-stimulating hormone. Case presentation: The patient is a 60-year-old female with a past medical history significant for hypothyroidism and gastric bypass at the age of 21 years old who came in with the chief complaints of cold intolerance, fatigue, and hair loss. She was taking max dose of levothyroxine 300 mcg five days a week and 450 mcg two days out of the week and had an abnormal thyroid-stimulating hormone level of 340.47 the normal range is (0.45-5.33). The free thyroxine level was 0.44 the normal range is (0.61-1.24). The patient had been on oral Levothyroxine for decades, remaining symptomatic with elevated thyroid-stimulating hormone. The patient was trialed on liquid levothyroxine same dose. After the patient started a liquid regimen of her levothyroxine, her fatigue diminished, her cold intolerance lessened, her hair loss decreased, her thyroid stimulating hormone normalized to 0.91 the normal range is ( 0.4-4.50), and the free thyroxine increased to 2.1 the normal range is ( 0.8-1.8). Her levothyroxine dose was reduced to 300 mcg six days a week and 450 mcg 1 day a week. Conclusion: In conclusion, levothyroxine liquid form has been able to help normalize thyroid function in a patient with a remote history of bariatric surgery with severely uncontrolled hypothyroidism in spite of very high doses of levothyroxine. Bariatric surgery has been associated with weight loss and more stable thyroid levels. However, it also can lead to decreased absorption of oral levothyroxine. There are limited studies showing increased liquid absorption of levothyroxine in patients with bariatric surgery compared to oral form. More research needs to be conducted to see if liquid thyroxine leads to symptom abatement and its role in gastric bypass surgery for patients with hypothyroidism. Reference:•Virili, Camilla, et al. “Levothyroxine therapy: Changes of TSH levels by switching patients from tablet to liquid formulation. A systematic review and meta-analysis.” Frontiers in Endocrinology, vol. 9, 2018, https://doi.org/10.3389/fendo.2018.00010. •Zendel, Alex, et al. “The impact of bariatric surgery on thyroid function and medication use in patients with hypothyroidism.” Obesity Surgery, vol. 27, no. 8, 2017, pp. 2000–2004, https://doi.org/10.1007/s11695-017-2616-7.

Presentation: 6/3/2024
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

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

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

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

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

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

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

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