bluuebunny/crossref_metadata_2025 huggingface dataset:
5160 Acute Onset Myxedema Coma After Pituitary Surgery
Authors: Krinsky Dana , Krug Ethan , Mullally Jamie Ann
Published: October 2024

Disclosure: D. Krinsky: None. E. Krug: None. J.A. Mullally: None.

Introduction: Myxedema coma is a rare endocrine emergency. The classic presentation is progressive worsening of hypothyroidism, over the course of months, usually in the setting of improper intake of levothyroxine. Here, we present a unique case in which a 91-year-old male presented with myxedema coma 3 weeks after resection of a non-functioning pituitary macroadenoma. Case Presentation: A 91-year-old male with history of hypertension and atrial fibrillation initially presented with progressive bitemporal hemianopsia due to an enlarging 2.4 cm pituitary macroadenoma with compression of the optic chiasm. Pre-operative pituitary labs, including thyroid function tests, were normal and he underwent transsphenoidal resection. Free T4 and cortisol levels were normal post-op day 3 and the patient did not require hormone replacement on discharge. 3 weeks later, the patient presented with hypotension and altered mental status. On admission, he was oriented to self only, able to follow simple commands, with dry oral mucosa, and bilateral non-pitting lower extremity edema. Laboratory studies indicated a normal TSH of 0.386 mlU/L (reference range 0.35-4.7). The following day, the patient became unresponsive, bradycardic, and had hypothermia to 30° C. His free T4 was found to be low at 0.4ng/dL (reference range 0.7-1.9) The diagnosis of myxedema coma was made, and intravenous levothyroxine was initiated after administration of intravenous hydrocortisone to prevent adrenal crisis. After initiation of treatment, the patient’s mental status improved, and he was discharged on long term thyroid hormone and glucocorticoid replacement. Discussion: Myxedema coma is a clinical diagnosis and requires urgent treatment as it has a mortality rate as high as 30-50%. This case was unusual because myxedema coma most often occurs in the setting of primary hypothyroidism with inadequate intake of thyroid hormone supplementation over the course of months. In contrast, our patient presented only 3 weeks after pituitary surgery, with a new diagnosis of central hypothyroidism and myxedema coma. Our case demonstrates central hypothyroidism and myxedema coma can develop quite rapidly after pituitary surgery. Clinical guidelines recommend checking a FT4 between 4-6 weeks after pituitary surgery. Our patient presented with severe biochemical hypothyroidism and myxedema coma only 3 weeks post-operatively despite having a normal FT4 3 days post-op. Based on our case, there may be a benefit to checking FT4 at an earlier post-op time point. Additionally, initially only a TSH was checked for our patient and was normal. When considering a diagnosis of myxedema coma in a patient with recent pituitary surgery, a FT4 must be checked as the TSH will not be reliable in central hypothyroidism. Clinicians should be aware of the potential for new central hypothyroidism and even myxedema coma within weeks of pituitary surgery.

Presentation: 6/2/2024
7079 Analysis of the Association Between Recent Exposure to Pregnancy and the Histological Subtype of Thyroid Cancer
Authors: Danehy T L , Manavalan A , Schechter C , Tomer Y
Published: October 2024

Disclosure: T.L. Danehy: None. A. Manavalan: None. C. Schechter: None. Y. Tomer: None.

Objective: Thyroid cancer is the second most common cancer diagnosed in pregnancy (1). Both HCG and estrogen have been implicated in this increased risk (2). While the classic variant of papillary thyroid cancer is the most common subtype in non-pregnant women, the effect of exposure to pregnancy on histological subtype remains unclear and could have clinical implications. Methods: This is a retrospective cohort study conducted at Montefiore Medical Center. All women of childbearing age (18-45) with a diagnosis of thyroid cancer between the years of 2015 -2020 (n=152) were identified. 43 participants were excluded due to missing data. The remaining 114 participants were divided into 2 groups; Group 1 or the exposed (n=25) included those diagnosed with thyroid cancer during pregnancy or in the 2 years postpartum and had carried their pregnancy to term, and Group 2 or the unexposed (n =89) included those who were nulliparous or diagnosed with thyroid cancer prior to pregnancy or more than 2 years post-partum. Charts were reviewed to obtain data on the initial histopathology and were classified into Follicular Thyroid Cancer (FTC), Hurthle cell carcinoma (HCC), Medullary Thyroid Cancer (MTC), and Papillary Thyroid Cancer (PTC). Results: Women in the unexposed group were significantly younger than those exposed to pregnancy (28.7 vs 32.7 p=0.005). The distribution of histological types in the two groups was as follows:Group 1: FTC (13.0%), HCC (0%), MTC (0%), and PTC (87%). Group 2: FTC (5.7%), HCC (2.3%), MTC (3.4%), PTC (88.5%). Thus, the incidence of follicular thyroid cancer in the exposed group was > 2-fold that observed in unexposed group, but this difference did not meet statistical significance (p=0.594). Conclusions: Our study showed a non-statistically significant increased incidence of FTC in women who were diagnosed with thyroid cancer during pregnancy or 2 years postpartum compared to unexposed women. While this did not meet statistical significance, our study sample was small and may have been underpowered. Therefore, our findings merit further investigation given their potential clinical implications. References: 1. Smith L.H., Danielsen B., Allen M.E., Cress R. Cancer associated with obstetric delivery: results of linkage with the California cancer registry. Am J Obstet Gynecol. 2003 2. Tafani M., De Santis E., Coppola L., Perrone G.A., Carnevale I., Russo A. Bridging hypoxia, inflammation, and estrogen receptors in thyroid cancer progression. Biomed Pharmacother. 2014;68(1):1-5

Presentation: 6/2/2024
7410 Bevacizumab Induced Hypothyroidism
Authors: McKenna Amanda L , Thota-Kammili Sanjana , Grennan Krista , Rao Sarika
Published: October 2024

Disclosure: A.L. McKenna: None. S. Thota-Kammili: None. K. Grennan: None. S. Rao: None.

It is known that thyroid dysfunction is an adverse effect of tyrosine kinase inhibitors (TKIs) via inhibition of the vascular endothelial growth factor receptor (VEGFR). The VEGF signaling pathway is important in regulating angiogenesis in tumors and normal tissue. As a highly vascularized gland, it is expected the thyroid may be compromised because of VEGFR inhibitors. Proposed mechanisms of thyroid dysfunction include capillary regression and constriction leading to reduced vascular perfusion to the gland. Bevacizumab is a monoclonal antibody that targets VEGF and inhibits activation of VEGFR, reducing angiogenesis; interestingly, this is not commonly reported in the literature. Here we present a case where bevacizumab altered thyroid function in a patient with pre-existing primary hypothyroidism. A 60-year-old woman presented with worsening hypothyroidism. She reported a history of nonautoimmune primary hypothyroidism diagnosed in her early 20s; she still had an intact thyroid with no history of head/neck radiation. In the months leading to the presentation, she had been receiving maintenance chemotherapy with 5 fluorouracil and bevacizumab every 2 weeks for metastatic duodenal carcinoma. Prior to starting chemotherapy, she had been on a steady dose of 112 mcg of levothyroxine (LT4) daily. After 6 months on chemotherapy, she reported symptoms of fatigue and hair loss. Workup revealed an elevated TSH of 41 mIU/L (reference 0.3-4.2 mIU/L). She denied any significant changes in weight or malabsorption issues. Aside from the chemotherapy, no other new medications were introduced. Her LT4 dose was increased to 137 mcg daily, and 3 months later, there was improvement in TSH to 6.5 mIU/L as well as her symptoms. At this point, bevacizumab was briefly on hold for 2 months due to an upcoming procedure, hence there was no change to LT4 to avoid over correction. Her TSH normalized and was trending lower while bevacizumab was on hold. Once bevacizumab resumed, LT4 was preemptively increased to 150 mcg daily. Four months after resuming bevacizumab, her TSH remains within the normal reference range on 150 mcg LT4. It is hypothesized that this VEGF blocker led to worsening of her underlying hypothyroidism.Given the shared down regulation in the VEGF signaling pathway, it would be expected that TKIs and monoclonal antibodies against VEGF would share similar adverse reactions to the thyroid. However, to our knowledge, there have been limited reports of bevacizumab induced thyroid dysfunction in the literature. Explanations to this may include the more targeted VEGF inhibition with bevacizumab versus the inhibition of multiple kinase receptors from the TKIs. Further research into this will be needed. This case demonstrates that bevacizumab can impact thyroid function and thyroid labs may need to be monitored at the onset and during VEGF inhibitor therapies.

Presentation: 6/3/2024
8596 Brain Type 3 Deiodinase Is Induced in Two Disease Models That Lead to Cognitive Impairment: Liver Dysfunction and Alzheimer Disease
Authors: Wajner S , Oliveira T , Dreher M , Ribeiro R , Gonçalves C , Alveres-da-Silva M R
Published: October 2024

Disclosure: S. Wajner: None. T. Oliveira: None. M. Dreher: None. R. Ribeiro: None. C. Gonçalves: None. M.R. Alveres-da-Silva: None.

Thyroid hormone is the leading regulator of cell energy production in most tissues, mainly the brain. While the activation process of T4 into T3 depends on D1 and D2 deiodinases, type 3 is the main enzyme that inactivates T3. Several mechanisms, among them oxidative stress, led by disease, imbalances and induces D3, diminishing T3 levels. The response of D3 in the brain in the context of different disease models has yet to be studied. Here we evaluated D3 induction in the brain in two animal disease models, one systemic and the other local. Methodology: To the metabolic dysfunction-associated steatosis liver disease model Male/adult Sprague Dawley rats (n=20) were assigned to control group (standard diet-2.93kcal/g) or high-fat-diet group (CDHF-4.3kcal/g). In the streptozotocin-induced (STZ) Alzheimer's model Adult Wistar rats (n=16) were allocated to the control group (5uL of citrate) or 5uL of streptozotocin. Sham animals were used as controls. D3 expression, oxidative stress parameters, endoplasmic stress and mitochondrial amount measured in the brain. Levels of D3 increased in the brain (∼30% in each group, P<0.0001) in both MASLD and STZ groups. Cerebral tissue from both groups had augmented carbonyl levels (P<0.001) and reduced sulfhydryl (P<0.001). Glutathione was diminished. Antioxidant defenses endoplasmic reticulum function and mitochondrial concentration were altered (P=0.001). The augmented T3 inactivation by D3 dysfunction in brain due to oxidative stress disrupts ER-mitochondrial contact interaction, changing the function of organelles in both brain disease models, shedding light to new mechanisms of action of thyroid hormone in severe brain disease.

Presentation: 6/3/2024
6504 Cerebellar Metastases from Papillary Thyroid Cancer; An Unusual Presentation
Authors: Chozet L E , Gilbert A , Escobar Vasco M A
Published: October 2024

Disclosure: L.E. Chozet: None. A. Gilbert: None. M.A. Escobar Vasco: None.

Background: Differentiated papillary thyroid cancer is known to have a very favorable prognosis. Brain metastases arising from papillary thyroid carcinoma are a very rare complication seen in approximately 1% of all cases of differentiated thyroid cancer with cerebellar metastases being even more uncommon. We present a case of a patient presenting with ataxia as the initial and only symptom of papillary thyroid carcinoma, found to have cerebellar metastases. Clinical Case: A 68-year-old man presented with ataxia for 1 week prior to arrival to hospital. CT head revealed hyperdense lesions in the right frontal lobe and left posterior cerebellar hemisphere. The patient underwent resection of left cerebellar mass with final pathology consistent with metastatic papillary thyroid carcinoma. Tumor cells were positive for TTF-1, thyroglobulin, CAM5.2, CK7, and PAX8, and negative for CK5/6, CK20, inhibin, and Napsin A. Ultrasound of the thyroid revealed multinodular goiter with dominant left thyroid lobe nodule 4 cm in size. PET CT showed left Thyroid mass with direct extension to adjacent lymph nodes, right anterior rib mass, left adrenal metastasis and right frontal lobe and left cerebellar metastasis. He received stereotactic radiosurgery with 5 out of 5 treatments completed. He subsequently underwent total thyroidectomy with left modified radical neck dissection, with pathology showing pT3bN1bM1. Next Generation Sequence positive for V600E, RADS1CR193, TERT PROMOTER -124C>T. After multidisciplinary team discussion, it was determined that the best course of action was to refer the patient to MD Anderson for evaluation, candidacy for prospective therapeutic clinical trials. Conclusion: This case demonstrates how differentiated papillary thyroid cancer, despite its favorable prognosis, can still prove to be a dangerous disease especially if undiagnosed for several years. This case also illustrates how papillary thyroid carcinoma can remain clinically silent for years and first present with atypical symptoms consistent with advanced metastases.

Presentation: 6/2/2024
7775 Clinical Features of NKX2-1 Gene-Related Diseases
Authors: Fukui Sadahiro , Tanimoto Eri , Ujita Nagisa , Miyagi Hajime , Yoshii Keisuke , Yasuhiro Naiki , Horikawa Reiko
Published: October 2024

Disclosure: S. Fukui: None. E. Tanimoto: None. N. Ujita: None. H. Miyagi: None. K. Yoshii: None. N. Yasuhiro: None. R. Horikawa: None.

Background: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The utilization of molecular genetic techniques has facilitated the detection of CH resulting from various single-gene mutations; NKX2-1 gene-related disease stands out as one etiology of symptomatic CH. We report the clinical course of three cases with CH caused by NKX2-1 pathogenic variants. Case 1: An 8-year-old boy. He was born at 40 weeks and six days of gestation, weighing 2845g, and was presented to our department by high TSH (76.1 µIU/mL) at newborn screening (NBS), and LT4 treatment was initiated. He showed motor developmental delay, and choreiform movements were exhibited at two years and 11 months without respiratory symptoms. Case 2: An 18-year-old female. She was born at 40 weeks and five days gestation, weighing 2680g, and was admitted to her previous hospital following poor weight gain at approximately six months. During hospitalization, she was initiated LT4 treatment with a TSH elevation(14.7μIU/mL). After receiving a diagnosis of idiopathic interstitial pneumonia, she was subsequently referred to our hospital. At the age of 11, an NKX2-1 mutation was identified. Case 3: An 18-year-old female. She was born at 41 weeks and three days of gestation, weighing 2364g.TSH elevation (27.9 µIU/ml) was detected at NBS, and LT4 treatment was started. Thyroid hormone levels were maintained within normal range. However, wheezing and tracheomalacia were noted around five months. Hypotonia and delayed motor development were evident, and an NKX2-1 mutation was identified at the age of 12 years. Discussion: Although NKX2-1 gene-related disorders can be readily suspected when typical symptoms of central nervous system, pulmonary, and thyroid dysfunction manifest concurrently, diagnosis is sometimes established later because of the diversity of the occurrence of these symptoms. Despite reports of choreiform movements being inevitable, they did not appear in Case 2.3 until the age of 18 years. Conversely, muscle hypotonia and delayed motor development were observed in all our cases. When atypical neurological symptoms combined with CH are observed, NKX2-1 gene-related disease should be considered since the disease is known to develop malignant tumors such as lung cancer and thyroid cancer, which can significantly affect the prognosis of patients. Conclusion: When muscle hypotonia and delayed motor development are observed in addition to hypothyroidism and respiratory symptoms, NKX2-1 gene-related disease should be suspected, and follow-up for complications, including malignancy, is essential after diagnosis.

Presentation: 6/2/2024
7925 Cowden Disease Occurring in Association with Common Variable Hypogammaglobulinemia: A Case Report
Authors: Shakir Mohamed K M , Ebrahim Ismail C , Maxwell Devin B , Vietor Nicole O , Hoang Thanh Duc
Published: October 2024

Disclosure: M.K. Shakir: None. I.C. Ebrahim: None. D.B. Maxwell: None. N.O. Vietor: None. T.D. Hoang: None.

Carriers of a pathogenic germline mutations in the PTEN gene, a tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, including thyroid, breast, endometrial and colon cancer, termed as PTEN Hamartoma Tumor Syndrome (PHTS). Recent studies have shown that PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. We are reporting a 47-year-old female with Cowden disease (CD) and common variable hypogammaglobulinemia (CVH). Our patient was diagnosed with CVH at the age of 25 after several episodes of pneumonia as well as poor wound healing. Since then, she is being treated with monthly intravenous immunoglobulin therapy. At the age of 24 years, she had a fainting episode and a diagnosis of gangliocytoma of cerebellum was made and she underwent resection of the tumor. At this time, she was also diagnosed with CD. She has a personal history of multiple other tumors including phyllodes tumor of breast, s/p bilateral mastectomy at the age of 32, status post hysterectomy for endometrial hyperplasia at the age 35. Hurthle cell adenomas of thyroid s/p total thyroidectomy at the age of 38. Her family history was significant for sister and father with CD. Physical examination was remarkable for only acral keratosis without mucocutaneous neuromas, oral papillomas and trichilemmomas. Cowden syndrome is the best-described phenotype of PHTS; it is characterized by mucocutaneous lesions and an elevated risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as various benign manifestations such as macrocephaly and dysplastic gangliocytoma of the cerebellum. Our patient was diagnosed with CD when she presented with gangliocytoma of the cerebellum. Immunodeficiency has been reported previously in patients with CD, and these patients often present with recurrent cellulitis and abscesses, and reduced T cell numbers and in vitro T cell proliferative function. Thus, PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. Additionally, a decreased ability of dendritic cells to prime CD8+ T cells may occur, leading to impaired tumor eradication. Immune dysfunction in PHTS patients might be a potentially manageable contributing factor to the increased cancer risk in PHTS. In conclusion, patients presenting with CD should also be screened for disorders of immunological dysregulation.

Presentation: 6/2/2024
8482 Genetic Aetiology Of Primary Adrenal Insufficiency In Sudan
Authors: Smith C J , Abdullah M A , Hassan S S , Fauzi L S , Qamar Y , Hall C L , Maitra S , Maharaj A V , Marroquin Ramirez L M , Read J E , Chan L , Metherell L , Musa S A
Published: October 2024

Disclosure: C.J. Smith: None. M.A. Abdullah: None. S.S. Hassan: None. L.S. Fauzi: None. Y. Qamar: None. C.L. Hall: None. S. Maitra: None. A.V. Maharaj: None. L.M. Marroquin Ramirez: None. J.E. Read: None. L. Chan: None. L. Metherell: None. S.A. Musa: None.

Primary adrenal insufficiency (PAI) in children is usually congenital with more than 25 causal genes with overlapping phenotypes. Genetic diagnosis helps to guide management and genetic counselling but can be challenging in resource limited settings. PAI is understudied in African children but in a cohort of Sudanese individuals (n>400) the majority had congenital adrenal hyperplasia (>73% CAH; mostly due to CYP21A2 mutation), with Triple A syndrome (AAAS), auto-immune polyendocrinopathy syndrome or adrenoleukodystrophy accounting for a further 11%. Here, we describe genetic characterization of the remainder of the cohort. 46 patients from 41 families (29 male and 17 female) with clinical presentation of PAI paired with biochemical finding of (low cortisol ± high ACTH and/or a negative response to Synacthen stimulation) were included in this study. Exclusion criteria were clinical and/or genetic diagnosis of CAH or Triple A syndrome. Candidate gene sequencing (CGS) of commonly causative genes in our global cohort (mostly European ancestry), MC2R, MRAP, CYP11A1 and STAR, was followed by whole exome sequencing (WES), in mutation negative individuals and family members. WES results and segregation within families were confirmed by Sanger sequencing. In silico tools were utilised for predicting the result of possible splicing mutations and these were functionally assessed using the Exon Trap vector (MoBi tech). The genetic aetiology was determined in over half of the families (23/41). Mutations in ABCD1 (7/23), NNT (5/23), AIRE (3/23) and CYP11A1 (3/23) were most common in this population with mutations in HSD3B2, MC2R, NR0B1, STAR and a CYP11B1-B2 fusion event accounting for the remaining genetically diagnosed families. 3 families had a splicing defect in NNT (c.9193G>A) and 2 families had a 5-exon deletion in AIRE, possibly representing founder mutations. PAI in Sudan has a heterogeneous aetiology with a different spectrum of PAI genes than our global cohort, resulting in fewer solved cases (53% compared to 85%) with only two families containing variants in common (European) candidate genes. While WES was pivotal in the study, in resource limited settings sequencing of founder mutations and region-specific, commonly mutated genes may be a cheaper alternative and both increase and hasten the diagnosis rate of at-risk patients. Whether the remaining cases without a diagnosis have unconventional defects in known genes, mutations in novel gene(s), and/or new syndromes incorporating permanent or transitory AI remains to be investigated.

Presentation: 6/2/2024
8675 Dosing of Radioactive Iodine for Papillary Thyroid Cancer in Advanced Chronic Kidney Disease
Authors: Cheatham Callie , Beckman Darrick
Published: October 2024

Disclosure: C. Cheatham: None. D. Beckman: None.

INTRO Radioactive Iodine (RAI) ablation is an important treatment for patients diagnosed with papillary thyroid carcinoma. Most studies completed on RAI in renal dysfunction were focused on End Stage Renal Disease (ESRD) patients on dialysis to establish protocols on timing of dialysis to allow desired clinical response to RAI without increased risks and minimizing exposure of dialysis staff to radiation dose. The ideal RAI dosing and monitoring of patients with advanced chronic kidney disease (CKD) stage 4 or 5 not requiring dialysis has not been systematically reviewed. CASE 26 year-old female with CKD stage 4/5 secondary to chronic hydronephrosis from vesicoureteral reflux with baseline eGFR 15-20 mL/min/1.73 m2 was diagnosed with papillary thyroid cancer. She underwent total thyroidectomy with central and left lateral neck dissection, resulting in pathologic stage I, pT2 N1b M0 disease, high risk for recurrence according to the 2015 American Thyroid Association guidelines due to 17 positive lymph nodes from left level II-IV and VI, multiple with extranodal extension, as well as 1 vessel angioinvasion. She was referred for adjuvant RAI ablation after withdrawal from thyroid hormone. Decision was made to proceed with a 50% dose reduction and close monitoring of radioactivity clearance as an inpatient given decrease of eGFR to 10-12 mL/min/1.73 m2. She was cleared for discharge 4 days after RAI dose of 74.8mCi when activity level dropped to <2mR/hr. Post-ablation whole body scan showed activity in the thyroid bed and parasternal notch without evidence of metastatic disease. Post-treatment non-stimulated thyroglobulin 6 weeks later was 0.4 ng/mL down from 269.7 ng/mL. DISCUSSION Given RAI is predominately renally cleared, decreased renal function affects clearance rates and associated exposure to radiation. Risks with decreased RAI clearance include bone marrow toxicity and prolonged isolation requirements. In a 2017 retrospective review, patients with eGFR <30 mL/min/1.73 m2 had delayed clearance leading to a mean proportional reduction of exposure rate at 48 hours of -67.2% compared to -94.3% in healthy controls. While protocols exist for patients on hemodialysis, no such protocols have been established for patients with advanced CKD not requiring dialysis. For this patient, after multidisciplinary discussion with nuclear medicine, health physics, and nephrology in setting of further eGFR reduction during hormone withdrawal, decision was made to reduce the intended dose by 50% with inpatient monitoring and backup to dialyze if no significant decrease in radiation activity level was seen or if she were to progress to anuric or oliguric renal failure. This case highlights the need for established protocols and long-term studies to evaluate risk and treatment response in relation to dosing of RAI in this population, but a 50% dose reduction appears to be effective without adverse event.

Presentation: 6/2/2024
6662 Effect of Selenium Supplementation on Mild Graves’ Ophthalmopathy at a Tertiary Hospital - A Six-Month Open-Labelled, Assessor-Masked, Randomized-Controlled Trial
Authors: Flores Joy Mangubat , Sioson Nina Angelica G , Uy-Ho Jean Dy , Suller-Pansacola Armida L
Published: October 2024

Disclosure: J.M. Flores: None. N.G. Sioson: None. J.D. Uy-Ho: None. A.L. Suller-Pansacola: None.

Graves’ orbitopathy is associated with increased oxidative stress. Selenium, with its antioxidant and immunoregulatory actions, has been proposed as an adjuvant therapy. Objective: This study was undertaken to determine whether selenium supplementation for six months can decrease signs and prevent worsening of mild Graves ophthalmopathy among Filipinos. Methods: We conducted an open-labelled, assessor-masked, Randomized-Controlled Trial on patients with mild Graves’ ophthalmopathy wherein one arm was assigned to standard of care (eye drops) only for a period of six months while another arm was assigned to 200 ug/day oral Selenium supplementation alongside standard of care. Population: Adult patients with Graves’ hyperthyroidism, with at least one sign of mild ophthalmopathy with GO disease duration of less than 18 months Results: Independent Sample T-test, Mann-Whitney U test and Fisher’s Exact/Chi-square test were used to determine the difference of mean, rank and frequency, between patients given Selenium versus patients given standard of care. Paired Sample T-test, Wilcoxon Sign rank test and McNemar test were used to determine the difference of mean, rank and frequency on patients from initial to 3rd month or 6th month observation. Null hypotheses were rejected at 0.05α-level of significance. There was a significant difference in Clinical Activity Score (CAS) between patients given selenium supplementation and those assigned to standard of care. On initial examination for the Selenium group, 14 eyes (33.33%) had a CAS score of 0, which increased to 27 eyes (64.29%) on the third month and ended to a 26 eyes (61.9%) at the sixth month of treatment. For the non-selenium group, 11 eyes had a CAS score of zero initially, increased to 16 eyes (and 38.1%) then finally arrived to a total count of 14 eyes (33.33%). Improvement in CAS may be attributed specifically to improvement in caruncle/plical swelling showing a significant difference (p-value 0.040). Comparing the two groups, a statistical significance in CAS is noted between the treatment versus the control group with a p-value of 0.017 on the 6th month. Conclusion: Selenium supplementation provided significant benefit in terms of decreasing signs and preventing worsening of mild GO through improved CAS score. Further studies exploring the baseline and end of treatment selenium concentrations in the Philippines may be warranted.

Presentation: 6/3/2024
7012 Genetic Defects Involved in the Progression from Differentiated to Anaplastic Thyroid Cancer
Authors: Gill Simranpreet , Chavez Luis F
Published: October 2024

Disclosure: S. Gill: None. L.F. Chavez: None.

Although much more invasive and with a disease specific mortality approaching almost one hundred percent, anaplastic thyroid cancers (ATC) are not mutually exclusive from their differentiated counterparts. Almost one third of patients diagnosed with ATC have a coexisting synchronous differentiated thyroid carcinoma (DTC). We describe a case of a 59 year old male with a 20 pack year smoking history who presented to the hospital for dysphagia and dyspnea after a recent diagnosis of papillary thyroid carcinoma (PTC) one month earlier after workup for an enlarged thyroid. Patient was unfortunately lost to follow up after initial diagnosis. Notably, immunohistochemistry (IHC) was positive for PAX8, TTF1, and BRAF V600E at that time. On arrival to the emergency department, patient described the dysphagia as progressively worsening from solids to liquids associated with a 20 pound weight loss since initial diagnosis of PTC. He had also been experiencing hoarseness of voice, intermittent fevers, night sweats, and hemoptysis. Physical exam revealed an enlarged thyroid mass with discrete nodularity. Labs were largely unremarkable but CT imaging of the neck and chest revealed a heterogeneous mass 6.3 cm in diameter centered within the upper esophagus causing mass effect on the upper airway and scattered bilateral pulmonary nodules. The thyroid was also heterogeneous appearing and had multiple peripheral calcified masses along with a 4.2 cm hypodense nodule in the left lobe. Patient underwent tracheostomy to secure the airway along with laryngoscopy, thyroid biopsy, and esophagoscopy with biopsies. The results of the thyroid biopsy once again showed PTC while the results of the esophageal biopsies showed ATC. Given extensive metastases, the patient was deemed to have stage IVC ATC and he was started on palliative chemotherapy and radiation therapy. Treatment was switched to BRAF inhibition in the outpatient setting after documentation of BRAF V600E mutation in the ATC component. IHC also revealed expression of PAX8, p53, CAM 5.2, and vimentin within the ATC component. And so, just one month after initial diagnosis of PTC, the patient developed ATC in the surrounding thyroid. This case highlights how DTC can serve as a stepping stone for the development of ATC. The mechanism at play may be due to genetic defects such as those in BRAF V600E and PAX8 that could be seen in both the DTC and ATC possibly signifying an underlying unifying pathway.

Presentation: 6/1/2024
6644 Glycosylation Patterns of the IgG Variable Region in Thyroglobulin Antibodies and Their Impact on Antigen Binding Affinity
Authors: Wang Shuaihang , Cao Yedi , Zhao Chenxu , Huang Chuncui , Zhao Keli , Li Yan , Huang Youyuan , Ying Zhang , Zhang Yang , Gao Ying
Published: October 2024

Disclosure: S. Wang: None. Y. Cao: None. C. Zhao: None. C. Huang: None. K. Zhao: None. Y. Li: None. Y. Huang: None. Z. Ying: None. Y. Zhang: None. Y. Gao: None.

Objective: Thyroglobulin antibodies (TgAb), key serological markers in Hashimoto's thyroiditis (HT) patients, are predominantly in immunoglobulin G (IgG) form. Prior research has highlighted the importance of increased glycosylation in TgAb IgG from HT patients. This study investigates the unique glycosylation patterns of F(ab')₂ fragments in TgAb IgG in HT patients, compared to healthy individuals. It focuses on how these patterns differ and their impact on binding to thyroglobulin (Tg). Exploring the role of N-glycosylation in the F(ab')₂ segment of TgAb IgG is crucial for understanding its effect on immune responses in HT, potentially unveiling key mechanisms of the disease. Methods: To assess serum TgAb levels in HT patients (n≥28), we used an electrochemiluminescence immunoassay, dividing patients into medium-level (mHT, n≥14) and high-level (hHT, n≥14) groups. TgAb IgG was isolated from serum of both HT and control groups (n = 14) using affinity chromatography. TgAb IgG was then cleaved with Ides enzyme to yield TgAb IgG F(ab’)2 and Fc fragments. The F(ab')2 fragment of TgAb IgG underwent MALDI-QIT-TOF-MS mass spectrometry for glycosylation profiling. Additionally, mixed TgAb IgG was separated using columns that recognize mannose and terminal sialic acid, yielding high mannose and high terminal sialic acid TgAb IgG. Different TgAb IgG glycoforms were prepared through enzymatic treatment with peptide-N-glycosidase F, β1-4 galactosidase, and α2-3,6,8 neuraminidase. The binding affinity of these TgAb IgG to Tg antigen was measured using Tg specific ELISA and surface plasmon resonance (SPR). Results: Using MALDI-TOF MS, we identified 22 IgG glycan types in both HT and control (Con) groups. In the hHT group, six glycan types (G0F, G1F, G2F, M5A1, A3G1F, A3F) were upregulated compared to Con, with statistical significance (p < 0.05). The mHT group showed increased levels of G1F and G2F compared to Con (p < 0.05). Between hHT and mHT, only A3F was significantly elevated (p < 0.05). Removal of N-glycosylation from IgG TgAb F(ab)2 reduced binding to Tg antigen. Presence of both mannose and terminal sialic acid in TgAb enhanced the binding to Tg. Conclusions: Most TgAb IgG in the variable region of HT patients contain N-glycans. The glycosylation patterns of TgAb IgG F(ab)2 in HT differ significantly from healthy controls, affecting antibody binding affinity. Our findings reveal the complex role of glycosylation patterns in TgAb IgG, providing new insights into HT pathogenesis and potential research directions.

Presentation: 6/1/2024
8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis
Authors: Aoun Laurence , Almardini Shaza , Anise Marina , Haddadin Fadi , Saliba Fares , Zaidan Julie
Published: October 2024

Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None.

Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks.

Presentation: 6/2/2024
6454 Identifying Gaps in Obtaining Germline RET Testing for Patients with Medullary Thyroid Cancer
Authors: Lim Alexandra N , Comeaux Jacob , Ricker Charite , Wei Kevin S , Angell Trevor E
Published: October 2024

Disclosure: A.N. Lim: None. J. Comeaux: None. C. Ricker: None. K.S. Wei: None. T.E. Angell: None.

Background: Medullary thyroid carcinoma (MTC) occurs sporadically or from germline pathogenic variants of the RET proto-oncogene in multiple endocrine neoplasia type 2 (MEN2). Current ATA guidelines recommend germline RET testing in all patients with C-cell hyperplasia or MTC. Because disparities may exist in the implementation of this recommendation, we analyzed records of patients with MTC to identify variables associated with germline RET testing. Methods: Patients with MTC were identified from a cohort study of all adult patients undergoing thyroid surgery from 2015-2022 at two affiliated academic centers: a private hospital or a safety-net hospital. Patients were categorized as RET-tested or not RET-tested. Data collection included: patient age, gender, ethnicity, nodule and lymph nodule findings on ultrasound (US), calcitonin and CEA levels, and surgical pathology results. Medical reports were reviewed for reasons that RET testing was or was not obtained. Results: Of 24 MTC patients, 50% were female, mean age ± SD was 50.8 ± 12.3, and 15 (62.5%) had Hispanic ethnicity. RET testing was performed in 14 (58.3%) patients and 3 (21.4%) had a pathogenic variant. RET-tested patients had a median nodule size of 3.45 cm (IQR 2.40-4.53) vs. 2.40 cm (IQR 0.98-3.25) in not-RET tested patients (p<0.05). There were no significant differences between groups in age, gender, ethnicity, preoperative US findings, preoperative calcitonin or CEA levels, or histopathologic status. RET testing was performed in 11/14 (78.6%) patients at the private hospital vs. only 5/10 (50.0%) patients at the safety-net hospital (p=0.20). Considering this, we further investigated the use of RET testing in the initial management of MTC patients. RET testing was performed or planned during initial management in 13/14 (92.9%) patients at the private hospital vs. only 5/10 (50%) patients at the safety-net hospital (p=0.05). At the private hospital, RET testing was requested for apparent sporadic disease (n=11), family history of MTC (n=1), and coexistent pheochromocytoma (n=1). At the safety-net hospital, RET testing was requested for apparent sporadic disease (n=4) and family history of MTC (n=1), but reportedly was not pursued in 5 patients because MTC appeared to be sporadic. Discussion: In this cohort of patients with MTC, larger nodule size was significantly associated with the rate of germline RET testing. Larger MTC tumor size alone may have prompted greater attention to germline testing, but also may have been associated with other findings, which could be further assessed with a larger sample size by multivariable analysis. The disparity in RET testing as part of initial management at the safety-net hospital may be multifactorial, but future analyses should explore provider decision-making, as well as facility and patient variables.

Presentation: 6/1/2024
7209 Immune Check Point Inhibitors And Periodic Thyroid Function Assessment
Authors: Farooqi A , Dewan S , Jun J Y , Farooqi S
Published: October 2024

Disclosure: A. Farooqi: None. S. Dewan: None. J.Y. Jun: None. S. Farooqi: None.

Introduction: Immune checkpoint inhibitors, namely anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death 1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they modify the immune system and destroy the immune cells, an array of immune related adverse effects has been noticed, with strong predilection to endocrine organs. Among endocrinopathies, thyroid dysfunction occurs frequently ∼5% especially with the use of anti-PD-L1. While the majority have been cases with destructive thyroiditis leading to transient thyrotoxic phase often followed by transient or permanent hypothyroid phase, the occurrence of hyperthyroidism or Basedow’s disease after the administration of anti CTLA-4 has also been reported. Case Presentation: We present a case of 66-year-old male with past medical history of ischemic cardiomyopathy, atrial fibrillation and metastatic cholangiocarcinoma diagnosed in August 2023. He was initially treated with combined chemotherapy and immunotherapy with duravulamab, anti PD-L1., and then later with duravulamab alone. Three weeks after the second cycle of duravulamab, he was admitted due to episodes of ventricular tachycardia with shock administered through his implantable cardioverter defibrillator. Further evaluation revealed thyroid stimulating hormone (TSH) of <0.01 (0.49-4.67 uIU/L), free T4 of 4.39 (0.61-1.60 ng/dL), total T3 of 160 [87-178 ng/dL], negative thyroid stimulating immunoglobulin and TSH receptor antibody. Of note, three months prior to immunotherapy, TSH was 6.52 uIU/L with normal free T4, pointing to subclinical hypothyroidism. Ultrasound of thyroid revealed enlarged heterogeneous thyroid gland related to thyroiditis. Prednisone 20 mg twice a day was prescribed for presumptive diagnosis of immunotherapy-induced thyroiditis. Patient continued prednisone for 14 days (about 2 weeks) until he ran out. Repeat TSH < 0.01 uIU/L and free T4 5.51 ng/dL with total T3 266 ng/dL confirming ongoing thyrotoxicosis and prednisone was further extended for 2-week period. Conclusion: Thyroid dysfunction is frequently observed during treatment with immune check point inhibitors. While increased body weight and elevated inflammatory markers at baseline are associated with development of thyroid dysfunction, there is no definite predictor identified. This case highlights the importance of periodic assessment of thyroid function test to identify and manage thyroid dysfunction in a timely fashion to avoid potential development of life-threatening consequences of thyroid dysfunction including thyroid storm.

Presentation: 6/3/2024
8390 It's not Cancer: Establishing the Diagnosis of Hyaline Trabecular Tumor
Authors: Zielinski R A , Khalifa M , Dillon M , Kaur M
Published: October 2024

Disclosure: R.A. Zielinski: None. M. Khalifa: None. M. Dillon: None. M. Kaur: None.

Background: Hyaline trabecular tumor (HTT) is a rare benign follicular thyroid neoplasm characterized by extensive intra-trabecular hyaline stromal material. Resemblances to other follicular neoplasms create difficulty in distinguishing HTT from its more nefarious counterparts such as medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC).Clinical Case:Our patient is a 56-year-old female with Hashimoto’s thyroiditis diagnosed in her twenties who has been on different strengths of levothyroxine based on her fluctuating TSH. A thyroid ultrasound done to evaluate left-sided neck fullness on physical exam showed a solid, hypoechoic 2.3 cm x 1.4 x 0.9 cm left middle thyroid nodule without calcifications (TI-RADS 4) and benign-appearing lymph nodes, the largest of which was 1.5 cm at level 1B. Cytology from a thyroid FNA biopsy was suspicious for PTC, Bethesda category IV. A thyrosure genetic panel was negative for genetic mutations. FNA biopsy of the 1.5 cm lymph node was negative for malignancy. The patient was referred for thyroid lobectomy but instead elected to undergo total thyroidectomy with level VI lymph node dissection. Pathology revealed a 2.2 cm HTT in the left lobe, scattered psammoma bodies in adjacent soft tissue, and a 0.2 cm multifocal papillary microcarcinoma in the right lobe. The microcarcinoma had negative margins, no lymphatic or vascular invasion, and 7/7 benign level VI lymph nodes; staging it as pT1aN0. Immunohistochemistry staining was positive for TTF-1 and thyroglobulin and negative for calcitonin, chromogranin, and synaptophysin. Post-thyroidectomy she was started on Tirosint 175 mcg daily with good response. No I-131 treatment was pursued due to the microcarcinoma being categorized as low risk.Discussion and Conclusion: HTT is a benign neoplasm and management is usually conservative with surgical excision. The diagnosis of HTT by cytology alone is challenging due to the presence of nuclear clearing, grooves and intranuclear pseudo-inclusions that may be mistaken for PTC or MTC. Cell membrane immunoreactivity of MIB1 monoclonal to Ki67 and the molecular identification of the novel PAX8-GLIS1 or PAX8-GLIS3 fusions may aid in making the correct diagnosis.References:Rossi ED, et al. The Diagnosis of Hyalinizing Trabecular Tumor: A Difficult and Controversial Thyroid Entity. Head Neck Pathol. 2020 Sep;14(3):778-784. doi: 10.1007/s12105-019-01083-5. Epub 2019 Sep 30. PMID: 31571046; PMCID: PMC7413943.

Presentation: 6/2/2024