bluuebunny/crossref_metadata_2025_split huggingface dataset:
7410 Bevacizumab Induced Hypothyroidism
Authors: McKenna Amanda L , Thota-Kammili Sanjana , Grennan Krista , Rao Sarika 
Published: October 2024

Abstract
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

Abstract
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&lt;0.0001) in both MASLD and STZ groups. Cerebral tissue from both groups had augmented carbonyl levels (P&lt;0.001) and reduced sulfhydryl (P&lt;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

Abstract
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&gt;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

Abstract
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

Abstract
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

Abstract
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&gt;400) the majority had congenital adrenal hyperplasia (&gt;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&gt;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

Abstract
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 &lt;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 &lt;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

Abstract
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