bluuebunny/crossref_metadata_2025_split huggingface dataset:
12233 Weight Gain Following Thyroidectomy For Benign Conditions
Authors: Krueger Abigail , Chiu Alexander , Pabich Samantha , Syed Shakera , Poloju Alekya , Holoubek Simon 
Published: October 2024

Abstract
Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None.
Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and &gt;5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age &lt;18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery.
Presentation: 6/1/2024
5118 When Thyroid Gland is Not Made of Thyroid Cells
Authors: Bulut A , Ma L , Noordzij J P , Lee S Y 
Published: October 2024

Abstract
Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None.
Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features.
Presentation: 6/1/2024
8790 A Case of Ectopic Cushing’s Syndrome Secondary to Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)
Authors: Goettemoeller T , Lopez Fanas R , Cedeno K , Manavalan A 
Published: October 2024

Abstract
Disclosure: T. Goettemoeller: None. R. Lopez Fanas: None. K. Cedeno: None. A. Manavalan: None.
Introduction: Ectopic Cushing’s syndrome is a rare disease accounting for &lt;20% of cases of endogenous Cushing’s syndrome. DIPNECH is a poorly understood lung disease characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It can be a precursor to pulmonary carcinoid tumors and has rarely been associated with ACTH production. Clinical Case: A 70-year-old female with intellectual disability and hypertension presented with diffuse edema and weakness. Examination was notable for hypertension, anasarca, and hirsutism. In addition to hypokalemia and metabolic alkalosis, hypercortisolism was observed: random serum cortisol - 50.1 ug/dL, late-night salivary cortisol - 1.72 mcg/dL (normal &lt; 0.09 mcg/dL) and 24-hour urine free cortisol - 1,845.9 mcg (normal: 4.0 – 50.0 mcg/24h). Cortisol level remained &gt; 25 ug/dL after high-dose dexamethasone suppression test. Ketoconazole was initiated and titrated to achieve normal 24-hour urine free cortisol levels and spironolactone was added to manage hypokalemia. An MRI of the sella and pituitary was unremarkable while an abdomen and chest CT identified a 2.5 cm well-circumscribed right middle lobe pulmonary nodule and mild thickening of the bilateral adrenal glands. A gallium-DOTATATE scan revealed a 2.1 cm right middle lobe pulmonary nodule with mildly increased uptake. A transbronchial biopsy of the right middle lobe nodule confirmed a carcinoid tumor. Immunohistochemistry (IHC) staining was positive for CHR, SYN, CD56, and AE1/3. Ki-67 stain showed a low proliferative index. A right middle lobectomy was performed with pathology revealing two typical carcinoid tumors measuring 2.8 and 0.7 cm each, with multiple carcinoid tumorlets and foci of neuroendocrine cell hyperplasia consistent with DIPNECH. IHC staining for ACTH was positive in the carcinoid tumors and tumorlets. Four days after surgery, AM cortisol was 8.1 ug/dL and potassium levels and blood pressure normalized off ketoconazole and spironolactone. The patient was discharged, but was readmitted a month later for anasarca, lethargy, hypokalemia, and metabolic alkalosis. A recurrence of Cushing’s syndrome was confirmed, and medical therapy was resumed. A chest CT revealed post-surgical changes. Her course was complicated by an aspiration event, septic shock, PEA arrest, resuscitation, and intubation. The patient’s care was ultimately transitioned to hospice. Conclusion: Florid Cushing’s syndrome due to ectopic ACTH production associated with DIPNECH is an exceedingly rare condition. Early recognition and treatment are crucial to prevent the numerous complications that may arise, and close follow-up after tumor removal is critical to ensure continued remission has been achieved.
Presentation: 6/1/2024
8338 A Case Series of 3 Patients with Unusual Miliary Lung Metastases in Paraganglioma: Diagnostic Workup, Treatment Challenges and Outcomes
Authors: Charles K M , Nazari M A , Jha A , Derkyi A , Talvacchio S , Kuo M J , Patel M , Prodanov T , Alzahrani A S , Chen A , Glod J , Del Rivero J , Gharib A M , Pacak K 
Published: October 2024

Abstract
Disclosure: K.M. Charles: None. M.A. Nazari: None. A. Jha: None. A. Derkyi: None. S. Talvacchio: None. M.J. Kuo: None. M. Patel: None. T. Prodanov: None. A.S. Alzahrani: None. A. Chen: None. J. Glod: None. J. Del Rivero: None. A.M. Gharib: None. K. Pacak: None.
Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are uncommon neuroendocrine tumors originating from adrenal medulla chromaffin cells and sympathetic/parasympathetic ganglia. Metastatic disease occurs in a subset of PPGLs, ranging from 5% to 30% depending on the underlying genetic factors. Metastases are typically found in the bone, lung, lymph nodes, or liver. Historically, there have been no reported cases of PPGL with miliary pattern of pulmonary metastases. Methods: Three patients were identified with pulmonary metastases. All patients were evaluated between 2016 and 2023, and all developed extensive pulmonary metastatic disease. The evaluation process involved reviewing their medical history, laboratory results, and potential therapeutic approaches. Each patient underwent surgical intervention for the primary tumor and received systemic therapies once metastatic spread was detected. Results: We present three patients with either germline succinate dehydrogenase subunit D (SDHD) or von Hippel-Lindau (VHL) pathogenic variants who developed this rare condition. Patient 1: a 14-year-old female with right PCC and a recurrent left neck PGL carrying VHL type 2 pathogenic variant: VHL c.250G&gt;T (p.Val84Leu) and received various chemotherapies with an unfavorable response. Patient 2: a 23-year-old female with a left jugular PGL carrying SDHD pathogenic variant: SDHD c.124_127delinsA TA (p.Glu42Ilefs*44). Patient 3: a 26-year-old female with a right PCC carrying a germline VHL type 2 pathogenic variant: VHL c.439C&gt;G (p.Leu147Val). The latter two patients experienced disease stabilization through chemotherapy and systemic targeted radiotherapy, respectively.Discussion/Conclusion: This case series is unique as it highlights the rare occurrence of miliary spread of pulmonary metastases resulting from PCC or PGL. It also provides insight into prospective treatments options and outcomes for clinicians administering care within this population of patients. Though it is not clear at this time, this case series may represent a new subset of PPGL that have different genomic features and require a different therapeutic approach.
Presentation: 6/1/2024
12312 A Comparative Genomic Analysis Between Parathyroid Adenomas And Carcinomas With Heterozygous Germline Cdc73 Mutations
Authors: Li Yulong , Simonds William F , Chen Haobin 
Published: October 2024

Abstract
Disclosure: Y. Li: None. W.F. Simonds: None. H. Chen: None.
Introduction: Parathyroid cancer is responsible for ∼1% of primary hyperparathyroidism. The hereditary form of this malignancy has been linked to germline mutations of the CDC73 gene. We previously reported that only the germline CDC73 mutations causing a significant impact on the function/expression of its encoded protein are associated with parathyroid carcinomas. On the other hand, these germline mutations may lead to only parathyroid adenomas or no parathyroid disease, suggesting incomplete penetrance. This observation raises the question of what additional genomic events are required for parathyroid tumorigenesis in carriers with germline CDC73 mutations. Methods: Twelve patients harboring heterozygous germline CDC73 mutations were included in this study. Whole exome sequencing was performed in all 12 parathyroid tumors (6 adenomas and 6 carcinomas) and the paired normal tissues. RNA sequencing was successfully performed in three of each parathyroid carcinomas, adenomas, and normal glands. The sequencing raw data were processed using the CCBR-Pipeliner. EnrichR, Gene Set Enrichment Analysis, and CIBERSORT were used for the downstream analyses. Results: All parathyroid carcinomas and adenomas had gained one somatic event predicted to cause a complete inactivation of the second CDC73 allele. Several distinctive genomic features were identified in parathyroid carcinomas compared to adenomas, including more single nucleotide variants bearing the signature of APOBEC deamination, frequent mutations among the genes involved in the PI-3K/mTOR signaling, and substantially more copy number variations and differentially expressed genes. Parathyroid carcinomas also share some genomic features with adenomas. For instance, both tumors have frequent somatic mutations and copy number loss that impact the genes related to T-cell receptor signaling and tumor antigen presentation, suggesting a shared strategy to evade immune surveillance. Consistent with these findings, an in silico estimation of immune cell composition in tumors found an absence of CD8+ T-cells in parathyroid adenomas and carcinomas. Conclusion: Our study provides evidence that biallelic inactivation of CDC73 is essential for parathyroid tumorigenesis in carriers with germline mutations of this gene. Despite sharing some genomic features with adenomas, parathyroid carcinomas have more distinctive alterations in the genome, some of which may be critical for cancer formation.
Presentation: 6/2/2024
7281 Increased Incidence Of Fracture And Predicted Fracture Risk In Patients With Mild Autonomous Cortisol Secretion
Authors: Sagar Rebecca , Saadulla Agink , Abbas Afroze 
Published: October 2024

Abstract
Disclosure: R. Sagar: None. A. Saadulla: None. A. Abbas: None.
Background: Mild autonomous cortisol secretion (MACS) is common in patients presenting with adrenal incidentalomas (AI) and has been associated with cardiovascular and metabolic co-morbidities. Whilst there is growing evidence to support the increased risk of cardiometabolic co-morbidity in this cohort, the bone health effects are less well characterised. Our study evaluated the prevalence of fragility fracture and fracture risk in patients with AI and MACS compared with a cohort of patients with benign, non-functional AI. Methods: Retrospective observational data were collected on 391 patients with MACS and an AI along with 626 patients with a benign, non-functional AI. Demographic, biochemical, radiological and bone health data were recorded. FRAX, a validated fracture risk stratifying tool, was used to calculated risk scores for all patients aged between 40 and 90 and risk category according to national guidance were also recorded. Results: MACS cohort (mean age 69±10 and 53% female) had a mean cortisol on overnight dexamethasone suppression test of 76.6±21nmol/l. Benign, non-functional patients had a mean age 61.4±12 and 57% female. Both cohorts had predominantly unilateral lesions (76% in MACS versus 84%). Patients with MACS had a significantly higher prevalence of all fragility fractures, 15.9% compared with 6.7% in the benign, non-functional group, p&lt;0.0001. Patients with MACS had a significantly higher 10-year risk of major osteoporotic fracture (10.6±3.8% versus 7.1±5.4%, p&lt;0.0001) and also hip fracture (7.2±4.1% versus 1.9±2.7%, p&lt;0.0001). 17% of MACS cohort were classed as either high or very high fracture risk, with a further 28% classed as intermediate risk requiring further assessment of bone health compared with 3% high/very high risk in the non-functional group. Despite this only 31% of the MACS group had undergone DEXA scan to assess bone mineral density compared to 13% of the non-MACS group. Only 5% of MACS patients were on osteoporosis treatment (3% in non-MACS cohort). Conclusions: Patients with MACS make up a large proportion of those presenting with adrenal incidentaloma. Our study suggests an increased prevalence of fragility fractures along with increased fracture risk in patients with MACS compared to those with non-functional AI. However, we also demonstrate an unmet need, with less than 1/3 of patients with MACS undergoing formal bone health assessment and just 5% of the total cohort on treatment for osteoporosis despite a significant proportion meeting intervention thresholds.
Presentation: 6/1/2024
8523 An Unconventional Estrogen Receptor Conformation Induces SUMO Expression in Breast Cancer Cells
Authors: Hancock Govinda R , Young Kristen , Greene Geoffrey L , William Fanning Sean 
Published: October 2024

Abstract
Disclosure: G.R. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: None.
Competitive allosteric regulators, selective estrogen receptor modulators (SERMs)/degraders (SERDs) differentially manipulate receptor structure to treat and prevent metastatic breast cancers. However, their utility is limited by the ∼40% rate of disease progression due to acquired therapy resistance. In this study, a new SERM based on a tetrahydro-6-isoquinoline (T6I) scaffold reveals the relationship between ERα conformation and therapeutic transcriptional pathways in drug-resistant breast cancers. Optimization of structure-activity relationships produced unique lead compound that engages transcriptional programs similar to the clinically approved SERD fulvestrant. Notably, both drugs induce the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to the pathogenic hormone 17β-estradiol. SUMOylation is a post-translational modification affecting protein-protein interactions, localization, stability and functional properties. High expression of SUMO1 is associated with better patient prognosis in ERα+ disease. SUMOylation in breast cancer will be elucidated through understanding how it’s induced, its structural basis, and its role in therapeutic response of antiestrogen treatments.
Presentation: 6/3/2024
8636 Characterization of the Role of Neutrophils in Promoting Progression of Lymphangioleiomyomatosis
Authors: Henson Thomas R , Minor Briaunna , Hammes Stephen R 
Published: October 2024

Abstract
Disclosure: T.R. Henson: None. B. Minor: None. S.R. Hammes: None.
Lymphangioleiomyomatosis (LAM) is a rare, multisystemic disease that is associated with cystic lung destruction. LAM is caused by small smooth muscle cell-like tumors throughout the lung that contain deleterious mutations in the tuberous sclerosis complex genes TSC1 or TSC2. This attenuates the activity of the mammalian target of rapamycin complex 1 (mTORC1) causing increased proliferation of the smooth muscle cells. LAM is a sexually dimorphic disease that primarily affects genetic females. Clinical observations implicate the role of estrogen in disease progression, as it is exacerbated during pregnancy and by use of exogenous estrogens in birth control. LAM tumor-derived cells lines have shown that direct estrogen stimulation of cell proliferation is modest compared to the dramatic in vivo effects of estradiol (E2) stimulation in a uterine-specific TSC2-null mouse model. Creation of a monoclonal cell line from these mice resulted in the generation of the LTM3 cell line, which also demonstrates low response to direct estrogen stimulation in vitro. This indicates that direct E2 stimulation may act upon other cell types in the tumor microenvironment. Immunophenotyping of uterine-specific TSC2-null mice has shown that the tumor microenvironment is enriched with myeloid cells specifically neutrophils. Functional analysis of neutrophil suppression in vivo has shown a reduction in myometrial growth in the uterine-specific TSC2-null mice, indicating a key role for neutrophil-mediated LAM tumor growth. Altered transcriptional regulation of neutrophils further highlights the importance of neutrophils in LAM progression. Bulk messenger RNA sequencing revealed E2 dependent increase in the neutrophil derived serine protease neutrophil elastase (NE). NE in vitro has been shown to increase migration, invasion, and proliferation of LAM cell lines, while inhibition in vivo has shown a reduction to the myometrial growth. Previously published data by the lab has shown that E2 increases tumor induced expansion of neutrophils in the bone marrow. Isolation and purification of Neutrophils from mouse bone marrow stimulated with tumor conditioned media from the LTM3 cells has shown signs of activation via upregulated gene expression. The focus of the current research has been the characterization of bone marrow derived neutrophils. Currently working with an in vitro system to study the proliferation of LTM3 and the rat leiomyoma (ELT3) cell lines when they are co-cultured with neutrophils. Understanding the mechanism by which neutrophils are activated and interact with LAM cells can give understanding to disease progression may provide insight into future treatment options.
Presentation: 6/3/2024