bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI369 SDHB Hereditary Pheochromocytoma Paraganglioma Syndrome With Biochemically Silent Pheochromocytoma
Authors: Skariah Annie M , Zacharia Christine C 
Published: October 2023

Abstract
Disclosure: A.M. Skariah: None. C.C. Zacharia: None.
Background: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal autonomic paraganglia. Majority of cases are sporadic but 30-50% are associated with genetic mutations. Patients with SDHB mutations can present with pheochromocytoma, paragangliomas or both. Lesions are usually extra-adrenal and typically secrete norepinephrine and occasionally dopamine. These cases are often associated with higher malignancy rates (up to 79%) compared to other SDH-x associated mutation cases. Clinical Case: Our patient is a 64-year-old female with history of secondary adrenal insufficiency, hypothyroidism, osteoporosis, GAD who presented in 2005 with left occipital headache and dysphagia. Workup was notable for a glomus tumor. She underwent tumor embolization, resection, radical neck dissection and radiation therapy. Genetic testing was not performed at the time of diagnosis. Routine biochemical surveillance was done postoperatively. In 2018, the patient was found to have a mild elevation of normetanephrine 248 pg/ml (&lt;148 pg/ml) and total metanephrine 297 pg/ml (&lt;205 pg/ml) levels. Subsequent plasma, urinary metanephrine/catecholamine studies were negative. In 2021, her brother was diagnosed with pheochromocytoma. Genetic testing was then pursued in the patient, and she was found to have a pathogenic mutation c.724C&gt;A (p.R242S) in the SDHB gene. In June 2022, CT chest, abdomen and pelvis with contrast was ordered, and she was found to have a homogeneously enhancing 1.3 x 1.1x 1.4 cm left adrenal nodule with indeterminate imaging characteristics. Following this CT, DOTATATE PET CT scan was done and demonstrated somatostatin avidity in the region of previously resected left glomus jugular tumor, right adrenal gland nodule and left inferior pubic ramus sclerotic lesion. Repeat biochemical testing remained negative for catecholamine excess. Despite being asymptomatic, there was concern for a biochemically silent pheochromocytoma. Alpha blockade was completed prior to right adrenalectomy in November 2022 and surgical pathology confirmed pheochromocytoma. The patient remains clinically stable, and she is now undergoing radiation therapy of her left pubic ramus lesion. Conclusion: It is important to have genetic evaluation early in the workup for a newly diagnosed PPGL. Additionally, suspicion for biochemically silent pheochromocytoma should be present even in the setting of negative biochemical workup and positive SDHB mutation.
Presentation: Friday, June 16, 2023
SAT187 A Case Of CDC73 Mutation Related Primary Hyperparathyroidism With Ectopic Parathyroid Hyperplasia
Authors: Wu Tao , Dhir Nikita , Bollineni Mohini 
Published: October 2023

Abstract
Disclosure: T. Wu: None. N. Dhir: None. M. Bollineni: None.
Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia, and most cases are sporadic. However, in 5-10% cases, it may occur as a syndromic and hereditary disease, like Multiple endocrine neoplasia type 1, type 2A, type 4, or CDC73 mutation related hereditary benign or malignant hyperparathyroidism. In patients with severe or early onset primary hyperparathyroidism, screening for genetic etiology should be considered. Case Presentation: A 35-year-old woman with a medical history of hypertension, kidney stones, and post-operative hypothyroidism presented to the endocrinology clinic due to recurrent hyperparathyroidism. She initially had a parathyroidectomy in 2008 and her calcium corrected at that time. She was again diagnosed with hypercalcemia due to primary hyperparathyroidism in 2021. She underwent re-exploration and had a right thyroid lobectomy with removal of three parathyroid glands. Her PTH was still 309 pg/mL (9-77 pg/mL) and calcium was 11.2 mg/dL (8.6-10.5 mg/dL), and she was started on Cinacalcet. The patient continued to have elevated calcium, bone pain, fatigue, and constipation. A 4D CT scan was ordered, which localized activity to a 1.5 cm arterial enhancing nodule in the anterior mediastinum, with intrathymic location. She underwent right video-assisted thoracoscopic total thymectomy with en bloc and the nodule was found to be ectopic parathyroid tissue. Post-operatively, her calcium normalized to 8.6 mg/dL and PTH was undetectable. She underwent genetic testing due to her recurrent hyperparathyroidism, which showed a CDC73 mutation. She is currently on calcitriol and calcium supplements, and serum calcium has been maintained in the low-normal range. Discussion: The CDC73 gene encodes a protein called parafibromin, which acts as a tumor suppressor, prohibiting cells from proliferating. Mutations in this gene are linked to jaw-tumor syndrome, familial isolated primary hyperparathyroidism (FIHP), and parathyroid carcinoma. These three CDC73-related disorders are clinically overlapping and inherited in an autosomal dominant manner. Biallelic mutations of the CDC73 gene are associated with a high risk of parathyroid cancer since the parafibromin protein is usually absent in parathyroid carcinoma and occasionally in atypical adenomas. FIHP tends to have a more severe clinical presentation with earlier onset (younger than 45 years). Additionally, patients with CDC73 related disorders are more prone to developing ossifying fibroma(s) of the jaw, uterine tumors, and various renal lesions. In summary, this case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed second surgery. Genetic testing is vital for early detection, surveillance, and familial genetic counseling in patients with CDC73 related disorders.
Presentation: Saturday, June 17, 2023
SAT607 Targeted Modulation Of Kisspeptin Neurons Improves Hyperandrogenism And Hyperactive LH Secretion In A Pre-clinical PCOS-like Mouse Model: Implications For Novel Therapeutics In PCOS Women
Authors: Coutinho Eulalia , Esparza Lourdes A , Kauffman Alexander S 
Published: October 2023

Abstract
Disclosure: E. Coutinho: Employee; Self; Crinetics. L.A. Esparza: None. A.S. Kauffman: Consulting Fee; Self; Crinetics.
Polycystic ovary syndrome (PCOS), a common reproductive disorder in women, is characterized by hyperandrogenemia, chronic anovulation, and/or cystic ovarian follicles. Another common hallmark of PCOS is LH hyper-pulsatility, believed to be driven by hyperactive GnRH neurons, but the reason for the increased GnRH secretion still remains unclear. We previously developed a PCOS-like mouse model using chronic letrozole (LET; aromatase inhibitor) and reported that LET females demonstrated multiple PCOS-like phenotypes, including polycystic ovaries, anovulation, hyperandrogenemia, enlarged ovaries, and hyperactive LH pulse secretion. Given the proposed role of hypothalamic arcuate kisspeptin neurons as the GnRH pulse generator, we determined that LET females have markedly elevated Kiss1 and Tac2 expression and increased Kiss1 neuronal activation in the arcuate nucleus, correlating with their hyper-pulsatile LH secretion. Thus, in the LET PCOS-like condition, and perhaps in PCOS women, increased hypothalamic kisspeptin and NKB neuron activity may be fundamental contributors to the hyperactive LH secretion and downstream hyperandrogenemia. We next tested this possibility using chemogenetics in transgenic PCOS-like mice to acutely and chronically suppress kisspeptin neuron activity. Acute inhibition of kisspeptin neurons successfully lowered abnormally high, rapid in vivo LH pulse secretion in PCOS-like females. Likewise, chronic in vivo suppression of endogenous kisspeptin neuron activity for several weeks dramatically lowered both circulating LH and T levels, and reduced ovarian weights, in females previously displaying a PCOS-like phenotype, with a trend towards improvement of overweight phenotype. These data support the hypothesis that overactive kisspeptin neurons may be one possible driver of neuroendocrine PCOS-like phenotypes. Importantly, these findings suggest that modulation of kisspeptin neurons may be a viable, novel therapeutic target to treat hyperandrogenism and hyperactive LH pulsatility in PCOS women. Indeed, although identical studies have not yet been done in humans, our findings complement recent clinical investigations using NKB receptor antagonists or dynorphin analogs to lower LH pulse secretion in PCOS women and other PCOS-like animal models.
Presentation: Saturday, June 17, 2023
SAT610 Multiple Endocrine Neoplasia Type 1 - The First Reported Case In An Indigenous Australian
Authors: Mignone Edward , Neal Kirsten 
Published: October 2023

Abstract
Disclosure: E. Mignone: None. K. Neal: None.
Background: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare and under recognised syndrome. It has not been previously reported in Indigenous Australians for this reason. Clinical Case: A 48-year-old Indigenous Australian female was consulted on by an inpatient endocrine team in March 2020 for persistent hypercalcaemia on a background of a parathyroidectomy in 2011 for primary hyperparathyroidism (PHPTH). She was admitted to a remote Australian hospital for investigation and management of acute on chronic abdominal pain. Relevant medical history included a parathyroidectomy at age 40, multiple PE/DVT, MI, AF, CTEPH, right heart failure, HTLV-1 and recurrent abdominal pain presumed secondary to GORD. Gastroscopy from 2013 revealed chronic gastritis with hundreds of gastric polyps discovered on subsequent gastroscopy in 2015. The young age of PHPTH combined with her chronic gastritis and polyps prompted neuroendocrine tumour (NET) screening, including MEN1. At time of consult in 2020, laboratory studies were consistent with recurrence of PHPTH with a corrected calcium of 2.9 mmol/L (2.15-2.57mmol/L), serum PTH level 31.5 pmol/L (1-7pmol/L), vitamin D level 30 nmol/L, 24-hour urinary calcium variable between low and high. NET markers were markedly elevated with a gastrin level of 14042 ng/L (&lt;100 ng/L), pancreatic polypeptide 2905 pmol/L (&lt;55 pmol/L), urine 5HIAA ratio 8 mmol/L (&lt;4 mmol/L), vasoactive intestinal peptide and glucagon levels normal. Pituitary studies, serum calcitonin, plasma metanephrines and PTH related protein levels were within normal limits. A CT of the abdomen showed thickened gastric folds, and persistent liver and IVC lesions from 2018. A diagnosis of Zollinger Ellison Syndrome (ZES) was made. Eventually, genetic testing was positive for a rare heterozygous variant of c.207dupC in exon 2 of MEN1 gene. A 68-gallium-DOTATATE PET/CT showed multiple avid pancreatic, gastric, nodal and liver lesions with high somatostatin receptor expression, suggestive of a neuroendocrine malignancy. Treatment was based largely on symptom control due to poor overall prognosis from underlying cardiorespiratory comorbidities. Abdominal pain from ZES was managed with a high dose PPI, H2 receptor antagonist and subcutaneous somatostatin analogue were trialled. Hypercalcaemia was treated with IV bisphosphonate therapy. Calcimimetic analogues were considered however patient declined. Genetic counselling was attempted however many cultural and logistical barriers were identified and family declined further testing. Unfortunately, our patient died in 2021 from presumed multifactorial respiratory failure. Conclusion: High index of suspicion is required to diagnose MEN1. This is particularly true within the Indigenous Australian population, with no prior documented cases reported.
Presentation: Saturday, June 17, 2023
SAT613 A Novel NF1 Mutation As The Underlying Cause Of Dysmorphic Features And Acromegaly In An Atypical Case Of Neurofibromatosis Type 1
Authors: Alsagheir Osamah , Alobaid Lulu Abdulaziz , Alswailem Meshael , Al-Hindi Hindi , Alzahrani Ali Saeed 
Published: October 2023

Abstract
Disclosure: O. Alsagheir: None. L.A. Alobaid: None. M. Alswailem: None. H. Al-Hindi: None. A.S. Alzahrani: None.
Introduction: Neurofibromatosis type 1 is an autosomal dominant disease with an estimated incidence of about 1:2000 cases. It is caused by genetic alterations in the gene NF1 encoding the tumor suppressor gene, neurofibromin. Patients with neurofibromatosis 1 are at an increased risk of a number of benign and malignant tumors including optic nerve gliomas, CNS tumors, malignant peripheral nerve sheath tumors, pheochromocytomas and many others. However, pituitary adenomas have been rarely described in neurofibromatosis type 1 and NF1 mutations have been found rarely in patients without manifestations of neurofibromatosis. In this report, we describe a patient with acromegaly who had some dysmorphic features but no clear skin or other manifestations of neurofibromatosis. He was found to have a deletion mutation in NF1 suggesting that his dysmorphic features and acromegaly are atypical manifestations of a previously undiagnosed neurofibromatosis type 1. Case Description: A 26-year-old-man presented at 18 years of age for evaluation of possible ventricular septal defect, which was ruled out by echocardiography, but he was found to have a subaortic membrane with moderate aortic regurgitation. He was also noticed to have coarse facial and body features which raised the possibility of acromegaly. He didn’t notice any facial changes, change in the size of hands and feet, headache or visual disturbances. In the family history, he reported that a number of his siblings are tall with large body habitus; none of them was evaluated or known to have medical illness. Physical examination: height 184 cm, weight 87 Kg, BMI 25, and BP 117/77 mmHg. He has frontal bossing, large supraorbital ridges, macrognathia, and hoarse deep voice but no skin tags, café au let spots, skin fibromas or freckling. Eye examination was unremarkable. Investigations: IGF-1 415 ng/ml (188-400), random GH 1.09 ng.ml (0.1-1.2). An oral glucose tolerance test showed baseline GH 0.99 increased to 8.05 ng/ml. An MRI of the pituitary gland showed a lobulated sellar and suprasellar heterogeneously enhancing pituitary adenoma. A Gallium 68 PET-CT scan showed an intense focus of uptake at the same location. Whole exome sequencing revealed a heterozygous NF1 mutation (NM_001128147.3: c.1782_*2del). This variant is likely pathogenic according to ACMG criteria. Conclusion: This case illustrates the value of whole exome sequencing for genetic testing in diagnosing atypical dysmorphia and other conditions when the diagnosis is not clear on clinical evaluation or conventional investigations. It also describes a rare association of acromegaly with neurofibromatosis.
Presentation: Saturday, June 17, 2023
THU133 Inpatient Hypoglycemia Management: Error Rates In Pediatric Diabetes Care
Authors: Odutayo Daniella A , Rizzi Elise M , Allen Natalie 
Published: October 2023

Abstract
Disclosure: D.A. Odutayo: None. E.M. Rizzi: None. N. Allen: None.
Hypoglycemia is a known side effect of exogenous insulin. During severe hypoglycemia, children with diabetes treated with insulin risk neurodevelopmental sequelae as protective glycolysis and ketogenesis are suppressed. Rapid treatment of hypoglycemia is crucial to prevent deleterious effects on neurocognition. There is a paucity of data elucidating inpatient hypoglycemia incidence and adherence to treatment standards in hospital care. The goal of this study is to assess the rate of hypoglycemia in children and adolescents with diabetes in the inpatient setting, and to assess adherence to American Diabetes Association (ADA) standards of care in treatment of hypoglycemia. Hypoglycemia is defined as blood glucose ≤ 70 mg/dL in children ≥5 years old, and ≤ 80 mg/dL in children&lt;5 years old. ADA guidelines advise treatment with 15 grams of fast acting carbohydrates and glucose recheck in 15 minutes. The study includes a retrospective chart review with patients 18 years of age and under with a diagnosis of either Type 1 or Type 2 diabetes, with inpatient admission to a tertiary care pediatric hospital in a 2-year period beginning January 1, 2020. Point-of-care blood glucose (BG) results were analyzed, as well as appropriate documentation of events and treatment. Time to repeat BG (TTR) was also analyzed and used as a measure of rapid treatment and assurance of resolution; acceptable time to repeat BG is 15 +/-5 minutes. The number of hypoglycemic events was also analyzed. Emergency room visits and venous glucose estimations were excluded. There were 422 hypoglycemic events in children &lt;5 years old, and 482 hypoglycemia events in children ≥5 years old. The median time to recheck was 41 min and 32.50 min with interquartile range of 12 to 65 min and 15 to 62.25 min respectively for children &lt;5 years and children ≥5 years. 4.62% of all reported blood glucose checks showed hypoglycemia. The percentage of rechecks occurring after 20 min were 24% and 65% for children &lt;5 years and children ≥5 years, respectively. Importantly, in the setting of severe hypoglycemia, defined as glucose &lt;55 mg/dL, the median time to recheck was 21 min with interquartile range 7.75 to 34 minutes. Based on the results of the study, ADA guidelines were not met, with the average glucose recheck times being over 15 +/-5 minutes in both groups of children. In the setting of severe hypoglycemia, recheck times were closer to ADA guidelines. Additionally, there was a correlation between increased recheck times and increased rates of hypoglycemia. The next proposed steps are to develop and implement a hypoglycemia algorithm for pediatric diabetes patients during hospitalization.
Presentation: Thursday, June 15, 2023
THU141 Clinical Characteristics Of Korean Youth-onset Type 2 Diabetes Patients With Remission
Authors: Shin Sohyun , Kim Hwa Young , Kim Se Young , Kim Jaehyun 
Published: October 2023

Abstract
Disclosure: S. Shin: None. H. Kim: None. S. Kim: None. J. Kim: None.
Backgrounds: Improvement of beta cell function can occur in some patients with type 2 diabetes mellitus (T2DM). However, studies on remission of youth-onset T2DM with pharmacotherapy are sparse. We aimed to identify the clinical characteristics of pediatric patients experiencing remission. Methods: Medical records of pediatric patients with T2DM who were followed up for at least 1 year at Seoul National Bundang Hospital (2015-2022) were retrospectively reviewed. Remission of T2DM was defined as a return of HbA1c to &lt;6.5% that persists for at least 3 months after discontinuation of glucose-lowering pharmacotherapy. Clinical characteristics between the remission and non-remission groups were compared at three time points (at diagnosis, 3 months after diagnosis, and remission). Results: Among 66 patients with T2DM (46 males, 69.7%), the mean age at diagnosis was 14.6±0.5 years, and the mean follow-up duration was 3.0±0.5 years. One (1.5%) patient underwent lifestyle modification only, 13 (19.7%) were treated with oral hypoglycemic agents only, and 52 (78.8%) were combined with insulin therapy at diagnosis. Twelve patients (18.2%) attained remission after a mean of 1.4±0.4 years from the time of diagnosis (at a mean age of 16.1±1.1 years). The remission group showed a higher proportion of males (100.0% vs. 63.0%, P = 0.012). At diagnosis of T2DM, urinary microalbumin-to-creatinine ratio (ACR) was lower in the remission group than in the non-remission group (2.0±1.6 mg/g vs. 11.2±2.9 mg/g, P = 0.010). There were no significant differences between the groups in the presence of initial diabetic ketoacidosis, HbA1c levels at diagnosis, and type of initial treatment. At the time of remission, HbA1c levels were significantly decreased (from 11.8% to 5.4%), while high-density lipoprotein cholesterol levels were increased (from 40.1 mg/dL to 45.7 mg/dL) than those at the time of diagnosis (both P &lt;0.05). Recurrence occurred in three of 12 (25.0%) patients after a mean of 1.9±1.7 years from the time of remission. Conclusion: In Korean youth with T2DM, remission was observed in 18.2% after a mean of 1.4 years of intervention with lifestyle and pharmacotherapy. Youth with T2DM remission showed male predominance, and lower ACR at the time of diagnosis. Further studies about underlying pathophysiology and long-term outcomes after remission are warranted.
Presentation: Thursday, June 15, 2023
THU142 One-year Change In Bile Acids And Its Association With Changes In Metabolic Profile After Sleeve Gastrectomy In Youth
Authors: Tuli Shubhangi , Kaur Snimarjot , Bredella Miriam , Misra Madhusmita , Singhal Vibha 
Published: October 2023

Abstract
Disclosure: S. Tuli: None. S. Kaur: None. M. Bredella: None. M. Misra: None. V. Singhal: None.
Introduction: Bile acids (BAs) are hydroxylated steroid acids. Primary (10) BAs (cholic acid (CA) and chenodeoxycholic acid (CDCA) are synthesized by the liver. Secondary (20) BAs (deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) are formed from 10 BAs by the action of intestinal flora. Preclinical studies indicate a role of BAs in weight loss and metabolic improvements after metabolic and bariatric surgery (MBS). Data are inconsistent regarding changes in BAs after sleeve gastrectomy (SG), the most common MBS. Further, how BA changes contribute to metabolic improvements after SG is unclear. Objective: Evaluate changes in serum BAs 1 year after SG in youth with obesity and associations with changes in metabolic parameters. Methods: 16 adolescents (75% females) 13-22 years old with severe obesity were followed for one-year post-SG with assessments at baseline and during a mixed meal tolerance test (MMTT). We measured fasting BAs, glucose, insulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipids. Blood was drawn at 15, 30, 60, 90, and 120 minutes for glucose and insulin and at 0, 15, 60, and 120 minutes for BAs. Data are reported as changes over 15 minutes [t15–t0 of MMTT (Δ15)], area under the curve (AUC), and % change. Results: BMI decreased by 25.7% (p&lt;0.0001). For 10 BAs: fasting CA levels decreased (33.3%, p=0.005), while Δ15 CA, CDCA and, total 10 BAs (113.3%, 188.9%, 152.9%, p&lt;0.005), and AUC for CDCA and total 10 BAs (34.2%, p=0.004; 30.3%, p=0.015) increased one-year post-SG. For 20 BA: Δ15 DCA and total 20 BAs (212.5%, p≤0.011; 195.2%, p=0.004), and AUC DCA and total 20 BAs (95.0%, p=0.031; 59.4%, p=0.035) increased. Δ15 and AUC total BA also increased (100%, p=0.002; 1060.9%, p≤0.0001). Insulin resistance (HOMA-IR) (58.6%), low-density lipoprotein (LDL) (11.2%), triglyceride (14.6%), and ALT (26.9%) decreased (p&lt;0.05), while high-density lipoprotein (HDL) levels (10.2%, p=0.04) increased. Decreases in AUC insulin were associated with increases in AUC 20/10 BA (ρ=-0.687, p=0.009). HBA1C decreases were associated with increases in AUC total BAs (ρ=-0.531, p=0.034). Increases in the insulinogenic index (Δ30 Insulin/ Δ30 glucose) correlated positively with fasting DCA (ρ=0.567, p=0.028). Increases in HDL were associated with increases in fasting CA (ρ=0.580, p=0.018) and UDCA (ρ=0.592, p=0.016). Conclusion: Total, 10, and 20 bile acids increase after SG in youth associated with improvements in metabolic profile.
Presentation: Thursday, June 15, 2023