bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT417 Comparison Of Mental Health Status In Transgender And Gender Diverse Versus Cisgender People
Authors: Pedreira Clarissa C , Tchir-Bourgeois Sophia , Tuli Shubhangi , Giancola Abigail , Lopez Lopez Ana P , Keuroghlian Alex S , Misra Madhusmita , Andreano Joseph M
Published: October 2023

Disclosure: C.C. Pedreira: None. S. Tchir-Bourgeois: None. S. Tuli: None. A. Giancola: None. A.P. Lopez Lopez: None. A.S. Keuroghlian: None. M. Misra: None. J.M. Andreano: None.

Background: In the last decade, there has been an increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and health care. These individuals are at a substantially increased risk for depression, anxiety and suicide relative to cisgender people. Some estimates suggest a lifetime prevalence of suicide approaching 40%, a rate ten times that of the general population. Nonbinary people appear to experience stressors that are both similar to and unique from those experienced by transgender (TG) men and women. Objective: To assess and compare the mental health status of TGD (before starting gender affirming hormone therapy) versus cisgender people. Methods: We collected cross-sectional data from 14 TGD (8 TG binary and 6 nonbinary) and 11 cisgender subjects before starting gender affirming hormone therapy. Subjects completed a series of self-reported inventories designed to assess depressive symptoms (Center for Epidemiological Studies Depression Inventory), anxiety (State/Trait Anxiety Inventory), traumatic experiences (Post-Traumatic Stress Disorder symptom self-report version), response to depressive mood (Ruminative Response Scale) feelings and emotions (Positive and Negative Affect Schedule), and personality (NEO Personality inventory). Results: Mean [SD] age was 25.8 [6.0], 27.6 [4.7] and 26.5 [4.3) years for TG binary, nonbinary and cisgender groups respectively. Mean [SD] age of gender dysphoria was 14.5 [4.9] and 14.5 [8.9] years for TG binary and nonbinary groups respectively. Compared with the cisgender group, the nonbinary group had higher scores for negative feelings and emotions [29.50 (19.25, 31.25) vs. 13.00 (10.00, 19.00), (p=0.005)], rumination [55.33 ± 4.72 vs. 41.36. ± 3.45 (p=0.03)], depression [15.83. ± 1.62 vs. 8.73 ± 1.20 (p=0.005)], anxiety [47.67 ± 3.72 vs. 34.82. ± 2.97 (p=0.02)], and neuroticism [41.83 ± 2.82 vs. 30.46. ± 2.57 (p=0.01)]. Traumatic experiences did not differ between the two groups. Compared to the TG binary group, the nonbinary group had higher scores for negative feelings and emotions [26.50 ± 2.59 vs. 17.13 ± 1.68 (p=0.01)] and depression [15.83. ± 1.62 vs. 9.50 ± 1.63 (p=0.02)]. Levels of anxiety, rumination, traumatic experiences and neuroticism did not differ between these groups. Conclusion: These results direct attention to the increased levels of negative feelings and emotions as well as depression in the nonbinary group compared to TG binary and cisgender groups. The data highlight the critical need for intervention approaches to mitigate these risks in nonbinary individuals.

Presentation: Saturday, June 17, 2023
THU506 A Not-So-Simple Case Of Hyperparathyroidism
Authors: Bhatt Plukshi J , Rabiei Samaneh , Kantorovich Vitaly
Published: October 2023

Disclosure: P.J. Bhatt: None. S. Rabiei: None. V. Kantorovich: None.

Multiple endocrine neoplasia 1 (MEN-1) is a rare autosomal dominant disorder caused by an inactivating mutation of the MEN-1 tumor suppressor gene and is associated with tumors of the parathyroid (95%), endocrine pancreas (40-70%) and anterior pituitary (30-40%). Primary hyperparathyroidism is the most frequent and earliest expression of MEN1 syndrome with a typical onset at age 20-25 in inherited cases, reaching 100% penetrance after age 50. Current guidelines recommend genetic testing in all individuals with primary hyperparathyroidism diagnosed at a young age, with multiglandular disease, or with family history of primary hyperparathyroidism. A 58 year old female with a history of L. breast cancer, pulmonary embolisms, DM2, and recurrent nephrolithiasis was diagnosed with primary hyperparathyroidism at age 36 and had a parathyroidectomy with 3.5 gland removal and later a total thyroidectomy. She continued to be symptomatic and was found to have an ectopic parathyroid gland in her chest requiring parathyroid gland reimplantation 18 years later. After 3 years, she was admitted for a CHF exacerbation and a pancreatic tail lesion was incidentally discovered. There was no mention of pancreatic lesions prior to this reading. Family history was pertinent for a father with nephrolithiasis. Her daughter had recurrent nephrolithiasis, hyperparathyroidism and was found to have a MEN 1 variant of uncertain significance, prompting the patient to seek genetic counseling. 22 years after her initial diagnosis of hyperparathyroidism, she tested positive for a likely pathologic heterozygous variant mutation of the MEN1 gene called 1747C>T. At endocrinology follow-up, she was asymptomatic. Labs showed elevated Chromogranin A at 1,799 ng/ dL [<311] and gastrin 174pg/mL [</=100]. FSH, LH, prolactin, free alpha subunit, cortisol, and IGF-1 were normal. Further imaging confirmed a DOTATATE-avid 1.1cm nodular lesion in the pancreatic tail, concerning for a neuroendocrine tumor. MEN1 gene mutation is associated with MEN1 syndrome, familial isolated hyperparathyroidism and has an autosomal dominant predisposition to thyroid cancer and paraganglioma-pheochromocytoma syndrome. The 1747C>T sequence change creates a premature translational stop signal in the MEN1 gene and disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation. Upon diagnosis of multiglandular hyperparathyroidism, the patient should have been sent for genetic testing and instead, became an example of a multisystem failure to identify and provide necessary testing and treatment. Until her variant diagnosis, her pancreatic tumor was not identified as such. The main cause of mortality in MEN-1 patients is malignant spread of neuroendocrine tumors, hence early detection and prompt treatment are of the utmost importance to preserve quality of life and improve survival.

Presentation: Thursday, June 15, 2023
THU521 A Case Of Multifocal Pancreatic Neuroendocrine Tumor With Multiple Twists
Authors: Syeda Asma , Kantorovich Vitaly
Published: October 2023

Disclosure: A. Syeda: None. V. Kantorovich: None.

Background: Multifocal pancreatic neuroendocrine tumors (PNETs) are rare and are usually associated with genetic syndromes like Multiple Endocrine Neoplasia 1 (MEN1). Sporadic multifocal PNETs have been infrequently reported. Case: A 68-year-old Caucasian female with a past medical history of hypertension, hyperlipidemia, type 2 diabetes mellitus, morbid obesity, multiple renal cysts, and Barrett’s esophagus presented to endocrinology for evaluation of PNET. An MRI performed for evaluation of renal cysts demonstrated pancreatic lesions suspicious for neoplasm. An endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (FNAB) of the largest lesion was consistent with low grade PNET positive for chromogranin A (CgA) and synaptophysin. Biochemical workup was remarkable for elevated CgA of 4800 ng/mL (n: <311 ng/mL) and elevated gastrin level of 700 pg/mL (n: <100 pg/mL); however, the patient was on proton pump inhibitors. A Ga-68 DOTATATE scan revealed 4 DOTATATE avid masses in the pancreatic head, neck, body and tail, the largest measuring 2.3 cm in the pancreatic head. No metastatic lesions were identified. Family history is significant for hyperparathyroidism in one sister and endometrial cancer in another sister. Genetic testing was negative for 86 genetic mutations including MEN1, VHL, TSC1 and TSC2. The patient underwent a successful total pancreatectomy, splenectomy and duodenectomy with a hepaticojejunostomy and gastrojejunostomy. Surgical pathology revealed 5 multifocal tumors, measuring 0.4-2.2 cm in diameter, with clear margins, without any lymphovascular invasion and 19 lymph nodes negative for malignancy. Mitotic rate was <2 mitoses per mm2 and Ki-67 index was < 3 %. Next Generation Sequencing of the surgical specimen was positive for ATM gene deletion. Interestingly, immunohistochemistry stained strongly for insulin, glucagon and INSM1 suggestive of nesidioblastosis although the patient did not have preoperative hypoglycemia that would raise a clinical suspicion. Discussion: This case highlights several unique features in a multifocal PNET. A recent study suggested that multifocality is not associated with worse prognosis or increased risk of recurrence. Another distinctive finding in our patient is the ATM gene mutation. Heterozygous pathogenic variants in ATM gene are known to be associated with hereditary pancreatic cancer but there has been no reported association with PNETs. ATM gene down regulation is linked with metastatic NETs and was proposed as a potential predictive marker for metastasis and as a novel target in metastatic gastroenteropancreatic NETs. Concurrent occurrence of nesidioblastosis and PNET has been rarely reported in the literature, however, it was a clinically silent phenomenon in our case.

Presentation: Thursday, June 15, 2023
SAT632 The Functional Role And Regulatory Mechanism Of FTO M6A RNA Demethylase In Human Uterine Leiomyosarcoma
Authors: Yang Qiwei , Al-Hendy Ayman
Published: October 2023

Disclosure: Q. Yang: None. A. Al-Hendy: None.

Introduction: Uterine leiomyosarcoma (uLMS) is the most frequent subtype of uterine sarcoma that presents a poor prognosis, high rates of recurrence, and metastasis. However, the origin and molecular mechanism underlying driving its clinical and biological behavior remain to be determined. Recently, we and others have revealed the role of microRNAs, DNA methylation, and histone modifications contributing to the pathogenesis of uLMS. However, the connectivity between reversible RNA m6A methylation and uLMS remains unclear. In this study, we assessed the role and mechanism of the m6A demethylase fat mass- and obesity-associated protein (FTO) in the pathogenesis of uLMS. Materials and Methods: We performed immunohistochemistry (IHC) and immunoblot analysis to measure the m6A erasers FTO and ALKBH5 protein levels in LMS and adjacent myometrium tissues (n=8) and cell lines. We performed LMS cell proliferation and cell cycle phase distribution analysis. RNA-seq was performed to determine the molecular mechanism underlying m6A eraser inhibition in LMS cells (n=4 for each group). The R package limma+voom was used for this analysis. Hallmark pathway analysis was used to identify enriched pathways in response to FTO inhibition. Real-time PCR was performed to validate the differentially expressed genes. Ingenuity pathway analysis (IPA) was performed to determine the upstream regulators targeting cell cycle-related genes. We used a cutoff −1.5 > fold-change > 1.5 and an adjusted p-value of 0.05. In addition, data were analyzed by a two-tailed unpaired Student’s t-test between any two groups. Results: IHC analysis revealed that m6A demethylases FTO and ALKBH5 are aberrantly upregulated in uLMS tissues compared to adjacent myometrium (p<0.01, H-score). Furthermore, inhibition of FTO with its small, potent inhibitor (Dac51) decreased the uLMS proliferation dose-dependently via cell cycle arrest at G1. Notably, RNA-seq analysis revealed that inhibition of FTO with Dac51 exhibited a significant decrease in the expression of multiple CDK members and a significant increase in the expression of CDKN1A. Furthermore, IPA analysis revealed that transcription factors, including SP1 and E2F members are the upstream regulators targeting CDK members in response to Dac51 treatment. Moreover, Dac51 treatment altered the expression of several epigenetic regulators, including Sirt1 and 2, HDAC10 and SUV39H1, and rewiring of several critical pathways, including inflammation response, G2M checkpoint, and C-Myc signaling, among others, leading to suppression of uLMS phenotype. Conclusion: Our findings uncover the anti-uLMS function of a potent FTO inhibitor via reprogramming the oncogenic epitranscriptome. Therefore, targeted inhibition of FTO may provide an additional regulatory layer for a promising and novel strategy for treating patients with this aggressive uterine cancer.

Presentation: Saturday, June 17, 2023
SAT289 Prevalence And Treatment Outcomes of Critical Illness-related Corticosteroid Insufficiency (CIRCI) In Septic Shock Patients In Medical Wards And Emergency Room In Thammasat University Hospital
Authors: Sanpawithayakul Kanokporn , Meepornbucha Kamonwan , Pirompanich Pattarin , Vibhatavata Peeradon
Published: October 2023

Disclosure: K. Sanpawithayakul: None. K. Meepornbucha: None. P. Pirompanich: None. P. Vibhatavata: None.

Background: The reported prevalence of critical illness-related corticosteroid insufficiency (CIRCI) varies widely, depending on the patient population studied and the diagnostic criteria used. Although hydrocortisone (HC) is widely used in patients with septic shock who respond poorly to adequate fluid resuscitation and vasopressors, clinical outcomes remain controversial. Objectives: To investigate the prevalence of CIRCI and to evaluate characteristics of septic shock patients treated with HC due to suspicion of CIRCI as compared to septic shock patients without CIRCI. Material and Method: Retrospective analysis of septic shock patients admitted in medical wards in Thammasat University Hospital, from January 2020 to June 2021, was performed. Prevalence of CIRCI in septic shock patients was explored by using different serum cortisol cutoff at 10 μg/dL (C-10) and 18 μg/dL (C-18), respectively. 28-day mortality, duration of hospital and intensive care unit (ICU) admission, mechanical ventilator usage, need for vasopressor support, and complications of HC use were also analyzed. Results: Of the 252 septic shock patients, 68 patients were met our inclusion criteria. Eight (11.8%) and 20 (29.4%) patients was diagnosed with CIRCI by serum cortisol cutoff 10 and 18 µg/dL, respectively. There were no significant differences in baseline characteristics (i.e., age, sex and preexisting diseases) between groups. Of the septic shock patients without CIRCI diagnosed by C-18 cutoff, initial SOFA and APACHE II, serum creatinine and lactate were significantly higher. Moreover, 28-day mortality rate was statistically higher in patients without CIRCI by C-18 cutoff (70.8% vs 40.0%, p=0.03). Multivariate analysis recognized the the amount of vasopressor use as significant predictor of 28-day mortality, with OR 19.04 (95%CI 1.23-293.80, p=0.04) and 19.34 (95% CI 1.27-293.50, p=0.03) in C-10 and C-18, respectively. However, in-patient mortality was not statistically different between groups regardless of the cortisol cutoff. Conclusion: Using a 18-C cutoff, there was a higher mortality rate in patients without CIRCI. Keyword: Septic shock, CIRCI, critical illness-related corticosteroid insufficiency

Presentation: Saturday, June 17, 2023
SAT325 Recurrent Pericardial Effusion As Initial Presentation Of Primary Adrenal Insufficiency
Authors: Ward Samuel , Champion Amber Laurel , Mrkaic Ana
Published: October 2023

Disclosure: S. Ward: None. A.L. Champion: None. A. Mrkaic: None.

Recurrent Pericardial Effusion as Initial Presentation of Primary Adrenal Insufficiency:

Background: Primary adrenal insufficiency (PAI) is a rare but serious endocrinopathy. High clinical suspicion is important to avoid delay in diagnosis and treatment. We present a rare case of recurrent pericardial effusion as initial presentation. Clinical Case: 63 year old male with hypertension and diabetes presented to ED complaining of SOB and chest pain. Workup revealed pericardial effusion causing cardiac tamponade treated with emergent pericardiocentesis. He was admitted to ICU for hypotension. He was also diagnosed with COVID-19 and acute kidney injury. Labs showed hyperkalemia ranging from 5.3 to 7.2 mmol/l (n= 3.5-5.1 mmol/l) and hyponatremia 132 mmol/L (n= 136-145 mmol/L). He was started on dexamethasone for COVID-19 infection. Etiology of pericardial effusion was unclear; infectious disease workup was unremarkable, cytology showed no malignant cells, autoimmune panel was negative. Initial echo showed EF >55%. After initiation of steroids, symptoms improved with normalization of electrolytes and improvement of hypotension, however was discharged on midodrine 2.5 mg TID. Seven days after discharge patient called 911 complaining of worsening shortness of breath. He was found to be severely hypotensive with BP 67/40. Echo showed moderate to large pericardial effusion causing tamponade. Emergent pericardial window was performed. Labs showed hyponatremia 123 mmol/L and potassium ranging from 4.9-5.4 mmol/L. Patient remained hypotensive requiring pressors despite pericardial effusion drainage. With persistent hypotension, hyperkalemia, and hyponatremia there was strong suspicion for adrenal insufficiency and workup was consistent with PAI. Labs showed 8:00 am cortisol 2.7 ug/dl (n= 3.7-19.4 ug/dl), ACTH 256.0 pg/ml (n=7.2-63.3pg/ml), aldosterone <1.0 ng/dL, renin 4.216 ng/mL/hr (n= 0.167-5.380 ng/mL/hr). Due to his critical illness patient was started on stress dose hydrocortisone 50 mg Q6 hr. With initiation of steroids, hyponatremia, hypokalemia, and hypotension resolved. Patient was weaned to physiological doses of hydrocortisone and started on fludrocortisone at time of discharge. Conclusion: Timely diagnosis of PAI is essential and can be lifesaving, if untreated it can lead to adrenal crisis with high mortality. Having a high clinical suspicion is crucial to a prompt diagnosis. Pericardial effusion should prompt clinical suspicion for PAI as multiple cases have now been reported in the literature. Our patient has multiple potential causes of pericardial effusion including PAI, acute kidney injury, and COVID-19 infection. Although we cannot show definitive causation from PAI, it most certainly contributed and prompt diagnosis and treatment may have prevented recurrence. It is important to raise awareness of PAI as a differential in pericardial effusion.

Presentation: Saturday, June 17, 2023
OR30-01 Waking Salivary 11-hydroxyandrostenedione And Cortisone As A Novel Non-invasive Test For Adrenal Insufficiency
Authors: Lawrence Neil Richard , Keevil Brian George , Elder Charlotte , Fearnside Jane , Caunt Sharon , Dixon Simon , Newell-Price John D C , Ross Richard John M , Debono Miguel
Published: October 2023

Disclosure: N.R. Lawrence: None. B.G. Keevil: None. C. Elder: None. J. Fearnside: None. S. Caunt: None. S. Dixon: None. J.D. Newell-Price: Consulting Fee; Self; Diurnal, Recordati, Crinetics, HRA Pharma. R.J. Ross: Employee; Self; Diurnal. M. Debono: None.

Background: The ACTH (Cosyntropin) stimulation test (AST) is the reference standard for diagnosis of adrenal insufficiency. We have demonstrated recently that home waking salivary cortisone accurately predicts the ACTH stimulation test outcome and confirms or excludes adrenal insufficiency in 70% of high-risk patients (in press: Home Waking Salivary Cortisone to Screen for Adrenal Insufficiency NEJM Evidence). 11-hydroxyandrostenedione (11-OHA4) is a weak adrenal androgen whose synthesis is dependent on CYP11B1. Since ACTH drives steroidogenesis, and adrenal androgens are low in patients with adrenal insufficiency, we hypothesised that waking 11-OHA4 could also predict adrenal status. Methods: A prospective, diagnostic accuracy study of waking salivary cortisone was performed in 173 patients at high risk of AI. All patients collected a salivary sample on waking, and then attended the endocrine clinic for an AST with the 30-minute cortisol used to diagnose AI. Salivary cortisone and 11-OHA4 was measured in the waking salivary sample. Biomarker discrimination was assessed by calculation of area under the curve (AUC) of the receiver operator characteristics (ROC) plot. Equivocal results were defined to maintain a sensitivity of 95% and specificity of 95%, and percentage of AST saved by calculating the number of AST needed if used only in equivocal cases. Results: The median (IQR) for 11-OHA4 for patients with AI and no AI was 55 (45 to 110) pmol/l vs 508 (255 to 765) pmol/l; p<0.0001. Salivary 11-OHA4 on waking was highly predictive of adrenal insufficiency (R2=0.63, ROC AUC 0.94), similar to waking salivary cortisone alone (R2=0.65, AUC 0.94). Waking 11-OHA4 performed better than either serum cortisol (R2=0.65, AUC 0.88) or salivary cortisone (R2=0.74, AUC 0.93) collected at the baseline of the AST. Combining both waking salivary 11-OHA4 with waking salivary cortisone further improved discrimination (R2=0.70, AUC 0.96), and using this combination would mean that 78% of ACTH-stimulation tests could be avoided. Conclusion: Waking salivary 11-OHA4 can accurately predict AI with similar discriminatory value as waking salivary cortisone. Combining waking 11-OHA4 with waking salivary cortisone improves discrimination for adrenal insufficiency, is a simple non-invasive test that can be used widely in clinical practice in the ambulatory setting, and obviates the need for AST in 78% of cases with greater patient convenience and lower costs.

Presentation: Sunday, June 18, 2023
THU461 Severe Hypercalcemia Associated With Perinatal Hypophosphatasia While Receiving Enzyme Replacement Therapy
Authors: Salama Mostafa , Tebben Peter J
Published: October 2023

Disclosure: M. Salama: None. P.J. Tebben: None.

Introduction: Hypophosphatasia (HPP) is characterized by defective bone mineralization due to reduced function of tissue non-specific alkaline phosphatase (TNSALP) from pathogenic ALPL gene variants. Initial presentation varies according to the clinical phenotype. Hypercalcemia is more common in the perinatal and infantile forms and may be mitigated or prevented with enzyme replacement therapy asfotase alfa (AA). Here, we report a patient who developed severe hypercalcemia while receiving AA and describe our management strategy. Case: A now three-year-old girl with perinatal hypophosphatasia presented with severe hypercalcemia at 9 months of age. Her prenatal ultrasound was suggestive of a skeletal dysplasia. She was diagnosed with HPP shortly after birth and initiated AA on day two of life. She had normal calcium of 10.5 mg/dl at diagnosis. Phosphorus 9.3 mg/dl, total alkaline phosphatase <5 U/L, pyridoxal 5-phosphata (PLP) 974 mcg/L and phosphoethanolamine (PEA) 1084 nmoL/mg. Calcium dropped to 6.8 mg/dL after starting AA for which calcium supplementation was transiently utilized. At nine months of age, she developed severe hypercalcemia (15.8 mg/dl). Her phosphorus was 5.5 mg/dl, PLP 14 mcg/l and 25 hydroxyvitamin D 28 ng/ml. Parathyroid hormone and calcitriol were appropriately suppressed at <6.0 pg/ml and <8.0 pg/mL respectively. She was receiving 2 mg/kg of Asfotase three times weekly. Initial management included intravenous fluids and a reduction in dietary calcium intake by 50%. Within 2 days, calcium came down to upper normal for age at 11 mg/dL. AA dose was increased to 3 mg/kg three times weekly due to hypercalcemia and mildly worsening radiographs. Hypercalcemia recurred and initially responded to IV fluids and further dietary calcium reduction (low calcium formula (2.9 mg/ 5 fl oz)). Despite these measures, she required a third hospital admission when calcitonin 4 IU/kg every 12 hours was added to her restricted dietary calcium intake and AA therapy. On this regimen, her calcium normalized without recurrence of severe hypercalcemia. Over the subsequent eight months, calcium intake was slowly increased, and calcitonin tapered and discontinued with maintenance of calcium within the normal range. Conclusion: Hypercalcemia is common in infants with untreated, severe HPP and is likely mitigated for most when treated with AA. This case highlights the importance of monitoring calcium concentrations and intake in infants with HPP. Although calcitonin is generally not considered a long-term therapy for hypercalcemia, bisphosphonates may worsen the bone disease of HPP and should be avoided. This case demonstrates the utility of calcitonin therapy added to low calcium intake and maximal AA dosing to treat severe, persistent hypercalcemia in an infant with perinatal HPP.

Presentation: Thursday, June 15, 2023
SAT232 Patients With Chronic Hypoparathyroidism Have Higher Risk Of Vertebral Fracture And Lower Risk Of Femoral Fracture Compared To Controls
Authors: Bjornsdottir Sigridur , Kamal Wafa , Lomholt Langdahl Bente , Spelman Tim , Lyman Clarke Bart , Kampe Olle
Published: October 2023

Disclosure: S. Bjornsdottir: None. W. Kamal: None. B.L. Langdahl: None. T. Spelman: None. B.L. Clarke: None. O. Kampe: None.

Context: Previous studies have shown that patients with hypoparathyroidism (hypoPT) have reduced bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increased risk of fractures in patients with hypoPT. Objective: The aim of this study was to evaluate the risk of fractures in patients with hypoPT in Sweden. Patients: The Swedish National Patient Register, the Swedish Prescribed Drug Register and the Total Population Register were used to identify 1982 patients with chronic hypoPT (duration ≥ 12 months), and 19820 controls matched by age, sex and county of residency between 1997-2018. The 10th revision of the International Classification of Diseases (ICD) was used to identify fractures. Results: Patients with hypoPT did not have higher risk of any fracture compared to controls (HR 0.96; 95% CI 0.86-1.08). However, patients with hypoPT had a slightly higher risk of vertebral fractures (HR 1.33; 95% CI 1.01-1.75), p= 0.047 and a lower risk of femoral fractures (HR 0.60; 95% CI 0.45-0.82), p= 0.001. There was no significant difference in the risk of fractures of the forearm, p= 0.177, proximal humerus, p= 0.096 or pelvis, p= 0.446. There was no difference in the risk of any fracture between females and males with hypoPT (p for interaction= 0.511). Patients with surgical hypoPT had a significantly higher risk of any fracture compared with patients with non-surgical hypoPT (p for interaction= 0.006). Conclusion: The risk of any fracture was not increased in patients with hypoPT. However, the risk of vertebral fracture was increased, and the risk of femoral fracture was lower than for matched controls. No difference was found in fracture risk between females and males. Patients with surgical hypoPT had a higher fracture risk compared to patients with non-surgical hypoPT.

Presentation: Saturday, June 17, 2023
SAT240 Recurrent Hypercalcemia Due To 1,25 Dihydroxy Vitamin D Elevation Of Unclear Etiology
Authors: Javvaji Abhiram , Anastasopoulou Catherine
Published: October 2023

Disclosure: A. Javvaji: None. C. Anastasopoulou: None.

Introduction: Recurrent Hypercalcemia is common with primary hyperparathyroidism and malignancy accounting for 90% of cases. Extra renal activation of 1α-hydroxylase with subsequent elevation of 1,25 dihydroxy vitamin D is a relatively uncommon cause of hypercalcemia. Herein, we report an unusual case of recurrent hypercalcemia due to elevated 1,25 dihydroxy vitamin D of unclear etiology, resistant to therapy with denosumab or bisphosphonate that responded to glucocorticoid therapy. Case Presentation: A 68 year old female was admitted to the hospital for worsening calcium with symptoms of polyuria and increased thirst. Review of systems and physical examination were otherwise unremarkable. Initial work-up demonstrated calcium level of 11.7mg/dL (8.7-10.3), creatinine 2.58 mg/dL (0.57-1), PTH 8pg/mL (15-65), Kappa/Lamba ratio 1.82 (0.26-1.6), PTHrP 11pg/mL (11-20), 25 (OH) Vitamin D 14ng/mL (30-100), 24,25 Dihydroxy Vitamin D ratio 25.81 (<25). Bone marrow biopsy, kidney biopsy, and myeloma work up were all unremarkable. Imaging studies including whole body CT and PET CT were also unremarkable. In the acute phase patient was treated with zoledronic acid and later denosumab with only temporary decrease in calcium levels. Ultimately, she responded well to prednisone therapy. Further work-up for finding the underlying cause of elevated 1,25 dihydroxy vitamin D remains ongoing. Discussion: Elevated 1,25 dihydroxy vitamin D level in granulomatous, neoplastic, and certain unusual diseases is well recognized as a cause of hypercalcemia. These levels may be exacerbated by increased intake of calcitriol, or by extra-renal production in granulomatous and lymphoproliferative diseases. Other rare causes of elevated 1,25 dihydroxy vitamin D include granulomatosis with polyangiitis, cat scratch fever, talc granulomatosis, Crohn’s disease, silicone granulomatosis. Patients with all these diseases respond well to steroids and that was another sign that further work-up to find the source of the elevated 1,25 dihydroxy vitamin D in our case is essential. Conclusion: In patients with recurrent hypercalcemia and elevated 1,25 dihydroxy vitamin D levels, a complete work-up for underlying malignancy, granulomatous or other unusual diseases is indicated. Glucocorticoid therapy is the most effective way to control the hypercalcemia related to increased 1,25 dihydroxy vitamin D even in the long-term phase, especially until the main cause of the problem is identified and treated appropriately.

Presentation: Saturday, June 17, 2023
SAT248 A Case Report Of Hypercalcemia Secondary To Calcium Sulfate Antibiotic Beads
Authors: Habibi Roshanak , Vahdani Golnaz , Ebrahimi Neda
Published: October 2023

Disclosure: R. Habibi: None. G. Vahdani: None. N. Ebrahimi: None.

Introduction: Periprosthetic joint infections are a rare and uncommon complication in arthroplasties of the hip or knee, happening in ∼0.7% of these procedures. Placement of antibiotic eluting beads, sometimes referred to as calcium sulfate beads (CSB), which are bio-compatible hydrophilic crystals used to deliver antibiotics locally, are one solution to prevent such complications. Hypercalcemia post-CSB placement is a very uncommon, rare and unusual complication that has only been presented in the literature a handful of times. Below, we report on a such a patient, illustrating the importance of surgical history in investigating the cause of hypercalcemia. Presentation: 63yo F with PMH of HTN, HLD, Crohn’s, T2DM, CKD3 who had a recent hospital admission 2 weeks prior for new arthritis secondary to pseudogout crystals, s/p bilateral synovectomy and CSB placement by orthopedics. She was subsequently discharged to nursing facility and re-presented to hospital for increasing AMS and worsening knee pain. Labs showed evidence of AKI with creatinine 1.9, severe hypercalcemia at 17.5 mg/dl with concomitant hypophosphatemia at 1.1 mg/dl. PTHrP WNL & PTH low at 7pg/ml and histo antigen neg, suggesting this was not related to PTH. Malignancy ruled out based on past imaging that was done in 2 months prior. MM ruled out since normal SPEP, UPEP, and kappa:lambda. Unlikely that this was milk alkali as patient did not have alkalosis. Vitamin 1,25 low at 10pg/ml ruling out sarcoidosis. Vitamin 25 WNL. Urine Ca 24hr WNL suggesting no FHH. Ca levels returned to normal after pamidronate, IV fluids and calcitonin. Chart review suggested that CSB implanted in her knees as the likely cause of her hypercalcemia. Discussion: It is important to bring awareness that one of the causes of severe hypercalcemia is post CSB placement. Vigilant monitoring of calcium levels pre and post operation after CSB placement is indicated, particularly in patients with a previous history of CKD. It has been hypothesized that there is a dose-dependent relationship between CSB volume and hypercalcemia, with suggestions that limiting CSB to less than 40ml per operation may be beneficial. A 10ml pack of CSB contains 5.73 grams of elemental calcium which is subsequently released over a 30-60-day interval. There is limited information on the mechanism of hypercalcemia secondary to CSB use, so further studies need to be implemented. Ultimately, it is crucial for physicians to have a high suspicion for CSB induced hypercalcemia post-arthroplasty as CSB use expands.

Presentation: Saturday, June 17, 2023
THU007 Improving Completeness Of Endocrinology Referrals Using Structured Templates
Authors: Arao Kevin , Wong Denise , Wormwood Jolie , Vimalananda Varsha
Published: October 2023

Disclosure: K. Arao: None. V. Vimalananda: None.

Objective: Endocrinologists rely on information in the referral to guide the focus and scope of their evaluations. However, endocrinology referrals frequently lack important clinical information, which may increase the risk of inefficiency, errors, and adverse outcomes. This quality improvement project aimed to improve the completeness of endocrinology referrals by utilizing structured referral templates for common endocrine conditions including diabetes, hypogonadism, osteoporosis, thyroid dysfunction (hyperthyroidism and hypothyroidism), and thyroid nodule. Methods: The project was implemented at a large Veterans Affairs Medical Center (VAMC) in New England. Structured referral templates were designed based on existing templates at other VA health systems, the American College of Physicians High Value Care Coordination Toolkit (developed in partnership with The Endocrine Society), and input from endocrinologists and primary care providers at the VAMC. Templates included fields for essential elements: a consult question, relevant clinical history and past medical history, type of visit preference, pertinent over-the-counter medications, and dates of relevant laboratory and imaging studies. We used functions including auto-population of data, checkboxes, and drop-down menus to ease usability. The templates were embedded into the electronic referral system. We conducted a retrospective chart review to compare referrals for a cohort of patients referred between 1/1/2021-9/1/2021 (pre-intervention) vs. a cohort referred between 10/1/2021-9/30/2022 (post-intervention). Each referral was rated using a scoring system derived from the criteria in the data abstraction tool formulated by the investigators. Results: On average, pre-intervention referrals included 52% of the essential elements and post-intervention referrals included 92%. Post-intervention referrals for diabetes, hypogonadism, osteoporosis, thyroid dysfunction (hyperthyroidism and hypothyroidism), and thyroid nodule improved from baseline by 44%, 45%, 39%, 39%, and 36% respectively. The greatest improvement was for the element “type of visit requested (one-time consultation, shared care, transfer of care, and consultant’s preference)”. A separate analysis excluding “type of visit” showed an average improvement from 64% of essential elements included pre-intervention to 92% included post-intervention. Conclusion: Structured referral templates embedded into an electronic referral system improves availability of essential information for the endocrine consultant. Our next steps are to modify the templates with the ongoing input of both endocrinologists and primary care providers. Future work should examine the effect of referral templates on specialist and primary care provider user experience, patient experience of care, efficiency, and clinical outcomes.

Presentation: Thursday, June 15, 2023
THU263 Intestinal Production of H2S And Its Regulation Of GLP-2
Authors: Hammond Joel , Yang Guangdong , Gagnon Jeffrey
Published: October 2023

Disclosure: J. Hammond: None. G. Yang: None. J. Gagnon: None.

Background: Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter that regulates a variety of physiological processes including hormone regulation. In individuals with Crohn’s disease or colitis, H2S is elevated. Whether this H2S plays a role in gut disease development or protection is not clear. Glucagon-Like Peptide-2 (GLP-2) is a gut health-promoting peptide hormone produced in the enteroendocrine L-cells located primarily in the distal GI tract. In the gut, GLP-2 increases cell proliferation, enhances barrier function, and decreases inflammation. Furthermore, GLP-2 administration has been shown to be protective in both Crohn’s and Colitis. Finally, our previous work has shown a role for H2S in the regulation of glucagon-like peptides. Hypothesis: We hypothesize that local H2S production in the distal GI tract and in enteroendocrine cells can regulate GLP-2 secretion and downstream gut physiology.Methods: GLP-2 secretion and gut physiology were examined in mice receiving exogenous H2S injections or lacking the H2S-producing enzyme cystathionine gamma-lyase (CSE). Additionally, H2S production and GLP-2 secretion were examined from mouse enteroendocrine L-cells (GLUTag). Results: CSE KO mice had significantly reduced intestinal H2S production. A slight increase in circulating GLP-2 was found in CSE KO mice. H2S was also produced directly from enteroendocrine cells which was partially blocked using CSE enzyme inhibitors. When enteroendocrine L-cells were treated with H2S donors (NaHS and GYY 4137), GLP-2 secretion was significantly reduced (with no effect on cell viability). Ongoing work will explore the direct effects of H2S administration in mice on circulating GLP-2, and any changes that occur in the gut epithelium as a result. Discussion/Conclusions: Our work indicates that the enteroendocrine cell can produce the gasotransmitter H2S, and that H2S donors can suppress GLP-2 secretion. These findings suggest that GLP-2 may play a role in the interplay between H2S and gastric health. These results could provide support for the potential use of H2S drugs in the treatment of GI diseases.

Presentation: Thursday, June 15, 2023
THU303 The Associations Between Rest-Activity Parameters, Sleep-Disordered Breathing Severity And Glucose Metabolism In Patients With Prediabetes
Authors: Paewponsong Jirayupa , Gerber Ben S , Chirakalwasan Naricha , Saetung Sunee , Anothaisintawee Thunyarat , Reutrakul Sirimon
Published: October 2023

Disclosure: J. Paewponsong: None. B.S. Gerber: None. N. Chirakalwasan: None. S. Saetung: None. T. Anothaisintawee: None. S. Reutrakul: None.

Background: Circadian rhythm abnormalities and sleep-disordered breathing (SDB) can have an adverse effect on glucose metabolism. In addition, studies have suggested that SDB itself could be associated with circadian disruption. This study aimed to determine if circadian characteristics, as measured by rest-activity rhythm parameters, were connected with SDB severity in individuals with prediabetes, and whether rest-activity rhythm parameters were related with glycemia. Methods: A total of 79 patients with prediabetes were enrolled. Actigraphy recordings (Actiwatch 2, Phillips Respironics) spanning 7 days yielded non-parametric rest-activity rhythm parameters and sleep duration. The parameters included M10 (mean activity of the most active 10-h period), L5 (mean activity of the least active 5-h period), intradaily variability (reflecting rhythm fragmentation), interdaily stability (reflecting sleep regularity across days), and relative amplitude (reflecting the activity between M10 and L5 activity). SDB was assessed using an overnight sleep monitor (WatchPAT200). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) were obtained via phlebotomy. Independent predictors of rest-activity rhythm parameters, FBG, and HbA1c were determined using multiple stepwise regression analyses. Model covariates included age, sex, body mass index (BMI), and SDB severity. Results: Increasing SDB severity was associated with lower M10 and greater intradaily variability, but not with FBG, HbA1c or other rest-activity rhythm parameters. After adjusting for age, sex and BMI, increasing SDB severity was independently related with lower M10 (B= -0.102, p=0.001). Further, bivariate analyses showed that a higher HbA1c was associated with a shorter sleep duration, lower relative amplitude, and higher L5. FBG was not related to any rest-activity rhythm parameters. After adjusting for age, sex, BMI and sleep duration, lower relative amplitude, but not L5, was independently related with higher HbA1c (B= −0.027, p=0.031). Conclusion: In prediabetes, a lower relative amplitude, indicating a less robust 24 hour rest-activity rhythm, was associated with a higher HbA1c. These findings suggest that circadian rhythmicity contributes to glycemic control. Greater SDB severity was correlated with decreased activity, but relationships with other rest-activity rhythm parameters were not observed.

Presentation: Thursday, June 15, 2023
THU334 Trends In GLP-1 Agonist Utilization In Diabetics With And Without Vascular Disease
Authors: Sargin Pinar , Barahona Maria , Rubayet Hossain , Leef George
Published: October 2023

Disclosure: P. Sargin: None. M. Barahona: None. H. Rubayet: None. G. Leef: None.

GLP-1 agonists (GLP1) have emerged as a breakthrough class of drugs for the management of Type 2 Diabetes (T2DM). Data from cardiovascular outcomes trials has shown benefits in patients with known atherosclerotic vascular disease, including reduced cardiovascular mortality and stroke. These agents are now considered preferred therapy, however, prior studies have shown low rates of utilization. We hypothesized that recent guidelines and provider education may lead to increased prescribing of GLP1. We analyzed a large, multicenter database to investigate recent trends in GLP1 utilization in patients with T2DM and vascular disease. We extracted all patients from the database with T2DM and excluded patients with diagnoses of Type 1 Diabetes, thyroid cancer, pancreatitis, or MEN syndrome type 2, or age >90. We then stratified the cohort to compare patients with a diagnosis of ischemic heart disease, peripheral vascular disease, or cerebrovascular disease since January 1st, 2021 against diabetic patients without these diagnoses. Patients were compared for rates of prescription of diabetes medications and baseline characteristics including age, sex, race, BMI, HgA1c, and creatinine. Our search generated a total of 408553 patients with T2DM and vascular disease (defined as at least one of the following: ischemic heart disease, peripheral vascular disease, cerebrovascular disease), and 520383 with T2DM and no known vascular disease. The vascular disease cohort was 56% male, 68% white, mean age 70±13. Ischemic heart disease was present in 78%, cerebrovascular disease in 43%, and peripheral vascular disease in 22%. The non-vascular disease cohort was 54% female, 57% white, mean age 63±16. In the vascular disease cohort, 56% were prescribed insulin, 47% metformin, 17% SGLT2, and 14% GLP1. In the non-vascular disease cohort, 43% were prescribed metformin, 32% insulin, 11% GLP1, and 8% SGLT2. The P-value was less than 0.001 for all comparisons. Rates of the utilization of GLP1 agents in our database are still relatively low, but higher than has been reported before. This might suggest a favorable trend compared with prior studies on this topic, although they are not directly comparable due to different patient populations. With only 14% of the T2DM-vascular disease population receiving one of these agents (after excluding those with a documented contraindication), more work needs to be done to enable all patients who would benefit from these medications to access them.

Presentation: Thursday, June 15, 2023
THU343 Potential Association Among Enteroviruses, Acute Flaccid Myelitis And Type 1 Diabetes
Authors: Anh Nguyen Thao , Huynh Ky , Azad Mazieyar , Perdomo Rodriguez Juan Pablo
Published: October 2023

Disclosure: T.A. Nguyen: None. K. Huynh: None. M. Azad: None. J.P. Perdomo Rodriguez: None.

Non-polio enteroviruses, like EV-D68, caused a nationwide outbreak of respiratory illness in the US in 2014, most recently in the fall of 2021. It has been shown that EV-D68 plays a role in causing acute flaccid myelitis (AFM). In addition, the association between enterovirus infections and type 1 diabetes (T1DM) has been widely studied and established. We report a case in which a 19-year-old male consulted for progressively ascending bilateral weakness in the lower extremities. Four weeks prior, he was diagnosed with T1DM and diabetic ketoacidosis (DKA). On exam, he had decreased sensation to light touch, vibration, and temperature below the knees, decreased motor strength 2/5 in bilateral lower extremities, and absence of patellar and Achille reflexes. Thyroid tests, Creatinine Kinase, Aldolase, and vitamin B12 were all normal. Spine MRI showed an enhancement along the L5 and sacral roots. CSF studies were significant for the positive oligoclonal band, the elevated protein level (87gm/dL), and no white blood cell count. CSF gram stain was negative for any organisms. EBV, HSV, and HIV testing were negative. A nonspecific respiratory panel only performed at the time of diagnosis with AFM was negative. The electromyogram did not show any type of acute inflammatory demyelinating polyneuropathy or evidence of myopathy. CT abdomen/pelvis demonstrated mild splenomegaly with small swollen lymph nodes of the periaortic and mesenteric area, which are commonly seen in viral infections. A Digital Subtraction Angiography study did not show any abnormality in spinal vessels. The patient received immunoglobulin and steroid, which was stopped early due to bradycardia and hyperglycemia. Neurology diagnosed the patient with AFM secondary to viral infection, in which the patient may have been infected prior to his diagnosis of DKA. The patient’s weakness resolved, and he was discharged with basal-bolus insulin and is to follow up with neurology and endocrinology outpatient. Enterovirus infection has been associated with T1DM and AFM. While the Respiratory PCR Panel was negative, it was only obtained several weeks after the onset of symptoms. Pathogenesis of extra-respiratory complications of enteroviruses may associate with viremia and systemic dissemination of the virus, which may not be detected by a respiratory PCR panel. Infection by an enterovirus remains the most likely etiology for both immune-mediated disorders, especially during a nationwide outbreak. We recommend providers consider enterovirus infection as a potential cause of AFM, and autoimmune diabetes in order to perform a throughout workup. In a patient with hyperglycemia and flaccid paralysis, T1DM should be suspected.

Presentation: Thursday, June 15, 2023