bluuebunny/crossref_metadata_2025_split huggingface dataset:
5117 Unusual Sarcoid Presentation as a Case of Hypercalcemia
Authors: Salim Michael , Chauhan Aditya , Avula Sreekant , Ahmed Ammar , Zekarias Kidmealem 
Published: October 2024

Abstract
Disclosure: M. Salim: None. A. Chauhan: None. S. Avula: None. A. Ahmed: None. K. Zekarias: None.
Background: Hypercalcemia may arise from a variety of causes and can pose challenging diagnostic dilemma. Clinical Case: An 89-year-old male presented with worsening malaise related to persistent hypercalcemia. He reported productive cough, polyuria, polydipsia, generalized muscle weakness and weight loss. Physical exam was remarkable for upper and lower extremities weakness. Laboratory tests showed calcium 11.6 (8.8-10.2 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), albumin 4.2 g/dL (3.5-5.2 g/dL), parathyroid hormone (PTH) 10 pg/mL (15-65 pg/mL), parathyroid hormone-related protein (PTH-rp) 4.5 pmol/L (0.0-2.3 pmol/L), TSH 6.24 (0.30 - 4.20 uIU/mL), free T4 1.10 ng/dL (0.90-1.70 ng/dL), GFR 61 mL/min/1.73m2, 25 OH Vit D 31 ng/mL (20-75 ng/mL), vit D 1,25-dihydroxy 134 pg/mL (19.9-79.3 pg/mL), calcium urine/creatinine 0.54. Hypercalcemia was first noted 11 months before the visit with a level of 14.0 mg/dL (8.8-10.2 mg/dL), phosphorus 3.5 mg/dL, PTH 11, PTH-rp 1.4 pmol/L, 25 OH Vit D 62 ng/mL, Vit D 1,25-dihydroxy 90 pg/mL, angiotensin-1-converting enzyme 12 U/L (16-85 U/L), serum and urine electrophoresis showed no monoclonal gammopathy present, and tuberculosis interferon-gamma test negative. Autoimmune workup was unremarkable, except for weak positive anti-signal recognition particle (SRP) antibodies and anti-Mi-2 antibodies. CT chest/pelvis/abdomen demonstrated peripheral predominant reticular opacities suggestive of interstitial lung disease and no malignant findings. Treatment history included zoledronic acid 11 months before the visit. The patient was referred for a granulomatous disease workup.Upon one month follow-up, the hypercalcemia symptoms were worsening. Repeat calcium was 12.3 mg/dL and fungal serologies were negative. The patient was started on prednisone empirically. PET CT was ordered and revealed patchy inflamed musculature of extremities suspicious of dermatomyositis/polymyositis. Further labs showed unremarkable myomarker panel, u3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) antibody, Anti-cN-1A antibody, ACE 53 U/L, creatine kinase 32 U/L (39-309 U/L), aldolase 5.4 U/L (1.2-7.6 U/L), soluble IL-2R 1,021 U/mL (137-838 U/mL), and lysozyme 3.89 ug/mL (&lt;2.75 ug/mL). A muscle biopsy was done, which showed benign skeletal muscle with patchy myofiber atrophy, patchy interstitial fibrosis, and focal interstitial mild chronic inflammation with no evidence of sarcoid granulomas in the sample. One week lab follow-up post initiation of steroid showed calcium of 10.1 mg/dL and subsequently improvement in his overall labs. Working diagnosis of sarcoid myositis was made. Conclusion: This case report highlights the approach of diagnosing a rare case of hypercalcemia due to sarcoid myositis. In a highly clinical suspicious patient, PET CT scan might be a necessary modality for diagnosis.
Presentation: 6/2/2024
8216 When calcium makes you breathless, exploring hypocalcemia-induced bronchospasm
Authors: Nikita Pereira Kristal , Sundaram Vignesh , Sai Sreemantula Harsha 
Published: October 2024

Abstract
Disclosure: K.N. Pereira: None. V. Sundaram: None. H.S. Sreemantula: None.
When calcium makes you breathless, exploring hypocalcemia-induced bronchospasm Hypocalcemia, characterized by low levels of serum calcium, is an uncommon yet potentially life-threatening condition with various clinical manifestations. This case report delves into an unusual manifestation of hypocalcemia-induced bronchospasm in a 54-year-old male with an extensive medical history, including chronic kidney disease, insulin-dependent type 2 diabetes mellitus, hypertension, hyperlipidemia, ascending aortic aneurysm and hyperthyroidism. Despite multiple interventions in the emergency department like nebulized bronchodilators and intravenous steroids, his 4 day misery of respiratory distress persisted. Physical exam was notable for tachypnea, audible wheezing, and accessory muscle use for respiration. Work up was negative for infectious and pulmonary causes including asthma or chronic obstructive pulmonary disease. However, his laboratory results unveiled severe hypocalcemia (calcium: 5.7 mg/dL), elevated creatinine (Cr: 5.90), and blood urea nitrogen (BUN: 64), profound vitamin D deficiency with a 25-OH vitamin D level below 7 and elevated parathyroid hormone (PTH- 375.7). He was ultimately diagnosed with hypocalcemia-induced bronchospasm as intravenous calcium gluconate administration led to gradual respiratory improvement. This case highlights the necessity of considering hypocalcemia-induced bronchospasm in respiratory distress differentials, even in patients with concurrent asthma or COPD histories. The rarity of this presentation, coupled with the patient's complex medical history, underscores diagnostic challenges, necessitating a high index of suspicion. Timely hypocalcemia assessment and calcium replenishment are vital in averting mortality linked to this unusual manifestation. Clinicians must exercise caution to prevent misinterpreting symptoms as asthma or COPD exacerbation, as this could lead to potentially fatal outcomes.
Presentation: 6/1/2024
9324 X-Linked Hypophosphatemic Rickets (XLH): Experience Argentina
Authors: Giacoia E , Cantó A C , Balonga M C 
Published: October 2024

Abstract
Disclosure: E. Giacoia: Research Investigator; Self; Ultragenyx. A.C. Cantó: Research Investigator; Self; Ultragenyx. M.C. Balonga: Research Investigator; Self; Ultragenyx.
Introduction: XLH is a genetic disease characterized by rickets and osteomalacia caused by pathogenic variants in PHEX with disruptions in bone mineral homeostasis. In adults, the deformities described in childhood persist, in addition to osteomalacia, pain, stiffness, enthesopathies, arthrosis, delayed fracture consolidation and hypoacusia1,2.Objective: To describe the clinical, biochemical characteristics and complications such as kidney stones, hypoacusia, enthesopathy and type of mutation (isolated or familiar).Materials and methods: Descriptive and analytical study. 10 patients diagnosed with XLH were analyzed and evaluated from January to December 2023. Laboratory samples and complementary studies were carried out. The PHEX gene mutation was searched. Informed consents were obtained. Results: P: Phosphate, Ca: Calcium, 25OHD: Vitamin D3/10 patients had kidney stones, 4/10 hypoacusia, 4/10 enthesopathies.3/10 were de novo mutations and rest were familial.Conclusions: We observed a tendency towards hypophosphatemia and slightly increased PTH values. We consider that the experience acquired through follow-up consultations is the best tool to advance medical knowledge and thus achieve early diagnosis, access to medical treatment and multidisciplinary teamwork for improving the quality and survival of life of patients with this rare disease. Reference: (1) Juan Guillermo Cardenas-Aguilera et al. Expert Consensus on evidence-based recommedations for the diagnosis, treatment, and follow-up of X-linked hypophosfatemic rickets (XLH). Revista colombiana de nefrología, vol 11, number 1, marzo 20242. Andrea Trombetti et al. Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia. Nat Rev Endocrinol. 2022 Jun;18(6):366-384.
Presentation: 6/1/2024
8449 A Chronic Treatment of Interleukin-12 Restores Diet-Induced Hepatic Insulin Resistance and Liver Fibrosis in Mice with Interferon-gamma Signaling Deficient Macrophages
Authors: Devarakonda Rao Suryateja , Kim Boyeon , Kyung Kim Bu , Kasina Kaushal , Narouz Emily , Tauer Lauren A , Hu Xiaodi , Kim Jason K 
Published: October 2024

Abstract
Disclosure: S.D. Rao: None. B. Kim: None. B. Kim: None. K. Kasina: None. E. Narouz: None. L.A. Tauer: None. X. Hu: None. J.K. Kim: Advisory Board Member; Self; Elevian.
Inflammation and insulin resistance play a major role in metabolic dysfunction-associated steatotic liver disease, and macrophages and their release of cytokines modulate the underlying pathogenesis. We have recently found that mice with interferon-γ (IFNγ) signaling-deficient macrophages (Lyz-IFNγR2 KO) are protected from diet-induced insulin resistance in the liver and further rescued from developing liver fibrosis following NASH diets. Here, we examined the role of interleukin-12 (IL-12) as a macrophage-derived pro-inflammatory cytokine mediating the effects of macrophage IFNγ signaling on liver pathology. Mouse recombinant IL-12 (0.05 ng/hour/g body weight) was chronically administered via subcutaneously implanted osmotic pumps for 2 weeks in male Lyz-IFNγR2 KO and wild-type (WT) mice after 10 weeks of a high-fat diet (HFD) (n=3∼4/group). A 2-hour hyperinsulinemic-euglycemic clamp with 3H-glucose and [1]4C-2-deoxyglucose was performed to measure insulin action and glucose metabolism in mice. A chronic IL-12 treatment caused hyperglycemia (179±15 mg/dl) and insulin resistance in the liver with 30.6±15.7% suppression of hepatic glucose production (HGP) during insulin clamps in HFD-fed WT mice. IL-12 treatment also restored hyperglycemia and hepatic insulin resistance in HFD-fed Lyz-IFNγR2 KO mice with 45.3±21.2% suppression of HGP during insulin clamps. This is in stark contrast to euglycemia (145±5 mg/dl) and 77.3±9.7% suppression of HGP during insulin clamps in HFD-fed Lyz-IFNγR2 KO mice that were protected from diet-induced insulin resistance in the liver. Next, mouse recombinant IL-12 was chronically administered for 2 weeks in male Lyz-IFNγR2 KO and WT mice after 8 weeks of a Gubra Amylin NASH (GAN) diet (n=4∼6/group). Using a 3D-ultrasound imaging system, we found that IL12-treated WT mice developed fatty liver (54.3±3.9 counts in brightness) and fibrosis (4.8±0.4 kPa in Young’s Modulus) after the GAN diet. Similarly, IL12-treated Lyz-IFNγR2 KO mice developed fatty liver (53.8±7.7 counts) and fibrosis (4.9±0.7 kPa) after the GAN diet. Histological analysis of liver samples from both groups of mice further confirmed fibrosis and lipid droplets after IL-12 treatment. Overall, these results showed that a chronic IL-12 treatment restored diet-induced hepatic insulin resistance and liver fibrosis after GAN diet in Lyz-IFNγR2 KO mice, indicating a critical role for IL-12 as a macrophage-derived cytokine and downstream effector of IFNγ signaling in mediating metabolic liver disease.
Presentation: 6/1/2024
6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation
Authors: Humrickhouse Ashley B , Peltsverger Maya 
Published: October 2024

Abstract
Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None.
Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(&lt;1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was &lt;0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A&gt;G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS.
Presentation: 6/1/2024
12355 An Adolescent Female With Congenital Lipodystrophy Presenting With Repeated Acute Metabolic Decompensations Rescued By A Novel Leptin Receptor Agonist
Authors: Chambers D M , Chan Y M , Crocker M K 
Published: October 2024

Abstract
Disclosure: D.M. Chambers: None. Y. Chan: None. M.K. Crocker: None.
Patient SH is a now 17-year-old female treated for generalized congenital lipodystrophy with a course complicated by severe hypertriglyceridemia, type 2 diabetes mellitus, hypertension, hepatosteatosis, and intermittent menstrual irregularity. She had been managed successfully with metreleptin for 2 years, but in 2022-2023, she developed repeated episodes of pancreatitis (4 times over a 14-month period) secondary to severe hypertriglyceridemia (serum triglycerides &gt;8000 mg/dL). During her admissions, she had markedly increased insulin requirements (up to 12 units/kg/day) with refractory hyperglycemia despite maximal treatment with metreleptin, empagliflozin, and oral semaglutide. In the clinical context of her acute metabolic worsening, she was suspected of having a neutralizing antibody against metreleptin. Serum leptin was undetectable 1 hour after observed metreleptin doses; direct measurement of neutralizing antibodies is pending. She was transitioned from metreleptin to mibavademab, an investigational leptin receptor agonist, on an expanded use IND. She subsequently experienced significant improvements in her fasting triglyceride levels (&lt;300 mg/dL) with no subsequent episodes of pancreatitis since starting therapy in August 2023. She has also had improvements in other aspects of her metabolic health including decreased insulin requirements with decreasing hemoglobin A1c, decreased need for adjunctive lipid and hypertension therapy, and improving menstrual regularity. Her clinical course demonstrates: 1) clinical indicators of a rare but serious loss of efficacy of metreleptin therapy; 2) adjunctive options for management of generalized lipodystrophy; and, 3) an individual experience with a novel leptin agonist therapy in the treatment of generalized lipodystrophy.
Presentation: 6/3/2024
7454 Angiotensin AT1 Receptor Type 1 (AT1) Autoantibodies In Patients with Primary Aldosteronism
Authors: Waraich Jotinder K , Kline Gregory , Choi May Y , Jeremy Sigal Ronald , Caughlin Cori , Przybojewski Stefan J , Leung Alexander 
Published: October 2024

Abstract
Disclosure: J.K. Waraich: None. G. Kline: None. M.Y. Choi: None. R.J. Sigal: None. C. Caughlin: None. S.J. Przybojewski: None. A. Leung: None.
Background: Primary aldosteronism (PA) is a condition characterized by excessive aldosterone secretion, and accounts for at least 10% - 20% of all cases of hypertension. Determination of PA subtype (i.e., unilateral vs. bilateral aldosterone hypersecretion) is clinically important to inform targeted treatment. We hypothesized that pathogenesis of PA is immune-mediated and autoantibodies to angiotensin receptor type 1 (AT1) may determine PA subtype. Aims: The aim of this study was to examine whether AT1 autoantibodies predict PA subtype. Methods: We conducted a cross-sectional study of patients with PA who were referred for adrenal vein sampling (AVS) for subtyping. AT1 autoantibody titres were measured using an enzyme-linked immunosorbent assay. AT1 antibodies were defined as present when the titre was &gt;17 U/mL, negative if &lt;10 U/mL, and indeterminate if between 10-17 U/mL. AVS was used as a gold standard to determine lateralization and PA . The frequency of positive AT1 autoantibodies was determined according to PA subtype and clinical predictors of lateralization. Baseline patient characteristics were reported as means (and standard deviations) for normally distributed variables, and medians (and interquartile ranges) for non-normally distributed variables. Fisher’s exact test was performed for categorical variables and Kruskal-Wallis test for continuous variables. Results: 54 patients had successful cannulation of both adrenal veins (mean age, 52.7 years; 46.3% male; mean body mass index, 31.2 kg/m2). AT1 antibodies were detected in 14 (25.9%) of the patients, absent in 32 (59.3%), and indeterminate in 8 (14.8%). Among the 25 patients with unilateral PA, 8 (32.0%) had positive AT1 antibodies, 15 (60.0%) negative, and 2 (8.0%) indeterminate. Similarly, among the 29 patients with bilateral PA, 6 (20.7%) had positive AT1 antibodies, 17 (58.6%) negative, and 6 (20.7%) indeterminate. There was no significant association detected between AT1 antibody status and lateralization (p=0.39). There were no associations between AT1 autoantibody status and any of the clinical factors traditionally predictive of PA, including sex (p=0.94), older age (p=0.76), hypokalemia (p=0.91), higher estimated glomerular filtration rate (p=0.46), or magnitude of aldosterone-to-renin ratio elevation (p=0.58). There was also no association between AT1 titres and these factors. Conclusion: AT1 autoantibodies are common in patients with PA; over a quarter of patients who underwent AVS in our study. Although they were not predictive of PA subtype, these results may still suggest that PA is immune-mediated. Future studies comparing AT1 autoantibodies in PA to other controls are underway.
Presentation: 6/1/2024
6649 Associations of Fibroscan Results with Body Composition and Laboratory Measures in Patients with Obesity and Inflammation
Authors: Lyman Alexa , Nwosu Ejike , Gopalakrishna Harish K , Rotman Yaron , Abdul Majeed Nehna , Lazareva Julia , Brady Sheila M , Paul Demidowich Andrew , Adam Yanovski Jack 
Published: October 2024

Abstract
Disclosure: A. Lyman: None. E. Nwosu: None. H.K. Gopalakrishna: None. Y. Rotman: None. N. Abdul Majeed: None. J. Lazareva: None. S.M. Brady: None. A.P. Demidowich: Grant Recipient; Self; Dexcom, Inc. J.A. Yanovski: Grant Recipient; Self; Soleno Therapeutics (DCCR), Rhythm Pharmaceuticals (setmelanotide), Hikma Pharmaceuticals (colchicine), Versanis Bio (bimagrumab.
Background: Obesity and inflammation are believed to contribute to hepatic dysfunction and risk for metabolic dysfunction-associated steatohepatitis (MASH). Fibroscan (Echosens) can non-invasively quantify liver fat content (LFC) by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by transient elastography as a surrogate for fibrosis. Other surrogate markers for liver fibrosis include Fibrosis-4 (FIB-4) and the AST-to-Platelet Ratio Index (APRI) indices. Central obesity is a stronger predictor of MASH than appendicular fat. It is unknown whether the associations between these measures hold in a population with obesity and inflammation. Hypotheses: We hypothesized that LFC and LSM would be positively associated with Body Mass Index (BMI), central obesity (trunk), but not appendicular fat percentage, as well as with HOMA-IR, hs-CRP, and both FIB-4 and APRI indices in patients with obesity and inflammation. Methods: A convenience sample of adult participants with BMI ≥30 kg/m2 and hs-CRP ≥2.0 mg/L in a clinical trial (n=38) underwent body composition by DXA, Fibroscan, and fasting blood sampling for glucose, insulin, hs-CRP, AST, ALT, and platelets, all on the same day. LSM results were considered valid if the interquartile range for &gt; 10 measurements was ≤30%. ANCOVA analysis was used to examine associations between these parameters. Results: The cohort had a mean age=48 years (SD=12.5 years), BMI=39.3 kg/m2 (SD=6.0 kg/m2,), CAP=296.0 dB/m (SD=54.0 dB/m), LSM=5.9 kPa (SD=2.4 kPa), hs-CRP=7.2 mg/L (SD=6.1 mg/L), HOMA-IR=5.9 (SD=4.5), FIB-4=0.80 (SD=0.33), and APRI=0.24 (SD=0.11). Using univariate linear regression analysis, we found CAP to be positively associated with increased trunk body fat % (p=0.009, partial η2=0.202) and BMI (p=0.006, partial η2=0.195) independent of sex. Similarly, LSM was positively correlated with increased trunk body fat % (p=0.047, partial η2=0.125), APRI (p=0.025, partial η2=0.156), and log-transformed HOMA-IR (p=0.018, partial η2=0.150). We did not observe significant associations between hs-CRP, FIB-4 or appendicular body fat % with CAP or LSM in our population. Conclusion: As hypothesized, measures of liver fat content and fibrosis by Fibroscan CAP and LSM were positively associated with body composition (predominantly trunkal fat), measures of insulin resistance, and laboratory indices of hepatic fibrosis and steatosis in people with obesity and inflammation.
Presentation: 6/3/2024