bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT252 Homozygous CYP24A1 Gene Mutation Induced Hypercalcemia During Pregnancy
Authors: Ankireddypalli Anvitha Reddy , Alameddine Hind 
Published: October 2023

Abstract
Disclosure: A.R. Ankireddypalli: None. H. Alameddine: None.
Introduction: The approach and management of hypercalcemia in pregnancy can be challenging. Pregnancy challenges the calcium homeostasis with physiological increase in 1,25 dihydroxy Vitamin D levels by kidneys and placental 1-alpha hydroxylase, however it rarely causes hypercalcemia. In PTH independent hypercalcemia, disorders in vitamin D metabolism should be considered. Here we report a case of PTH independent hypercalcemia due to autosomal recessive homozygous CYP24A1 gene mutation. Case: A 25-year-old primigravid female presented to the clinic at 26 weeks of gestation for management of hypercalcemia. At 25 weeks gestation, laboratory workup revealed calcium: 13.9 mg/dL, albumin: 2.9 g/dL, PTH: &lt; 6 pg/mL, vitamin D: 45.17ng/mL, creatinine: 1.02 mg/dL, alkaline phosphatase (ALP): 117mcg/L. Since getting pregnant she reported nausea and vomiting. She reported excessive thirst, memory loss, fatigue, exertional dyspnea and 10 lbs weight loss. She denied any personal history of kidney stones or family history of calcium or bone disorders. She stopped her prenatal vitamins at the time of hypercalcemia diagnosis. Her work-up was suggestive of PTH independent hypercalcemia. Differential diagnosis included granulomatous disease, malignancy, benign PTHrP secreting tumors, vitamin D metabolism dysfunction and milk-alkali syndrome. Further work-up revealed ionized calcium: 6.2 mg/dL, PTHrP: 5.3 pmol/L, bone specific ALP: 11.8 mcg/L, 25 hydroxy vitamin D: 132 mcg/L, 1, 25 dihydroxy vitamin D: &gt; 200 pg/mL, 24,25 dihydroxy vitamin D: 1.16 ng/mL, 25-hydroxy vitamin D to 24,25 dihydroxy vitamin D ratio: 75.0, which was indicative of CYP24A1 mutation, an enzymatic defect in vitamin D metabolism. Molecular testing confirmed autosomal recessive homozygous CYP24A1 gene mutation. With elevated 24,25 dihydroxy vitamin D levels, it was unlikely that her 1,25 dihydroxy vitamin D was elevated due to malignancy or granulomatous disease. Treatment with prednisone 60 mg daily for 1 month did not improve her calcium levels. She was recommended to limit her calcium intake, avoid vitamin D supplements or sun exposure. At 38 weeks, she delivered a healthy baby without neonatal complication. Postpartum day 2, her labs revealed calcium: 10.7mg/dL with albumin: 2.7mg/dL. Discussion: Diagnosis of CY24A1 gene mutation associated hypercalcemia is based on increased 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D ratio and confirmed by genetic analysis. Recommendations are adequate hydration, limiting calcium intake, avoiding vitamin D supplements and preventing sun exposure. It is important to monitor for neonatal hypocalcemia and worsening of maternal hypercalcemia during breastfeeding. We report this case to raise awareness of this rare cause of hypercalcemia in pregnancy and the importance of checking calcium and vitamin D levels prior to vitamin D supplementation.
Presentation: Saturday, June 17, 2023
OR29-03 Social Isolation Stress Leads To Bone Loss In Adult Male, But Not Female, C57BL/6J Mice
Authors: Mountain Rebecca , Langlais Audrie , Hu Dorothy , Baron Roland E , Lary Christine , Motyl Katherine J 
Published: October 2023

Abstract
Disclosure: R. Mountain: None. A. Langlais: None. D. Hu: None. R.E. Baron: None. C. Lary: None. K.J. Motyl: None.
Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising “Epidemic of Loneliness”. Social isolation is associated with increased risk for many health conditions, including mental health disorders, as well as higher overall morbidity and mortality. Previous clinical research has demonstrated that psychosocial stressors, and subsequent mental health disorders, are major risk factors for osteoporosis and fracture, which disproportionally affect older adults. The effects of social isolation on bone, however, have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks (N=16/group). Social isolation significantly decreased trabecular bone parameters, including bone volume fraction (BV/TV) by 26% (Grouped: 21.9 ± 3.6%; Isolated: 16.2 ± 2.1%) (p &lt; 0.0001), as well as BMD, Tb. N., and Tb. Th, in the femur of male, but not female, mice. Femoral cortical bone parameters were also significantly decreased in isolated male mice, including a 9% decrease in cortical thickness (Ct.Th.) (Grouped: 0.187 ± 0.011 mm; Isolated: 0.169 ± 0.009 mm) (p &lt; 0.0001), as well as Ct.Ar., Ct.Ar./Tt.Ar., and pMOI. There were no significant differences in cortical measurements in females. Additionally, isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers and osteoblast-related gene expression, and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. The magnitude of bone loss in isolated males is as high as that seen in previous studies 4 weeks after orchiectomy or ovariectomy. Overall, our data suggest that social isolation has a dramatic negative effect on bone in males, but may operate through different mechanisms or in a different time frame in females. Future studies will focus on investigating potential mechanisms involving changes in endocrine signaling via glucocorticoid, sympathetic nervous system, and estrogen pathways. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.
Presentation: Sunday, June 18, 2023
OR02-01 Somatic Mutations In The Zinc Transporter ZnT1 Cause Primary Aldosteronism
Authors: Rege Juilee , Bandulik Sascha , Nanba Kazutaka , Kosmann Carla , Blinder Amy , Plain Allen , Vats Pankaj , Kumar-Sinha Chandan , Marcondes Lerario Antonio , Else Tobias , Yamazaki Yuto , Satoh Fumitoshi , Sasano Hironobu , Giordano Thomas J , Ann Williams Tracy , Reincke Martin , Turcu Adina , Udager Aaron , Warth Richard , Rainey William E 
Published: October 2023

Abstract
Disclosure: J. Rege: None. S. Bandulik: None. K. Nanba: None. C. Kosmann: None. A. Blinder: None. A. Plain: None. P. Vats: None. C. Kumar-Sinha: None. A.M. Lerario: None. T. Else: None. Y. Yamazaki: None. F. Satoh: None. H. Sasano: None. T.J. Giordano: None. T.A. Williams: None. M. Reincke: None. A. Turcu: None. A. Udager: None. R. Warth: None. W.E. Rainey: None.
Primary aldosteronism (PA) is the most common form of endocrine hypertension and affects approximately one in 50 adults. PA is characterized by inappropriately elevated adrenal aldosterone production via renin-independent mechanisms. Aldosterone-driver somatic mutations in a G protein-coupled inwardly rectifying potassium channel (KCNJ5), Na+/K+ and Ca2+ ATPases (ATP1A1 and ATP2B3, respectively), L-type and T-type voltage-gated calcium channels (CACNA1D and CACNA1H, respectively), and chloride voltage-gated channel (CLCN2) have been found in approximately 90% of adrenal aldosterone-producing adenomas (APAs). Other causes of lateralized adrenal PA include aldosterone-producing nodules (APNs). Using next-generation sequencing, we identified recurrent in-frame deletions in SLC30A1 in four APAs and one APN (p.L51_A57del, n=3; p.L49_L55del, n=2). SLC30A1 encodes the ubiquitous zinc efflux transporter ZnT1 (zinc transporter 1). The identified SLC30A1 variants are situated in close proximity to the zinc-binding site (His43 and Asp47) in transmembrane domain II and likely cause abnormal ion transport. PA cases with the unique SLC30A1 mutations showed male dominance and demonstrated increased serum aldosterone and 18-oxo-cortisol concentrations. Functional studies of the mutant SLC30A151_57del variant in a doxycycline-inducible adrenal cell system revealed pathologic Na+ influx caused by the mutant. Aberrant Na+ current led to the depolarization of the resting membrane potential, and thus to the opening of voltage-gated calcium channels. This resulted in an increase in cytosolic Ca2+ activity, which stimulated CYP11B2 mRNA expression and aldosterone production. Collectively, these data implicate the first-in-field zinc transporter mutations as a dominant driver of aldosterone excess in PA.
Presentation: Thursday, June 15, 2023
OR02-06 FGFR2 Mediates Zona Glomerulosa Morphogenesis, Aldosterone Secretion And Β-Catenin-induced Adrenal Hyperplasia
Authors: Chortis Vasileios , Dulanjalee Kariyawasam , Guagliardo Nick A , Shah Manasvi S , Claudio Ribeiro , Barrett Paula Q , Silva Borges Kleiton , Carlone Diana L , Breault David T 
Published: October 2023

Abstract
Disclosure: V. Chortis: None. K. Dulanjalee: None. N.A. Guagliardo: None. M.S. Shah: None. R. Claudio: None. P.Q. Barrett: None. K.S. Borges: None. D.L. Carlone: None. D.T. Breault: None.
Fibroblast Growth Factor Receptors (FGFRs) are tyrosine kinase receptors with critical roles in organogenesis and tissue homeostasis. We have recently shown that Fgfr2 deletion in the outermost zone of the mouse adrenal cortex (zona Glomerulosa, zG) during post-natal development leads to disordered morphology. Interestingly, Fgfr2 is up-regulated in the zG of mice with adrenal hyperplasia due to constitutive activation of Wnt/beta-catenin signaling. Here, we seek to delineate the role of FGFR2 in adrenal morphology and function during postnatal development, adulthood homeostasis, as well as during β-catenin-induced adrenal hyperplasia. To address this, we used i) a mouse model of conditional Fgfr2 loss (Fgfr2-cKO), in which zG-specific Fgfr2 deletion begins during early post-natal development, and ii) an inducible mouse model (Fgfr2-icKO), in which Fgfr2 deletion in the zG during adult life is tamoxifen-dependent. Fgfr2 loss in Fgfr2-cKO mice disrupted zG cell differentiation in steroidogenically mature cells and limited their capacity to proliferate and undergo trans-differentiation into the adjacent zona Fasciculata. zG cell de-differentiation was also evident upon acute loss of Fgfr2 in adult Fgfr2-icKO mice. Furthermore, Fgfr2 loss in a mouse model of beta-catenin-induced zG hyperplasia was sufficient to fully abrogate adrenal hyperplasia. Treatment with pan-FGFR small molecule inhibitors suppressed cellular proliferation in the mouse zG and inhibited aldosterone secretion. Taken together, these results suggest FGFR2 has a critical role in normal adrenal development and tissue homeostasis and is an essential mediator of beta-catenin-induced adrenal hyperplasia. FGFR2 targeting may be meaningful in patients with conditions associated with aldosterone excess.
Presentation: Thursday, June 15, 2023
THU405 A Delicate Balance
Authors: Mohan Nikita , Sanjiv SHAH Manasi 
Published: October 2023

Abstract
Disclosure: N. Mohan: None. M.S. Shah: None.
Introduction: Primary hyperparathyroidism is a disorder of excessive parathyroid hormone production causing increased calcium levels, usually due to a parathyroid adenoma. Commonly these cases are asymptomatic and detected incidentally on routine labs. They can be managed conservatively with sufficient fluid intake and avoiding dehydration. Congestive heart failure patients on diuretics with primary hyperparathyroidism require a delicate balance of their volume status to prevent exacerbation of either condition. We present a case of a woman with repeated hospitalizations due to poor volume status control. Clinical Case: An 82-year-old female with congestive heart failure (CHF), primary hyperparathyroidism (diagnosed 17 years ago), sick sinus syndrome with a pacemaker, and persistent atrial fibrillation presented to the emergency room with worsening b/l lower limb swelling for a few months. The remaining review of systems was largely negative. At home, she was on Losartan, Furosemide, and Carvedilol. Vitals were stable and physical exam revealed b/l lower extremity pitting edema. Chest x-ray showed cardiomegaly with mild pulmonary vascular congestion. Pertinent labs were NT pro-BNP 2190, Calcium 11.3 mg/dL, PTH 143 pg/mL, and Vit D, 25-hydroxy 48.6 ng/mL. The patient was started on IV diuretics and her home medications for CHF exacerbation. ECHO showed EF 39%, grade III diastolic dysfunction, severe pulmonary hypertension, mitral and tricuspid regurgitation. She was managed conservatively for her hypercalcemia and advised to maintain hydration at home. Spironolactone and Dapagliflozin were added to her regimen, and Furosemide was increased at discharge. The patient was re-admitted three weeks later with fatigue and decreased fluid intake. Vitals were stable and physical exam revealed dehydration. Pertinent labs were Calcium 13.4 mg/dL, Potassium 5.7 mmol/L, Creatinine 1.7 mg/dL (baseline 1.0), PTH 204 pg/mL, and Vit D 54.1 ng/mL. Repeat ECHO showed EF 15%. She was started on gentle 0.9% NS IV fluid to correct the hypercalcemia while preventing volume overload. Hypercalcemia and acute kidney injury improved with hydration. She was put on Cinacalcet 30 mg and home medications were modified for better volume control at discharge. Conclusion: This case highlights the complications of balancing the volume status with primary hyperparathyroidism and CHF. This patient’s primary hyperparathyroidism was well-controlled for more than fifteen years on adequate hydration. However, worsening CHF resulted in a higher requirement for diuretics, thereby worsening her hypercalcemia. Even though parathyroidectomy is an established treatment modality, she was not a suitable candidate due to age and comorbidities. Hence, to prevent such complications, parathyroidectomy must be considered early in patients with heart disease and even in asymptomatic hyperparathyroidism.
Presentation: Thursday, June 15, 2023
THU588 Sparing Confirmatory Testing In Primary Aldosteronism: The Combination Of Renin, Aldosterone And Potassium Levels
Authors: Chua Ong Lopez Albert Macaire , Mandocdoc Dimayuga Diana Colleen , Leo Estabillo Tiu , Castillo Dampil Oliver Allan , Mendoza Erick , Lim Villa Michael , Macabuag-Oliva Andrea Marie 
Published: October 2023

Abstract
Disclosure: A.C. Ong Lopez: None. D.M. Dimayuga: None. L.E. Tiu: None. O.C. Dampil: None. E. Mendoza: None. M.L. Villa: None. A.M. Macabuag-Oliva: None.
Background and Objective: The diagnosis of primary aldosteronism (PA) is comprehensive which includes case-detecting testing, case confirmation followed by subtype classification. In certain instances, one may not proceed with further confirmatory testing in the setting of spontaneous hypokalemia, suppressed renin, and PAC &gt; 15 ng/dL. However, this quality of evidence is very low. This study sought to determine the optimal laboratory combination patterns that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various combination settings and correlating to the recent evidence and clinical practice guidelines. Methodology: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study with a sampling total of 116 participants aged 18 years and above who underwent saline infusion test between January 2010 to March 2023. The main outcome measures comprise the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia) which include the sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.0.0 & MedCalc 20.218. Results: Of the 116 patients who underwent saline infusion test, 76 (65.52%) were diagnosed with PA. A PAC of &gt; 25 ng/dL plus PRA &lt; 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 89.11%, 100.00%) and positive predictive value at 100% (95% CI 82.35, 100.00%). The optimal combination criteria with the best balance of the diagnostic performance indices were determined to be a PAC of &gt; 20 ng/dL plus PRA &lt; 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has a sensitivity of 34.72% (95% CI 23.88% , 46.86%), specificity of 93.75% (95% CI 79.19%, 99.23%), positive predictive value (PPV) of 92.59% (95% CI 75.71%, 99.09%), negative predictive value (NPV) of 38.96% (95% CI 28.05%, 50.75%), positive likelihood ratio (LR+) of 5.56 (95% CI 1.40, 22.06), negative likelihood ratio (LR-) of 0.70 (95% CI 0.58, 0.84), and a diagnostic accuracy of 52.88% (95% CI 42.85%, 62.75%). Conclusion: Hypertensive patients with spontaneous hypokalemia who had initial screening test results of PAC &gt; 20 ng/dL and PRA &lt; 0.6 ng/ml/hr can be diagnosed as overt primary aldosteronism and may not proceed with dynamic confirmatory testing. This is in line with the 2016 Endocrine Society Clinical Practice Guideline recommendation.
Presentation: Thursday, June 15, 2023
FRI089 Massive Hypertriglyceridemia? Think Oral Contraceptive Pills!
Authors: Ali Israa , Hamdi Mohammed 
Published: October 2023

Abstract
Disclosure: I. Ali: None. M. Hamdi: None.
Introduction: Oral contraceptive pills (OCPs) are common cause of Hypertriglyceridemia (TG) that should be recognized early by clinicians. Concern is raised regarding pursing further genetic test for Familial hypertriglyceridemia for female who developed massive hyper triglyceridemic after starting hormonal therapy. Case: A 37-year-old female patient with history of prediabetes with A1c of 5.7% and one attack of pancreatitis. Normal BMI, No regular medications, negative family history for lipid disorder. Rare social intake of alcohol. Routine annual lab showed triglycerides level of 164 in 2016, otherwise normal biochemical evaluation. No treatment pursued. Later She was started on OCPs (Kariva 0.15-0.02 mg) for contraception. Late 2019, blood work-up showed cholesterol level of 979, TG of 3170 and HDL level of 22. She was started on a statin therapy and fenofibrates beside stopping OCP, she maintained normal lipid profile while being off OCPs, until 2022 when she restarted an OCPs (Lo Loestrin 1mg-10 mcg) for 2 months that resulted in elevated cholesterol level of 1222, triglycerides of 5177 and HDL of 10.OCP was stopped, lipids level trended down with cholesterol of 961, triglycerides of 2005 and HDL of 22 then normalized after 2 months. Patient did not have any clinical symptom or complain. Discussion: High triglyceride concentration is an independent predictor of coronary heart disease and ischemic stroke. Many patients with triglycerides &gt;1000 mg/dl have familial hypertriglyceridemia with superimposed additional exogenous factors which further raise triglyceride concentrations like exogenous estrogens, SERMs, hyperestrogenemia of pregnancy, poorly controlled diabetes mellitus, hypothyroidism, alcohol excess, exogenous corticosteroids, and drugs including isotretinoin and protease inhibitors. OCP induced hypertriglyceridemia occurs due to estrogen’s action in decreasing hepatic triglyceride lipase and lipoprotein lipase activity. This causes an overall increase in low and intermediate-density triglycerides and cholesterol that can increase free fatty acids to toxic level. The marked increase of TG and cholesterol in this patient while being on OCP is unusual and strongly indicate underlying familial hypertriglyceridemia exacerbated by starting OCP. Further genetic work up is being done. As OCP or other estrogen therapy are frequently given unwittingly to women with preexisting hypertriglyceridemia that lead to severe clinical consequences. Estrogen containing medication should not be considered if fasting triglyceride is above 500 mg/dl. In women on hormonal treatment with treatment-resistant hypertriglyceridemia, the likelihood that the hormonal treatment is nullifying drug efficacy is high so it should be stopped for a short trial while continuing modifying triglyceride-lowering medications.
Presentation: Friday, June 16, 2023
FRI093 Severe Hypertriglyceridemia Post Liver Transplant- A Multifactorial Disorder
Authors: Saand Aisha R , Drinnon Alexsandra R , Mubeen Faiza , Shakil Jawairia 
Published: October 2023

Abstract
Disclosure: A.R. Saand: None. A.R. Drinnon: None. F. Mubeen: None. J. Shakil: None.
Introduction: Hypertriglyceridemia (HTG) is a known complication in solid organ transplant patients. In addition to increasing cardiovascular complications and mortality risk, these metabolic abnormalities also increase the risk of allograft atherosclerosis and vasculopathy. Although medications used in post-transplant management have a well-documented effect of worsening lipid profile, multiple factors may be contributing in the development of severe HTG. Case Description: We describe a 68-year-old male with elevated triglycerides (TG) of 3957 mg/dL on hospital admission for pneumomediastinum. He received liver transplant 2 years prior due to alcohol-related liver cirrhosis. He had normal TGs prior to the transplant. Immunosuppressant regimen included tacrolimus (TAC) and methylprednisone. Lipoprotein electrophoresis was normal. Intravenous insulin infusion was initiated with moderate improvement however, upon transition to oral medications: fenofibrate, omega-3 fatty acids, niacin and rosuvastatin, TGs continued to increase. Reinitiating insulin infusion showed no improvement. TAC was switched to cyclosporin with transient decrease in TGs. Upon discharge amylase and lipase levels remained normal despite TG elevation. When readmitted for an unrelated reason, his TGs were elevated at 2218 mg/dl. Plasmapheresis was initiated but was complicated by anaphylaxis with angioedema requiring intubation. After partial plasmapheresis, TGs significantly decreased and soon returned to normal. Post-discharge, the patient was changed back to previous TAC dosage due to cyclosporin related renal injury. His steroid dose was reduced and icosapent was added, resulting in no further recurrence of HTG. Discussion: Following liver transplant, about 15-40% recipients have increased cholesterol levels and about 40% have HTG. Although, immunosuppressant-induced dyslipidemia is seen frequently, additional risk factors have been identified. A retrospective study of 85 patients post liver transplant showed HTG developed early within the first month in about 67% patients and persisted throughout the first year. Some common factors predictive of HTG post liver transplant include pre-liver transplant hepatocellular disease and post-transplant renal dysfunction. A study in pediatric patients post liver transplant observed that changes in lipoprotein and HDL subfraction post-transplant may lead to hypertriglyceridemia. Our case suggests that HTG may be multifactorial given the persistent elevation of TGs despite the change in immunosuppressant regimen. Patient factors as well as genetic characteristics of the donor liver may be potential causes. Recognizing this variation in patient populations may be extremely important due to high risk for pancreatitis and cardiovascular events. Early identification and management may prevent complications.
Presentation: Friday, June 16, 2023