bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP629 A Case of Juvenile Onset Hypophosphatasia Diagnosed In An Elderly Patient With Recurrent Fractures.
Authors: Matos Moises , Peña Ernesto Muñoz , Surya Sowmya K 
Published: November 2022

Abstract

Background
Hypophosphatasia (HPP) is a rare genetic disorder characterized by defective bone mineralization. Here we report a case of juvenile onset HPP in an elderly man. CASE A 77-year-old man presented for management of osteoporosis. He complained of joint pains and trouble walking. He had recurrent non-traumatic fractures since his teenage years and he and his sister were diagnosed with childhood rickets. He sustained fractures of both forearms, right ankle, right hip and left femoral neck, and had undergone right hip replacement and left femoral neck internal fixation. In his 20's, following a MVA he had several tooth extractions and eventually required dentures. He was misdiagnosed with osteogenesis imperfecta, vitamin D deficient osteomalacia and pseudogout, and had been treated with cholecalciferol and alendronate in the past. On exam, we noted a waddling gait, short stature and bowing of his knees. Labs revealed normal vitamin D 25-OH 48 ng/mL (30-100), and PTH 18 pg/mL (14-64), borderline corrected calcium 10.5 mg/dL (8.4-10.6) and elevated phosphorous 4.4 mg/dL (2.2-4.3). ALP was notably low 30 U/L (40-150) and had ranged between 15-46 U/L since 2009. These findings caught our attention and we ordered Vitamin B6 levels which were elevated &gt;250. 0 ng/mL (2.1-21.7). Genetic testing identified two ALPL gene variants, a rare C.340G&gt;A variant and a c.571G&gt;A variant which has been found to be causative of HPP. His DXA scan showed normal L-spine (T-score 3.3) and significantly decreased BMD of the proximal 1/3 of the left forearm (T-score -4.4). Hip and femur were not assessed due to presence of hardware. He is scheduled to start treatment with Asfotase alfa.

Conclusion
HPP is caused by ALPL gene mutations, which lead to loss of function of the enzyme tissue nonspecific alkaline phosphatase (TSNALP). Clinical manifestations such as seizures, recurrent fractures and premature dental loss are observed. Pseudogout may occur due to intraarticular calcium pyrophosphate deposition, as in our patient. Characteristic lab findings are elevated metabolites of TNSALP, including urine inorganic pyrophosphate (PPi) and serum pyridoxal 5'phosphate (PLP) (biologically active metabolite of vitamin B-6). A persistently low ALP is most suggestive and may be a clue for early referral. Genetic testing is confirmatory, but novel mutations may be missed. Delayed diagnosis in our patient led to increased morbidity, potentially avoidable surgeries and inappropriate treatment with bisphosphonate which are contraindicated as they may increase risk for atypical fractures. Asfotase alfa is a TNSALP enzyme replacement therapy designed to address the underlying cause of HPP and studies show improvement in bone mineralization, fracture healing, decreased concentration of PLP and PPi, and improved physical function and quality of life. Cost and availability remain a barrier to many patients.
Presentation: No date and time listed
OR01-2 Increased Fracture Risk in Patients Using Insulin Compared to Metformin, Attenuated in Patients Using Combination of Insulin and Metformin: Based on Common Data Models
Authors: Kim Kwangsoo , Kim Sang Wan , Kimg Jung Hee , Lee Seulbi , Lee Si-Yeon , Shin Chan Soo , Kong Sung Hye 
Published: November 2022

Abstract

Objective
Despite their normal to high bone mineral density, fracture risk was increased in patients with type 2 diabetes. Antidiabetic medications have been suspected to account for the excess risk partly. However, longitudinal comparative studies on the effects of various antidiabetic medications on fractures are limited. We aimed to evaluate the fracture risk of patients using various antidiabetic medications compared to those using metformin.

Methods
We included 6,694 patients aged ≥ 50 years from the common data model (CDM) database between 2008 and 2012, who used the same antidiabetic medications over a year. The patients were grouped as metformin, insulin, sulfonylurea, dipeptidyl-4-inhibitor (DPP4i)+metformin, insulin+metformin, sulfonylurea+insulin, sulfonylurea+metformin, DPP4i+sulfonylurea+insulin, and sulfonylurea+insulin+metformin. The risks of major osteoporotic fractures (MOF) and hip fractures in each group were analyzed using the Cox proportional hazards model compared with the metformin group as a reference.

Results
During a median follow-up duration of 6.1 years, the incidence rates of MOF and hip fracture were 8.36 and 1.53 per 1000 person-year. The mean age was 65.8 years, and 47.7% were women. Compared to metformin users, insulin users showed an increased risk of MOF (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.28-3.02) and hip fracture (HR 3.06, 95% CI 1.21-7.77) after multivariate adjustments, including age, sex, body mass index (BMI), HbA1c, history of fracture, secondary osteoporosis, rheumatoid arthritis, cardiovascular, cerebrovascular disease, dementia, chronic kidney disease, use of steroid, proton pump inhibitor, and warfarin. Besides, the risk became insignificant in patients using a combination of insulin and metformin in both MOF (HR 1.32, 95% CI 0.77-2.27) and hip fracture risks (HR 2.68, 95% CI 0.56-12.80) after covariates adjustments. In subgroup analysis, insulin users harbored a significantly higher risk for MOF than metformin users only in patients withHbA1c &lt; 7%, or BMI &lt; 25 kg/m2.

Conclusion
From real-world data, we found that insulin users were at elevated risk of MOF and hip fracture compared to metformin users, which might be attenuated in users with a combination of insulin and metformin. The increased fracture risk in insulin users was exaggerated in non-obese and well-controlled diabetic patients, indicating the need for routine fracture risk assessment in these patients.
Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.
PSAT176 Molecular Analysis of AMBRA1 as a Candidate Tumor Suppressor in Sporadic Parathyroid Adenomas
Authors: Arnold Andrew , Costa-Guda Jessica , Chinwo Stephanie , Bellizzi Justin 
Published: November 2022

Abstract
Primary hyperparathyroidism is a common endocrine disorder that is most often caused by a sporadic single-gland parathyroid adenoma. Currently, the only known and experimentally validated oncoprotein for parathyroid adenomas is cyclin D1. The overexpression of cyclin D1 protein has been reported in twenty to forty percent of cases. Eight percent of this overexpression can be explained by DNA rearrangement involving the cyclin D1 locus. The remaining molecular mechanisms behind this overexpression have yet to be identified. In this study, we explored a potential parathyroid tumorigenic mechanism that could increase cyclin D1 stability through a defect in the AMBRA1 E3 ligase adaptor, a molecule responsible for its degradation. Evidence that AMBRA1 may be a tumor suppressor gene includes the accumulation of cyclin D with hyperproliferation in AMBRA1-deficient cells, the context-dependent growth of tumors in Ambra1-deficient mice, and the finding that low levels of AMBRA1 correlated with poor clinical outcomes in The Cancer Genome Atlas (TCGA). We have therefore proceeded examine AMBRA1 for evidence of tumor suppressor-type inactivation within a cohort of parathyroid adenomas. Genomic DNA from twenty-six typical sporadic parathyroid adenomas was subjected to PCR-amplification of all eighteen coding exons of AMBRA1, followed by Sanger sequencing. Sequences were analyzed by comparison to the normal reference sequence, seeking to assess any observed intragenic or splice-site variants as potential or likely loss-of-function mutations. Thus far, with ninety-seven percent of the coding region fully sequenced, no intragenic AMBRA1 inactivating mutations were observed. Three known single nucleotide polymorphisms, considered non-pathogenic, were identified: missense variant c.3028G&gt;T, and 3' UTR variants c.*491T&gt;C and c.*576A&gt;T, each in a single tumor. Future study of increased numbers of parathyroid adenomas is needed to exclude the possibility that AMBRA1 inactivation could play a driver role in a small percentage of cases, and the possibility that AMBRA1 might contribute less directly e.g. via secondarily altered expression also warrants investigation. Nonetheless, our current observations strongly suggest that AMBRA1 does not have a frequent role as a classic 2-hit tumor suppressor gene in sporadic parathyroid adenomas.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT183 Severe Hypocalcemia Precipitated by COVID-19 Infection in a Patient with Albright Hereditary Osteodystrophy and Pseudohypoparathyroidism
Authors: Siddiqui Samrah , Anokwute Akudo , Zahedi Tooraj , Zhang Fan 
Published: November 2022

Abstract

Background
Hypocalcemia is a common endocrine manifestation of COVID 19 infection. We present a rare case of severe hypocalcemia in a patient with a history of Pseudohypoparathyroidism (PHP) type 1A after COVID-19 infection. PHP is a genetic disorder that presents with hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism due to marked target-organ unresponsiveness to parathyroid hormone (PTH). PHP type 1A also has a characteristic somatic phenotype known as Albright Hereditary Osteodystrophy (AHO), including short stature, brachydactyly, shortened metatarsals, and often reduced intelligence.

Case Presentation
This is a 53-year-old female with PHP type 1A, diabetes mellitus type 2, hypothyroidism, vitamin D deficiency, mild intellectual disability, and hypertension. She presented with new onset of seizures. She was also found to be positive for COVID-19 infection. On Review of systems, she had diarrhea but denied perioral or extremity paresthesia, palpitations, muscle spasms and bone pain. She reported compliance with calcitriol and calcium supplements at home. She had short stature, round face, short neck, obesity, brachydactyly (short digits of right 4th and 5th fingers) and shortened left 4th metacarpal. Labs revealed corrected serum calcium from baseline of 7.8 mg/dL to 4.4 mg/dL, ionized calcium 2.9 mg/dL, vitamin D 12.8ng/ml, PTH 142pg/ml and phosphorus 6.2mg/dl. EKG showed T wave inversions and prolonged QT interval. She did not have tetany, carpopedal spasm, paresthesia, Chvostek's sign, or Trousseau's sign. After receiving a total of 11 grams of elemental calcium, calcitriol, and ergocalciferol, her corrected calcium level improved to 7.4 mg/dL and EKG normalized. She was discharged home with calcium carbonate 1,250 mg twice a day and calcitriol 0.5 mcg daily.

Discussion
PHP type 1A is an autosomal dominant mutation of the stimulatory G protein alpha subunit (G alpha or GNAS) derived from the mother due to genomic imprinting which leads to PTH resistance in the kidneys and parathyroid glands. Our patient had a long-standing history of mild hypocalcemia with calcium and calcitriol supplements. Sudden worsening of hypocalcemia was likely related poor calcium and calcitriol absorption induced by COVID-19 infection. Patient with chronic hypocalcemia may not present with typical hypocalcemia signs or symptoms due to their tolerance.

Conclusion
Clinicians should be aware of the risk of developing severe hypocalcemia in patients who are calcium dependent or vitamin D deficient, malnourished during critical illness, or have COVID-19 infection which may decrease serum albumin and reduce total serum calcium level.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF06 | PSAT152 Associations between Bone Mass, Hormone Levels and Body Composition in Postmenopausal Women
Authors: Fighera Tayane , dos Santos Betânia Rodrigues , Lima Letícia Kortz Motta , Spritzer Poli Mara 
Published: November 2022

Abstract
Emerging evidence suggests an association between FSH and bone mass in peri- and postmenopausal women. The aim of the present study was to assess body composition parameters and hormone levels as risk factors for low bone mass in women with recent menopause. In this cross-sectional study, we analyzed biorepository samples from 139 postmenopausal women aged 42 to 68 years with no evidence of clinical CVD. Inclusion criteria were as follows: menopause, defined as last menstrual period at least 12 months of amenorrhea and/or 6 months or more of amenorrhea plus FSH levels ≥35 mIU/mL occurring after 40 years of age, and no use of hormone therapy (HT) in the past 3 month. BMD and body composition were assessed by dual-energy X-ray absorptiometry (DXA), SHBG and FSH levels were measured in all patients. Serum estradiol levels were measured by gas chromatography/tandem mass spectrometry assay (GC/MS/MS) in a subset of 57 participants and free estrogen index (FEI) was estimated by dividing estradiol by SHBG × 100. Low bone mass was considered osteoporosis and osteopenia. The mean age was 54.33±5.30 years and median time since menopause was 4 (2 - 9) years. The mean BMI was 26.73±4.38 kg/m2 and 66% of participants were classified as overweight or obese. BMI, BMD and T-sc, lean mass index (LMI) and fat mass index (FMI) were lower, and SHBG was higher in women with FSH levels above the median values (83.6mUI/mL). FSH was inversely correlated with FEI (rho=-0.283, p=0.033) as well as with FMI (rho=-0.288, p=0.001) and LMI (rho=-0.186, p=0.029), but significance was lost after adjustment for estradiol levels (p=0.651). In the univariate linear regression analysis, FSH, FEI, time since menopause, SHBG, FMI and LMI were significant predictors to total femur bone mass, explaining 3.8%, 11.9%, 7.4%, 14.7%, 19.7% and 8.4% of variance in BMD at this site, respectively. In the multivariate model, the association of FSH, time since menopause and FMI with hip bone mass was no longer significant after inclusion of FEI in the respective model. The present results indicate that the negative association between FSH levels and femoral BMD in postmenopausal women are influenced by endogenous estradiol levels, time since menopause and fat mass. Additional studies are needed in order to further analyze whether some direct effect of FSH on bone mass may be additive to the presence of low bone mass in this population.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF06 | PSAT154 Osteoporosis Likely Increases the Risk of Dementia in Vietnamese Immigrants
Authors: Kim Yu N , Arif Saleena 
Published: November 2022

Abstract
Osteoporosis is a common systemic skeletal disease that predominantly affects people older than 50 years and often co-occurs with dementia. Studies have been conducted to find out the relation between the two, but this is not well studied in the Vietnamese population. This study aimed to analyze the impact of osteoporosis on the risk of dementia in Vietnamese immigrants.
We identified 38(female(F) 26, male(M) 12) community-dwelling Vietnamese patients aged ≥ 55 seen at the cognitive assessment clinic in a community health center 1/2021-8/2021 through chart review. Because either DEXA was not performed or the results were unavailable, 23 patients (F 12, M 11) were excluded. We assigned the patients with normal cognitive tests results or a diagnosis of mild cognitive impairment to the control group and those diagnosed with dementia to the study group.
Among 15 patients, 10(F 9, M 1) patients were diagnosed with dementia. Seven patients (F 6, M 1) had osteoporosis. Five patients (F 5) were assigned to the control group, and two patients had osteoporosis. (OR 3.5000, P = 0.2736)
The odds of developing dementia were 3.5 higher given osteoporosis diagnosis than with no osteoporosis. These results suggested a positive association between osteoporosis and dementia in Vietnamese immigrants. More studies with a larger number of patients in this cohort are needed to investigate this further.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m.
RF30 | PSAT177 A Case of Hypercalcemia Related to Immune Checkpoint Inhibitor-Induced Sarcoidosis-like Granuloma
Authors: Donangelo Ines , Koh Michelle , Lei Lei 
Published: November 2022

Abstract

Background
Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case.

Clinical Case
A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia.

Conclusion
Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
ODP147 Free fatty acids stimulate aldosterone secretion in human adrenal carcinoma HAC15 cells
Authors: Ling Guoyu , Bruno Jonathan , Albert Stewart G 
Published: November 2022

Abstract
Primary hyperaldosteronism (PA) accounts for 5-10% of hypertension overall and up to 35% in people with obesity and sleep apnea. It has been postulated that the hyperaldosteronism, in these latter cases, is induced by factors independent of renin/angiotensin activation, but rather through soluble molecules associated with obesity. It has been shown that in obesity, free fatty acids (FFA) are associated with insulin resistance and hypertension. To test the relationship of free fatty acids with aldosterone synthesis, the human adrenal cell line HAC15, which has been extensively studied for adrenal steroidogenesis, was evaluated with regard to both aldosterone (ALDO) synthesis (by ELISA) and the induction of the rate limiting enzyme for aldosterone synthesis (CYP11B2, by quantitative PCR and Western blot). HAC15 responded appropriately to stimulation by angiotensin 2 (AII) with a 2.1-fold rise in ALDO. When this system was challenged with palmitate at 0.8 mM, there was a 1.8-fold increase in ALDO and 8-fold increase in CYP11B2 at mRNA and protein levels. These increases were not associated with the likelihood that the FFA were simply providing metabolic substrate as the effect was not blocked by the carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir. However, palmitate treatment when compared to controls, was associated with ER stress, as measured by a four-fold induction of ER stress marker C/-EBP homologous protein mRNA, and with mitochondrial membrane dysfunction, as measured by a 24% decrease of Tetramethylrhodamine, ethyl ester (TMRE) fluorescence. These results suggest that in people with obesity and insulin resistance, FFA may augment or precipitate a state of primary hyperaldosteronism. Further studies are warranted to explore the underlying mechanisms of FFA augmentation of ALDO and its clinical significance.
Presentation: No date and time listed
ODP150 Hypertriglyceridemic Induced Acute Pancreatitis with Diabetic Ketoacidosis Treated with Insulin: A Case Report
Authors: Alam Saima , Khan Areej , Natesan Saikavitha , Oelberg David 
Published: November 2022

Abstract

Introduction
Acute pancreatitis due to hypertriglyceridemia with DKA is a unique entity. The diagnosis of acute pancreatitis in DKA is challenging as most patients present with abdominal pain, and elevated amylase, and lipase are quite common in DKA. Hypertriglyceridemia-induced pancreatitis (HTGP) accounts for 1 to 35 percent of all cases of acute pancreatitis. Pancreatitis may occur in DKA with high anion gap metabolic acidosis. Lack of insulin results in lipolysis with release of free fatty acids. Increased free fatty acids presented to the liver, causes increased VLDL, which inhibits lipoprotein lipase in peripheral tissues and results in elevated triglycerides.

Case presentation
A 29-year-old morbidly obese male with Asperger's syndrome, prediabetes, and hyperlipidemia presented with a 3-day history of sharp, non-radiating, and progressively worsening right upper abdominal pain, associated with nausea, non-bilious vomiting, and shortness of breath. His past medical history was notable for a prior bout of gallstone pancreatitis, for which he underwent a laparoscopic cholecystectomy. On his arrival in the emergency department, he was afebrile, but tachycardic (HR 139), mildly hypertensive (BP 149/98) with a Kussmaul breathing saturating 98% on room air. His lung sounds were clear but diminished and his abdomen was soft but diffusely tender, without peritoneal signs. Initial laboratory tests showed a neutrophilic leukocytosis of 12K, glucose of 867 mg/dL, hyponatremia (corrected 131), ketonuria, with elevated lipase 1,164 U/L. Venous blood gas showed a pH of 7.18 and PCO2 24 mmHg. He also had severe hypertriglyceridemia with a total triglyceride level of &gt; 9,000 mg/dL. His CT abdomen showed peripancreatic inflammation consistent with acute pancreatitis. He was admitted to the ICU, and initially managed with aggressive intravenous fluids and pain control, then was started on an insulin drip for diabetic ketoacidosis and hypertriglyceridemia. His hospital course was notable for the development of acute kidney injury requiring hemodialysis. His triglyceride level gradually decreased and was 396 U/L on hospital day #9. He was discharged on fenofibrate, Lantus 20 units daily and insulin lispro 10 units with meals.

Conclusion
Hypertriglyceridemia is an uncommon but a well-established cause of acute pancreatitis leading to significant morbidity and mortality. In this case, a prediabetic patient presented with DKA and further investigation revealed HTGP. There is currently a paucity of data to support an optimal treatment for this condition; however, both insulin and plasmapheresis have been successfully employed. Plasmapheresis helps remove plasma lipoproteins and reduces triglyceride more rapidly than insulin and has been recommended for severe cases. In our case, insulin infusion alone significantly reduced the triglyceride level.
Presentation: No date and time listed