bluuebunny/crossref_metadata_2025_split huggingface dataset:
8660 Bodipy Labeled Vitamin D3 Associates With Lipid Droplets In Adipocytes
Authors: Ucar N , Deeney J T , Pickering R , Kirber M T , Fan T Y , Loo R , Holick M F 
Published: October 2024

Abstract
Disclosure: N. Ucar: None. J.T. Deeney: None. R. Pickering, PhD: None. M.T. Kirber: None. T. Fan: None. R. Loo, PhD: Research Investigator; Self; Carbogen Amcis BV. M.F. Holick: Grant Recipient; Self; Carbogen Amcis BV. Research Investigator; Self; Carbogen Amcis BV.
Obese patients are often found to be deficient in vitamin D, requiring higher levels of supplementation than normal weight subjects. While this has been attributed to vitamin D3‘s lipid solubility and accumulation in fat tissue, little is known about how vitamin D3 enters adipocytes and associates with the intracellular lipid droplet. The goal of this study was to investigate this association using a novel fluorescently labelled vitamin D3. Bodipy, 4,4-difluoro-1,3,5, 7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503), was covalently linked to vitamin D3 and its structure was confirmed by NMR and mass spectroscopy. Murine 3T3L1 and primary adipocytes were used for our study. Mouse 3T3L1 preadipocytes were cultured in multiwell plates or glass bottom dishes in high glucose DMEM media and differentiated for 7-14 days. Primary adipocytes were obtained by collagenase digestion after surgical extraction of adipose tissue from male/female C57BL/6J mice and attached to glass bottom dishes. The cultured adipocytes were exposed to 10 microM BODIPY labelled Vitamin D3 (vitD-B). BODIPY was added to cultured cells and served as the control. Cells were imaged at various times on a wide-field epifluorescence microscope and analysed with NIH ImageJ software. VitD-B adipocyte uptake and accumulation in lipid droplets was observed over 24 hrs. Isolated lipid droplets were also incubated with vitD-B and BODIPY. VitD-B in mature 3T3L1 cells was observed in lipid droplets after 1h incubation and increased fluorescent intensity was observed over the next 24 hrs. BODIPY was observed in the lipid droplets after 15-20 mins. As a negative control, non-differentiated 3T3L1 cells did not exhibit staining by BODIPY even after 24-hrs. When vitD-B was added to primary cultured adipocytes, it appeared in the adipocytes within 1-hr. Fluorescence intensity of primary adipocytes was increased 1.2-fold at 8 hrs and 5.7-fold at 24 hrs compared to 1 hr. For comparison the positive control treated with BODIPY exhibited rapid fluorescence uptake into primary adipocytes that was increased 29-fold higher than that of vitD-B at 1 hr. VitD-B and BODIPY both demonstrated rapid uptake into isolated lipid droplets (less than 2 min) based on fluorescence microscopy.These results hold promising implications for understanding of the interaction between vitamin D and intracellular lipid droplets. Keywords: Adipocyte, Vitamin D3, BODIPY, adipocytes, lipid droplet, fluorescent labelled vitamin D3
Presentation: 6/2/2024
7002 Building Poor Bone, A Rare Presentation Of Skeletal Fluorosis
Authors: Pham Christopher , Lopresti Jonathan S 
Published: October 2024

Abstract
Disclosure: C. Pham: None. J.S. Lopresti: None.
Skeletal fluorosis is a rare disease associated with osteosclerosis and fractures. Case: 26 year old male presented with a history of multiple traumatic fractures but no childhood or family history of fractures. Initial labs revealed a corrected calcium of 8.1 mg/dL (8.5-10.3), ALP 1,504 U/L (40-129), PTH 131 pg/ml (15-65), 25-OH D 14 ng/ml (30-100), PO4 3.7 mg/dl (2.5-4.5) and normal creatinine. X-Rays demonstrated osteosclerosis and cortical expansion of bone and nuclear bone scan demonstrated diffuse increased uptake. Further history revealed huffing of computer inhalants (10 cans daily) for years. Due to these findings, urine fluoride 16.88 mg/L (0.20-3.20 mg/L) and serum fluoride 0.40 mg/L (&lt;0.05 mg/L) were obtained and vitamin D was started. 4 months later, his vitamin D level improved to 21 while calcium levels normalized despite ongoing inhalant use. ALP (878) and PTH (92) continued to be elevated albeit at improved levels. Conclusion: Exposure to fluoride leads to a rare condition called skeletal fluorosis causing accelerated osteogenesis and bone turnover leading to weak bone. Symptoms include bony pain, fractures, and osteosclerosis on radiographs. Differential diagnosis includes other conditions associated with osteosclerosis such as Paget’s disease and myelofibrosis. However, diffuse osteosclerosis and vertebral osteophytosis are noted only in skeletal fluorosis compared to other potential causes, though our patient did not have a CT spine done to assess for osteophytes. Biochemical studies can include hypocalcemia and hyperparathyroidism. It is thought that low calcium intake contributes to the hyperparathyroidism. Elevated serum and urine fluoride levels are also diagnostic and can persist for months after cessation of fluoride intake. Sodium fluoride has been posited as a treatment for osteoporosis due to its tremendous ability to build bone; however, the quality of bone made is poor leading to unacceptable fracture rates. Skeletal fluorosis should be suspected in any patient with history of diffuse osteosclerosis and hyperparathyroidism; and vitamin D supplementation should be initiated. In our case, hypocalcemia and PTH levels were improved despite active inhalant use after vitamin D supplementation. This suggests that Vitamin D deficiency and fluoride may be two independent driving factors in hyperparathyroidism in patients with fluorosis. Increased calcium absorption with vitamin D provides therapeutic benefit in both cases.
Presentation: 6/1/2024
6542 Burosumab In Unresectable/Unidentifiable Tumor-Induced Osteomalacia
Authors: Shan Der Yi , Kumar Chaubey Santosh , Kumar Sinha Ashim 
Published: October 2024

Abstract
Disclosure: Y. Der: None. S.K. Chaubey: None. A.K. Sinha: None.
Introduction/Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, typically arising from small, benign, slow-growing mesenchymal tumors, that secrete fibroblast growth factor (FGF23) and other phosphaturic proteins. It is characterized by hypophosphatemia, phosphaturia, reduced serum 1,25 dihydroxyvitamin D and bone demineralization. While complete resection of the causative tumor is the curative approach, unresectable or unidentifiable cases necessitate medical therapy with oral phosphate and calcitriol. Unfortunately, this option proves suboptimal, plagued by low compliance due to intolerable gastrointestinal side effects. A recent stride in treatment includes the approval of burosumab, an anti-FGF-23 monoclonal antibody, for TIO in the USA. Clinical Case: We report a perplexing TIO case where the underlying tumor remains elusive to-date. The patient, a 41-year-old former Filipino national swimmer, presented at the age of 35, wheelchair-bound, with a four-year history of progressive functional decline, secondary to diffuse osteomuscular pain and multiple fractures. Investigations revealed hypophosphatemia (0.28mmol/L; reference range: 0.75-1.5), phosphaturia, elevated ALP, low 1,25 dihydroxyvitamin D, and elevated peak FGF23 at 217ng/L (reference range: 23.2-95.4). Despite exhaustive imaging studies and stepwise venous sampling, tumor localization proved elusive. The patient experienced improvement in overall mobility and functional status on regular phosphate and calcitriol supplements. Cinacalcet was later added to reduce secondary hyperparathyroidism, FGF levels, and the need for phosphate supplements. Nevertheless, her chronic pain and limited mobility persisted, along with supplementation-associated gastrointestinal symptoms. The ionized calcium and phosphate remained low/low normal. In September 2023, the patient was commenced on subcutaneous burosumab via special access scheme, initially at 0.5mg/kg/month, subsequently uptitrated to the current 1mg/kg/month dosage. Remarkable improvements in pain and physical performance ensued, as evidenced by functional assessment and questionnaire tools. Serum phosphate levels are currently maintaining at 0.8mmol/L, with the most recent FGF level following her third burosumab injection improved to 88.4ng/L. Currently, four months into treatment, no side effects have been reported, and all previous supplementation and cinacalcet has been discontinued. Clinical Lessons/Conclusions: To our knowledge, this represents the first TIO case in Australia treated with burosumab. This case highlights favorable effects, including serum phosphate normalization and significant improvements in mobility, pain and quality of life. Thus, this case underscores the potential of burosumab in managing unresectable or unidentifiable TIO cases.
Presentation: 6/1/2024
6725 CDC’s Efforts In Standardizing Of Vitamin D Tests: Challenges And Potential Patient Misclassifications
Authors: Sugahara Otoe , Buchannan Tatiana , Danilenko Uliana , Ribera Ashley , Collins Lynn , Pokuah Fidelia , Lyle Alicia N , Vesper Hubert W 
Published: October 2024

Abstract
Disclosure: O. Sugahara: None. T. Buchannan: None. U. Danilenko: None. A. Ribera: None. L. Collins: None. F. Pokuah: None. A.N. Lyle: None. H.W. Vesper: None.
Accurate and reliable tests are critical for the correct diagnosis and treatment of patients, correct interpretation of research data, and effective evidence-based clinical decision-making. CDC’s Clinical Standardization Programs (CDC CSP) assist with assessing and improving the analytical performance of biomarker tests, such as vitamin D, performed in patient care, public health, and research. CDC CSP established the Vitamin D Standardization-Certification Program (VDSCP) in 2013. The program has seen improvements in calibration bias since its inception. In 2022, mass spectrometry-based assays had a mean bias of 0.55% and immunoassays had a mean bias of 0.86%, for all assays enrolled in VDSCP. This indicates that overall, the assays enrolled in the VDSCP are well-calibrated. However, with improvements in calibration, sample-specific inaccurate results became more apparent. These observations can be explained by a lack of analytical specificity and cross-reactivity, as well as incomplete analyte recovery. For example, some mass spectrometry-based assays measure C3-epi-25-hydroxyvitamin D3 in addition to 25-hydroxyvitamin D3 causing falsely elevated results in some samples. Some immunoassays appear to show cross-reactivity with 24,25-dihydroxyvitamin D3 also causing falsely elevated vitamin D concentration. These inaccuracies may result in incorrect patient classification. Preliminary assessment of data reveals evidence that could lead to patient misclassification. According to the Endocrine Society’s guideline, a vitamin D level of 50 nmol/L or less is considered as deficiency and a vitamin D level of 50-75 nmol/L is considered as insufficiency. For example, a VDSCP sample with a vitamin D reference value of 55.1 nmol/L should be classified as insufficient in vitamin D. However, 44 % of results reported would classify this sample are deficient. Another sample with a vitamin D reference value of 45.4 nmol/L should be classified as deficient in vitamin D. However, 18 % of the results reported would classify this sample as insufficient. While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients.
Presentation: 6/2/2024
7297 Clinical Characterization Of FHH Patients With Functional Assessment Of Novel CaSR Variants
Authors: Tora R , Canaff L , Welch J , Bliss L , Weinstein L S , Simonds W F , Agarwal S K , Blau J , Goltzman D , Jha S 
Published: October 2024

Abstract
Disclosure: R. Tora: None. L. Canaff: None. J. Welch: None. L. Bliss: None. L.S. Weinstein: None. W.F. Simonds: None. S.K. Agarwal: None. J. Blau: None. D. Goltzman: None. S. Jha: None.
Familial Hypocalciuric Hypercalcemia (FHH) is characterized by hypercalcemia and low urinary calcium excretion from birth and its diagnosis is confirmed by the presence of a pathogenic germline heterozygous variant in CaSR, AP2S1, or GNA11. Establishing the diagnosis is important as it prevents unnecessary parathyroidectomies as surgery is not curative. We identified patients with germline variants in CaSR, AP2S1, or GNA11 seen at our institute and performed a retrospective review of available clinical parameters. 43 patients (31 kindreds) with 28 unique CaSR variants (15 pathogenic, 13 variants of uncertain significance [VUS]) and one pathogenic AP2S1 variant were identified. Median age at diagnosis was 35 [IQR: 25 - 39] years, with the youngest patient diagnosed at 4.5 months. Median serum calcium was 10.70 [10.25 - 11.00] mg/dL (ref: 8.4 - 10.2) with a median PTH of 51.7 [35.8 - 74.0] pg/mL (ref: 15 - 65). The median fractional excretion of calcium (FECa) was 1.00 [0.54 - 1.40] while median serum magnesium was 2.30 [2.19 - 2.43] mg/dL (ref: 1.6 - 2.6). 5/43 (12%) patients developed kidney stones and 6/43 (14%) men ≤ 50 years and premenopausal women developed osteoporosis with median age at diagnosis of 38 [28.50 - 45.75] years and no alternate underlying secondary cause. Longitudinal follow-up available on 9/43 patients with median duration of 14.4 ± 4.5 years showed no significant changes in serum and urine biochemistries. 23/43 (53%) patients had undergone failed parathyroidectomy prior to diagnosis, of which 20/23 (87%) had multiple glands removed including one who became hypoparathyroid. Functional characterization was performed for 8/13 CaSR VUS (p.D217G, p.C546Y, p.F563S, p.C694Y, p.A880P, p.E109Q, p.D382N, and p.A880S) in HEK293 cells by examining intracellular Ca2+ and ERK/MAPK responses to extracellular Ca2+ using NFAT-Luc and SRE-Luc constructs, respectively. Compared to the wild type (WT) receptor, p.D217G, p.C546Y, p.F563S, and p.C694Y showed less of the cell-membrane-localized mature glycosylated species in Western blots and a significant rightward shift in their concentration-response curve in both SRE- and NFAT-Luc assays. p.A880P showed a significant rightward shift in its concentration-response curve, while p.E109Q, p.D382N, and p.A880S showed no differences on Western blot or concentration-response curves as compared to WT. Further work to characterize the remaining variants (p.T14A, p.T609M, p.V268_P278del, p.G36R, and p.F589V) is ongoing. We conclude that the diagnosis of FHH is frequently missed and that patients with the disease may rarely develop target organ damage.
Presentation: 6/2/2024
12472 Clinical Features Of Adult Hypophosphatasia And Correlation Between Laboratory Findings And Patient’s Symptomatology: A Retrospective Review At The Penn Bone Center
Authors: Ocampo Mascaro Javier , Tran Richie , Kallish Staci , Berman Jessica , Al Mukaddam Mona 
Published: October 2024

Abstract
Disclosure: J. Ocampo Mascaro: None. R. Tran: None. S. Kallish: Consulting Fee; Self; Sanofi, Amicus. Research Investigator; Self; Ipsen, Sanofi, Incyte, Idorsia. Speaker; Self; Sanofi, Amicus. J. Berman: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding.
Hypophosphatasia (HPP) is an inborn error of metabolism resulting in low activity of the enzyme tissue non-specific alkaline phosphatase (ALP). It primarily involves bone and teeth mineralization. HPP has a wide clinical spectrum. It may present with rickets, fractures, failure to thrive, weakness, respiratory complications, and seizures in its more severe perinatal/infantile forms. Childhood forms tend to be milder but may have substantial musculoskeletal complications and early teeth loss. The clinical picture in adults is extremely variable too. It is usually mild with stress fractures and/or teeth loss in most individuals but can be debilitating in others due to musculoskeletal pain and recurrent fractures. This retrospective study describes the characteristics of 35 adult patients (ages 22-74 years) with HPP based on clinical presentation +/- molecular testing at the Penn Bone Center, located at a US-based large academic hospital. Out of 35 patients, 26 had an ALPL variant in genetic testing (12 pathogenic, 5 likely pathogenic, and 9 of uncertain significance), 3 were negative, and 6 did not undergo testing yet. ALP values ranged from 11 to 39 U/L (N: 38-126). Serum fasting vitamin B6 levels (off supplements) ranged from normal range to 18 times the upper limit of normal. Main symptoms reported were fractures (74%), arthralgias/myalgias (51%), diffuse bone pain (29%), atraumatic teeth loss (20%), muscle weakness (14%), and nephrolithiasis (9%). We found no significant negative correlation between ALP levels and number of symptoms (rs -0.026) or age of first symptom occurrence (rs 0.205). We also found no significant positive correlation between B6 elevation and number of symptoms (rs 0.236) or age of first symptom occurrence (rs -0.175). Six patients within our cohort had previous or current treatment with asfotase alfa. This is an FDA-approved therapy for the treatment of perinatal, infantile, and childhood HPP and has been used in adult patients if one of the presenting symptoms was before age 18 years. Response to therapy in our patient cohort was mixed. Three out of six patients discontinued treatment due to lack of clinical benefit. Continued research of the clinical characteristics of adult HPP is needed to better understand its natural history, markers of severity of disease, and how to determine who may potentially benefit from asfostase alfa therapy.
Presentation: 6/1/2024
8179 Complicated Pancreatitis Unveiled: A Case Of Untreated Primary Hyperparathyroidism
Authors: Rehan A , Al Jumaili H , Lim J 
Published: October 2024

Abstract
Disclosure: A. Rehan: None. H. Al Jumaili: None. J. Lim: None.
Introduction: Acute pancreatitis (AP) triggered by hypercalcemia stemming from primary hyperparathyroidism (PHPT) is an infrequent occurrence, with a prevalence of about 1.5-7%. The proposed mechanism involves deposition of calcium in the pancreatic ducts and activation of pancreatic enzymes. While a causal connection between AP and PHPT has been described, it remains controversial. Calcium levels are thought to play a major role in determining the severity of the pancreatitis. Additionally, it is thought that genetic mutations may contribute to the development of AP in PHPT. Here, we report a case of necrotizing pancreatitis in a patient with untreated PHPT. Clinical Case: Patient is a 59-year-old male with a medical history of hypertension, nephrolithiasis and PHPT secondary to parathyroid hyperplasia (scheduled for parathyroidectomy) who presented with abdominal pain, nausea, vomiting and was found to have AP. He reported no history of alcohol use, trauma or insect bites. His workup was unrevealing for cholecystitis, choledocholithiasis or hypertriglyceridemia. He represented with calcium level of 16 mg/dL (NR 8.7-10.1) due to PHPT. PHPT was deemed the likely cause of AP. Course was further complicated by necrotizing pancreatitis and pseudocyst. A few months later, patient started having coffee ground emesis, worsening epigastric pain and weight loss of 60 lbs due to poor oral intake. CT abdomen/pelvis showed walled off pancreatic necrosis with peripancreatic stranding and concern for gastric outlet obstruction. EGD with PEG-J placement was done with plans for future endoscopic drainage. Few weeks after, he had another bout of worsening abdominal pain. Labs at the time showed corrected calcium between 11-13 mg/dL, PTH 147 pg/ml (NR 5-44), phosphorus 1.6 mg/dL (NR 2.5-4.5), vitamin D 25 hydroxy 19.5 ng/ml (NR 22-110). His condition became more complex with a hemorrhagic walled off pancreatic necrosis and splenic artery pseudoaneurysm requiring ICU care. The repeated escalation of symptoms resulted in multiple delays for the scheduled parathyroidectomy. Patient was started on treatment with Cinacalcet and vitamin D while in the hospital. Due to constraints in resources, he was unable to continue Cinacalcet outpatient. He subsequently was able to undergo parathyroidectomy with pathology showing benign adenoma. Conclusion: Hypercalcemic hyperparathyroidism causing AP, although rare, is often severe and poses a greater risk of complications making it important to be aware of this association, especially when more common causes have been excluded. Imaging techniques like cervical ultrasound, CT, and scintigraphy using 99mTc-Sestambi should be utilized to confirm suspicion. Surgical resection is the mainstay treatment, and having a multidisciplinary team with gastroenterologists, endocrinologists, and surgeons helps improve outcomes.
Presentation: 6/2/2024
8063 Cystic Parathyroid Adenoma: A Rare Cause Of Severe Hypercalcemia
Authors: Owrangi M E , Hasan F 
Published: October 2024

Abstract
Disclosure: M. Owrangi: None. F. Hasan: None.
Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism, but within this category, a rare subtype exists - cystic parathyroid adenomas (CPAs). Comprising only 0.5-1% of all parathyroid lesions, CPAs present unique diagnostic and therapeutic challenges. We report a case of a female patient presenting with severe hypercalcemia caused by a CPA. Case presentation: A 44-year-old African American female with a history of nephrolithiasis presented with abdominal pain and signs of dehydration. Labs were remarkable for serum calcium 13.2 mg/dL, albumin 4.0 g/dL, phosphorus 1.8 mg/dL, iPTH 617.7 pg/mL, 25-OH vit D 12.1 ng/mL, creatinine 0.85 mg/dL. She was initially resuscitated aggressively with IV fluids resulting in an improvement in serum calcium level to 10.3 mg/dL. Thyroid US showed a cystic nodule deep to the left thyroid lobe. Sestamibi parathyroid scan was consistent with a left superior parathyroid adenoma. She underwent 2 gland parathyroidectomy 3 months after the initial presentation. Intraoperatively serum PTH decreased by 91% after resection of the 2 parathyroid adenomas. Pathology confirmed the presence of 2 parathyroid adenomas, the larger one measuring 2.8 cm and weighing 3.8 g. Discussion: We describe a case of a middle-aged female presenting with severe hypercalcemia due to CPA. Her initial presentation was concerning for parathyroid carcinoma given the severity of hypercalcemia. However, the radiologic findings, coupled with surgical pathology, indicated that she had CPA. CPAs can be either functional, causing primary hyperparathyroidism (PHPT) with elevated serum calcium levels, or non-functional, remaining asymptomatic. Clinical features of PHPT associated with CPAs are similar to those with solid adenomas and include fatigue, GI symptoms, nephrolithiasis, bone pain, and neuropsychiatric manifestations. However, CPAs may exhibit certain distinct presentations: i) higher pre-operative serum calcium levels; and ii) increased risk of symptomatic hypercalcemia. Despite their rarity, CPAs deserve special attention due to their unique presentation, challenging diagnosis, and potential for severe hypercalcemia. Surgical parathyroidectomy is the definitive treatment for functional CPAs. Accurate localization and complete excision of the adenoma are crucial to avoid recurrence. Most CPAs occur in the fourth and fifth decade of life and are more common in women (female to male ratio of 2.5:1). 65-85% of cases are located in the neck and the majority arise from the inferior parathyroid glands and are left-sided, and may very rarely be intrathyroidal.
Presentation: 6/2/2024