bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU471 Resolution Of Elevated Alkaline Phosphatase After Joint Replacement In Severe Osteoarthritis
Authors: Rakholiya Jigisha , Nagaraj Sanchitha , Sharma Pranjali 
Published: October 2023

Abstract
Disclosure: J. Rakholiya: None. S. Nagaraj: None. P. Sharma: None.
Introduction: Alkaline phosphatase (ALP) elevation is commonly seen in hepatobiliary disorders. Conditions of high turnover such as healing fractures, hyperparathyroidism, Pagets’ disease of the bone, also lead to ALP elevation (1). Osteoarthritis (OA), characterised by degeneration of articular cartilage, joint space narrowing, and osteophyte formation, rarely causes ALP elevation. We present a case of ALP elevation that resolved after the arthritic joint was replaced. Case Presentation: A 60-year-old female with history of bilateral knee OA presented to the endocrinology clinic due to elevated ALP for over a year. She reported chronic fatigue, sleep disturbance, dry skin, hair loss, inability to lose weight and anxiety. ALP level at presentation was 165 U/L. An extensive work-up showed unremarkable serum and ionized calcium, serum phosphorus, parathyroid hormone, vitamin D 25-OH, calcitriol, 24-hour urine calcium, serum protein electrophoresis, and 24-hour urine protein electrophoresis. Dual x-ray absorptiometry (DXA) scan was normal with Fracture risk assessment tool (FRAX) score 5.9% for major osteoporotic fracture and 0.2% for hip fracture. Patient underwent total left knee arthroplasty following which ALP improved from 165 U/L to 135 U/L within 9 weeks of the procedure. Five months later, ALP was elevated (164 U/L) again. She then underwent right knee arthroplasty and ALP dropped to normal level (114 U/L) within 1 week post-surgery. Discussion: We report the rare phenomenon of ALP elevation in severe OA, that resolved after joint replacement. OA is characterised by inflammation mediated cartilage destruction, subchondral bone change, osteophyte formation, and alterations of ligaments and meniscuses. Bone change in severe OA is associated with increased synovial fluid ALP level. However, there is a paucity of literature studying the association of ALP with OA. A cross-sectional study of 3060 patients demonstrated higher serum ALP with symptomatic knee OA. Another study showed higher ALP levels with increased joint stiffness. The ALP elevation was attributed to low grade inflammation causing an inflammatory response in chondrocytes, and osteoarthritic pain. There is a need for more studies to evaluate the utility of serum ALP as a biomarker for severe OA.
Presentation: Thursday, June 15, 2023
FRI671 Association Of Insulin-like Growth Factor-1 (igf-1) With Bone Mineral Density (bmd) In Survivors Of Childhood Acute Leukemia
Authors: Kim Seulki , Park Su Jin , Sim Soo Yeun , Eon Kim Sung , Bae Ahn Moon , Shin Hee Kim , Kyung Cho Won , Kyung Soon Cho , Ho Jung Min , Suh Byung-Kyu 
Published: October 2023

Abstract
Disclosure: S. Kim: None. S. Park: None. S. Sim: None. S. Kim: None. M. Ahn: None. K. Shin Hee: None. W. Cho: None. C. Kyung Soon: None. M. Jung: None. B. Suh: None.
Purpose: To investigate bone mineral deficit in children survivors of childhood acute leukemia and analyze the association of IGF-1 with BMD status Methods : A total 214 patients (aged 8.47±4.42 for girls and 8.31±4.09 for boys at diagnosis) who were treated for acute leukemia were retrospectively reviewed. Types of leukemia, transplantation, and radiation therapy were investigated. Standard deviation scores (SDSs) of height, weight, body mass index (BMI), and lumbar spine BMD were measured at the end of treatment. Lumbar spine BMD was measured using dual-energy x-ray absorptiometry (DXA). Its relationships with calcium, phosphorus, alkaline phosphatase, bone specific alkaline phosphatase, calcitriol, parathyroid hormone, growth hormone, IGF-1, and insulin-like growth factor-binding protein-3 (IGFBP-3) were analyzed. Low BMD was defined lumbar spine BMD SDS less than -2.0 according to International Society for Clinical Densitometry guideline. Results: The overall prevalence of low BMD was found to be 15% (32/214). Age at diagnosis, transplantation, and radiation therapy were not significantly different between low BMD and normal BMD groups, however, BMI SDS and IGF-1 SDS were different between those two groups (-0.84±1.94 vs. 0.17±2.09, P = 0.012; -1.23 ±0.82 vs. -0.72 ± 0.78, P = 0.001, respectively). Correlation analysis showed that IGF-1 SDS is associated with BMI SDS and lumbar spine BMD SDS (rho=0.19, P=0.006; rho=0.248, P=0.001, respectively). Lumbar spine BMD SDS was related to BMI SDS and IGF-1 SDS by multivariate linear regression analysis (β = 0.15, P = 0.003; β = 0.31, P = 0.021, respectively). Multivariate logistic regression analysis showed that higher IGF-1 SDS was associated with a decreased of prevalence of low BMD (odds ratio: 0.42, 95% confidence interval: 0.24-0.75, P = 0.003). Conclusion: IGF-1 SDS was related to BMD, especially lumbar spine BMD, and a risk of prevalence of low BMD in children and adolescents. IGF-1 SDS seems to be a good tool for evaluating and predicting osteoporosis in children and adolescents.
Presentation: Friday, June 16, 2023
FRI692 Severe Hyperparathyroidism And Nephrolithiasis In An Adolescent Male Due To CDC73 Positive Parathyroid Carcinoma
Authors: Nguyen Jennifer T , Geller David Harry , Ryabets-Lienhard Anna 
Published: October 2023

Abstract
Disclosure: J.T. Nguyen: None. D.H. Geller: None. A. Ryabets-Lienhard: None.
Introduction: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism in the pediatric population, with only 20 previously reported cases. Variations in the CDC73 gene have been associated with sporadic parathyroid carcinoma, autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT), and familial isolated hyperparathyroidism (FIHP). To our knowledge, only 3 cases of pediatric parathyroid carcinoma with confirmed variants of CDC73 have been reported. We present a case of severe hyperparathyroidism and nephrolithiasis due to parathyroid carcinoma caused by a pathogenic variant in CDC73 in a pediatric patient, highlighting the importance of early recognition and management. Clinical Case: An otherwise asymptomatic 14-year-old male presented with one year of recurrent nephrolithiasis. Initial tests demonstrated hypercalcemia (13.8 mg/dL, 8.4-10.2 mg/dL), normal phosphorous, elevated PTH (1,379 pg/mL, 7.5-53.5 pg/mL), and elevated alkaline phosphatase (514 U/L, 30-250 U/L). The hypercalcemia was treated with hyperhydration, furosemide, and pamidronate. Sestamibi scan revealed a focus of abnormal uptake suggestive of a left parathyroid mass, with ultrasonographic demonstration of a predominantly solid, hypoechoic, and vascular mass centered posterior to the inferior left thyroid lobe. Skeletal survey was notable for trabecular abnormalities and osteopenia. He underwent a left parathyroid mass excision. Final pathology confirmed the parathyroid carcinoma, with multiple foci of vascular invasion without evidence of capsular involvement. Immunohistochemistry demonstrated diffuse positivity for PTH and loss of parafibromin expression by the tumor cells. Genetic testing revealed a pathogenic germline heterozygous nonsense variant in CDC73 (c.376C&gt;T(p.Arg126Ter)) resulting in protein truncation. Post-operative PTH was undetectable with normal calcium and phosphorous. Calcitriol, cholecalciferol, and calcium carbonate supplementation were implemented to prevent further hypocalcemia due to transient hypoparathyroidism and hungry bone syndrome. Calcium supplementation was discontinued within one year of his surgery. Serial thyroid ultrasounds and CT scans have been negative for recurrent or residual disease without evidence of metastasis. Mandibular x-ray showed no evidence of tumors or lesions involving the jaw. He has been noted to have small right renal cysts without other kidney abnormalities. Conclusion: Severe hyperparathyroidism due to parathyroid carcinoma can present as recurrent nephrolithiasis in an otherwise asymptomatic individual. Pediatric patients with a longstanding history of kidney stones should undergo screening for hypercalcemia and hyperparathyroidism even in the absence of other signs and symptoms of elevated calcium to ensure timely diagnosis and appropriate management.
Presentation: Friday, June 16, 2023
FRI695 Hypercalcemia Mediated By Granulomatous Disease Due To Polymethylmethacrylate (pmma) Injection Utilization For Gluteal Augmentation
Authors: Mishra Tinni , Craven James 
Published: October 2023

Abstract
Disclosure: T. Mishra: None. J. Craven: None.
Introduction: While etiologies for hypercalcemia commonly include hyperparathyroidism, malignancy or vitamin D intoxication, unusual causes should also be considered. We present a case that describes a patient who presented with hypercalcemia in the setting of granulomatous reaction to PMMA filler for gluteal augmentation. Clinical case: A 52 year old female with a past medical history of hypertension, stage III chronic kidney disease, nephrolithiasis, depression was admitted to the hospital with a peak calcium of 15.8 mg/dl (n: 8.4-10.4mg/dl). Hypercalcemia was incidentally noted while she was undergoing workup for her chronic kidney disease. Initial testing revealed PTH of 22 pg/ml (n: 22-94). 25 hydroxy vitamin D 24ng/ml, (n: 30-80), 1, 25 dihydroxy D2 markedly elevated at 258 pg/ml (n: 19-79). SPEP/UPEP normal. PTHrp was found to be 5.9 pmol/L(n: 0-3.4pmol/L). High-resolution CT chest did not show evidence of granulomatous disease or lung masses. A PET scan was obtained which showed extensive hypermetabolic activity in the bilateral gluteus medius and maximus muscle consistent with her history of PMMA injection for buttock augmentation. She was placed on aggressive maintenance intravenous fluid hydration. In addition, Lasix, zoledronic acid and calcitonin were administered. With these measures her calcium improved to a level of 10.7mg/dl. She did not tolerate high dose glucocorticoids. With her treatment intolerance and progressive renal disease in mind, plastic surgery has been consulted to explore surgical options for PMMA debulking. Conclusion: This represents a case of hypercalcemia mediated by elevated levels of calcitriol due to granulomatous inflammation caused by a foreign body reaction to PMMA injection. Polymethylmethacrylate is primarily used in South/Central America as a synthetic filling agent in cosmetic procedures, but is not FDA approved for gluteal injection. To our knowledge, there is only one other case report of MMA mediated hypercalcemia in the US. Given the rise in cosmetic tourism and the lag time between PMMA injection and development of hypercalcemia (mean time to presentation of 7 years), this complication is likely to become increasingly prevalent in North America.
Presentation: Friday, June 16, 2023
SAT179 Germline And Somatic Inactivating FLCN Variants In Parathyroid Cancer and Atypical Parathyroid Tumors
Authors: Jha Smita , Welch James , Tora Rana , Lack Justin , Warner Andrew , Del Rivero Jaydira , Mercedes Sadowski Samira , Nilubol Naris , Schmidt Laura , Linehan W M , Scott Weinstein Lee , Simonds William F , Kishore Agarwal Sunita 
Published: October 2023

Abstract
Disclosure: S. Jha: None. J. Welch: None. R. Tora: None. J. Lack: None. A. Warner: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. L. Schmidt: None. W.M. Linehan: None. L.S. Weinstein: None. W.F. Simonds: None. S.K. Agarwal: None.
Background: Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease. Methods: We analyzed the germline DNA of 19 patients with “sporadic” (PC) and 2 with atypical parathyroid tumors (APT) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including two patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants. FIindings: We identified germline FLCN variants in three unrelated patients with PC. The two frameshift variants have been described in patients with Birt-Hogg-Dubé (BHD) syndrome while the pathogenicity of the missense variant c.124G&gt;C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential impact on post-translational modification. All three patients with germline FLCN variants were noted to have renal cysts and two had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (one APT) of 16 patients with PC/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing however, LOH at the locus was demonstrated in 2 of 3 patients with identified germline FLCN variant. Interpretation: The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.
Presentation: Saturday, June 17, 2023
SAT184 Improving Access To Osteoporosis Specialists Using Electronic Consultations
Authors: Sethuram Claire , Brown Warren , Gill Gurleen , Liddy Clare , Afkham Amir , Keely Erin 
Published: October 2023

Abstract
Disclosure: C. Sethuram: None. W. Brown: None. G. Gill: None. C. Liddy: None. A. Afkham: None. E. Keely: None.
Background: Timely access to osteoporosis specialists remains a challenge in Canada, where patients face long wait times for specialist care. Electronic consultations (eConsults) help address this issue by allowing primary care providers (PCPs) to pose clinical questions to specialists using a secure online platform. This study identifies the types of osteoporosis-related questions being asked by PCPs and describes the impact of the advice provided by osteoporosis specialists using eConsult. Methods: We performed a cross-sectional study of osteoporosis-related eConsults submitted to endocrinologists between January 2018 and December 2020 on the Champlain BASE™ eConsult Service in Ontario, Canada. Each eConsult was coded according to clinical question and answer type through consensus between two authors, based on pre-determined taxonomies established by the reviewers. We analyzed eConsult utilization data, including response times, PCP satisfaction, and referral outcomes, which were collected via PCP surveys following completion of the eConsult. Results: Of the 2534 eConsults sent to endocrinologists during the study period, 408 (16%) were specific to osteoporosis. The most common questions asked by PCPs were regarding whether or not to start treatment (18%), the initial therapy choice (13%), and how often to complete bone mineral density scans (8%). The most common responses from specialists included recommendations for bone mineral density scanning (13%), recommendation to start therapy (9%), and recommendation to treat using a bisphosphonate without the dose specified (9%). The median response interval was 3.1 days, and the median time spent by endocrinologists responding to the eConsult was 10.0 minutes. Eighty-four percent of cases were resolved without requiring an in-person referral. A course of action that PCPs already had in mind was confirmed in 42% of cases. Clear advice for a new course of action for PCPs to implement was provided in 54% of cases. Conclusion: Osteoporosis eConsults provide timely access to valuable specialist advice while avoiding unnecessary face-to-face clinic visits. Further, we identified commonly recurring osteoporosis questions asked by PCPs, which can be used to inform planning of future continuing professional development events.
Presentation: Saturday, June 17, 2023
SAT186 Young Patient With Primary Hyperparathyroidism And Mutation Of CDKN1B Gene MEN 4 Variant
Authors: Faria Briceno Judith Jackelyn , Jande Suraj S , Lairmore Terry , Rajini Kanth Reddy Yatavelli 
Published: October 2023

Abstract
Disclosure: J.J. Faria Briceno: None. S.S. Jande: None. T. Lairmore: None. R.R. Yatavelli: None.
Background: Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT)accounting for 80-85% of the cases. PHPT most commonly manifests between 50-60 years of age and when it presents at younger age, it can be associated with inherited genetic conditions like multiple endocrine neoplasia or Hyperparathyroid Jaw tumor syndrome. Clinical Case: A 34-year-old male without significant past medical history was noted to have elevated serum calcium on routine lab work and was advised to promptly go to the emergency room for further evaluation. In the ED, the patient’s corrected calcium was 13.8 mg/dL (normal range 8.7 - 10.5 mg/dL), ionized calcium elevated at 1.77 mmol/L (normal range 0.90 - 1.20 mmol/L), PTH was 786.2 pg/mL (normal range 9 - 77 pg/mL). The patient denied any history of fractures, kidney stones or bone pain. Patient was treated medically with IV fluids and calcium lowering agents. Given the elevated PTH, ultrasonography of the neck was done which revealed an oval, hypoechoic lesion measuring 1.2 x 2.25 cm with increased vascular flow posterior to the right thyroid lobe consistent with parathyroid adenoma. Parathyroidectomy was performed with excision of right inferior parathyroid adenoma measuring 2.7 x 1.2 x 0.6 cm (1.25 grams). The preoperative PTH level was 997.7 pg/mL, which rapidly improved 20 minutes post tumor excision to 75.9 pg/mL, a 90% fall in PTH level suggestive of successful tumor excision. The patient’s post-operative period was uneventful. Considering the very young age of presentation; hyperparathyroidism genetic panel was obtained to rule out any inherited conditions like MEN1 or Hyperparathyroid Jaw tumor syndrome. Genetic testing revealed a germline missense mutation in CKDN1B (variant c.287C &gt, heterozygous) and classified as Variant of Uncertain significance). Mutations in the cyclic dependence kinase inhibitor 1B (CDKN1B) have been identified as the culprit for tumor growth seen in multiple endocrine neoplasia 4. MEN4 is a rare autosomal dominant endocrine tumor syndrome characterized by hyperparathyroidism and pituitary adenomas. The variant described in our patient has classically not been associated with other tumors and the available evidence is currently insufficient to determine the role of this variant in disease and hence classified as Variant of Uncertain Significance. Conclusion: Genetic testing should be considered in patients with primary hyperparathyroidism who present at very young age or have multiglandular disease. Our patient does not have any other classic features of MEN 4 and as the genetic mutation is classified as Variant of Uncertain Significance, patient would be monitored clinically, and caution exercised before using this result to inform clinical management decisions.
Presentation: Saturday, June 17, 2023
SAT189 Giant Parathyroid Adenoma
Authors: Shah Siddharth , Fujikawa Priscilla 
Published: October 2023

Abstract
Disclosure: S. Shah: None. P. Fujikawa: None.
Parathyroid adenomas rarely weigh more than 4 grams. Our patient had a 5.3gram adenoma causing bilateral knee pain limiting mobility, constipation, low back pain, and frontal headache. Presenting with calcium of greater than 17 mg/dL, patient was treated with 2 rounds of hemodialysis, calcitonin, Zoledronate, and aggressive IV hydration to decrease calcium levels prior to parathyroidectomy. Patient then went onto develop Hungry bone syndrome which was treated with calcium carbonate and calcitriol. This rare giant parathyroid adenoma presents a unique opportunity to learn about pathogenesis and treatment of longstanding hyperparathyroidism causing hypercalcemia associated symptoms and hungry bone syndrome after parathyroidectomy.
Presentation: Saturday, June 17, 2023
SAT228 Denosumab Associated Severe Hypocalcemia Due To Vitamin D Deficiency In A Patient With Undiagnosed Primary Hyperparathyroidism
Authors: Reddy Bendaram Snigdha , Bhatt Plukshi J , Kantorovich Vitaly 
Published: October 2023

Abstract
Disclosure: S. Bendaram: None. P.J. Bhatt: None. V. Kantorovich: None.
Background: The Human monoclonal antibody, Denosumab is a widely used antiresorptive therapy for Osteoporosis, which in the presence of risk factors can lead to hypocalcemia. We present an interesting case of severe and prolonged hypocalcemia due to Denosumab therapy, due to Vitamin D deficiency from malabsorption, despite the presence of undiagnosed Primary Hyperparathyroidism (PHPT). Case Presentation: 74-year old white female with a history of Crohn’s disease s/p ileostomy, Osteoporosis on Denosumab, Seizure disorder on Divalproex, and Parkinson’s disease presented to the ED for worsening altered mental status and decreased oral intake for at least 2 weeks prior to admission. On presentation, she was alert, oriented to person only, complaining of body aches. She was on no vitamin D supplements. Vital signs were unremarkable except for low BMI of 17.05 kg/m2. Physical exam revealed a chronic upper extremity tremor and a new facial mouth tremor associated with bruxism. Chvostek and Trousseau signs were negative, however this was after 1 dose of IV calcium gluconate in the ED. On presentation, initial labs revealed total calcium of 5.3 mg/dL [8.7-10.5], Albumin 4.7 g/dL [3.4-4.8], Magnesium 1.2 mg/dL [1.6-2.7], creatinine 1.5 mg/dL [04-1.1] (baseline 1.0). Further testing showed ionized calcium of 0.56 mmol/L [1.17-1.33], 25 Hydroxy Vitamin D 9 ng/mL [30-100], PTH 777 pg/mL [15-65] and phosphorus 3.6 mg/dL [2.7-4.5]. She was treated with IV calcium gluconate, 50,000 IU weekly vitamin D3 and calcium citrate 950mg oral BID, followed by which her total calcium went up to 12 mg/dl, with ionized calcium elevated at 1.36 mmol/L, while herPTH levels stayed inappropriately normal at 55 pg/ml. On the day of discharge, 25-OH-Vitamin D was 15 ng/dl, PTH 222 pg/ml and ionized calcium 1.07 mmol/L, when she was alert, oriented, with resolution of bone pains. Conclusion: Hypercalcemia in PHPT is from activation of osteoclasts and when these cells are inhibited by antiresorptive therapy, intestinal absorption will remain the primary source of plasma calcium levels. This explains the severe and prolonged hypocalcemia caused by Denosumab owing to its mechanism of action and long elimination half life, in our patient with Vitamin D deficiency on the background of malabsorption, despite a combination of primary and secondary elevation of PTH. Careful baseline assessment of calcium and Vitamin D levels, along with adequate supplementation and regular monitoring should be undertaken in all patients treated with Denosumab to avoid this.
Presentation: Saturday, June 17, 2023