bluuebunny/crossref_metadata_2025 huggingface dataset:
12350 A Rare Case Of Giant Parathyroid Adenoma Managed Medically For 8 Months: A Case Report
Authors: Labram Saffi , Bilandzic Luka
Published: October 2024

Disclosure: S. Labram: None. L. Bilandzic: None.

Background: Single parathyroid adenoma is the most common cause of primary hyperparathyroidism, and is attributed to approximately 85% of cases[1]. However, those classified as giant (weighing over 3.5 g and having a size greater than 2cm2) are exceedingly rare. This reports a rare case of primary hyperparathyroidism caused by giant parathyroid adenoma and details biochemical response following medical and surgical management. Case Report: A 64 year old black female presented with severe abdominal pain, confusion and constipation. Investigations revealed severe hypercalcemia of 17.3 mg/dl with massively elevated parathyroid hormone of 1255 pg/mL. Ultrasound showed a large hypoechogenic lobulated mass inferior to the left thyroid lobe representing a giant parathyroid adenoma. Due to delayed surgery the patient was initially treated medically over the course of 8 months. Over these months she was admitted to hospital 3 times for symptomatic hypercalcemia and received a total of 3 zolendronic acid infusions. Despite this she was unable to achieve long term remission of hypercalcemia. Cinacalcet was added and tolerated at the dose of 30 mg daily. Hypercalcemia improved, but remained elevated at a range of 11-13 mg/dL and the symptoms of brain fog and constipation did not subside entirely. She was eventually able to undergo surgical resection, and a giant parathyroid adenoma weighing 8.9 g was excised. Intraoperative intact parathyroid hormone (IOiPTH) sampling showed > 50% reduction (prior to removal 878pg/mL, 10 minutes after removal 132 pg/ml, 20 minutes after removal 96pg/mL). Pathological review showed an atypical parathyroid tumor. As the tumor lacked invasive growth it did not meet criteria for carcinoma. Conclusions: This is a rare case of primary hyperparathyroidism caused by a giant solitary parathyroid adenoma. The gold standard for management of primary hyperparathyroidism secondary to parathyroid adenoma is minimally invasive parathyroidectomy. However in our case, due to inability to access immediate surgery, challenging and prolonged medical treatment of severe hypercalcemia followed for 8 months. Ultimately, normalization of calcium level was achieved only by surgical intervention. IOiPTH measurements showed appropriate decrease confirmatory for the complete removal of the adenoma. References: 1. Dr Jacqueline Payne (2016). Hyperparathyroidism. [online] Patient.info. Available at: https://patient.info/doctor/hyperparathyroidism-pro#nav-2. 2. Rahim Mahmodlou, Amin Sedokani, Apameh Pezeshk and Bita Najafinejad (2022). Giant parathyroid adenoma: a case report. Journal of Medical Case Reports, 16(1). doi:https://doi.org/10.1186/s13256-022-03401-y.

Presentation: 6/2/2024
7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia
Authors: Abdelmasih Randa , Ali Israa
Published: October 2024

Disclosure: R. Abdelmasih: None. I. Ali: None.

Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, <20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients.

Presentation: 6/2/2024
7330 Acute Hypercalcemic Renal Failure As A Presenting Manifestation Of Primary Hyperparathyroidism Due To Atypical Adenoma
Authors: Gomes Kellyann M , Davydov Emily , Wu Lahiri Sharon
Published: October 2024

Disclosure: K.M. Gomes: None. E. Davydov: None. S.W. Lahiri: None.

Atypical parathyroid adenomas have uncertain malignant potential and are a rare cause of primary hyperparathyroidism. Compared to typical parathyroid adenomas, patients with atypical parathyroid adenomas have higher preoperative serum calcium and parathyroid hormone (PTH) levels. However pre-operative distinction between atypical parathyroid adenomas, typical adenomas and parathyroid carcinoma is challenging, and histological evaluation is needed for definitive diagnosis. A 59-year-old female with history of nephrolithiasis presented with syncope. Laboratory evaluation revealed a serum calcium of 21.3 mg/dL (8.2-10.2), creatinine of 2.35 mg/dL with GFR of 36 mL/min/1.723 m2, PTH of 3711 pg/mL (15-65), 25-hydroxy vitamin D of 12 ng/mL, phosphorus of 5.6 mg/dL (2.5-4.5). She incidentally tested positive for COVID-19. CT abdomen/pelvis demonstrated bilateral obstructive renal calculi requiring stent placement. Despite treatment with intravenous normal saline, 4 mg of zoledronic acid, two doses of 300 units of calcitonin, and cinacalcet 30 mg twice daily, repeat calcium and creatinine were 17.9 mg/dL and 3.64 mg/dL, respectively, and hemodialysis was initiated. CT neck and chest identified a 2.0 x 2.3 x 3.8 cm hypodense nodule inferior to the left thyroid lobe. A parathyroid planar scan with SPECT/CT showed uptake within the hypodense nodule. Bone scan did not reveal any disease. The enlarged left parathyroid gland was removed. Intra-operatively, PTH decreased to 302 pg/mL. Pathological evaluation of the left inferior parathyroid gland revealed a 4.2 cm partially encapsulated hypercellular neoplasm weighing 7.3 grams with increased mitotic activity and focally thickened fibrotic capsule and no extracapsular or vascular invasion consistent with atypical parathyroid adenoma. On postop day 4, her calcium declined to 7.1 mg/dL and PTH was 383 pg/mL. Calcium supplementation was initiated due to concern for hungry bone syndrome. On postop day 14, calcium increased to 10.3 mg/dL and supplementation was discontinued. Her calcium levels have remained normal without supplementation three months after surgery. Severe hypercalcemia causing renal failure is an uncommon manifestation of primary hyperparathyroidism. Preoperative differentiation of parathyroid carcinomas and parathyroid adenomas is difficult, but important since surgical management of these two distinct entities differs. Higher preoperative calcium and PTH levels and concomitant renal failure suggest parathyroid carcinoma. This case highlights the challenge of differentiating atypical parathyroid adenomas from parathyroid carcinoma since both conditions can present with severe hypercalcemia and renal failure. Further research on the risk of carcinoma and recurrence of hypercalcemia in atypical parathyroid adenoma is needed.

Presentation: 6/2/2024
8305 Assessing The Relationship Between Oral Health And Bone Disease Among Post-menopausal Women
Authors: Tahir Nataliyah , Ahmad Sophie , Batra Kavita , Gupta Ashok , Izuora Kenneth E
Published: October 2024

Disclosure: N. Tahir: None. S. Ahmad: None. K. Batra: None. A. Gupta: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk.

Background: Menopause is associated with significant bone loss and worsening oral health, especially periodontal disease (PD). The purpose of this study was to understand the relationship between oral health and bone loss and the factors that influence this relationship. This will help better understand their pathophysiology and provide guidance for more appropriate care. Methods: ​​This cross-sectional study included post-menopausal women undergoing routine bone density evaluation at a diagnostic radiology center. After participants signed informed consent, histories were collected via an investigator-administered questionnaire, the oral cavity was inspected for teeth loss and PD, and a bone density assessment, interpreted by a radiologist, was obtained. The significance level was set at 5% and data were analyzed using chi-square and logistic regression tests. Results: In a sample of 100 eligible participants, the mean age and body mass index (BMI) were 68.17 ± 8.33 years and 29.59 ± 6.13 kg/m2 respectively. Twenty-three participants (23.0%) had T2DM, 29 (29.0%) had < 20 natural teeth and 17 (17.0%) had normal bone mineral density. In an unadjusted simple logistic regression, age, BMI, race/ethnicity, number of natural teeth, history of PD, and history of osteoporotic fracture were associated with bone loss. However, in the binary logistic regression, the only significant predictors of bone loss included age (aOR 1.171, p<0.001), BMI (aOR 0.763, p<0.001), and the history of osteoporotic fractures (aOR 21.273, p=0.021). Conclusion: Clinical variables associated with bone loss in our study included older age, lower BMI, and history of osteoporotic fracture. These are established risk factors for bone loss. Although unadjusted results suggest a relationship between oral health measures and bone loss, these relationships were not present when other factors were included in a multivariate model. These findings suggest PD by itself may not be a risk factor for bone loss but may reflect the similarity in the risk factors for both conditions.

Presentation: 6/3/2024
8317 Biochemical Adequacy And Renal Complications In Long-Term Management Of Patients With Postsurgical Hypoparathyroidism
Authors: Hong A Ram , Yong Park Ji , Choi Wonsuk , Yoon Jee Hee , Kim Hee Kyung , Kang Ho-Cheol
Published: October 2024

Disclosure: A. Hong: None. J. Park: None. W. Choi: None. J. Yoon: None. H. Kim: None. H. Kang: None.

Background: Hypoparathyroidism (HypoPT) most commonly develops after neck surgery, particularly thyroid surgery. Permanent postsurgical HypoPT necessitates calcium and active vitamin D supplementation for 12 months or more due to irreversible parathyroid damage following surgery. This study investigated the biochemical adequacy of conventional therapy (i.e., active vitamin D and/or calcium) in patients with permanent postsurgical HypoPT based on recent guidelines and assessed the incidence of renal complications. Materials and Methods: The study included 62 adult patients with permanent postsurgical HypoPT who underwent total thyroidectomy for papillary thyroid cancer at Chonnam National University Hwasun Hospital. Biochemical parameters, including albumin-adjusted serum total calcium, ionized calcium, phosphate, creatinine, parathyroid hormone, magnesium, 25-hydroxyvitamin D (25[OH]D), and 24-h urine calcium, were measured. Renal ultrasound and KUB X-ray were performed for all patients. Results: The mean age of the patients was 55.5 ± 12.4 years, with 48 (77.4%) being female. The median follow-up duration after surgery was 10.6 years (interquartile range 9.0-15.5 years). At the time of evaluation, all patients were treated with calcitriol. Additional treatment, including calcium carbonate or cholecalciferol, was received by 43 (69.4%), and 28 (45.2%) were given thiazide diuretics. Thirty-seven (59.7%) patients had values below the recommended serum calcium (albumin-adjusted or ionized) concentration, while three (4.8%) had values above the upper normal limit of serum phosphate level. Serum 25(OH)D levels were maintained within the normal range (30-50 ng/mL) in 27 (43.5%) patients, and 47 (75.8%) patients met normal serum magnesium levels. Hypercalciuria, defined as >7.5 mmol/day in men and >6.25 mmol/day in women, was observed in 12 (19.4%) patients. Nephrolithiasis and nephrocalcinosis were present in 2 (3.2%) patients each. No patient had chronic kidney disease (CKD), defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Conclusion: Conventional management for permanent postsurgical HypoPT appears suboptimal for certain patients. However, the incidence of renal complications, such as hypercalciuria, nephrolithiasis/nephrocalcinosis, and CKD, was not commonly observed in a real-world setting during the 10 years of follow-up. This observation may be associated with a higher prescription rate of thiazide diuretics.

Presentation: 6/2/2024
12538 Blocking Oxidized Phospholipids Improves Bone Mass In Mice By Transcriptional Reprogramming Of Osteoblastic Cells: Analysis At The Single Cell Level
Authors: Palmieri Michela , Nookaew Intawat , Almeida Maria , Joseph Teenamol E , O’Brien Charles A , Ambrogini Elena
Published: October 2024

Disclosure: M. Palmieri: None. I. Nookaew: None. M. Almeida: None. T.E. Joseph: None. C. O'Brien: None. E. Ambrogini: None.

Oxidized phospholipids containing phosphatidylcholine (PC-OxPLs), present on oxidized low-density lipoproteins (OxLDL) and apoptotic cells, are pathogenic in many diseases, including osteoporosis. The E06 IgM antibody binds PC-OxPLs and blocks their adverse effects. In our studies, six-month-old female and male mice overexpressing a single chain (scFv) form of the antigen-binding domain of E06 IgM (E06-scFv) have high cancellous and cortical bone mass. In addition, E06-scFv transgenic mice are protected against high fat diet- and age-induced bone loss. E06-scFv increases osteoblast number, bone formation rate and reduces osteoblast apoptosis. To investigate the effect of E06-scFv on osteoblastic cells transcriptional reprogramming, we performed single cell RNA-sequencing (scRNA-seq) of mesenchymal cells from long bones of 6-months old WT and E06-scFv transgenic female and male mice. Based on the total of over 7,500 osteoblastic cells, we focused the analysis on 3 cell clusters, pre-osteoblasts, identified by high levels of osteopontin (Spp1), osteoblasts, identified by high expression of osteocalcin (Bglap) and adipo-CAR expressing the adipogenic marker Adipoq in addition to high expression of the stromal marker Cxcl12. In both males and female transgenic mice, the relative number osteoblasts increased [12.0 % in females and 23.7 % in males; conversely, the relative number of adipo-CAR cells decreased [18.2 % in females and 15.1 % in males] compared to WT. We performed the analysis of functional enrichment-based gene ontology by piano software package and found that, in the three clusters of both male and female transgenic mice, there was an upregulation of gene expression, with a range of 37-125 genes per cluster, related to extracellular matrix organization [p range 0.0003-3.95E-09], bone mineralization [p range 0.04-0.0022] and cell adhesion [p range 0.019-0.00008]. Consistent with these results, bulk RNA sequencing indicated that these ontology terms were downregulated in calvaria-derived osteoblasts treated with OxLDL [extracellular matrix organization p= 1.19E-13; bone mineralization p= 0.0018655; cell adhesion p= 2.73E-12]. Based on these results, we conclude that PC-OxPLs not only affect osteoblast number but also decrease osteoblast activity on a single cell basis.

Presentation: 6/1/2024
5159 Bone Disease Related To PLS3 Gene Mutation
Authors: Saberi Sima , Helen Esfandiari Nazanene
Published: October 2024

Disclosure: S. Saberi: None. N. Esfandiari: None.

Background: A variety of genes play a role in the development of osteoporosis. One of these is PLS3, located on the X chromosome. PLS3 gene mutation leads to defective function of the protein Plastin 3. Plastin 3 functions in the binding and bundling of F-actin, a main component of the actin cytoskeleton. In the skeletal system the actin cytoskeleton regulates adaption to gravity and mechanical stress. Dysregulation of this gene is associated with diseases of the bone, including osteoporosis. Clinical Case: A 60-year-old man with a history of hearing loss since age 52, hypothyroidism diagnosed at age 57 presents to the Genetics Clinic after 2 grandsons were diagnosed with osteogenesis imperfecta. The mothers (his two daughters) of the two grandsons were found to be carriers of the PLS3 gene mutation. Because of their carrier status the patient was screened and a pathogenic partial gene deletion of exons 8 to 16 in the PLS3 gene was detected. The patient has a history of a right wrist fracture at age 16 in a fall from 8 feet height from a ladder, right leg fracture at age 45 when his leg got caught and twisted in a ladder rung, 5 rib fractures and shoulder fracture at age 53 in a fall from 3 feet into a utility hole. A DXA scan showed osteopenia in his left femoral neck (T-score -1.3), normal bone density in his total hip (T score -0.1) and lumbar spine (L1-L4 T-score -0.4). FRAX score for major osteoporotic fracture was 9.4% and hip fracture was 1.2%. Labs for secondary causes of osteoporosis were normal. Due to his gene mutation and fracture history a bisphosphonate was recommended.Clinical Lessons:Obtaining a thorough family history in people with fractures can determine the need for screening for gene mutations associated with osteoporosis. This can identify patients who need more aggressive management.

Presentation: 6/2/2024
7159 Brown Tumor As Primary Presentation Of Parathyroid Carcinoma In A Young Female
Authors: Zachariah S G , Anand R , Wong B Y , Lee H J
Published: October 2024

Disclosure: S.G. Zachariah: None. R. Anand: None. B.Y. Wong: None. H.J. Lee: None.

Title Brown Tumor as Primary Presentation of Parathyroid Carcinoma in a Young Female Introduction/Background: Parathyroid carcinoma (PC) is a rare cause of hyperparathyroidism (HPT) accounting for less than 1% of primary HPT cases. The mean age of PC presentation is 62 years. Long-standing HPT can lead to the formation of osteitis fibrosis cystica (brown tumors). In today’s world of advanced screening, they are an increasingly rare presentation of HPT. We present a case of PC presenting as multiple brown tumors in a young woman. Case: A previously healthy 32-year-old woman presented to the emergency department with right shoulder pain after a mechanical fall. MRI revealed multiple osseous lesions of the proximal humerus, glenoid, and scapula, concerning for possible metastatic malignancy. Notable labs: calcium 13.6 mg/dL [8.5 - 10.5 mg/dL], phosphorus 1.7 mg/dL [2.5 - 4.5 mg/dL], alkaline phosphatase 2,369 U/L [< 130 U/L], 25-OH vitamin D 0.8 ng/mL [30 - 60 ng/mL], and parathyroid hormone greater than 2,500 pg/mL [20-80 pg/mL]. Albumin and renal function were normal. CT chest/abdomen/pelvis showed lytic lesions of the left 7th rib, anterior superior iliac spine (with nondisplaced fracture), pelvis, and sacrum. Subsequent pelvic biopsy showed fragmented bony trabeculae with osteoblastic rimming and rare osteoclasts, fragments of fibrous tissue with few plasma cells and hemosiderin laden macrophages, possibly consistent with brown tumor. On parathyroid ultrasound, a 2.2 cm cystic mass was seen along the left common carotid artery. CT neck confirmed the location and also reported C7-T1 spinal lesions. Calcium levels stabilized with IV fluids and 90 mg IV pamidronate. She underwent a left parathyroidectomy and left hemithyroidectomy with central neck dissection. Pathology was consistent with a low-grade parathyroid carcinoma, with a foci of angioinvasion and capsular invasion without lymph node metastases. The Ki-67 index was less than 1%. Post-operatively, the patient was started on calcium and calcitriol supplementation and did not experience hungry bone syndrome. On further discussion, the patient noted that she had a jaw tumor that was previously biopsied and found to be benign. The patient has since been referred for genetic testing. Conclusion/Clinical Lessons: Both PC and its initial presentation with brown tumors are uncommon. Even more rare is the presentation of both in a young, otherwise healthy female. In this context, it is also important to note that brown tumors can mimic osseous metastases and appropriate biochemical, imaging, and histopathological evaluation is needed. The diagnosis of PC under 40 years of age is uncommon and genetic testing is indicated. Syndromes including multiple endocrine neoplasia type 1, familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor syndrome are potential causes of inherited PC.

Presentation: 6/3/2024
5105 Characterization Of Novel PHEX Variants In X-Linked Hypophosphatemic Rickets And Genotype-PHEX Activity Correlation
Authors: Wu Huixiao , Zhao Wanyi , Chen Xinyu , Gao Ling , Xu Chao , Zhao Jiajun
Published: October 2024

Disclosure: H. Wu: None. W. Zhao: None. X. Chen: None. L. Gao: None. C. Xu: None. J. Zhao: None.

X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by mutations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Till now, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully determined. Here we summarized clinical features of 49 HR patients and detected 17 novel PHEX variants and 5 novel non-PHEX variants. Then we explored the pathogenesis of new-found variants from protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering the length and localization of the protein, while truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein retained in cells. No evident correlation was observed between mutation types and clinical phenotypes. However, for the first time ever, we analyzed the relationship between PHEX activity and serum phosphorus level and found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Then we established two new knock-in XLHR mouse models by introducing into mice two novel Phex variants (c.T1349C and c.C426G) found in patients using CRISPR/Cas9 technology. Both demonstrated the clinical manifestations of XLHR seen in the patients and PhexC426G mice showed more severe phenotype than PhexT[1]349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study promoted the understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation provided scientific support for precise diagnosis and treatment of XLHR.

Presentation: 6/3/2024
12324 Clinical Features And PHEX Variants Of Adults With X-Linked Hypophosphatemia
Authors: Valadares L P , Carvalho D R , Lopes F S , Oliveira R S , Castro L G
Published: October 2024

Disclosure: L.P. Valadares: None. D.R. Carvalho: None. F.S. Lopes: None. R.S. Oliveira: None. L.G. Castro: None.

X-linked hypophosphatemia (XLH), caused by loss-of-function PHEX mutations, is a lifelong renal phosphate-wasting disorder and the main cause of inherited hypophosphatemia. In adults, chronic hypophosphatemia leads to impaired bone mineralization and persistent osteomalacia. Short stature, lower limb deformities and musculoskeletal chronic pain can significantly impact the daily lives of affected individuals. This study aimed to describe the clinical and molecular profiles of 23 adults with genetically proven XLH who are being followed at a tertiary medical center in Brazil. We conducted a retrospective analysis of their medical records. The median age at diagnosis was 3.0 years (IQR 2.0-8.0) and the mean age at first visit at the adult care unit was 30.5 years (±12.7). Their mean final height was 144.2 cm (±10.5), with a mean body mass index (BMI) of 28.1 kg/m2 (±4.9). Nine patients were overweight, and seven were obese. Sixteen patients had a positive family history of rickets, and nine had offspring with XLH. Among the 14 different PHEX mutations that were identified, six had not been previously reported. Hypophosphatemia was observed in 21 patients at presentation at the adult care unit, increased serum alkaline phosphatase levels in 19, and 12 showed increased PTH levels. Chronic bone and muscular pain were reported by sixteen patients, eighteen had lower limb deformities, and six had a history of fractures and/or pseudofractures. Seventeen patients underwent orthopedic surgeries, with an average of 3.8 surgical interventions per patient. Nephrolithiasis and/or nephrocalcinosis were observed in nine patients, but none had glomerular filtration rate below 60 mL/min adjusted to 1.73 m2 of body surface. Three patients were on conventional treatment (phosphate and calcitriol) upon presentation at the adult care unit, five patients had never received XLH-specific treatment, and fifteen discontinued conventional therapy after completing skeletal growth, with a mean therapy duration of 12.1 years (±3.5). Out of the 20 patients without treatment, 16 were initiated on pharmacological therapy based on symptoms and signs of persistent osteomalacia. Eleven started combined phosphate and calcitriol supplementation, while five received calcitriol monotherapy. This cohort underscores that adults with XLH experience significant musculoskeletal morbidity throughout their lives, and require long-term follow-up, including assessment of energy metabolism. Importantly, most of them benefits from maintaining pharmacological treatment in adulthood.

Presentation: 6/2/2024
12492 Clinical Resolution Of Parkinsonism And Dementia Following Radio Frequency Ablation Of A Parathyroid Adenoma
Authors: Finny Philip , George Tom , Francis Anju K
Published: October 2024

Disclosure: P. Finny: None. T. George: None. A.K. Francis: None.

Background: Parkinsonism is a rare neurological manifestation of primary hyperparathyroidism. Radiofrequency ablation (RFA) of parathyroid adenomas is a novel treatment modality. Clinical Case: A 78 year old lady presented to our Emergency department with hypercalcemic encephalopathy. She had long standing Diabetes mellitus, Bronchial asthma and Parkinsonism with dementia for the past 14 years. She was bed bound with dependence on carers for activities of daily living (ADL). She had been diagnosed elsewhere in 2018 to have primary hyperparathyroidism due to a right inferior parathyroid adenoma and had a right hemithyroidectomy with a failed parathyroidectomy. She was being managed with Cinacalcet 60 mg daily for the past 4 years. Prior to this admission she had discontinued Cinacalcet for a few days. Her initial serum calcium was 15.3 mg/dl (8.7-10.7), phosphorus 1.80 mg/dl (2.5-4.5) and PTH 451 pg/ml (15- 88). She was aggressively treated with intravenous normal saline hydration followed by Furosemide injection. Then she was given Calcitonin injections subcutaneously and IV Zoledronic acid infusion. Her calcium dropped to 11.8 mg/dl within 48 hours of admission, and her sensorium improved. Imaging studies showed no visible parathyroid adenoma on ultrasound, but the 4D CT scan of the neck revealed a left inferior parathyroid adenoma of size 1.1 x 1.2 cm. This was concordant on the Technetium 99m Sestamibi scan. Her MRI Brain showed bilateral globus pallidus calcification. In view of her multiple comorbidities making her a poor candidate for general anaesthesia, non-surgical options were considered. A percutaneous ultrasound guided RFA of the left parathyroid adenoma was successfully performed. Post procedure the PTH dropped from 321 pg/ml to 54.9 pg/ml within 24 hours. The calcium, phosphorus and PTH remained normal. Her Parkinsonism and dementia significantly improved and we could wean her off the anti- parkinsonian and anti-psychotic medication. She became ambulant and regained her cognitive functions. This clinical and biochemical remission was maintained over the next 22 months of follow up. Conclusion: RFA is a novel therapeutic option in treating parathyroid adenomas among surgically unfit patients. Reversal of advanced Parkinsonism following correction of chronic hypercalcemia led to this patient regaining a good quality of life. 4D CT scan of the neck is useful in localizing the parathyroid adenoma when there is discordance between the ultrasound and Sestamibi scan. References: (1) Mishal BR, Kachhadiya KJ, Chandalia SH, Bhansali MS, Wadia PM. Hyperparathyroidism: A rare cause of worsening of parkinsonism. Annals of Movement Disorders. 2020 Sep 1;3(3):181-4.(2) Hussain I, Ahmad S, Aljammal J. Radiofrequency ablation of parathyroid adenoma: a novel treatment option for primary hyperparathyroidism. AACE Clinical Case Reports. 2021 May 1;7(3):195-9.

Presentation: 6/1/2024
7336 Decades In The Dark: The Long Road To Diagnosing And Treating Hypophosphatasia
Authors: Alkeshbhai Mendpara Vaidehi , Madrigal Loria Gloriana , Zeinab Khan Leila
Published: October 2024

Disclosure: V.A. Mendpara: None. G. Madrigal Loria: None. L.Z. Khan: None.

Background: Hypophosphatasia (HPP) is a rare bone disorder that results from deficient activity of the tissue non-specific isoenzyme alkaline phosphatase (ALP).[1] This case highlights a patient whose diagnosis of this treatable genetic condition was significantly delayed for almost two decades, despite receiving care at a prominent academic institution. The patient's persistently low ALP levels in routine lab tests were overlooked by multiple clinicians, leading to a delay in her care and eventual treatment. Case presentation: A 61-year-old Caucasian woman presented at the endocrinology clinic with complaints of severe fatigue, generalized pain, multiple childhood fractures, and ongoing dental issues. The rheumatology clinic to which she was referred for polyarthralgia diagnosed her with Hypophosphatasia (HPP) after noting chronically low alkaline phosphatase (ALP) levels from her previous charts ranging from 15 to 24 U/L (normal range: 34 to 123 U/L) over two decades. Her serum calcium, parathyroid hormone (PTH), and 25-hydroxy vitamin D levels were within normal ranges. A DEXA scan revealed normal bone density, effectively ruling out osteoporosis. Further investigation showed elevated Vitamin B6 levels at 219.6 nmol/L (normal range: 20.0 to 125.0 nmol/L), raising suspicion for HPP. The patient's family history provided additional insight, with her mother having a history of short stature and fractures and her son experiencing premature tooth loss at the age of 2. A genetic evaluation identified a heterozygous pathogenic variant in the ALPL gene (c.881A>C, p.Asp294Ala), confirming the diagnosis of autosomal dominant HPP. Initiating treatment with Asfotase alfa, a medication targeting HPP, resulted in a marked improvement in the patient's symptoms. Discussion: This case shows the diagnostic complexities of HPP, stressing the significance of actively screening for this condition via ALP levels in routine laboratory testing or during osteoporosis evaluations. The diagnostic process is critical to distinguish HPP from primary osteoporosis, as treatment and potential risks differ significantly. Inadvertent use of bisphosphonates can worsen hypomineralization and lead to atypical femoral fractures in HPP patients. Asfotase alfa enzyme replacement therapy, available since 2015, offers a targeted approach by replacing the enzyme defect, thereby mitigating symptoms. Heightened awareness among healthcare providers of HPP in adults holds the potential to enhance diagnosis rates and facilitate improved treatment outcomes for this highly treatable condition.[1] Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. ASBMR.

Presentation: 6/2/2024
12344 Four-Month Delay In Denosumab Induced Severe Hypocalcemia And Hypophosphatemia. Case Report
Authors: Mohamed Eid Mennaallah , Reutrakul Sirimon
Published: October 2024

Disclosure: M.M. Eid: None. S. Reutrakul: None.

Introduction: Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa Β ligand, blocks osteoclast function and reduces bone resorption. Case: A 91 year old male with history of osteoporosis, type 2 diabetes, chronic kidney disease (CKD) and prostate cancer. Presented with fatigue and cold intolerance. Denied confusion, muscle cramp, perioral numbness/tingling, bowel habit change. Medications included empagliflozin 12.5 mg/day, leuprorelin 45 mg every 6 months since 2021 and cholecalciferol 1000IU/day. On examination, he was alert and oriented x 3 with stable vital signs. No thyromegaly. Chvostek's sign was negative. Labs: serum calcium (Ca) 6.5 mg/dl, corrected Ca (Co Ca) 6.7mg/dl(N 8.7-10.4), ionized Ca 0.7mMol/l (N 1.13-1.32), TSH 131uIU/ml (N 0.55-4.78), free T4 0.72ng/dl (N 0.89-1.76), creatinine 1.55mg/dl, GFR 42ml/min/1.73m2, HbA1C 6.1%. EKG with corrected QT interval of 499 msec. Hypocalcemia work up : parathyroid hormone (PTH) 762 pg/ml (N 18.4-80.1), 25 OH vitamin D (Vit D) 37ng/ml (N 30-100), 1,25 OH Vit D 77pg/ml (N 18-72), phosphorus (Phos) 1mg/dl (N 2.4-5.1), magnesium (Mag) 1.7mg/dl (N 1.6-2.6),ALP 59U/L(N 45-117). Clinical impressions were a new diagnosis of primary hypothyroidism and non PTH mediated hypocalcemia with secondary hyperparathyroidism. A thorough review of medication revealed that he received the first dose of denosumab 60 mg 4 months prior to this presentation. Baseline labs 1 month prior to denosumab: Ca/Co Ca 9.1/9.2mg/dl, Phos 4.5mg/dl, PTH 199.6pg/ml, Mag 2.1mg/dl,TSH 2.72 uIU/ml. 2 months after denosumab administration, serum Ca/Co Ca 8.8/8.6mg/dl. He was admitted and received Ca gluconate 2gm IV pushes, calcitriol 0.5 mcg/day and levothyroxine 50 mcg/day and kept on cardiac monitoring. He remained asymptomatic. On the 5th day, serum Ca/Co Ca 8.4/8.6mg/dl, Phos 3mg/dl, Mag 2mg/dl. He was discharged on oral Ca Carbonate, calcitriol and levothyroxine. The second denosumab dose was cancelled. Conclusion: Denosumab is an effective anti-osteoporotic medication but can cause hypocalcemia. The risks for denosumab induced hypocalcemia include renal impairment, Vit D deficiency and lack of Ca/Vit D supplementation. Hypocalcemia usually occurs 1 - 2 weeks after denosumab, corresponding to its peak of action. Checking serum Ca and Vit D with correction of deficiencies before starting denosumab is recommended. In high risk patients with CKD, daily Ca and Vit D supplements are recommended (1). Our case has CKD and developed severe hypocalcemia and hypophosphatemia 4 months after receiving denosumab without other apparent causes for hypocalcemia. Hypothyroidism is likely an incidental diagnosis and not contributing to hypocalcemia in the absence of rhabdomyolysis. Reference: 1.Jalleh R, Basu G, Leu RL, Jesudason S: Denosumab induced severe hypocalcemia in chronic kidney disease. Case Rep Nephrol.2018

Presentation: 6/2/2024
12268 Hypercalcemia Alert: Exploring The Link To Isolated Bone Marrow Sarcoidosis
Authors: Renzu M , Hubers C M , mehta v , Qazi A , Yerasuri D K
Published: October 2024

Disclosure: M. Renzu: None. C.M. Hubers: None. V. mehta: None. A. Qazi: None. D.K. Yerasuri: None.

Introduction: Sarcoidosis, a complex disorder marked by granuloma formation in diverse organs, often affects the lungs, but can involve various systems as well. Rare cases of bone marrow involvement may mimic conditions like multiple myeloma, emphasizing the need to consider sarcoidosis in patients with bone marrow abnormalities, especially those without typical myeloma features. Case Presentation: A 79-year-old white male with a medical history of hypertension, hyperlipidemia, deep venous thrombosis, prostate cancer in remission, chronic knee pain, and basal cell carcinoma presented for pre-operative evaluation, as he was scheduled for an elective orthopedic procedure. On routine lab work, he was found to have acute hypercalcemia and normocytic anemia. This finding raised suspicion for an underlying systemic pathology. He reported that he did not take any calcium or vitamin D supplements at home. Subsequent endocrine assessment, including evaluation of parathyroid hormone and vitamin D levels, revealed a non-PTH-mediated hypercalcemia. The persistence of hypercalcemia prompted further investigations, including assessments for multiple myeloma by oncology. The workup was negative for multiple myeloma but significant for granulomas on bone marrow biopsy, a finding consistent with sarcoidosis. Additionally, angiotensin converting enzyme levels were elevated at the time of diagnosis. Interventions led to the resolution of hypercalcemia following steroid therapy of prednisone 20 mg daily and close follow up with endocrinology. As part of his follow up, ACE levels are being regularly monitored, with the patient going for lab work every other month. Discussion: Bone marrow biopsies rarely reveal granulomas and sarcoidosis accounts for only a very small percentage of these findings. The standard workup for sarcoidosis typically does not include bone marrow biopsies. By integrating biopsies into the standard diagnostic protocol researchers may gain insights into the etiology and mechanisms driving this manifestation of sarcoidosis, ultimately improving diagnostic accuracy and patient care. Distinguishing sarcoidosis from multiple myeloma also poses diagnostic challenges, necessitating thorough evaluation in patients with bone marrow abnormalities. Despite its rarity, clinical suspicion for sarcoidosis should be considered in patients with underlying hematologic disorders or malignancies. Additionally, sarcoidosis exhibits geographical variation, being less common in Japanese men and more prevalent in African American women. This highlights the importance of considering demographic factors when evaluating patients for sarcoidosis and its extrapulmonary manifestations. Long-term outcomes in isolated bone marrow sarcoidosis remain unclear, warranting surveillance for progression to multiple myeloma or other lymphoproliferative disorders.

Presentation: 6/2/2024
7298 Hyperventilation Associated Hypophosphatemia, Hypocalcemia, Hypokalemia And Paralysis
Authors: Afreen S , Afreen N
Published: October 2024

Disclosure: S. Afreen: Research Investigator; Self; Tandem Diabetes Care, Yes. N. Afreen: None.

Introduction: Hyperventilation is over-breathing in excess of the metabolic needs of the body, which can result in respiratory alkalosis and a wide range of electrolyte abnormalities. Case: A 38 year old male with a past history of hypertension, OSA and cholecystectomy reported having episodes of palpitations, tachypnea with respiratory rate as high as 80 breaths/ minute, associated with facial numbness and tingling, tetany, progressing to paralysis of his extremities. These episodes started 7 years ago but gradually became more frequent. He denied anxiety or stressors prior to these episodes. The episodes almost always result in emergency room visits. During one of these episodes he was found to have the following labs: ionized calcium-1 mmol/l, serum phosphorus- 0.8 mg/dl, serum potassium- 2.7 mmol/l, 1.25(OH)2D- 44pg/ml, alkaline phosphatase- 60 IU/l, glucose- 94 mg/dl and GFR- 90 ml/min/1.73m2. VBG during this episode: pH - 7.59, PCO2- 23 mm Hg, and bicarbonate - 22 mmol/l. Of note, the electrolytes are normal in between the episodes. Thyroid labs are normal. Off of phosphate supplementation for 3 days, in between episodes, his serum phos- 4.2mg/dl, cr - 0.84 mg/dl. Second morning urine phos - 84 mg/dl and urine cr - 206.81 mg/dl. Tubular phosphate reabsorption was 91.9%. He had negative Holter, nuclear stress testing and MRI of the brain. No mutations were identified on genetic analysis of CACNA15, KCNJ2, RYR1, SCN4A. During his recent endocrine clinic visit, on physical exam: height- 5 feet 11 inches, weight- 366 lbs weight, BMI- 51.1 kg/m2, BP- 129/89 mm Hg, heart rate- 81 bpm and respiratory rate- 18 breaths/minute. He did have one palpable 1.5 cm left thyroid nodule. Otherwise, the exam was unremarkable. The patient was referred to pulmonology to be evaluated for potential diaphragmatic and lung causes of his tachypnea. He was also referred to psychiatry for evaluation of underlying anxiety. Since these episodes of hyperventilation associated electrolyte abnormalities lead to paralysis, he was started on calcitriol 0.25mcg daily along with 1250 mg potassium phosphate daily. Discussion: Hyperventilation can lead to a respiratory alkalosis and corresponding increase in intracellular pH. High intracellular pH can lead to increased phosphofructokinase activity and glycolysis, resulting in increased intracellular phosphate shift. Acute respiratory alkalosis can also result in ionized calcium binding to albumin. Moreover, acute respiratory alkalosis results in reduction in hydrogen ion in the intracellular fluid with extracellular potassium ion shift into cells leading to hypokalemia.These electrolyte abnormalities can cause myopathies, cardiac arrhythmias, respiratory failure, paralysis, seizures, coma and death. Physicians should be aware of the possibility of electrolyte imbalance due to hyperventilation to prevent the development of life threatening complications.

Presentation: 6/1/2024
12213 Is Atrial Fibrillation An Adverse Cardiovascular Effect Of Romosozumab
Authors: Martinez Suzanne , Anez David , Shahid Maham
Published: October 2024

Disclosure: S. Martinez: None. D. Anez: None. M. Shahid: None.

Osteoporosis and cardiovascular disease are both common in older populations. Therefore, it is not uncommon to find the two disorders in a single individual and yet it may be difficult to establish whether the diseases are coincident or the result of complex hormonal processes interacting with multiple systems, including possibly sclerostin. Indeed, pre-existent cardiovascular disease predisposes to osteoporotic bone loss and increased fracture risk. To date, a number of studies have linked the incidence of major adverse cardiovascular events (MACE) with various osteoporosis treatments while other treatments have demonstrated no associated or a reduced cardiovascular risk. Here we discuss the possibility of romosozumab-induced sudden, new onset atrial fibrillation (a fib) in a 70-year-old female with no known risk factors other than age. A 70-year-old female with a 20-year history of osteoporosis presented to establish care. After 5 years of alendronate therapy, she was switched to denosumab injections, 60 mg every 6 months. During Covid the patient’s physicians closed their office and denosumab therapy was interrupted for approximately 18 months. Therefore, when the patient established care with a new rheumatologist she was started on romosozumab. After 6 months of romosozumab the patient developed new onset atrial fibrillation. The cardiovascular safety of romosozumab, in particular, has been adjudicated in two large trials describing predominantly major cardiovascular events such as myocardial infarction, stroke, heart failure and cardiovascular death. In one of those trials, two reports of atrial fibrillation were also included in the adverse events but further details were not available. These increased MACEs prompted a safety warning from the FDA such that use of romosozumab in patients who have experienced a myocardial infarction or stroke within the year prior to its use is contraindicated. Recently atrial fibrillation and congestive heart failure were documented in 78-year-old woman who had been receiving romosozumab for three months for the treatment of osteoporosis. Our case represents a second report of a temporal relationship between the initiation of romosozumab and the onset of atrial fibrillation raising the question of a possible cause and effect. Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

Presentation: 6/3/2024