bluuebunny/crossref_metadata_2025 huggingface dataset:
7655 Genetic Mysteries Unveiled: Unusual Mutation Unraveled In Hypophosphatasia
Authors: Sharma Akanksha , Katikaneni Padma , Tanveer Saira , Selk Karen
Published: October 2024

Disclosure: A. Sharma: None. P. Katikaneni: None. S. Tanveer: None. K. Selk: None.

Introduction: Hypophosphatasia (HPP), an inherited dental-osseous metabolic illness, is caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which leads to a decrease in TNSALP enzymatic activity. Patients with HPP typically experience dental and skeletal mineralization issues as their most common symptoms; musculoskeletal abnormalities, numerous fractures, tiredness, and migraines are less common clinical presentations. Case Report: Our 75-year-old male patient initially presented 1.5 years prior following a spontaneous T12 vertebral fracture. A bone biopsy was performed and did not reveal evidence of malignancy. Testing for SPEP/UPEP was not consistent with myeloma, and thyroid testing was also unrevealing. His alkaline phosphatase level was consistently <40 IU/L since 1999. An evaluation was done for low alkaline phosphatase and secondary reasons for bone loss. This testing did not reveal vitamin D deficiency, parathyroid disease, hypophosphatemia, laboratory evidence of celiac disease, hypogonadism, or hypomagnesemia. A vitamin b6 level was markedly elevated at 119 ng/mL (ref range 2.1-21.7) while not on supplementation. He had noticed multiple fractures as a child, but he had written them off as minor injuries. He could clearly remember breaking his right wrist and clavicle. As an adult, he had rib fractures and a foot fracture. He was unable to recollect losing his primary teeth. Almost all his teeth are crowns or implants despite taking exceptional care of them. He did not have joint hypermobility. Genetic testing revealed the patient was heterozygous for an ALPL gene variant, c.876_882delinsT. It was a variant of undetermined significance at that time. His daughter also was found to have a low alkaline phosphatase and the same genetic test result. She also has experienced dental carries and joint pain. Our patient initiated teriparatide due to the need for more urgent therapy for extensive spinal surgery. He was later transitioned to asfotase alfa therapy and has not had any further fractures at the time of this report. Discussion: Hypophosphatasia is a rare inborn disorder due to mutations in the tissue nonspecific alkaline phosphatase gene ALPL and is characterized by low ALP levels. Affected individuals will also have elevated vitamin b6 levels and urinary phosphoethanolamine (PEA) levels. Early diagnosis of HPP is necessary to prevent bone fracture pain and improve quality of life. Inaccurate assessments can miss diagnoses of parents and other family members and even lead to lost opportunities to treat a patient with a substantial illness burden. This case highlights the mutation c.876_882delinsT as a likely pathologic variant in the ALPL gene. It also supports that patients with HPP can also respond to teriparatide treatment.

Presentation: 6/2/2024
6864 Genetic Profile And Identification Of A Novel Mutation In PHEX In X-Linked Hypophosphatemia (XLH) Patients At A Brazilian Research Center: Insights And Implications
Authors: Rodrigues da silva Maisa Monseff , de Araújo Iana Mizumukai , A de Paula Francisco J
Published: October 2024

Disclosure: M. Monseff Rodrigues da silva: None. I.M. de Araújo: None. F.J. de Paula: None.

Background: X-Linked Hypophosphatemia (XLH) is a rare genetic disorder characterized by low phosphate levels in the blood, primarily caused by mutations in the PHEX gene, leading to bone skeletal deformities and reduced quality of life. XLH genetics is extensively studied with over 500 pathogenic mutations in the PHEXgene having been identified. Common mutations include missense, nonsense, and splicing, accounting for approximately 50% of cases. However, genotype-phenotype correlations remain unclear. Methods: We conducted a cross-sectional study using a convenience sample selected from the osteometabolism an outpatient clinic in Brazil. Genetic analysis was performed using next-generation sequencing (NGS; Ilumina) in collaboration with Mendelics Laboratory. Results: In our study, 9 out of 10 patients showed previously known and reported mutations, with 60% exhibiting common mutation types. The mutations occur in different codons; however, the most prevalent consequence was the substitution of glycine (G) with adenine (A), present in 40% of the patients. One patient, however, showed a unique missense mutation in PHEX gene (arginine to glutamate at codon 266), which leads to a premature stop codon, a mutation absent in over 183,000 X chromosomes from XLH individuals. Even though this mutation was novel, no significant diferences in the phenotype of this patient were seen in comparision with the rest of the cohort. Discussion: The findings of our study underscore the genetic heterogeneity characteristic of XLH, as evidenced by the fact that 90% of our patient cohort exhibited mutations previously identified in the literature, with a significant 60% showing common mutation types. This highlights the recurring genetic patterns in XLH, which can be instrumental for diagnostic and - perhaps in the future - therapeutic strategies. Particularly notable is the predominant mutation involving the substitution of glycine with adenine, found in 40% of our patients, underscoring its potential role as a key mutation in the pathogenesis of XLH. Furthermore, the discovery of a novel missense mutation in one patient, resulting in a premature stop codon, enriches the mutation spectrum of XLH and suggests a deeper complexity in the genetic landscape of the disease. This mutation, not previously documented in the extensive database of over 183,000 X chromosomes from XLH individuals, opens new avenues for research into the disease's molecular mechanisms and potential genotype-phenotype correlations. Conclusion: This study underlines the genetic diversity within XLH, emphasizing the need for comprehensive genetic analysis to understand the full spectrum of the disease. More studies are yet necessary to elucidate if there is a genotype-phenotype correlation.

Presentation: 6/1/2024
7337 High Parathyroid Hormone (PTH) Due To Immunoassay Interference
Authors: Alkeshbhai Mendpara Vaidehi , McShane Adam J , Zeinab Khan Leila
Published: October 2024

Disclosure: V.A. Mendpara: None. A.J. McShane: None. L.Z. Khan: None.

Background: PTH levels are not always accurate. This case illustrates immunoassay interference in a female with markedly abnormal PTH values. Understanding immunoassay interference in diverse hormonal assessments can prevent diagnostic inaccuracies. Clinical Case: A 63-year-old female with osteopenia underwent serum parathyroid hormone (PTH) testing as part of a thorough bone evaluation. The initial PTH level revealed an abnormal level of 4008 pg/mL (normal range: 15 to 65 pg/mL). The follow-up PTH level with the same assay continued to result in elevated values of >5000 pg/mL. The medication list was negative for biotin use, which is a well-known interfering substance in the PTH assay. Clinical evaluation was negative for hyperparathyroidism symptoms, and thyroid/parathyroid ultrasound was normal, as were serum levels of phosphate, vitamin D, and calcium. No PTH values had been checked for patients in the past after an extensive review of prior records. The initial PTH testing used the Roche Elecsys PTH STAT assay. To investigate a potential immunoassay interference, the following studies were performed: First, the sample was diluted with polyethylene glycol (PEG) to precipitate large molecular weight proteins; second, the sample was treated with a commercial heterophilic blocking reagent (Scantibodies Laboratory); and lastly, the sample was assayed utilizing a different PTH vendor (Siemens Atellica, chemiluminescent immunoassay). The PEG and heterophilic blocking treatments resulted in significantly lower PTH concentrations of 895.6 and 40.7 pg/mL, respectively. We do not anticipate a change in PTH levels in samples supplemented with blocking reagents or PEG without interference. The result from Siemens’ assay was markedly lower at 43.4 pg/mL. Both the Siemens and Roche assays employ mouse antibodies; however, the antibodies are proprietary between the vendors. This results in potentially different anti-mouse antibody epitope targets. Due to a history of advanced ovarian cancer, the patient was taking Oregovomab, a murine monoclonal antibody, as therapy for her advanced disease. It is unclear if this medication resulted in assay interference, but it is possible. Discussion: In summary, the discrepancy in PTH assay results highlights the need to consider immunoassay interference, particularly in patients with a history of cancer on immunotherapy agents. Our case highlights the importance of the clinician’s review of medications when assessing patients. While prior PTH assays were not conducted before the patient started Oregovomab, the potential development of interfering antibodies warrants consideration. Clinicians should be vigilant for atypical results and collaborate closely with laboratory professionals, as detecting interfering substances can result in misdiagnosis.

Presentation: 6/2/2024
6871 Hungry Bone Syndrome After Parathyroidectomy in End-Stage Kidney Disease: A Case Report Analysis
Authors: Rani Richa , Mullarkey-Desapio Cathleen
Published: October 2024

Disclosure: R. Rani: None. C. Mullarkey-desapio: None.

Introduction: Hungry Bone Syndrome (HBS) is a rare yet severe complication following parathyroidectomy, characterized by pronounced hypocalcemia subsequent to a rapid decline in parathyroid hormone (PTH) levels. Renal hyperparathyroidism (RHPT) carries a heightened risk of HBS compared to primary hyperparathyroidism (PHPT), with prevalence varying from 15% to 25% in PHPT to as high as 75-92% in RHPT. This elevated risk in RHPT is attributed to chronically elevated PTH levels, both in terms of duration and intensity as compared to PHPT. Preoperative predictors for HBS occurrence and severity include younger age, larger gland size, lower preoperative calcium levels, elevated bone turnover markers, and the magnitude of PTH elevation. Case Report: We present a case of a 36-year-old female with End-Stage Renal Disease (ESRD) requiring dialysis, complicated by renal osteodystrophy and a radial fracture, unresponsive to medical therapy, who was admitted for parathyroidectomy. Preoperative labs revealed calcium at 8.3 mg/dL, phosphate at 4.1 mg/dL, alkaline phosphatase (ALP) at 797 IU/L, and an extremely elevated parathyroid hormone (PTH) level at 4139 pg/ml. Within 24 hours of parathyroidectomy (three and a half glands were removed, the largest weighing 0.7gm), her PTH levels declined to the 130s, accompanied by symptomatic hypocalcemia (calcium 6.5mg/dL). Initial management involved intravenous calcium gluconate and subsequent high-dose oral calcium (up to 10-16gm daily) with Calcitriol 1 mcg twice daily. Despite repletion, her calcium levels remained low on postoperative day 4 (calcium 6.8mg/dL, phosphate 1.9 mg/dL, magnesium 1.7mg/dL) with PTH at 131 pg/ml, confirming Hungry Bone Syndrome. After seven days of aggressive intravenous and oral calcium supplementation with high-dose Calcitriol, she was discharged with a calcium level of 8.9mg/dL. Discussion: Management of HBS following renal hyperparathyroidism surgery presents significant challenges due to associated comorbidities and other electrolyte abnormalities, with limited literature providing guidance on prevention and management. Our case demonstrated that early suspicion and aggressive management improved patient outcomes. Suspecting HBS in high-risk individuals and initiating interventions pre and post-surgery, including pre-treatment with calcitriol, bisphosphonates, and early aggressive intravenous calcium supplementation post-surgery, could potentially reduce morbidity and length of hospital stay.

Presentation: 6/1/2024
7434 Modulation of FGFR-FGF2-FGF23 Signaling Partially Rescues Osteoarthritis in Hyp Mice Homolog of Human X- Linked Hypophosphatemia
Authors: Hurley M M , Xiao L
Published: October 2024

Disclosure: M.M. Hurley: None. L. Xiao: None.

Human with X-linked hypophosphatemia (XLH) and its Hyp mice homolog develop several phenotypic abnormalities due to phosphate wasting mediated by abnormal Fibroblast Growth Factor Receptor-1 (FGFR1) and Fibroblast Growth Factor 23 (FGF23) signaling. XLH and Hyp mice also develop severe osteoarthropathy (OA) whose etiology is not fully defined. We previously reported that Fibroblast growth factor 2 (FGF2) regulates FGF23, specifically, mice overexpressing the high molecular weight FGF2 isoforms (HMWFGF2) in osteoprogenitors phenocopy Hyp mice including development of OA that worsens with age. Since we also reported that Hyp mice overexpress HMWFGF2 isoforms in osteoblasts and osteocytes, we examined whether the knee OA phenotype in Hyp mice was associated with aberrant FGFR1, FGF2, FGF23 signaling in knee joint articular cartilage and subchondral bone and whether in vivo FGFR tyrosine kinase inhibitor BGJ398 would modulate the OA phenotype in knee joints of Hyp mice. Ten weeks-old Control and Hyp mice were treated with Vehicle or BGJ398 for 12 weeks. Safranin-O staining of knee articular cartilage for proteoglycan revealed decreased staining in Hyp vehicle-treated mice that was partially restored to the cartilage thickness of Control mice in the Hyp-BGJ398-treated group. Significantly increased degradative enzyme matrix metalloproteinase-13 (MMP-13) in Hyp vehicle-treated knee articular cartilage was significantly reduced by BGJ398. Immunostaining revealed significantly increased phosphorylated FGFR1, FGF2 and FGF23 in both articular cartilage and subchondral bone. While BGJ398 significantly reduced immunostaining for phosphoFGFR1 and FGF2 in both articular cartilage and subchondral bone, it significantly reduced FGF23 in subchondral bone but not in articular cartilage. Significantly increased phospho-ERK1/2 labeling in Hyp-vehicle treated articular cartilage was partially rescued by BGJ398. This study demonstrates that increased FGFR1/FGF2 signaling contributes to OA in Hyp mice that can be partially rescued by FGF receptor inhibitor via reduction in MAPK signaling.

Presentation: 6/1/2024
6577 National Trends in Fragility Hip Fractures Among Community Dwelling Women With Low Femoral Neck Bone Mineral Density
Authors: Atri Avica , Anastasopoulou Catherine
Published: October 2024

Disclosure: A. Atri: None. C. Anastasopoulou: None.

Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population.

Presentation: 6/2/2024
7752 Navigating Hypercalcemia in Pregnancy: A Case Report
Authors: Gabbay Jacob , Steinmetz-Wood Samantha
Published: October 2024

Disclosure: J. Gabbay: None. S. Steinmetz-Wood: None.

Introduction: Primary hyperparathyroidism (PHPT) in pregnancy is rare but presents many diagnostic and therapeutic challenges. Prompt diagnosis and treatment are important due to associated maternal and fetal risks, however evaluation of urine calcium to differentiate from Familial Hypocalciuric Hypercalcemia (FHH) becomes less reliable due to physiologic changes in pregnancy, sestamibi scans. CT scans require radiation, parathyroidectomy introduces surgical risk, and medical alternatives like bisphosphonates can interfere with fetal skeletal development. Clinical Case: A 24-year-old woman who presented to the emergency room for progressive nausea and abdominal pain was found to be pregnant with elevated serum calculated calcium to 11.4 mg/dL (2.84 mmol/L). She had a history of renal stones, longstanding hypercalcemia of unknown etiology and a remote family history of parathyroid “issues”. Follow up laboratory work showed a PTH of 75.8 pg/ml (8.04 pmol/L) with an elevated 24-hour urine calcium and a low 25OH vitamin D. Given her history of kidney stones and overt symptoms it was our clinical judgement that this was not a case of FHH. She was started on IV fluids twice weekly. After an unrevealing neck ultrasound, an MRI neck showed a 7 mm lesion along the posterior aspect of the left thyroid suggestive of a parathyroid adenoma. Sestamibi scan was avoided due to the risks of radiation to the developing fetus. Given the presumptive diagnosis of parathyroid adenoma, the lack of response to aggressive hydration, and the maternal and fetal risks of hypercalcemia during pregnancy, parathyroidectomy was pursued in her second trimester. Intra-operative inspection and biopsy showed the lesion to be only a lymph node. She underwent 4-gland exploration and the left inferior parathyroid gland, which appeared abnormal and enlarged, was removed. The intra-operative PTH dropped only from 98 to 80 (10.4 to 8.5 pmol/L). She otherwise had an unremarkable hospital course and at discharge her calcium was normal with an undetectable PTH, which can be an expected finding in pregnancy. On follow up she was feeling well with sustained normocalcemia and low PTH levels. Given the age at which her hyperparathyroidism started, she was referred to genetics for further evaluation. Clinical Lessons/Conclusion: There were significant biochemical and radiological limitations in the management of this case. Normally an inappropriately normal PTH with elevated serum calcium and normal urine calcium/creatinine clearance ratio confirms the diagnosis of PHPT, however in pregnancy it should be noted that FHH could also present with normal or elevated urine calcium due to absorptive hypercalciuria in pregnancy. Additional clinical history and reasoning was needed for management as well as a skilled surgeon, where preoperative localization was limited and was not ultimately helpful.

Presentation: 6/2/2024
7219 Ocular Findings in Jansen Metaphyseal Chondrodysplasia
Authors: Obiezu F , Pan K , Ninan A , Roszko K L , Weinstein L S , Ferreira C R , Gafni R I , Quadros Costa T Magone De , Collins M T , Jha S
Published: October 2024

Disclosure: F. Obiezu: None. K. Pan: None. A. Ninan: None. K.L. Roszko: None. L.S. Weinstein: None. C.R. Ferreira: None. R.I. Gafni: None. T. Magone De Quadros Costa: None. M.T. Collins: None. S. Jha: None.

Jansen Metaphyseal Chondrodysplasia (JMC) is an ultra-rare disorder, with only 30 patients estimated to have the disease globally. It is caused by heterozygous pathogenic variants in PTHR1 that result in constitutive activation of parathyroid hormone type 1 receptor (PTHR1) signaling. A detailed description of craniofacial manifestations of the disease is lacking. Here we characterize the ophthalmological manifestations in patients with JMC. Six patients (4 males, 67%) with genetically confirmed JMC underwent a detailed ophthalmological evaluation, spectral-domain optical coherence tomography (OCT), craniofacial CT and 18F-NaF PET/CT scans. Median age at the time of the visit was 27.5 [IQR: 29] years. On physical examination, all patients were noted to have widely spaced eyes; 5 of the 6 had down slanted palpebral fissures, proptosis, or ptosis. Two patients had incomplete or defective closure of the eyelids (lagophthalmos), of which one had a history of progressive right facial nerve palsy with profuse epiphora. The second patient had central visual field defects, bilateral moderate optic disc pallor and bilateral retinal nerve fiber layer (RNFL) atrophy on OCT exam with bilateral optic canal narrowing on CT. Notably, comparison of these findings with a prior scan performed 5 years earlier showed progressive decrease in RNFL bilaterally. This patient had a history of prolonged intravenous bisphosphonate therapy, initiated in infancy for hypercalcemia and continued for over a decade. A third patient had normal vision, subtle temporal pallor of the optic nerve heads on dilated fundus exam, normal average RNFL, but decreased retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4 of the 6 patients compared to age-matched reference range indicating a chronic optic nerve atrophic process. These data represent the first comprehensive report of the ophthalmologic findings in a cohort of patients with JMC. They demonstrate that patients with JMC have significant eye findings that appear to be more prevalent and pronounced with age. This suggests age-related, progressive optic neuropathy, which can be assessed by demonstrating OCT retinal GCA and RNFL loss and, may be a feature of JMC. The benefit and effect of long-term bisphosphonate therapy in patients with JMC remains unclear. Patients with JMC should undergo regular ophthalmologic examination including optic nerve OCT, visual field testing, and craniofacial imaging.

Presentation: 6/1/2024
12453 Osteoporosis Screening In A Primary Care Clinic: Barriers And Solutions
Authors: Laquidara Bethany M , Mistry Sohi , Fang Guo Ling , Groubert Jordan , Oravec Michael
Published: October 2024

Disclosure: B.M. Laquidara: None. S. Mistry: None. L. Guo: None.

Purpose/Objective: Osteoporosis is a prevalent bone disorder that affects over 10 million people in the United States. The US Preventive Services Task Force (USPSTF) recommends screening females aged 65 and older with a baseline DEXA scan and to screen postmenopausal females younger than age 65 who have an increased risk of osteoporosis. Despite these guidelines, the screening rate for osteoporosis remains very low. Our quality improvement project seeks to first identify at what rate eligible patients in our residency primary care clinic are being screened for osteoporosis and what barriers (patient, provider, or clinical factors) to screening may decrease this rate. Methods: We reviewed a random sample medical records of 300 female patients aged >/= 50 years who visited our clinic within the last two years. We collected patient demographics, insurance status, presence of ≥1 risk factor of osteoporosis (fracture, heavy alcohol use, tobacco use, steroid use, BMI<19), MyChart activity, provider training level, diagnosis code, and whether a baseline DEXA was ordered and/or completed. We compared patient characteristics by DEXA order status using descriptive statistics, and used multivariable regression models to determine odds of DEXA order and completion. Results: The patients who were at high risk for osteoporosis were more likely to have an order without completion (OR 6.11, p <0.001). Increased age was associated with increased odds of having an order (OR 1.09, p<0.001). Increasing BMI was associated with decreased odds of having an order. Black patients and current smokers were less likely to have a DEXA scan ordered and completed after controlling for age and other confounding factors (p= 0.002 and 0.001 respectively). Among the 96 patients who had a completed DEXA scan, 74 had osteoporosis. The only significant predictor for having osteoporosis was low BMI (OR 0.87%, p<0.001). Conclusion: The results of this study suggest that while patients with a clinically high risk for osteoporosis are more likely to have an order placed for a DEXA scan, these patients often do not have a completed scan. Patients who have an ICD-10 diagnosis of high-risk for osteoporosis or osteoporosis in their electronic medical record are more likely to have both an ordered and completed scan. Utilizing this data, we will develop a variety of interventions such as a clinical didactic case for osteoporosis, a flow-sheet summary of proper osteoporosis screening and treatment initiation to be distributed in the clinic setting, and a short presentation during noon didactics where we review the proper screening method for osteoporosis. Following our intervention, we will re-examine the screening rate in our residency clinic to evaluate the effect of our intervention.

Presentation: 6/3/2024
12313 Parathyroid Carcinoma Presenting As Right Foot Pain And Swelling In A Young Male - A Case Report
Authors: Esclanda Sorsona Francis , Kristine Lopez Lizette
Published: October 2024

Disclosure: F.E. Sorsona: None. L. Lopez: None.

Parathyroid carcinoma is a rare cause of hyperparathyroidism that is challenging to diagnose. We report a case of parathyroid carcinoma with an unusual initial presentation of right foot pain and swelling in a young 26-year-old Filipino male. Physical examination revealed a palpable 1 x 1 cm mass with tenderness on his right foot. Initial work-up showed a persistently elevated serum ionized calcium (range: 1.7 - 2.19 mmol/L) with markedly high intact parathyroid hormone (1,890 pg/ml). A right foot x-ray revealed a lytic bone lesion on the 3rd metatarsal. Skeletal survey revealed diffuse lytic bone lesions. Comprehensive neck ultrasound showed a 4 x 1.6 x 2.5 cm complex nodule adjacent to the inferior pole of the left lobe of the thyroid gland with intralesional calcifications. A 4D CT scan showed a 3.3 x 2.2 x 2 cm hypervascular nodule inferior to the left thyroid lobe with early contrast washout, likely parathyroid in origin, and a possible brown tumor in the right fourth rib. Patient underwent parathyroidectomy with intraoperative PTH monitoring showing a marked reduction of intact PTH by 87% (235.9 pg/ml from 1,890 pg/ml), accompanied by reduction of serum ionized calcium. The histopathology reported parathyroid carcinoma highlighted by lymphovascular invasion, atypical round cells in sheets and nests, with enlarged, mildly pleomorphic, hyperchromatic nuclei and prominent nucleoli. Two months after surgery, normal serum ionized calcium was maintained with calcium supplementation with reported relief of right foot pain and swelling. The patient continues to follow up regularly for monitoring of treatment response.

Presentation: 6/2/2024
8620 Prevalence of Osteopenia of Prematurity and Risk Factors in Neonatal of Maternity Hospital
Authors: Lopes Bastos Dyrlanne Marcia , da Cunha Joao Gabriel Freire , da Cunha Ana Clara Freire
Published: October 2024

Disclosure: D.M. Bastos: None. J.G. Bastos: None. A.C. Bastos: None.

Introduction: The osteometabolic disease of prematurity (ODP), formerly known as osteopenia of prematurity, corresponds to a disorder of bone mineralization in the neonatal period in very low birth weight premature newborns. The estimated prevalence is about 30% when the birth weight is less than 1,500 grams and around 60% when it is less than 1,000 grams. There is no specific clinical picture, and it can present with mild manifestations, growth deficit, or even evolve with severe rickets and fractures. To qualify the care of premature newborns (NB) in our Service, we question what is the local prevalence of ODP and what are the clinical, biochemical, or imaging risk factors that are potentially related to a greater predisposition to this condition. Objective: Evaluate the prevalence of ODP and recognize potential risk factors in NBs in a neonatal ICU of a reference maternity hospital in Curitiba/ PR. Method: Retrospective longitudinal study, with analysis of medical records of patients born with a gestational age less than 34 weeks and birth weight less than 1,500 grams, born between January/2013 to August/2016. Discussion: Prematurity is the significant factor, followed by low birth weight, for osteopenia. Newborns (NB) with a birth weight below 1500g should receive 40mg/Kg of calcium and 50 mg/Kg of phosphorus. Supplementation of human milk should be started from 15 days of life or when oral intake reaches 100ml/Kg per day (1g/20 ml of milk). In this study, the classification of the growth curve and prevalence by sex were divergent with the literature. The most vulnerable are those with parenteral nutrition or prolonged fasting, as the adequate diet is the basis of prevention and treatment, similar data being found, as well as association with prolonged use of diuretic, presence of sepsis diagnosis and bronchopulmonary dysplasia. However, there is still a lack of specific and sensitive markers for early diagnosis and treatment. Conclusion: The prevalence of Osteopenia of Prematurity was lower than that found in the literature. The risk factors bronchopulmonary dysplasia and use of diuretics were statistically significant when evaluated in patients with osteopenia. However, no relationship was found between ODP and sepsis, as well as a relationship between ODP and Necrotizing Enterocolitis. Regarding the days kept fasting, use of TPN and Use of antibiotics, a longer duration of use was obtained when compared with the group that did not develop the disease.

Presentation: 6/3/2024
7506 Rare Case of Hyperparathyroidism in Third Trimester Pregnancy Requiring Urgent Parathyroidectomy
Authors: Costris A Rothstein , Davydov E , Levy S
Published: October 2024

Disclosure: A. Rothstein Costris: None. E. Davydov: None. S. Levy: None.

Introduction: Primary hyperparathyroidism (PHPT) during pregnancy has risks to both the mother and her fetus. Complications include maternal pre-eclampsia, miscarriage, hyperemesis gravidarum, nephrolithiasis and pancreatitis. Fetal complications encompass hypocalcemia, tetany, intrauterine growth retardation and fetal demise. Though medical treatment is available, parathyroidectomy is the only definitive treatment. Traditionally, surgery is done in the second trimester of pregnancy. We report a case of a third trimester parathyroidectomy in a 29 yo female with PHPT. Case representation: A 29-year-old G1P0 woman at 28 weeks gestation presented with persistent nausea and vomiting, constipation, joint pain, and increased forgetfulness. She has moved to USA from Saudi Arabia and had not received prenatal care in the USA. She was found to have a PTH of 224 (15-65 pg/mL), Calcium of 13.5 (8.2-10.2 mg/dL), Ionized Calcium of 1.63 (1.00-1.35 mmol/L), and a corrected Calcium of 14.2 (8.7-10.1 mg/dL). Electrolyte abnormalities were also noticed, with a Potassium of 2.8 (3.5-5 mmol/L), Phosphorus of 1.7 (2.5-4.5 mg/dL) and Magnesium of 1.2 (1.8-2.3 mg/dL). Vit. D levels were found to be extremely low <7 (20-40 ng/mL). Due to severe dehydration, persistent nausea, vomiting, and hypercalcemia, the patient received fluid resuscitation and Vit. D supplementation. A neck CT scan identified an 11 x 6 x 14 mm arterially hyperenhancing soft tissue structure at T1-T2, suggesting a probable parathyroid adenoma in the right paratracheal region. Management options included surgery or conservative therapy with fluids and Cinacalcet. A joint decision was made between Maternal Fetal Medicine, ENT and Endocrinology to proceed with parathyroidectomy. Surgical excision revealed an enlarged, hypercellular right inferior parathyroid gland (0.51g). Postoperative laboratory studies at 2 weeks showed normal PTH, Ca, Ionized Ca. Conclusion: It is preferable to conduct surgery for PHPT during the second trimester of pregnancy. However, when PHPT leads to severe symptoms, surgery might be considered in the third trimester. The severity of our patient’s symptoms led to inability to tolerate oral intake, deeming surgery necessary. The multidisciplinary team agreed that surgery in the third trimester would be the best course of treatment as it will result in normocalcemia immediately. Second trimester parathyroidectomy is viewed as safer due to the completion of organogenesis and lower teratogenicity risks. Performance of surgery during the third trimester may lead to an increase in the risk of premature birth. However, untreated hypercalcemia may increase fetal loss and thus third trimester parathyroidectomy can be considered as a treatment option for PHPT in pregnancy. It is also imperative to discuss all options with the patient. In our case, the patient had opted for surgery which was successful.

Presentation: 6/3/2024
7388 Rare Case of Mediastinal Parathyroid Carcinoma
Authors: Esaki Yumiko , Moalem Jacob , Israel Anna-Karoline , Shafiq Ismat
Published: October 2024

Disclosure: Y. Esaki: None. J. Moalem: None. A. Israel: None. I. Shafiq: None.

Introduction: Parathyroid carcinoma accounts for 1% of primary hyperparathyroidism with an estimated prevalence of 0.005% of all cancers. Ectopic locations of parathyroid tumors have been found in 6-16% of cases, most commonly in the thyroid, the thymus, or behind the esophagus. Parathyroid carcinoma is rarely found in the mediastinum and only 30 cases have been reported in the literature. Clinical Case: A 68-year-old male without significant past medical history was evaluated by his primary care physician for constipation, polyuria and 20 lb weight loss over the past year. He presented to the hospital after blood work revealed serum calcium of 13.5 mg/dl (8.6-10.2 mg/dl). Initial hospital workup demonstrated serum calcium 12.9 mg/dl, phosphorus 2.6 mg/dl (2.7-4.5 mg/dl), 25-OH vitamin D 21 ng/ml (30-60 ng/ml), 1,25-(OH)2 vitamin D 143.0 pg/ml (19.9-79.3 pg/ml), PTH-related protein < 2.0 pmol/L (0.0-2.3 pmol/L) and PTH 1,250.0 pg/ml (15.0-65.0 pg/ml). CT scan revealed a 3.5 cm x 2.6 cm heterogeneous right paratracheal soft tissue mass with areas of calcifications with mass effect on SVC. Thyroid ultrasound showed multinodular thyroid tissues with a left 1.1 cm heterogeneous solid nodule along the mid posterior aspect as well as a 0.5 cm hypoechoic lesion inferior to the left lobe. Sestamibi scan demonstrated a large area of increased uptake corresponding to the mass seen in the superior mediastinum on CT imaging. He underwent neck exploration and left hemithyroidectomy as well as median sternotomy with resection of the paratracheal mass. Intraoperative PTH decreased from the baseline of 1,177.0 pg/ml to 65.6pg/ml following the removal of the paratracheal mass. The final pathology of right anterior mediastinal mass was consistent with a 5 cm parathyroid carcinoma with angioinvasion, intermediate lymphatic invasion, invasion into adjacent structures, and Ki67 proliferative index focally > 5%. His post-operative course was complicated by hypocalcemia, which improved with treatment with calcitriol and calcium supplementation. He declined the genetic testing. His calcium and parathyroid hormone have remained in the normal range after 1 year. Conclusion: This case illustrates a rare case of parathyroid carcinoma found in the mediastinum. It is important to recognize that parathyroid carcinoma can present in ectopic locations including the mediastinum, as this can affect the preoperative investigation and management. Fine needle biopsy (FNA) prior to the initial operation is not recommended as it is difficult to differentiate the parathyroid carcinoma from benign disease based on FNA, and it may cause tumor rupture and seeding. Also, in the mediastinal parathyroid carcinoma, localization of the lesions including the size and invasiveness is critical in order to allow for radical surgery.

Presentation: 6/3/2024
7987 Ravenous Bone
Authors: Oo Yadana , Srisawitri Liana , Patel Purva , Zaw Thein Min
Published: October 2024

Disclosure: Y. Oo: None. L. Srisawitri: None. P. Patel: None. M. Thein: None.

Introduction Hungry bone syndrome ( HBS ) is the rapid drop in serum total calcium concentration of less than 2.1 mmol/L and/or prolonged hypocalcemia for more than 4 days postparathyroidectomy. It is more frequent in hemodialysis patients with secondary hyperparathyroidism (SHPT). The severe hypocalcemia after the parathyroidectomy is believed to be due to the increased usage of calcium by the starving bones. The key management is to replenish the severe calcium deficit aggressively. Clinical Case A 44-year-old Hispanic male patient with ESRD on hemodialysis was admitted for elective parathyroidectomy for SHPT from ESRD. The hospital course was complicated with profound hypocalcemia after the surgery. The pertinent lab results before surgery were total calcium level of 7.2 mg/dl ( normal 8.4 - 10.2 ), ionized calcium level of 4.9 ( normal 4.48 - 4.92 ), and PTH level of 2184 pg/ml (normal 15 - 65). After the parathyroidectomy, the ionized calcium level became 3.4 mg/dl and the PTH level trended down to 56 pg/ml. On the post-op day ( POD ) 1, the patient was started on calcitriol 1 mcg BID and calcium carbonate 600 mg QID and also got the hemodialysis with a high calcium bath. Even with the replacement, the calcium level kept worsening and calcium gluconate infusion was started on POD 4. On POD 5, calcium gluconate infusion was on hold as the ionized calcium was improved. On POD 7, calcitriol was increased to 2 mcg BID as ionized calcium was 3.2 mg/dl and restarted on calcium gluconate infusion. On POD 8, ionized calcium was 3.5 mg/dl, and calcium gluconate infusion was titrated down. On POD 9, as the total calcium level was 8.8 mg/dl, the calcium gluconate infusion was discontinued and he was discharged with calcium carbonate 1200 mg TID and calcitriol 2 mcg TID. Unfortunately, 13 days from the discharge date, he was readmitted with the volume overload, and on this second admission, the total calcium was 7 mg/dl and ionized calcium was 3.2 mg/dl. The calcitriol dose was increased to 2 mcg TID and the same dose of calcium carbonate which was 1200 mg TID. He got hemodialysis with a high calcium bath. After being treated for the volume overload, he was discharged with calcitriol 2 mcg TID and calcium carbonate 1200 mg TID and followed up with the endocrinology team in 2 weeks. Conclusion Even with the aggressive and constant replacement of calcium, the HBS cases are challenging in terms of achieving and maintaining a normal calcium level after surgery. We, the clinicians, need a better understanding of how to avoid the development of HBS or at least minimize the severity of hypocalcemia in the postoperative course and the ultimate management regimen to maintain the normal calcium level in both inpatient and outpatient settings.

Presentation: 6/1/2024
9397 Shatter Proofing Bones: Revamping Osteoporosis Screening
Authors: Subramani Rashmi , Gupta Tanya , Anwar Maheen , Pamula John
Published: October 2024

Disclosure: R. Subramani: None. T. Gupta: None. M. Anwar: None. J. Pamula: None.

Background: Osteoporosis is a common disease characterized by low bone mass, structural deterioration of bone tissue, and increased risk of fractures. The World Health Organization (WHO) has defined osteoporosis based on bone density measurements. According to their definition, osteoporosis is diagnosed when the bone density at the hip or spine is at least 2.5 standard deviations (SDs) below the mean bone density of a reference population of young, healthy women (T score ≤ -2.5). According to NHANES data from 2017-2018, the overall prevalence of osteoporosis among adults over 50 was found to be 12.6%. It was observed that the prevalence of osteoporosis was higher among women (19.6%) compared to men (4.4%). According to US Preventative Services Task Force (USPSTF), the guidelines for screening are as follows: BMD Testing (DEXA) for all women aged 65 and older, postmenopausal women younger than 65 with clinical risk factors for fracture including advancing age, previous fracture, glucocorticoid therapy, parental history of hip fracture, low body weight, current cigarette smoking, excessive alcohol consumption, rheumatoid arthritis, secondary osteoporosis. BMD Testing for Men is not recommended. The most used bone measurement test to screen for osteoporosis is central DXA which measures BMD at the hip and lumbar spine. Goal: To improve the osteoporosis screening using DXA scan in the outpatient internal medicine resident patient panel by 5% Study Design:Subjects were identified by an EPIC report and will include retrospective chart review of records from July 2022 and prospective screening until April 2024 for the outpatient IM clinic list of patients including both resident panel. Methods: Pre-intervention data analysis of current rates; Educating residents about appropriate screening; Utilization of osteoporosis screening as care-gap in EPIC ;Calling patients who are due for screening from IM residents patient panels; Post-interventional data analysis Results: The total number of patients on the residents panel was 196. Before interventions, screening rate for osteoporosis were 71.2% among residents' patients. After intervention, screening rates increased to 75.5%. There was a 4.3 % improvement in screening rate. Conclusion: Resident education, addressing Osteoporosis care gaps in EPIC and patient outreach are effective interventions to improve screening rates. Discussion: Osteoporosis screening remains an area of needed improvement in IM clinic. EPIC system should not only take age for prompting osteoporosis screening but also other factors such as family history, pre-mature fractures, steroid use, etc. Adding osteoporosis screening into the metric system are few steps to be considered for future directions.

Presentation: 6/3/2024
5043 Skeletal Microstructure in Men with Celiac Disease
Authors: Rubenstein Ayelet , Kondapalli Ananya , Agarwal Sanchita , Bucovsky Mariana , Colon Ivelisse , Kil Nayoung , Lewis Suzanne , Lebwohl Benjamin , Green Peter , Walker Marcella
Published: October 2024

Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc..

The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p<0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were < 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p<0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD.

Presentation: 6/3/2024