bluuebunny/crossref_metadata_2025 huggingface dataset:
PSUN23 Clinical and Surgery Approach in Pheocromocytomas: A Cross-Sectional Study at a Referral Center in Ecuador
Authors: Vega Jorge Salazar , Estrada Mariela Villagomez , Pazmino Paola Solis , Urbaez Rossana Ruiz , Herrera Gabriela Torres , Koupermann Gabriela Jaramillo , Silva Carlos Reyes , Otañez Veronica Remache , Guadalupe Ramiro , Velandria Francisco Garcia
Published: November 2022

Background

An annual incidence of pheochromocytoma (PHEO) has been reported between 0.4 to 9.5 cases per million inhabitants and a prevalence of 2.13 per 100 000 people. More than 40% of patients have a genetic predisposition, and its presentation is heterogeneous, from incidental findings (10-49%) to prominent clinical pictures attributable to hypersecretion of catecholamines. The epidemiological and descriptive studies referring to pheochromocytomas in South America are scarce. This study aimed to show a retrospective analysis of patients with pheochromocytomas attending in a cancer referral center to determine the clinical, histology, and surgery outcomes.

Methods

From January 2015 to December 2021, a cross-sectional study was conducted in a regional reference public hospital for endocrine neoplasia in adults. We identified the clinical manifestations, pharmacologic and surgical treatment modalities from a patient interview and review of clinical records.

Results

Twelve patients were included, with a mean age of 44.9 (SD 10.5) years old. Around 58.3% (n=7) of the patients were male, and 16.6% (n=2) had a family history of MEN2A. Clinical characteristics of PHEO were identified in 83.3% (n=10) of the patients. The most common clinical presentation included: hypertension 10/12, palpitations and headache 9/12, diaphoresis and dyspnea 8/12, abdominal pain, nausea, and vomiting 7/12, and sensation of heat and dizziness 6/12. The classic triad of headache, palpitations, and sweating was observed in 8 patients. The CT image revealed adrenal tumors in the left (n=7/12), right (n=4/12), and one bilateral. The mean tumor diameter was 70.5 mm (SD +39.8 range 38 - 180 mm), and 91.7% of the patients (n=11/12) had tumors ≥ 4 cm. Most of the patients, 54.5%, underwent a laparoscopy procedure (n=6/11). In 2 cases, the procedure was converted to open surgery. The mean operative time was 201 ± 77.2 min. After surgery, all patients were admitted to the intensive care unit, where 75% (n=9/11) required vasoactive therapy with satisfactory recovery. The postoperative outcome showed 81.8% with normal blood pressure (n=9/11).

Conclusion

Most patients presenting to our hospital had large intra-abdominal tumors with a high cure rate and low mortality. Accurate diagnosis and optimal treatment are best achieved at 'centers of excellence' with expert multidisciplinary teams.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN27 Largest Cohort of Cervical Spine Metastases of Pheochromocytoma/Paraganglioma in the Setting of SDHB Mutation
Authors: Pacak Karel , Prodanov Tamara , Jha Abhishek , Patel Mayank , Talvacchio Sara
Published: November 2022

Background

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells in adrenal or extra-adrenal locations, respectively. Overall, 10 to 20% of PPGLs are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B (SDHB)-related tumors (up to 90%). Metastatic PPGLs are diagnosed based on the presence of tumor cells of chromaffin origin in a location outside the site of normal development (adrenal medulla and the sympathetic chain) in the bones and lymphatic nodes per 2017 WHO guidelines. Studies evaluating both metastatic pheochromocytomas and extra-adrenal PGLs have reported bone to be the most common site of metastasis.

Clinical Case

We reviewed the metastatic patients in our PPGL cohort and found 40 (29.85%) out of 134 patients with SDHB-related metastatic PPGLs developing metastatic lesions in the cervical spine. The related descriptive analyses were as follows: 25 (62.5%) were males, 15 (37.5%) females. Fourteen patients (35%) have died due to metastatic PPGL complications. The average age of patients at the time of the primary tumor diagnosis was 30.3 ± 35 years and the age at the initial metastatic tumor diagnosis was 34 ± 33 years. The average time interval to metastatic disease was 7.4 ± 38 years.

At their initial presentation, there were 25 (62.5%) patients with solitary tumors; 1 (2.5%) with multiple primary tumors; and 14 (35%) with metastatic tumors. All the patients either developed or had metastatic lesions in the cervical vertebrae. Nine (22.5%) patients required surgical fusions of the vertebrae to manage their pathological fractures and another 9 (22.5%) patients received radiation therapy.

Conclusion

Genetic testing is recommended for all patients with PPGLs. Genetic analysis, especially finding a SDHB mutation may be helpful in determining metastatic potential. Most patients with spinal metastatic lesions are asymptomatic, but when clinical symptoms arise, the most common clinical symptom involves pain and neurological deficit. Metastasis to the spine is an important complication that can lead to significant pain and disability and requires surgical interventions or radiotherapy. Awareness for such spinal tumors is essential for offering the correct treatment to the patients.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF09 | PSUN06 ARMC5 as a possible regulator of acetylation in the adrenal cortex in partnership with SIRT1
Authors: Berthon Annabel , Faucz Fabio , Feldman Benjamin , Drougat Ludivine , Espiard Stephanie , Cavalcante Isadora , Ragazzon Bruno , Bertherat Jérôme , Stratakis Constantine
Published: November 2022

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARMC5 can regulate SIRT1 and its signaling in adrenocortical cells. Accordingly, the expression of the desacetylase SIRT1 is significantly increased in PBMAH tissues mutated for ARMC5 compared to tumors without mutations. However, this overexpression of SIRT1 is associated with an elevation of the profile of acetylated protein in the absence of ARMC5 suggesting that SIRT1 activity is actually decreased and that SIRT1 expression could increase to maintain its activity. Consistently, the measurement of SIRT activity on PBMAH tissues demonstrate a decrease of its activity when ARMC5 is mutated. Similar results are obtained in adrenal cells of 18-month-old Armc5+/- mice that are also hyper-corticosteronemic. Altogether, these data support that ARMC5 could regulate SIRT1 expression and/or activity. In vitro measurement of purified SIRT1 activity in the presence of ARMC5-enriched protein extracts demonstrated that the presence of ARMC5 protein does indeed alter SIRT1 activity. We hypothesize, therefore, that ARMC5 may be a new regulator of SIRT1 function but the underlying mechanism and the consequences of abnormal acetylated proteins on adrenocortical function require further investigation.

Presentation: Saturday, June 11, 2022 1:36 p.m. - 1:41 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF19 | PSUN33 Adrenocortical Carcinoma as a Rare Manifestation of Birt-Hogg-Dubé Syndrome
Authors: Else Tobias , Habra Mouhammed , Hamidi Oksana , Hammer Gary D , Murvelashvili Natia , Osborne Jenae , Wolf Katherine
Published: November 2022

Adrenocortical carcinoma (ACC) can occur as part of hereditary cancer syndromes, particularly Lynch syndrome and Li-Fraumeni syndrome. Here we describe 5 patients (3 women) with adrenal tumors and Birt-Hogg-Dubé syndrome (BHDS). BHDS is a hereditary tumor syndrome characterized by fibrofolliculomas/trichodiscomas, renal tumors, lung cysts, and spontaneous pneumothoraces.

All five patients had a confirmed germline FLCN pathogenic variant. One case was previously reported by our institution. Age of diagnosis (AD) ranged from 36 to 62 years with a mean AD of 46 years. All patients identified as Caucasian. Three patients had non-functioning adrenal tumors, while the remaining two patients did not undergo biochemical assessment preoperatively but did not have symptoms or history of adrenal hormone excess.

Histologically, four patients had confirmed ACC while one had an adrenocortical tumor of uncertain malignant potential, most consistent with an oncocytoma. All patients were initially treated with mitotane. Three patients developed metastatic disease requiring additional systemic chemotherapy, immunotherapy, and/or radiation.

A total of 8 confirmed ACCs in patients with BHDS have been reported to date, raising suspicions that these tumors might be a part of the BHDS tumor spectrum. When BHDS patients are screened for renal malignancies, special attention should be paid to the adrenal glands. Adrenal nodules should undergo prompt assessment as >50% of reported cases developed metastatic disease. Given possible association with BHDS, testing for FLCN pathogenic variants should be considered during the genetic evaluation of patients with ACC.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m.
RF21 | PSAT93 Improvement of Final Height in Congenital Adrenal Hyperplasia Patients Treated With Recombinant Growth Hormone
Authors: Costa Fernanda C , de Sousa Donaldt L , Madureira Guiomar , Mathias Patrícia M B R , Mendonca Berenice B , Miranda Mirela C , Silva Mylena C M , Bachega Tânia A S S
Published: November 2022

Final height (FH) in congenital adrenal hyperplasia (CAH) patients is frequently under -1.5 SDS in relation to the normal population, even in those with good compliance, chronic androgen exposure or supraphysiological glucocorticoid doses could corroborate to this finding. Recombinant human growth hormone (GH) has been used as adjuvant therapy to improve FH in many disorders, but there are scarce data in CAH patients.

Objective

to analyze the effect of GH therapy on final height of CAH patients with compromised height prediction.

Patients and Methods

data of 26 patients (7F/19M) were retrospectively evaluated: 10 salt wasting-SW, 11 simple virilizing-SV and 5 with nonclassical form-NC. The SW patients were diagnosed at the neonatal period, SV and NC patients at mean chronological age of 3.6±2 and 7.2±3.8 yrs, respectively. All patients received cortisone acetate, hydrocortisone equivalent dose of 12.6±6.6 mg/m2/day in classical and 8.24±4.7 mg/m2/day in NC form; SW patients also received fludrocortisone 36±9.6mcg/m2/day. Near final height (NFH) was considered as BA of 13yrs for girls and 15yrs for boys; height and target height (TH) were described as SDS. All patients presented hormonal/molecular CAH diagnosis. The t test was used in the statistical analysis.

Results

Mean chronological and bone age (BA) at the beginning of GH therapy was 9.0±2.4 and 12.3±2yrs, respectively, mean duration of GH therapy was 4.1±1.9yrs and daily dose was 0.15 UI/kg/day. All patients were submitted to pubertal blockage with leuprorelin acetate 11.25 mg each 3 months during 3.9±1.1yrs or cyproterone acetate, mean dose 70±19 mg/m2/d during 4.7±2.5yrs. At the last evaluation, 19 patients (14M/5F) achieved FH: at the beginning of GH therapy mean H/BA in males was -2.1±0.38 and after -0.65±1 SDS (p<0.001). Mean FH in males was 165.7±5.9 cm and mean TH 170.7±8 cm (p>0.05); the TH-FH was -0.6±1.2 SDS. Among females, mean H/BA at the beginning of GH therapy was -2.2±0.7 and after -0.84±0.9 SDS (p=0.01). Mean FH in females was 156±8 cm, mean TH was 160±5.8cm (p>0.05); the TH-FH was -0.6±0.7 SDS. Considering patients with FH and NFH, the FH-TH in males was 0.4±0.2 SDS and -0.15±0.9 SDS in females. An improvement of approximately 12.7cm in males and 12.4cm in females was observed. No patient presented hypertension and 7/26 patients presented insulin resistance, which normalized after GH withdrawal.

Conclusion

we observed that GH therapy associated with puberty blockers allowed the achievement of final height in the expected range of target height, without significant side effects.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.
RF33 | PSUN01 Clinical Course of Benign Adrenal Cysts: A Single-Center Experience of 90 Patients
Authors: Young William F , Dogra Prerna , Rivera Michael , McKenzie Travis , Lyden Melanie , Foster Trenton , Dy Benzon , Bancos Irina
Published: November 2022

Introduction

Benign adrenal cysts (BACs) comprise 1% of adrenal incidentalomas. Scarce data are available to guide hormonal evaluation and management. We aimed to describe the clinical presentation, imaging characteristics and outcomes of patients with BACs.

Methods

This was a single center retrospective study of patients with histologically or radiologically confirmed BACs evaluated between 1995-2021. Other cystic adrenal lesions (such as cystic pheochromocytoma and adrenocortical cancer) were excluded. Medical records were reviewed for clinical, biochemical, radiological, and surgical information. Subgroup analyses based on surgical versus nonsurgical management was performed.

Results

BACs were diagnosed in 92 patients (53, 57% women) at a median age of 45 years. Mode of discovery was incidental on imaging in 81 (88%), symptoms of mass effect in 9 (9.8%), and other in 2 (2.2%). Majority (89, 97%) of patients had unilateral cysts (45 right, 44 left) with a median size of 48 mm (range 4-200) at diagnosis. On imaging, most cysts were round/oval (85.4%), homogenous (83.2%) lesions with calcifications (64.0%) and no vascular enhancement (97.7%). During a median follow-up of 65 months (range 7-288), adrenal cysts demonstrated minimal enlargement (median size change 6 mm, median growth rate 2 mm/year).Age of diagnosis, sex, site and initial size of BAC were not associated with an increase in size during follow up. On hormonal evaluation, 10% (5/50 tested) had an abnormal overnight dexamethasone suppression test, and 9.5% (4/42 tested) had an abnormal case detection testing for primary aldosteronism. Adrenalectomy was performed in 46 (51%) patients. Patients treated with adrenalectomy (46, 50%) were younger (36.9 vs 50.8 years, P=0.0009) and had more rapidly enlarging cysts (median growth rate 5.5 vs 0.4 mm/year, P=0.0002).

Conclusions

BACs are usually incidentally discovered and nonfunctional lesions with excellent prognosis, irrespective of management. On imaging, benign adrenal cysts appear as large, homogenous lesions without vascular enhancement that demonstrate slow growth. Adrenalectomy should be reserved for the minority of patients with abnormal hormonal evaluation or imaging characteristics (heterogenous, vascular enhancement) concerning for an alternate etiology, or those who develop symptoms of mass effect.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.
ODP595 Case Series Of Idiopathic Hypercalciuria And Secondary Osteoporosis
Authors: Mirza Fayal , Faisal Sobia , Azmath Misbah
Published: November 2022

Background

Secondary causes for low bone density may be present in 30% of women and up to 50% of men with low bone density and osteoporosis. Idiopathic hypercalciuria is associated with lower bone density and higher bone turnover, and an increased risk of fractures. Thiazide diuretics have been used often for treatment for idiopathic hypercalciuriaCase Series: We present a case series of 9 patients who presented for low or declining bone density. They underwent workup for secondary causes of osteoporosis and were noted to have idiopathic hypercalciuria with high bone turnover on initial evaluation. They were started on thiazide diuretics or amiloride and the dose titrated up daily based on their blood pressure tolerance. They were monitored for hypokalemia and hyponatremia. Several of these patients exhibited a > 30% decrease in bone resorption, as measured by urine N-telopeptide on a second fasting specimen. Follow-up bone density at 1 year and 3-year after starting diuretic therapy showed stability or significant increase in bone density. Some of these patients were able to maintain bone density in the osteopenic range on follow up for > 6 years.

Conclusion

Some patients with idiopathic hypercalciuria may have a more robust response to thiazide diuretics compared to others even in the absence of anti-resorptive therapy. Significant reduction of > 30% in bone resorption markers may identify patients who are more likely to have a robust response in the bone density after starting thiazide medications.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP069 A Clinical audit on the diagnosis and management of Vitamin D Deficiency at Scarborough General Hospital, United Kingdom
Authors: Abraham Santhosh , Patel Ramesh , Humphriss David , Pawlak Tadeusz , Ssemmondo Emmanuel
Published: November 2022

Introduction

A rising problem in the United Kingdom, Vitamin D deficiency is common in the elderly due to inadequate sunlight exposure and poor intake. Vitamin D deficiency is defined as 25-OH Vitamin D levels less than 30nmol/L.

Objectives

The principal aim of this audit was to ascertain how close and efficiently the patients were managed with Vitamin D deficiency at Scarborough General Hospital when compared to the York NHS Trust guidelines. Another goal was to have a consensus with regards to improving our practices in the management of Vitamin D deficiency.

Methodology

Data was collected retrospectively over 12 months (2020 March to 2021 March) on adults attending the General Hospital as outpatients as well as those who were admitted as inpatients. The questionnaire proforma for the audit was based on guidelines recommended by York Trust. A total of 30 cases were randomly chosen and data were sought from case notes and Electronic health care records. Data were analyzed by Microsoft Excel.

Results

This audit showed that 64% met the criteria for testing, 3% did not meet it and in 33% of cases it was not documented. Chronic wide spread pain (53%) was the most common factor that prompted vitamin D testing in the group who met the criteria. 67% had a vitamin D level between 20 and 29 nmol/mL while 33% had a level between 10 and 19 nmol/mL. Most of them (80%) were symptomatic; in 17% no symptoms were documented. Serum Calcium was normal in 77% and Serum Phosphate was normal in 73% of cases. The loading dose of Vitamin D was 50,000 IU for 6 weeks in 70% of the patients and in 70% the duration of the loading dose was 6 week. In 57% of the cases, Calcium supplementation was not required. In those who were prescribed with Calcium, 85% had them rechecked in the follow up visits. In the follow up visits, Vitamin D level was checked in only 53% of cases, in 40% cases it was unknown and in 7% cases it was not done. The advice to the GP did not include patient recommendations about regular exposure to sunlight and dietary sources as recommended by the guideline.

Conclusion

Chronic pain was the single best reason for Vitamin D testing and most of the patients were symptomatic which emphasizes Vitamin D deficiency to be considered especially in the elderly population. In addition to the routine information given to the GP it will be good to reiterate dietary management and regular exposure to sunlight as this helps in augmenting Vitamin D apart from supplementation. As a significant proportion received inadequate follow up it is important to follow up with rechecks including vitamin D levels.

Presentation: No date and time listed
ODP070 A deep learning-based osteopenia and osteoporosis screening system with lateral lumbar spine X-ray in women aged 50 years or older and men aged 60 years or older
Authors: Chung Yoon-Sok , Noh Sung Hyun , Kim Bum Taek , Kong Sung Hye , Kim Jung Hee , Park Sung Bae , Yoon Hongjun , Choi Jong Mun , Kim Taegyu
Published: November 2022

Bone mineral density (BMD) measured by Dual-energy X-ray absorptiometry (DXA) is the gold standard to diagnose osteopenia or osteoporosis. However, this method is not always available and underutilized to screen for osteoporosis. An artificial intelligence system using plain radiography is suggested in this study to enable easy and convenient prediction. This study is conducted on Korean women and men with data derived from two university hospitals (Ajou University and Seoul National University). Retrospective data from the years 2005 to 2021 with 20,100 subjects (women 60%) were analyzed. GE Healthcare and Hologic DXA, and lumbar spine lateral X-rays were used for performance, approved by the Institutional Review Boards. Inappropriate vertebral segments (compression fracture, degenerative change, etc.) were excluded from the analysis. A total of 79,400 lumbar spine segments (L1, L2, L3, and L4) were extracted from lumbar spine BMD data are compared and analyzed. BMD is classified into three categories: normal, osteopenia, and osteoporosis by World Health Organization criteria. 34% of segments are classified with osteopenia, and 24% osteoporosis. The area under the curve of the receiver operating characteristic of training results of deep learning artificial intelligence demonstrates predictability for osteopenia of 82% and osteoporosis of 95%. A deep learning algorithm may be regarded as one of the valuable and accessible screening methods for predicting osteopenia and osteoporosis with plain X-rays in clinical settings. This study was supported by funding from the National Information Society Agency and the Ministry of Science and ICT of the Republic of Korea.

Presentation: No date and time listed
ODP071 A Fit of Hypophosphatemia
Authors: Naha Sowjanya , Salam Waqar
Published: November 2022

Background

Hypophosphatemia is a commonly encountered electrolyte disturbance that is seen in association with a broad range of disorders. Severe hypophosphatemia can be life threatening and is known to cause seizures. Clinical case: A 65 year old female was found down at home by emergency medical services. She was noted to be frothing and had irregular breathing. She was still confused when she was brought to the emergency department but had no focal neurological deficits on examination. Her mentation subsequently improved without intervention. Her past history was notable for a left parafalcine meningioma which was resected in 2019. Her vital signs were stable at presentation. Laboratory evaluation showed critically low phosphate (0.6 mg/dL, n: 2.5-4.5 mg/dL); other electrolytes including sodium, potassium, calcium and magnesium levels were all normal. Additional work up showed slightly elevated parathyroid hormone level (86.8 pg/mL, n: 15-65 pg/mL), borderline low vitamin D (29.5 ng/mL, n: 30-80 ng/mL) and elevated lactate (2.9 mmol/L, n: 0.5-2.2 mmol/L). The patient was immediately treated with 45 mmol of IV sodium phosphate. Repeat serum phosphate showed rapid normalization and the patient was ultimately discharged without any phosphate supplements. Repeat serum phosphate three months later was normal.

Conclusion

Although severe hypophosphatemia is known to precipitate seizures, seizure activity itself can induce transient hypophosphatemia. In fact, hypophosphatemia has been proposed as a means to diagnose convulsive seizures and distinguish them from syncopal episodes. Transcellular shift has been proposed as a mechanism to explain this phenomenon. In this case, we believe the patient developed seizures as a sequela of brain surgery and that hypophosphatemia developed as an epiphenomenon. Rapid resolution of hypophosphatemia after cessation of seizures and absence of a credible alternative cause should alert physicians to the possibility of this effect.

Presentation: No date and time listed
ODP078 An Unsolved Mystery of Hyperparathyroidism for 12 Years
Authors: Pant Nicole , Oktaei Hooman
Published: November 2022

Introduction

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and elevated or inappropriately normal levels of parathyroid hormone (PTH). It results from excessive secretion of PTH from one or more of the parathyroid glands. The number and location of the parathyroid glands can be variable. The organogenesis of the parathyroids determines the definitive location in adulthood. We hereby present an interesting case of primary hyperparathyroidism caused by the ectopic parathyroid gland. Clinical case 85-year-old Black female with papillary thyroid cancer status post total thyroidectomy and RAI in 2011, hypertension, hyperlipidemia, osteoporosis, long standing PHPT referred to ER for hypercalcemia from a physician's office. A review of the system was significant for unintentional 40 lb. weight loss over the past several months and increased urinary frequency. She denied confusion, abdominal pain, constipation, paresthesia. On physical exam she was afebrile, BP 144/63 mm Hg, pulse 56/min and respiratory rate of 18. The rest of the detailed physical examination was unremarkable. She was initially diagnosed with primary hyperparathyroidism in 2009 based on PTH- 196 pg /ml (n 10-65 pg/ml), and corrected calcium- 11. 0 mg/dl (n 8.5-10.1 mg/dL) . Laboratory on this admission (2021) revealed PTH - 411.8 pg/ml (n 10-65 pg/ml), corrected calcium - 12.9 mg/dL (n 8.5-10.1 mg/dL) with albumin 4 g/dl (3.4-5. 0 g/dL), ionized calcium-7.30 mg/dL (n 4.5-5.3 mg/dL), 1,25-(OH) 2 vitamin D level -50.2 pg /mL (n 20-82 pg/mL),25-(OH) vitamin D level of 37.2 ng/mL (n 30-100 ng/mL) and GFR-40 mL/min/1.73m 2 (n >=60. 0 mL/min/1.73m 2). She underwent a total of 4 Sestamibi scans and 1 MRI chest with and without contrast since 2009 that failed to localize defective parathyroid gland . But on this admission an incidental finding of right neck mass measuring 3. 0×1.2×2.7 cm was noted in MRI cervical spine that led to US head and neck soft tissue. It showed a solid and cystic mass with a concern for ectopic parathyroid gland posterior to the right submandibular gland. ENT was consulted, and the patient underwent right neck exploration with the removal of the neck mass. Pathology resulted as hyperplastic parathyroid tissue most congruent with a parathyroid adenoma.

Conclusion

Ectopic parathyroid glands occur in approximately 15% of patients with PHPT. Embryologically, the third pharyngeal pouch gives rise to the inferior parathyroid glands, and the superior parathyroids arise from the fourth pharyngeal pouch. It can occur from the angle of the mandible to the mediastinum according to the developmental and migratory aberrations. Parathyroidectomy remains the definitive cure for PHPT and is recommended in all symptomatic patients.

Presentation: No date and time listed
ODP085 Denosumab Induced Severe Hypophosphatemia
Authors: Del Mar Morales Hernandez Maria , Castellanos-Diaz Jessica , Kadiyala Sushma , Xhikola Majlinda
Published: November 2022

Introduction

Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used for treatment of osteoporosis and bone metastases in patients with solid tumors. Denosumab induced hypophosphatemia has been reported in less than 1% of patients, and in most cases described as mild to moderate in severity. We present a case of severe hypophosphatemia after denosumab treatment for diffuse bone metastases due to prostate cancer.

Case report

A 78-year-old male patient with history of diffuse bone metastases due to prostate cancer, schizophrenia on treatment and intermittent alcohol use, presented to the hospital with suicidal ideation and worsening fatigue. Patient was found to have a phosphorus levels of <1. 0 mg/dL (2.5-4.6 mg/dL), corrected calcium of 8.2 mg/dL (8.4-10.5 mg/dl), vitamin D 25 OH of 36.34 ng/mL (30-100 ng/mL), magnesium of 2.3 mg/dL (1.7-2.5 mg/dL), parathyroid hormone (iPTH) level of 379 pg/mL (10-65pg/mL) and serum creatinine of 1.1 mg/dL (0.5-1.2 mg/dL). Urinary studies showed 24 hour urinary phosphate 1282 mg/24h (360-1600 mg/24h), urine creatinine 1570 mg/24h (500-2150 mg/24h). There was no evidence of acidosis, chronic kidney disease, preexisting osteomalacia or vitamin D deficiency. The patient had no recent alcohol consumption and his alcohol level was undetectable. After reviewing the outside medical records it was noted that the patient had received denosumab 120 mg, 11 days prior to the hospital admission, as part of the management of bone metastases due to prostate cancer. The patient's baseline phosphorus prior to denosumab was in the low normal range. The severe hypophosphatemia and secondary hyperparathyroidism were attributed to denosumab administration. Patient was initially treated with intravenous phosphate and then transitioned to oral phosphate along with elemental calcium and calcitriol during the course of his hospitalization. Patient's phosphorus improved to 2.3 mg/dL by the time of discharge.

Discussion

In patients treated with denosumab, the primary concern is potential post-treatment hypocalcemia, however, our case brings attention to severe hypophosphatemia as a serious side effect to treatment with denosumab. Multiple specialties are involved in the treatment of osteoporosis and metastatic bone lesions, and each should be aware that denosumab can lead to lower serum phosphate levels due to its effects on bone resorption and reduction of proximal tubular reabsorption of the phosphate resulting in clinical symptoms of muscle weakness, bone pain, fractures and even stupor, coma and death. We therefore conclude that monitoring phosphate levels should be part of the pre- and post-treatment evaluation in patients who are candidates for treatment with denosumab, particularly high-dose denosumab.

Presentation: No date and time listed
ODP087 Dose-dependent effect of long-term statin use on risk of osteoporotic fracture in elderly patients
Authors: Ahn Seong Hee , Hong Seongbin , Suh Young J , Seo Da Hea , Jeong Yujin , Cho Yongin , Kim So Hun
Published: November 2022

Introduction

Studies have been conducted to assess the association between the use of statin and risk of new onset osteoporosis or osteoporotic fractures, however, they have shown conflicting results. We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in elderly population.

Methods

In this population cohort study with Korean National Health Insurance Service-Senior Cohort database, a total of 365,656 elderly (≥60 years) without previous history of osteoporosis were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to December 2012. Incidences of major osteoporotic fractures and site specific fractures were compared using the Cox proportional hazards model with use the inverse probability weighting method.

Results

During years follow-up period, 54,959 major osteoporotic fractures occurred; the risk of major osteoporotic fractures was significantly reduced (OR,0.769; 95% CI,0.716-0.826) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for both vertebral fracture (OR,0.701; 95% CI,0.641-0.767) and non-vertebral fracture (OR,0.807; 95% CI,0.726-0.898). Longer duration and higher cumulative dose of statin, defined by cumulative daily defined dose, were negatively associated with the risk of major osteoporotic fracture.

Conclusion

In this population-based cohort study, the use of statin was associated with significant reduction in the risk of osteoporotic fractures in elderly patients without previous history of osteoporosis.

Presentation: No date and time listed
ODP090 Fragility Fractures and Osteoporosis Screening in Patients with Chronic Lymphocytic Leukemia
Authors: Petty Lloyd , Stephens Deborah , Sharma Anu
Published: November 2022

Chronic lymphocytic leukemia (CLL) and osteoporosis are diseases of older adults with high prevalence rates. CLL infiltrates the bone marrow, increasing bone resorption and demineralization which contribute to the pathophysiology of osteoporosis. Despite this, there are limited clinical data describing the association of CLL with osteoporosis and fracture risk. We hypothesized that osteoporosis and fragility fractures (FF) are common in patients with CLL. The Huntsman Cancer Institute (HCI) has a CLL database which includes all patients diagnosed with CLL since January 1, 2000 and received care at the HCI. Patients included were identified from the CLL database with ICD-9 and 10 codes associated with osteopenia, osteoporosis and/or presence of a FF. Of the 57 patients included, 67% were female (n=38) with a mean age of 69 ± 10 years and 93% Caucasian. 60% (n=34) had RAI stage of 0-1 with genetic changes noted as follows: Del(13q) 46% (n=26), Del(17p) 7% (n=4), Del(11q) 5% (n=3), and Trisomy 12 14% (n=8). IGVH mutation was present in 31.6% of patients (n=18). 47% (n=25) of patients were treated with chemotherapy, of which Rituximab (n=14), Bendamustine (n=7), Cyclophosphamide (n=5), and Ibrutinib (n=5) were the most frequently used. 58.5% (n=32) had a history of FF, with 84% occurring in the spine (n=27/32). Assessment for Vitamin D deficiency and hyperparathyroidism were performed in 54% (n=31) and 21% (n=12) of the cohort respectively. Even though every patient in the study either had a diagnosis of osteoporosis by ICD code or FF, only 44% (n=25) of patients had an available DXA scan for our review, and only 31% (n=18) received treatment for osteoporosis. Of those with a DXA, the worst T score was in the right femoral neck (T score -1.9, IQR -1.5 to -2.5) with 44% (n=14/32) either having T scores in the normal or osteopenic range. Interestingly, FF was associated with higher T scores in the spine (FF spine T score -1. 0±1.5 vs no FF T score -2.2±0.8, p=0. 03). Clinical factors associated with FF were male sex (83% men vs 46% women, p<0. 01) and positive smoking history (93% smokers vs 46% non-smokers, p<0. 01). Use of chemotherapy and hip T scores were not associated with FF. The data from our study suggests that patients with CLL are predisposed to axial fragility fractures despite non-osteoporotic T scores. In addition, osteoporosis screening with DXA is under-utilized in the CLL population, despite meeting age-appropriate screening guidelines. Increased awareness and screening for axial fragility fractures, especially in men and smokers, should be recommended in the long term follow up of patients with CLL. Further study is needed to understand the pathophysiology of osteoporosis and FF in patients with CLL to develop improved methods for prevention of these morbid fractures.

Presentation: No date and time listed
ODP100 Hypoparathyroidism in the Setting of COVID-19: Increasingly Common Phenomenon
Authors: Markov Alexander , Krutilova Petra , Salam Maamoun
Published: November 2022

Background

Acquired hypoparathyroidism (HPT) in adults is most commonly caused by post-surgical or autoimmune damage to the parathyroid glands. Genetic defects causing abnormal gland development, impaired parathyroid hormone (PTH) production or action are rare and typically diagnosed in childhood. Recent literature suggests surprisingly high prevalence of hypocalcemia in patients with SARS-CoV-2 infection and this finding is associated with poor outcomes. [1] We present a case of new onset HPT in a patient admitted with respiratory failure due to COVID-19.

Case presentation

A 63-year-old woman with history of obesity, GERD, asthma, presented to the ED with fever, cough, dyspnea, and diarrhea. She was found to have low O2 saturation, CXR revealed multifocal interstitial and airspace opacities. Her PCR SARS-CoV-2 test was positive and she was admitted to ICU. She was incidentally found to have severe hypocalcemia Ca 5.2 mg/dL (8.5 - 10.3 mg/dL), ionized Ca 2.46 mg/dL (4.50 - 5.10 mg/dL), albumin 3.7 g/dL (3.5 - 5. 0 g/dL). She denied any history of neck surgery, radiation or trauma and personal or family history of autoimmune or calcium disorders. Her calcium levels were normal over the past 4 years. She denied symptoms of hypocalcemia prior to presentation and reported leg cramps and finger numbness in the ED. Further work-up revealed PTH 13 pg/mL (15 - 65 pg/mL), 25-OH vitamin D 16 ng/mL (30 - 80 ng/mL), Mg 1.2 mg/dL (1.4 - 2.5 mg/dL), phosphorus 4.9 mg/dL (2.3 - 4.5 mg/dL), bicarbonate 26 mmol/L (22 - 32 mmol/L). Patient was started on Ca (IV and PO), Mg, and vitamin D replacement. PTH reassessment on days 6, 14, and 19 showed persistently low/inappropriately normal PTH (22, 14, and 8 pg/mL respectively) despite normalization of magnesium levels. Patient was discharged on Ca, Mg, and vitamin D supplementation with follow-up in Endocrinology clinic for further evaluation of her hypoparathyroidism progression.

Conclusion

SARS-CoV-2 infection causes a hypersensitive immune reaction and widespread inflammation. Emerging evidence suggests that this cytokine-mediated reaction and hypoxia associated with COVID-19 can affect the parathyroid glands, resulting in impaired PTH secretion. Furthermore, direct parathyroid tissue invasion and destruction by means of entry via angiotensin-converting enzyme 2 receptors has also been proposed [2]. Hypocalcemia in our patient could be multifactorial, however we believe that COVID-19 induced HPT was the leading mechanism. We hope that further research explores this hypothesis and elucidates the underlying pathophysiology. References: [1] Martha JW, Pranata R. Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis. Diabetes Metab Syndr. 2021 Jan-Feb;15(1): 337-342. [2] Abobaker A, Alzwi A. The effect of COVID-19 on parathyroid glands. J Infect Public Health. 2021;14(6): 724-725.

Presentation: No date and time listed
ODP103 IPN60130 for the Treatment of Fibrodysplasia Ossificans Progressiva: Methodology of the Randomized, Double-Blind, Placebo-Controlled Phase II FALKON Trial
Authors: Karimian Negar , Powell Christine , Shih Fei
Published: November 2022

Objectives

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder caused by activin receptor-like kinase-2/activin A receptor type 1(ALK2/ACVR1) mutation and characterized by heterotopic ossification (HO) inducing progressive restriction of mobility. IPN60130 is a selective ALK2/ACVR1 inhibitor, currently being investigated for the treatment of FOP. 1 Here, we describe methodology of the FALKON trial (NCT05039515) designed to compare efficacy and safety of IPN60130 with placebo in patients with FOP.

Methods

Patients will be randomized to oral placebo, or low or high dose IPN60130 for 12 months; patients receiving placebo will then transition to IPN60130 for 12 months. Patients will be randomized to receive placebo, or low or high dose IPN60130 orally for 24months. Enrollment criteria include: age of ≥5years, clinical FOP diagnosis with a disease-causing mutation, and either a flare-up, new HO, new joint ankylosis, or increase in Cumulative Analogue Joint Involvement Scale (CAJIS) score in the prior year. Recruitment is ongoing to enroll 90 patients. The primary efficacy outcome will be the annualized change from Baseline (CfB) in HO volume to Month 12, assessed using low-dose whole-body computed tomography (CT). Secondary efficacy outcomes to be compared with placebo at Month 12 include: CfB in volume of new HO lesions, CfB in number of HO lesions, flare-up rate and number of flare-up days, number of body regions with new HO, CfB in pain intensity, and the proportion of patients with any new HO. Additional secondary endpoints include CfB in HO volume in treated patients versus placebo and participants receiving standard of care in a FOP natural history study (NCT02322255) at Month 24. Safety will be assessed via the incidence of adverse events (AEs) and serious AEs over 25 months. Patients aged ≥15 years will be eligible for a sub-study assessing HO using [ 18 F]NaF positron emission tomography-CT.

Results from the FALKON trial, expected to complete in August 2025, will enable evaluation of the efficacy and safety of IPN60130 in patients with FOP.

References

1. Davis A et al. J Bone Miner Res 2019;34(Suppl 1): 290Funding: Sponsored by Ipsen

Presentation: No date and time listed
ODP112 Post-infusion ECG Changes in Patients Receiving Intravenous Bisphosphonates: a Systematic Review and Meta-Analysis
Authors: Shoung Alex , Rodriguez Alexander J
Published: November 2022

Bisphosphonates are the first-line treatment for several bone and mineral disorders. Randomized trials and cohort studies have reported increased rates of atrial fibrillation in patients receiving bisphosphonates, however, uncertainty remains as to whether other electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting ECG findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE on 06/01/2022 for studies reporting ECG parameters following administration of intravenous bisphosphonates. We excluded studies that only reported atrial fibrillation, case reports and animal or cell-based studies. Study quality was assessed using the Newcastle-Ottawa Scale. Continuous data were meta-analysed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95%CI). Heterogeneity was determined by the I 2 statistic. All data were computed using R (4.1.1). We found 1,123 records of which six met our inclusion and exclusion criteria, of which five had data for meta-analysis. Studies were of low to moderate quality. Five studies used zoledronic acid while one study used pamidronate. Most studies [n=4] were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases and one study was conducted in children with cerebral palsy and osteoporosis. Most studies [n=4] reported outcomes in the sub-acute (>24 hours) phase. Study populations ranged from n=15 to n=116. There was a significant difference in QTc dispersion (SMD= -0.456 milliseconds [95%CI: -0.800 to -0.113]; I 2 = 0%; n= 67 patients; k= 2 studies) but no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc (maximum), QTc (minimum), or QTc. The correlation between pre- and post-infusion QTc dispersion was rho= 0.981 (p=0.866). Results were unchanged when analysing studies reporting acute or sub-acute phase ECG changes. Overall, there is insufficient and low quality evidence to support an association between intravenous bisphosphonate administration and acute phase dysrhythmias. These data underscore the importance of performing a pre-infusion ECG to evaluate potentially unreported conduction abnormalities.

Presentation: No date and time listed
ODP133 Rare Case of Primary Hyperparathyroidism Causing Hypercalcemic crisis in Systemic Lupus Erythematosus (SLE)
Authors: Kedarisetti Sreekari , Rajmohan Divya , Simon Nicole
Published: November 2022

Introduction

Hyperparathyroid crisis is a rare endocrine emergency with a high mortality. Primary hyperparathyroidism (PHP) can present as severe hypercalcemia. There are very few cases documented in literature of patients with concomitant SLE and PHP. We present a case of hypercalcemic crisis in a patient with untreated primary hyperparathyroidism with a history of SLE.

Case description

A 46 year old woman was found to have hypercalcemia of 12.9 mg/dl on routine lab work. Her medical history is significant for SLE (diagnosed 9 years prior) and osteoarthritis. She had no physical complaints. Further workup confirmed primary hyperparathyroidism with PTH of 322.8 pg/ml and findings consistent with parathyroid adenoma on Sestamibi scintigraphy. Parathyroidectomy was strongly recommended however the patient refused. She was then offered medical management but did not show up for any follow up appointments. Two years later, she presented to the emergency department with altered mentation, lethargy, poor oral intake and abdominal pain for 2 days. She was found to have severe hypercalcemia with a serum calcium of > 24.8 mg/dl and was in acute renal failure. On admission, EKG changes suggestive of pseudoinfarct pattern from severe hypercalcemia were present. She was managed in the intensive care unit with intravenous hydration, calcitonin, zoledronic acid and hemodialysis. Shortly after initiation of hemodialysis, the patient succumbed to a cardiac arrest.

Conclusion

Hyperparathyroid crisis when untreated has a 100% mortality rate. Early management with surgical intervention is the only confirmed cure for PHP. There are only 18 cases reported in literature of hypercalcemia in SLE. Mechanisms involved are believed to be stimulatory PTH antibodies, PTHrP and osteoclastic activity due to inflammatory cytokines. To our best knowledge this is the 6th case report of a patient with concomitant SLE and PHP. A prospective study by Norman et. al 1 done in 10000 PHP patients demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/ml . Her baseline calcium at diagnosis was 13mg/dl and intact PTH was 322.8 pg/ml which is higher than seen in the normograms as per the study. In our patient, we believe SLE could have exacerbated the hypercalcemia caused by PHP. It is important to perform further studies to identify if any association exists between the two conditions. Physicians must recognize their concomitant occurrence as prompt management of hypercalcemia becomes even more crucial in these cases. References: 1) Norman J, Goodman A, Politz D. Calcium, parathyroid hormone, and vitamin D in patients with primary hyperparathyroidism: normograms developed from 10,000 cases. Endocr Pract. 2011 May-Jun;17(3): 384-94. doi: 10.4158/EP09346. OR. PMID: 21134884.

Presentation: No date and time listed