25-OH Vitamin Research Articles

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

Is 25OH Vitamin D Excess before 36 Weeks Corrected Age an Independent Risk Factor for Bronchopulmonary Dysplasia or Death?

Low 25-Hydroxyvitamin D (25(OH)D) in preterm infants is a risk factor for bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate a beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and histological alterations in the lung evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120 nmol/L are also a risk factor for BPD or death. This retrospective single-center cohort study included only infants born at <31 weeks gestational age without major malformations with at least a determination of 25(OH)D at <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120 nmol/L (50.5% vs. 43.9%, p = 0.53). The logistic regression identified weight (OR 0.997, 95% CI [0.995-0.998]) and term (OR 0.737, 95% CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95% CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis

BackgroundCognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. MethodsIn this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25‑hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. ResultsAt univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. ConclusionsLower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

Comparison of Hand-Wrist Findings of Rheumatoid Arthritis Patients According to the Use of Synthetic and Biological Disease-Modifying Antirheumatic Drugs (DMARDs): A Clinical, Radiographic, and Ultrasonographic Study.

The aim of this study is to evaluate the hand-wrist findings in patients with rheumatoid arthritis (RA) using synthetic and a combination of synthetic and biological disease-modifying antirheumatic drugs (DMARDs) in terms of ultrasonographic, clinical, and radiographic data. The study is designed as a cross-sectional study, and 31 RA patients followed up in the rheumatology outpatient clinic were enrolled. Nineteen patients were using only synthetic DMARDs, and 12 patients were using a combination of synthetic and biological DMARDs. The clinical data of each patient were recorded simultaneously. Disease Activity Score-28 (DAS-28) was used for the assessment of disease activation, and the Health Assessment Questionnaire (HAQ) score was used for the evaluation of general health status. Bilateral proximal interphalangeal (PIP), metacarpophalangeal (MCP) joints, and the radiocarpal, ulnocarpal, and midcarpal joints of the patients were examined by ultrasonography (US). The Sharp-van der Heijde modified score was used to determine the radiographic damage. There was no significant difference between the two groups in terms of demographic data, clinical findings, ESR, and CRP. When the groups were compared in terms of right and left PIP, MCP, and radiocarpal, ulnocarpal, and midcarpal synovitis grade total scores, no significant difference was found between the two groups. Radiographic total joint space scores were significantly lower in the group receiving only synthetic DMARD treatment (p=0.047) and 25-OH vitamin D levels were significantly higher (p=0.008). This study revealed that there was no significant difference between groups except radiographic total joint space scores.

THU472 Novel And Multifactorial Case Of Severe Hypercalcemia Due To Primary Hyperparathyroidism And Heterozygous Mutation Of CYP24A1

Abstract Disclosure: J. Liu: None. P. Angelos: None. M. Barhoum: None. R. Jain: None. Background: Mutations of CYP24A1 are known to be associated with hypercalcemia due to disruptions in 24-hydroxylase’s ability to break down 1,25-OH Vitamin D. A case involving heterozygous mutation of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been reported. Clinical Case: A 23-year-old female presented with severe fatigue and was found to be newly hypercalcemic to 13.2 mg/dL. There was no clear family history or exogenous source. Her PTH was 62 pg/mL and 1,25-OH vitamin D was elevated to 242.7 pg/mL. Her other laboratory work-up demonstrated: albumin 4.0 g/dL, magnesium 2.2 mg/dL, Phosphate 2.1 mg/dL, creatinine 0.72 mg/dL, 25OH Vitamin D 28.2ng/mL, 24hr urine calcium 150 mg/24hr, BSALP 32 ug/L, and within normal limits SPEP, PTHrP, TSH, Free T4, ACE, metanephrines, calcitonin, and ferritin. She required multiple administrations of pamidronate or zoledronic acid every 4-6 weeks. She was started on cinacalcet without substantial effect on hypercalcemia or need for bisphosphonate. She was also started on Vitamin D supplements, while further workup was pursued due to concern of non-PTH mediated causes of hypercalcemia. She had a bone scan, CT scan of the whole body, thyroid ultrasound, and Sestimibi scan that were read as normal. She was referred to an academic metabolic bone disease center. Vitamin D supplements were stopped and a 25-OH Vitamin D to 24,25-OH Vitamin D ratio was found to be elevated at 25.18 (Normal &amp;lt;25). She was referred to an endocrine surgeon, who felt there was localization on Sestimibi and performed a parathyroidectomy with removal of a 3.5g parathyroid adenoma. Pathology showed a parafibromin deficient parathyroid neoplasm. Genetic testing was sent for CYP24A1 and CDC73. The patient’s CYP24A1 was positive for heterozygous pathogenic mutation with normal CDC73. Post-operatively, she had a low PTH level of 14 pg/mL but normal calcium level 9.6 mg/dL. 1,25-OH Vitamin D levels decreased to normal value 58 pg/mL (reference 18-72 pg/mL). She was weaned off calcium supplements and advised to be cautious with Vitamin D supplements. Genetic counseling was recommended. Conclusion: We report a case where a young woman with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism that was exacerbated by an underlying heterozygous mutation in CYP24A1. Our case suggests that patients with mild PTH elevation and severe hypercalcemia should be screened with 1,25-OH Vitamin D levels and 25-OH to 24,25OH Vitamin D ratio for CYP24A1 mutations. While gentle Vitamin D supplementation is often recommended in primary hyperparathyroidism, in patients with mild PTH elevations but severe hypercalcemia, CYP24A1 mutations should be considered, and Vitamin D supplements should be avoided. Finally, our case suggests that primary hyperparathyroidism with underlying CYP24A1 mutation may be poorly responsive to cinacalcet. Presentation: Thursday, June 15, 2023

THU233 Reduction Of Overutilization Of 1,25-Dihydroxyvitamin D

Abstract Disclosure: J. Brown: None. M. Dewan: None. J. Courter: None. A. Spooner: None. J. Treasure: None. K. Kaplan: None. N.A. Crimmins: None. Unnecessary testing may lead to patient harm, inappropriate treatments, and/or increased cost. Per the Endocrine Society, in conjunction with Choosing Wisely, 1,25-dihydroxyvitamin D (1,25-OH D) should not be measured unless a patient has hypercalcemia or decreased kidney function. This study sought to evaluate overutilization of 1,25-OH D at Cincinnati Children's Hospital Medical Center. We queried EPIC for all 1,25 OH vitamin D tests drawn in all patients (inpatient and outpatient) between 01/01/2021 and 12/31/2021. We then cross-referenced each test with all patient ICD10 codes associated with each patient’s chart. Appropriate ordering was defined as the patient having an ICD10 code related to calcium disorders or renal disease (531 codes included, data not shown). Out of a total of 1,057 1,25-OH D tests ordered, we found that only 19.4 percent were in patients whose chart contained a code that clinically would indicate testing. Further analysis showed most of these tests were obtained by psychiatry (22.7%) and community general pediatricians (14.6%) and not by endocrinology (12.5%) or nephrology (2.2%) providers. We will use this as baseline data to design quality improvement interventions to reduce unnecessary ordering of 1,25 OH vitamin D, including an ordering pathway in Epic to provide point of care education and guidance regarding appropriate Vitamin D test selection. In summary, inappropriate ordering of 1,25 vitamin D is common, likely due to misunderstanding of the best test to determine vitamin D sufficiency. Presentation: Thursday, June 15, 2023

SAT256 Buschke Loewenstein Tumor Presenting With Hypercalcemia

Abstract Disclosure: K. Jones: None. P. Krutilova: None. J.B. McGill: None. Introduction: Humoral hypercalcemia of malignancy is known to be associated with squamous cell carcinomas (SCC), although rarely seen in the setting of skin cancer. We present an interesting case of a young patient with giant condyloma acuminatum complicated by SCC presenting with severe hypercalcemia. Case Description: A 37-year-old man presented with pain and purulent drainage due to bacterial superinfection of genital warts. He had recurrent and locally advanced condylomas, first occurring more than 10 years ago. Skin lesions in the genital and perianal area never resolved and he required multiple surgical interventions including sigmoid colostomy placement due to Fournier gangrene. His laboratory evaluation this admission was notable for an elevated calcium level (13.0 mg/dL [8.5-10.3], albumin 3.4 g/dL [3.5-5.0]), phosphorus 3.9 mg/dL [2.3-4.5], and normal kidney function. He did not have history of hypercalcemia and was not taking any calcium supplements. Hypercalcemia prompted work-up including: PTH 4 pg/mL [15-65], 25-OH vitamin D 36 ng/mL [30-80], unremarkable SPEP/UPEP, TSH 0.91 mcIUnit/mL [0.3-4.2]. Initial differential diagnosis included hypercalcemia due to granulomatous process and increased production of calcitriol vs. PTH-related protein (PTHrP) mediated hypercalcemia. 1,25-OH vitamin D was normal (33 pg/mL [18-64]) and PTHrP was elevated (6.7 pmol/L [&amp;lt;4.2]). The patient subsequently underwent biopsy of groin lesions which demonstrated SCC in situ. PET/CT only demonstrated hypermetabolic changes in the perineum and groins bilaterally. Inguinal lymph node biopsy was negative for malignancy. His hypercalcemia persisted despite administration of IV fluids and he was treated with IV zolendronic acid. Calcium level subsequently normalized (9.1 mg/dL). He underwent extensive excision of the tumor involving the right gracilis muscle, left testicle, portions of the perineum, and penile shaft skin. Discussion: While cases of hypercalcemia in malignancy are common, this is an unusual case of giant condyloma acuminata (GCA) heralding development of SCC by elevated calcium levels. GCA also known as Buschke-Loewenstein tumor is a rare disease with estimated incidence of 0.1% in the general population and a male-to-female ratio of 2.7:1, typically associated with human papilloma virus subtypes 6 and 11. It is a locally aggressive tumor with a potential for destructive growth and malignant transformation (estimated rate up to 56%), very high rate of recurrence after excision (66%), and overall mortality of approximately 20%. Early recognition and treatment of GCA is essential in order to prevent devastating complications. Purzycka-Bohdan D, Nowicki RJ, Herms F, et al. The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview. Int J Mol Sci. 2022;23(9):4547. Published 2022 Apr 20. doi:10.3390/ijms23094547 Presentation: Saturday, June 17, 2023

SAT208 Hypercalcemic Crisis In Metastatic Parathyroid Carcinoma: An Unusual Presentation Of A Rare Endocrine Disease

Abstract Disclosure: A. Barnett: None. T. Sliker: None. R.J. Harper: None. G. Elshimy: None. Introduction: Hypercalcemia can be life-threatening with a wide differential, including parathyroid carcinoma (PC), which accounts for only 0.005% of all malignancies in the U.S. Maintaining an index of suspicion for PC in PTH-mediated hypercalcemia is vital for improving long-term survival and outcomes. Frozen section can be misleading when PC is suspected. We describe a case of hypercalcemia due to recurrent metastatic PC 9 years after initial diagnosis. Case: A 57-year-old male presented for endophthalmitis and altered mentation. Records revealed primary hyperparathyroidism with calcium 11.7 mg/dL, PTH 337 (11.1-79.5pg/mL), and 24-hour urine calcium 810 mg/day. Sestamibi showed right lower parathyroid adenoma and a possible right upper parathyroid adenoma. Right superior parathyroidectomy revealed PC invasive into adipose tissue, increased vascularity and positive margins. A hemithyroidectomy and central neck dissection was performed with intraoperative report noting normal-appearing right inferior parathyroid affixed to thyroid, confirmed by frozen section biopsy. The right inferior parathyroid was minced and re-implanted into the right strap muscle. Patient did not return for follow-up. Recent admission labs showed calcium 15.2 mg/dL, ionized calcium 6.8 (4.5-5.3mg/dL), PTH 546 pg/mL, creatinine 1.54 mg/dL, 25-OH vitamin D 21.64 ng/mL, and phosphorus 1.9 mg/dL. He was treated with intravenous fluids, zoledronic acid, and calcitonin. Due to a high suspicion of locally recurrent or metastatic PC, further imaging obtained. A Neck CT and US showed no abnormalities of right surgical bed or cervical lymphadenopathy. Sestamibi revealed a right lower lung lobe nodule, measuring 2.3cm, with intense immediate and delayed uptake concerning for metastatic or primary lung neoplasm and mild focal retention in the right paratracheal region, suspicious for tumor recurrence. PTHrP was negative. He underwent video-assisted thoracoscopic right lower lobectomy that showed an ovoid, well-circumscribed 2.5 x 2.3 x 2.3cm tumor, which stained positive for PAX-8 and synaptophysin, consistent with PC. Discussion: Clinicians should suspect PC in cases with severe hypercalcemia or absolute PTH above 500mg/dL to allow for better surgical planning. Complete en bloc resection is the standard treatment to improve long-term outcomes and reduce disease recurrence. Diagnosis of PC following incomplete surgical resection has increased recurrence rates of greater than 50%. Our patient’s recurrence was 9 years after diagnosis, but most recurrences occur within 2-3 years and occasionally more than 20 years later. The ipsilateral parathyroid was re-implanted based on frozen section results in this patient, which may have been misleading. Frozen sections of parathyroid tissue are notoriously difficult to distinguish normal parathyroid versus PC and only diagnostic in 15% of cases as described in one case series. To reduce the risk of recurrent disease, physicians shouldn’t entirely depend on these results when there is high suspicion for PC. Presentation: Saturday, June 17, 2023

SAT247 CODE STEMI Due To Excessive Ingestion Of TUMS

Abstract Disclosure: E. Hershkop: None. Hypercalcemia is defined as a serum calcium greater than 10.5mg/dL. It is most commonly caused by malignancy or hyperparathyroidism; a less common cause is excess calcium ingestion, referred to as Milk Alkali Syndrome (MAS). Severe hypercalcemia can lead to renal failure, arrhythmias, and coma. A rare EKG finding is ST elevation mimicking an acute ST Elevation Myocardial Infarction (STEMI). We describe a case of severe hypercalcemia caused by excessive ingestion of TUMS antacids that presented as diffuse ST elevations on EKG which were mistaken for an acute MI. To our knowledge, this is the first case in the literature describing hypercalcemia with ST elevations caused by excessive TUMS ingestion. Case: A 74 year old male with a history of diabetes, hypertension, stroke, and acid reflux presented for recurrent falls due to leg weakness. He endorsed constipation with bowel movements every 5-6 days. Upon further questioning, he reported taking 6 to 7 TUMS antacid tablets (each containing 200mg calcium) daily for the past two months to treat ‘heartburn’. He denied having chest pain. His medications included hydrochlorothiazide, losartan, amlodipine, atorvastatin, glimepiride, and famotidine. On physical exam he had reduced strength in both lower extremities - 1/5 left, 3/5 right. EKG on arrival showed ST elevation in leads III, aVF, and V1-V5, with T wave inversions in aVR and aVL, suggestive of a STEMI. A STEMI code was called. Since he denied chest pain, troponins were lateralized at 0.1 ng/mL, and an echocardiogram showed no wall motion abnormalities, cardiology recommended conservative management. Laboratory evaluation revealed calcium of 15.5 mg/dL, albumin of 3.8 g/dL, BUN of 39 mg/dL, creatinine of 2.2 mg/dL, magnesium of 1.4 mg/dL, phosphorus of 3 mg/dL, 25-OH vitamin D of 24 ng/mL, PTH of 9 pg/mL, undetectable 1-25 OH vitamin D and PTHrP, and normal TSH and SPEP. CT head/chest/abdomen/pelvis showed no evidence of malignancy. He was treated with IV hydration and 1 dose of calcitonin. His calcium level, leg strength, and ST elevations began to improve within 12 hours and returned to normal within four days. Conclusion: Our patient had severe hypercalcemia likely secondary to excessive consumption of oral antacid tablets, as other causes were ruled out, and his EKG findings masqueraded as a STEMI-a rare presentation of hypercalcemia. Consumption of supplements may be overlooked when investigating hypercalcemia and should be specifically asked about. In addition, providers should be aware of EKG changes found in hypercalcemia to avoid unnecessary cardiac intervention. Presentation: Saturday, June 17, 2023

SAT196 COVID-19 Pneumonia And Primary Hyperparathyroidism Exacerbation

Abstract Disclosure: A. Khan: None. P. Rimal: None. M. Biggs: None. A. Ahmed: None. C. Musurakis: None. J.L. Gilden: None. A. Moid: None. Introduction: It is well known that COVID-19 virus damages the body by either inflicting the injury directly, or by initiating a systemic immune response, resulting in inflammation. Our case report explores how parathyroid glandular dysfunction and calcium levels (Ca) can be affected in a patient with active COVID-19 pneumonia. Clinical Case: A 58-year-old male, unvaccinated for COVID-19, with COPD, primary hyperparathyroidism (PHPT), chronic kidney disease, and ethanol use presented to the emergency room with confusion, vomiting, and lethargy. Preadmission medications included hydrochlorothiazide. Following a positive COVID-19 test, he was diagnosed with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. After emergent treatment with BiPAP and IV steroids, he was transferred to the ICU, where he completed treatment with remdesivir, dexamethasone, and baricitinib. He was also treated for ethanol withdrawal. Notably, this patient had a history of chronic asymptomatic hypercalcemia secondary to PHPT with Ca prior to admission ranging from 10.9-13.6 mg/dl (nl=8.5-10.1mg/dl), PTH range 145-345 pg/ml (nl=14-65 pg/ml), creatinine (Cr) 1.2-1.4 mg/dl (nl= 0.67-1.17 mg/dl). On this admission, Ca was 12.2mg/dl, albumin 2.4 g/dl (3.4-5.0 g/dl), PTH 531 pg/ml, Cr 3.4 mg/dl, 25OH vitamin D 29.3 ng/mL (nl= 30-100 ng/mL). After fluids, Ca initially improved to 10.9mg/dl and Cr soon after normalized. Mental status also improved after hydration. However, Ca then rose significantly to 14.1mg/dl with mental status decline. IV zoledronic acid was administered, resulting in lowering serum calcium and improvement of mental status. Conclusion: This patient’s clinical course was notable for the improvement of Ca initially with hydration. However, a significant rise in Ca approaching parathyroid crisis range was seen shortly thereafter, despite normalization of Cr. Whereas hypocalcemia has been noted in most cases of Ca dysfunction associated with COVID-19 infection, in this case, we postulate that the COVID-19 infection may have triggered parathyroiditis, thus exacerbating the underlying PHPT. One such mechanism is the use of receptors like angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) by COVID-19 virus, which are found on endocrine glands including the parathyroid. Similarly, COVID-19 virus exerts its inflammatory effects using IL-6, which is also a key cytokine that causes hypercalcemia by stimulating bone resorption. Furthermore, COVID-19 infection is notorious for causing nausea/vomiting, and diarrhea, culminating in dehydration which worsens hypercalcemia. It is therefore necessary that physicians foresee impending complications of COVID-19 infection with concurrent parathyroid disease and take early steps to prevent and treat them. Presentation: Saturday, June 17, 2023

SAT260 Asymptomatic Vitamin A Toxicity Causing Hypercalcemia

Abstract Disclosure: N. Seshan: None. G. Goswami: None. Background: Vitamin A toxicity is an overlooked cause of hypercalcemia. Most cases of hypercalcemia are secondary to primary hyperparathyroidism or malignancy. High levels of Vitamin A are thought to have a direct effect on the bone by stimulating osteoclast resorption or inhibiting osteoblastic formation, therefore increasing the fracture risk. Clinical Case: 56 year old female with history of alcoholic cirrhosis complicated by hepatic encephalopathy, acute kidney injury and now status post liver transplant five months prior that was admitted for asymptomatic hypercalcemia. Initially, hypercalcemia was thought to be secondary to cyclosporine, so medication was discontinued. Hypercalcemia resolved after hydration however she was again readmitted for hypercalcemia found on routine labs. She did not show any other signs of excess vitamin A. Lab work showed calcium 12.5 mg/dL (8.6 - 10.2mg/dL), albumin 4g/dL (3.4 - 4.8g/dL), normal 24 hour urine calcium excretion, eGFR 33mL/min, parathyroid hormone 16.9 pg/mL (8.7-77pg/mL), normal 1,25-OH and 25-OH vitamin D, PTHrP 25pmol/L, AM Cortisol 9mcg/dL, TSH 1.7 mIU/L (0.35 - 4.7mIU/L), serum protein electrophoresis unremarkable. Her vitamin A level was elevated to 113 ug/dL (30-75mcg/dL) and was diagnosed with hypercalcemia due to elevated vitamin A levels. Treatment involved hydration and discontinuation of her multivitamin containing vitamin A. Current limited literature suggests discontinuing vitamin A supplements will normalize vitamin A levels over time. Her vitamin A levels improved over several months. Incidentally, due to complaints of back aches from prior injury, imaging showed acute compression fracture deformities of two thoracic vertebrae. Bone density scan showed normal bone density. Bone turnover markers were elevated indicative of increased bone resorption. Clinical Lesson/Conclusion: Hypervitaminosis A is a rare etiology of hypercalcemia. Vitamin A toxicity may be due to excess ingestion of preformed vitamin A through supplements and animal sources. Though not well understood, the proposed mechanism of vitamin A actions on the bone involves stimulation of bone resorption through increase in osteoclastic activity and inhibition of bone formation through osteoblastic suppression, leading to high serum calcium and increasing the risk of fractures. We present a unique case in a patient who developed hypercalcemia secondary to hypervitaminosis A. Presentation: Saturday, June 17, 2023

SAT202 A Case Of Primary Hyperparathyroidism Secondary To Ectopic Intrathymic Parathyroid Adenoma

Abstract Disclosure: S. Pandiri: None. Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. Majority of cases are due to a single adenoma. In about 6-16% of cases, the parathyroid adenoma is in an ectopic location. Accurate preoperative imaging is key in localizing ectopic parathyroid adenomas. Clinical Case: 64 year old man with hypercalcemia was referred to endocrinology for further evaluation. His symptoms included fatigue, nausea, polydipsia and polyuria. There was no history of fractures, radiation therapy or family history of hypercalcemia. The patient’s past medical history is significant for nephrolithiasis, thyroid nodules and hypertension. He was started on Cinacalcet 30 mg, twice daily, by his primary care physician about 6 weeks prior to the initial visit. Physical exam was unremarkable. Lab studies were significant for elevated albumin-corrected calcium: 11.2 mg/dl (8.6-10.3 mg/dl), elevated PTH: 578.1 pg/ml (12-88 pg/ml), 25-OH vitamin D: 17 ng/ml (&amp;gt;30 ng/ml), phosphorus: 2 mg/dl (2.5-4.5 mg/dl) TSH: 0.54 mIU/L (0.40-4.50 mIU/L), 24 hr urine calcium: 429 mg (&amp;lt;250 mg/24 hr). The lab findings were consistent with hypercalcemia due to primary hyperparathyroidism. Neck Ultrasound showed bilateral thyroid nodules but no parathyroid adenoma. Tc-99m sestamibi scintigraphy was significant for 2.8 x 1.5 x 3.4 cm mass in the anterior mediastinum but did not show uptake in the neck. CT Neck showed a mass in the anterior mediastinum measuring 1.6 x 2.7 cm. Bone density was significant for osteopenia. He underwent robot assisted mediastinal mass excision two months after the initial evaluation. The pathology was significant for ectopic, intrathymic parathyroid adenoma, watery cell type with nuclear atypia, measuring 3.8 x 3.1 x 1.3 cm. Labs at the follow up visit showed normal albumin-corrected calcium of 8.6 mg/dl, improved PTH of 110.3 pg/ml. His symptoms improved significantly after surgery. Conclusion: This case demonstrates that preoperative localization of an ectopic parathyroid adenoma can prevent recurrent surgeries and persistent hypercalcemia. It is important for physicians to be aware of the various ectopic locations of parathyroid adenomas during the diagnostic workup of PHPT. Reference: Roy M, Mazeh H, Chen H, Sippel RS. Incidence and localization of ectopic parathyroid adenomas in previously unexplored patients. World J Surg. 2013 Jan;37(1):102-6. doi: 10.1007/s00268-012-1773-z. PMID: 22968537. Presentation: Saturday, June 17, 2023

SAT246 Ectopic (Penile) Calcification in 1, 25 Vitamin D Induced Hypercalcemia

Abstract Disclosure: J. Berquist: None. D.S. Reddy: None. A 60-year-old male with a history of well controlled type 2 diabetes and HTN presented with acute renal failure (initial creatinine 19.9 mg/dL, GFR 11). Kidney biopsy during admission was consistent with acute tubular necrosis and mild diabetic nephropathy. Serum calcium was normal at that time. He received temporary dialysis and eventually discharged home with improved (though still elevated) creatinine. On follow up labs a month later, he was noted to have high serum calcium. He was temporarily lost to follow up and was readmitted four months later due to persistent severe hypercalcemia. Peak serum calcium on his new admission was 13.2 mg/dL. Phosphorus level three months prior was 5.9 mg/dL, though had now improved to 2.7 mg/dL. Other labs this admission include creatinine 2.54 and GFR 33 (which was consistent with previous months), PTH 11 pg/mL, 25-OH Vitamin D 10 ng/mL, 1,25-Dihydroxy Vitamin D elevated at 84.8 pg/mL and magnesium low at 1.5 mg/dL. SPEP and UPEP were both negative and PTHrP was not measured. Kappa/Lamda free light chain ratio was mildly elevated at 1.77 (0.26-1.65). QuantiFERON Gold, HIV, Beta-2 microglobulin, ANA, and flow cytometry were negative. He received calcitonin x 2, IVF, zoledronic acid, and denosumab (three days later), which improved his calcium to 11.5 by discharge 11 days later. He underwent a CT Chest/Abdomen/Pelvis, T spine, and L spine that were remarkable for multiple bilateral partially calcified pulmonary nodules and hepatic steatosis with splenomegaly. PET CT showed 20 hypermetabolic osseous lesions throughout axial skeleton, multiple pulmonary, liver, and splenic lesions and lymphadenopathy in the head, neck, chest, abdomen. There was also diffuse calcification of the penile corpora. Pathology via biopsies of a retroperitoneal lymph node as well as bone marrow showed non-caseating granulomas. Lastly, 1-2 months ago, he noticed pain and hardening of his penis. On exam, there is a deep firmness with palpation and distal penile tenderness. There are no cutaneous lesions on the penis or anywhere else on the skin. Calciphylaxis was a consideration, but isolated penile involvement is rare. Additionally, it is rare to develop calciphylaxis without end stage renal disease. A review of the literature showed many cases of penile calciphylaxis, though none were without cutaneous involvement. Sarcoidosis of the penis is also very rare and cases in the literature cite either a cutaneous or intraurethral lesion. This case appears unique in the findings of penile calcification palpable on exam and visible on imaging, without any cutaneous manifestations, in the setting of previous though recovered acute renal failure and 1, 25 Vitamin D-mediated hypercalcemia in sarcoidosis. Presentation: Saturday, June 17, 2023

THU455 Sclerostin Inhibitor Use In The Medical Management Of Osteogenesis Imperfecta Type III

Abstract Disclosure: M.D. Lundholm: None. A. Derkyi: None. S. Talvacchio: None. J.C. Marini: Other; Self; Ultragenyx, Amgen Inc. L.Z. Khan: None. Background: Osteogenesis imperfecta (OI) is a rare collagen-related hereditary skeletal disorder with an increased fracture risk from minimal trauma, short stature, and bone deformity. OI is associated with defects in collagen structure or synthesis, high bone turnover, and paradoxical bone hypermineralization. The optimal medical therapies for bone health in these patients are unknown. Clinical Case: A 27-year-old woman with OI presented to clinic for bone health. She was diagnosed with OI type III by phenotype, collagen biochemistry, and genetic analyses (heterozygous for a COL1A1 Gly187Ala substitution) following fractures at age 4 mos. She experienced dozens of fractures, has had orthopedic hardware in bilateral femora, left tibia, humerus, and radius, and right tibia, as well as spine fusion at age 7 yrs. She had not fractured in over 3 yrs which she attributed to the stability of her automatic wheelchair. She had no family history of OI and had been in studies at the NIH; from ages 6-9 yrs she received pamidronate (1 mg/kg/cycle q3m) with BMD improvement. Presently, her vitals were normal, with height of 3’6” (25-50th percentile for type III OI females) and weight of 64 lbs (BMI 25.5 kg/m2). On exam she had blue sclera, midface hypoplasia, dentinogenesis imperfecta, severe kyphosis and scoliosis, and a barrel chest. She had normal calcium, PTH, and 25-OH vitamin D levels. Skull CT showed 1 mm increase in basilar invagination (16 to 17 mm). DEXA demonstrated progressive decline in radial BMD from 0.671 g/cm2 to 0.625 g/cm2 over 3 yrs (z-score -0.4 to -1.1) into the osteopenic range. For worsening bone disease, she is starting romosozumab 210 mg monthly. Discussion: While several agents increase BMD in OI, there are no placebo-controlled studies to show an effect on fracture rate. Bisphosphonates including pamidronate are used most commonly, with increased areal BMD, decreased bone turnover, but also increased mineralization of already brittle bone. Overall, two Cochran reviews failed to support decreased fracture rates from bisphosphonates, and there is risk of adynamic bone with chronic use. There is even less evidence for use of denosumab which is additionally associated with a rebound effect upon discontinuation. Sclerostin inhibitors are the newest agents with both anabolic and antiresorptive effects and good results in OI mouse models. Phase 2 data with sestrusumab showed increased BMD and decreased bone turnover. Ongoing studies are looking at sclerostin inhibitor use in adults and adolescents. From a practical standpoint, romosozumab has a shorter effect with quicker offset than bisphosphonates if needed to stop for fracture healing. Conclusion: Sclerostin inhibitors are an option for the medical treatment of OI. Further investigation is needed to determine long-term safety, optimal duration, and use of sclerostin inhibitors in combination with antiresorptive agents in OI. Presentation: Thursday, June 15, 2023

SAT219 Severe Isolated Hypocalcemia With Cetuximab &amp; Irinotecan Chemotherapy

Abstract Disclosure: M. Thomas: None. N. Janakiram: None. J. Leary: None. K.E. Foster-Schubert: None. R.R. Narla: None. Background: Electrolyte disorders are commonly seen with chemotherapy (CTX) agents. Cetuximab is an epidermal growth factor receptor inhibitor and irinotecan is topoisomerase 1 inhibitor. Both agents have been associated with hypomagnesemia which can adversely lead to hypocalcemia (HC). Case: A 66-year-old woman with osteoporosis (last bisphosphonate use was 24 months ago), primary hyperparathyroidism status post parathyroidectomy in 2015 (R inferior and superior glands) and 2017 (L inferior gland) with recent diagnosis of metastatic adenocarcinoma of unknown primary who presented with nausea, tetany, leg cramps and found to have severe HC of corrected calcium (CCa) of 5.7, a week post-chemotherapy. On the day of her CTX, her CCa was 7.0, ionized calcium (iCal) of 1.7 with Magnesium (Mg) of 2.0; she received IV calcium (Ca), then underwent CTX. She was prescribed Ca supplements and reports adherence. She returned endorsing the above symptoms with positive Chvostek and Trousseau sign on exam. Labs were notable for CCa of 5.7, iCal of 1.6, Mg of 1.6, Phosphorus of 4.5, PTH 123 (ULN 65), 25-OH vitamin D of 28.6 and normal eGFR. She was hospitalized and received multiple infusions of IV Ca and CCa improved to 7.5. She was discharged on Ca carbonate 1000 mg TID, Mg oxide 420 mg BID and Vitamin D. Before her second cycle of CTX with same agents, she received IV Ca for CCa of 7.3. She remained on Ca and Mg supplements. One week later, she endorsed paresthesia, diarrhea and was admitted again for HC. She was initiated on calcitriol on this admission and 24-hour urine studies showed low Ca excretion and elevated fractional excretion of magnesium (FeMg). Her CCa was 8.0 and she was discharged on calcitriol 0.25 mg BID. Oncology discontinued this CTX regimen. Her HC resolved and calcitriol and Ca supplements were gradually weaned off. Discussion: After both rounds of cetuximab and irinotecan, our patient developed profound HC without hypomagnesemia. Cetuximab can cause occasional Mg wasting syndrome with inappropriate urinary excretion. However, she was started on Mg since her first hospitalization despite normal serum Mg levels. Interestingly, her 24-hour urine studies revealed FeMg of 6.5% suggestive of renal Mg wasting. In the literature, there is a case report of severe HC with irinotecan but they had speculated germline mutations in Ca metabolism genes. It remains unclear how these CTX agents impact Ca homeostasis. It is difficult to discern if the severe HC in our patient could be attributed to Mg wasting with normal Mg levels. It is evident that her HC was associated with the timing of her CTX regimen. Therapy for HC can be complex, involves short- and long-term interventions, and correction is critical. Serum Ca surveillance before and during CTX management of cancer patients may reveal more instances and provide insight into the exact mechanisms. Presentation: Saturday, June 17, 2023

THU473 Acute Hypercalcemia In The Setting Of Acute Fatty Liver Of Pregnancy, A Case Report

Abstract Disclosure: M. Ahmad: None. M. Mack: None. A. Arif: None. L.A. Tejada: None. U. Siddiqui: None. Introduction: Hypercalcemia in pregnancy is rare and often goes unrecognized due to the overlapping symptoms of hypercalcemia and pregnancy. The most common cause of hypercalcemia in pregnant patients is primary hyperparathyroidism, with malignancy, milk alkali syndrome and familial hypocalciuric hypercalcemia being less common. Additionally, endogenous PTHrP production by breast and placental tissue have also been described as rare causes of hypercalcemia in pregnancy. We describe an interesting case of severe hypercalcemia in a pregnant woman presenting with acute fatty liver of pregnancy (AFLP) which rapidly corrected after delivery. Case description: The patient was a 32-year-old female with a past medical history of hypothyroidism and type 2 diabetes mellitus who presented to the emergency department at 32 weeks gestation due to four days of nausea, vomiting and epigastric pain. The patient’s vital signs were as follows: blood pressure: elevated to 133/79 mmHg, heart rate: 75 beats per minute, temperature: 36.7 C, and respiratory rate: 12 breaths per minute. On physical exam, the patient had diffuse abdominal tenderness with no vaginal bleeding. The patient’s blood work was significant for: bicarbonate: 17 mmol/L, creatinine: 1.26 mg/dL (baseline 0.7 mg/dL), corrected calcium of 15.1 mg/dL, ALP: 438 IU/L, AST: 653 IU/L, ALT: 666IU/L, total bilirubin: 2.3 mg/dL, INR 1.3, and ammonia: 43 mcmol/L. She was taken to the operating room for emergent cesarian delivery for concerns of AFLP. Further workup of the patient’s hypercalcemia, revealed a low normal PTH level of 11 pg/dL (normal 11-65 mg/dL), PTHrP level of &amp;lt;5 mg/dL, TSH of 1.37 uIU/ml, 25-OH vitamin D 55 ng/ml, and 1,25-OH vitamin D: 20 pg/ml. After delivery, the patient had alleviation of her symptoms and was kept on dextrose 5% with lactated ringers at 100 cc/h for a total of two days and had complete resolution of her hypercalcemia (corrected calcium of 10.2 mg/dL on discharge). The patient follows with endocrinology as an outpatient and since has had normal calcium levels. Discussion: Hypercalcemia in pregnancy is rare, only affecting 0.03% of women in the reproductive age group, with primary hyperparathyroidism being the most common cause. Hypercalcemia in pregnancy can often be missed due to the hemodilution of serum calcium in pregnancy and also the nonspecific symptoms present in pregnant patients. Our case describes a patient presentation of severe hypercalcemia with AFLP, who had rapid correction of her calcium levels after delivery. The exact mechanism of her severe hypercalcemia developed remains unclear, however, given its rapid resolution with delivery of the placenta potential etiologies include the AFLP itself or possibly the placenta contributing to hypercalcemia. Through this case report, we hope to highlight a possible association between AFLP and hypercalcemia. Presentation: Thursday, June 15, 2023

THU422 Laboratory Evaluation For Etiologies Of Secondary Osteoporosis

Abstract Disclosure: N. Shah: None. H. Galitzer: None. D. Sellmeyer: None. Data on the prevalence of laboratory abnormalities in individuals with osteoporosis is limited. The purpose of this study was to quantify the frequency of test results indicative of secondary osteoporosis in patients referred for skeletal fragility. A retrospective chart review was conducted on 653 consecutive patients referred for low bone density or fracture at Stanford Medical Center from October 2018 to December 2021. Patients were asked to complete a standardized set of laboratory tests including comprehensive metabolic panel, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), thyroid testing, complete blood count, phosphorus, celiac screening, and 24 hour urine calcium. Demographics, bone density, and laboratory results were extracted from the medical record; statistical analysis was performed using STATA. Subjects were 65 +/- 14 (mean+SD) years old. The majority were White (59%) or Asian (24%). Most (81%) were postmenopausal women, 10% were men &amp;gt;50 years old, 9% were men under 50 and premenopausal women. Of men over 50/postmenopausal women, 32% had osteopenia and 67% had osteoporosis. Among premenopausal women/men under age 50, 67% had Z-scores of −2 or less. Over 99% of serologic testing was completed; however urine calcium testing was completed in 46% of subjects. Overall, 66% of subjects had at least one lab abnormality. The most common abnormalities were of PTH and 25OHD with 20% of each test showing abnormal results. Anemia was present in 16% of subjects, alkaline phosphatase and TSH each were abnormal in approximately 11% of subjects; serum phosphorus and calcium each were abnormal in 5% and celiac testing was positive in 1.2% of subjects. Of 299 subjects who completed urine collections, 27% had hypocalciuria (&amp;lt;100 mg), 24% had hypercalciuria (&amp;gt;250 mg). There was no difference in the prevalence of laboratory abnormalities among individuals with Z-scores &amp;lt;=−2, p=0.14. CKD stage 3 or lower was present in 15% of subjects; this was not counted in the overall rates of lab abnormalities as it was anticipated this was known. The prevalence of any lab abnormality was higher (77% vs 64%) among subjects with eGFR&amp;lt;60, p=0.01. PTH was significantly higher in individuals with 25 OH vitamin D levels &amp;lt;30, p=0.006. This study reveals a high prevalence of laboratory abnormalities while screening for secondary osteoporosis. While urine collection can be cumbersome, the high prevalence (52%) of abnormal results demonstrates the importance of this test. The rate of celiac disease is low, however, these patients were asymptomatic other than low bone density and otherwise would be undiagnosed. Low Z-score did not predict lab abnormalities. Current guidelines do not provide consensus on laboratory testing for secondary etiologies of osteoporosis due to the paucity of data. This study highlights the importance of screening patients with metabolic bone disease to identify secondary contributors. Presentation: Thursday, June 15, 2023

SAT223 Persistent Hypocalcemia After Thyroidectomy

Abstract Disclosure: R. Subramani: None. F. Manas: None. A. Kauser: None. S. Yavuz: None. Introduction: Hypocalcemia is one of the serious complications after total thyroidectomy with a reported incidence of 27.4% (transient)and 12.1% (permanent) probably related to iatrogenic parathyroidectomy. Here we report a case of hypocalcemia after thyroidectomy in the setting of normal parathyroid hormone levels. Summary: A 42-year-old female with medical history of multinodular goiter s/p thyroidectomy 2019 on thyroid hormone replacement presented with hypocalcemia since 2021. During the first-year post thyroidectomy, patient was doing well until she acquired COVID-19 in 2020 and started developing symptoms of paresthesia, and muscle spasms. Other parameters such as phosphorus, and 25 OH vitamin D were normal. Despite being on a high-dose calcium supplement 1200 mg every hour for 10 times daily and calcitriol 0.75 mg twice daily, her calcium levels were persistently low ranging between 7.1 to 8 mg/dl and normal albumin levels of 3.9 and 4.3, but parathyroid level (PTH) remained normal (27.7-37.5). The patient was also symptomatic. She was later switched to liquid calcium 1000 mg 6 times daily for better absorption. It is noted that she had recurrent symptomatic hypocalcemia episodes requiring multiple emergency room (ER) visits during times of stress such as viral illness. The patient was treated with a trial of teriparatide, after which her symptoms improved and there were no further ER visits. Her calcium level increased from 7.4 to 8.4 and calcium supplement requirement reduced to 1200 mg daily. During recent outpatient visit, the patient had hypocalcemia episodes after missing teriparatide doses as expected. Conclusion: Despite our patient had normal PTH levels, the parathyroids glands did not respond appropriately to hypocalcemia. Promberger et al studied a case of eight patients with hypocalcemia with normal PTH following thyroidectomy. All these patients had normal PTH levels during post-op period, but persistently low and ionized calcium levels 12 months after surgery. This suggests during persistent hypocalcemia normal parathyroid levels may indicate an inadequate PTH response. In our case, developing hypocalcemia long after surgery and relation to COVID-19 infection may suggest autoimmune phenomenon as developing PTH-antibodies or receptor malfunction, theory yet to be investigated. In cases of severe symptomatic hypocalcemia requiring significant amount of calcium supplement PTH analogs are very effective treatment. Presentation: Saturday, June 17, 2023

SAT206 A Case Of Parathyroid Carcinoma Presenting As A Parathyroid Adenoma

Abstract Disclosure: P. Subarajan: None. A. Boutsicaris: None. C.A. Poku: None. N. Lopez: None. Distinguishing between parathyroid adenoma (PA) and parathyroid cancer (PC) in patients with primary hyperparathyroidism (PHPT) can be difficult to determine before pathology results. Estimates vary between studies, but roughly 85% of cases of PHPT are PAs. We present a case of a PC that presented clinically as a PA. A 59 year old female presented to Endocrinology for hypercalcemia that was incidentally noted to be 13.8 and 12.8 on initial recheck. Endocrinology completed a secondary workup of the hypercalcemia which noted a PTH of 147 in the setting of a calcium (Ca) of 12.6. Lab review showed that her corrected Ca had been elevated over the preceding 2 years. She had a replete 25-OH vitamin D of 43 and a GFR of 29. A neck ultrasound revealed a 2.1 cm mass suspicious for a parathyroid mass. A sestamibi scan was consistent with increased focal uptake at the inferior pole of the right thyroid lobe. She had renal dysfunction, hypercalcemia and newly diagnosed osteoporosis which prompted referral to endocrine surgery. Intraoperatively, an enlarged right inferior parathyroid gland and a large mass encompassing the inferior thyroid pole extending into the anterior mediastinum with lymphadenopathy were noted. En Bloc resection was completed and final pathology was consistent with high grade parathyroid carcinoma infiltrating the adjacent thyroid gland. Genetic testing for HPT-JT was negative and ultrasound monitoring has remained negative. PC is rare and typically has a clinical presentation and course that sets it apart from PA. The PTH is typically 3-10 times above the upper limit of normal in PC and only 1-2 times above the upper limit of normal in PA. As a result of the variation in PTH, serum Ca is more elevated in PC than PA. PC patients typically present with a parathyrotoxicosis that is profound. A palpable neck mass can be present in 40-70% of individuals with PC. Our patient had an equivocal presentation that appeared more consistent with PA, which can be problematic when deciding on the optimal surgical approach. Amino-PTH is hypersecreted in PC and reacts with 3rd generation PTH assays, but not second generation assays. Clinically, using a third/second generation PTH assay ratio &amp;gt;1 can support a possible clinical suspicion of PC over PA. En Bloc resection is the surgical approach of choice for suspected PC. En Bloc resection may not always be done for a patient with a presentation and evaluation consistent with PA: data shows that only 12.5% of PC patients underwent En Bloc resection, as opposed to 78.6% who underwent parathyroidectomy alone. This puts patients at risk of requiring repeat surgical intervention and poses a higher risk for recurrence. It brings to question whether every PA should be addressed with an En Bloc resection to avoid this inherent risk. This case adds to the literature of PC presenting as PA and supports the argument for standard En Bloc resection in all cases. Presentation: Saturday, June 17, 2023

FRI693 Pthrp Mediated Hypercalcemia In A Patient With Recurrent Hepatocellular Carcinoma

Abstract Disclosure: D. Bondarenko: None. M. Ahmad: None. M. Mack: None. P. Ucciferro: None. Background: Humoral hypercalcemia is seen in 30 percent of cancer patients, most commonly driven by parathyroid hormone related peptide (PTHrP) production, osteolytic cytokine production, and 1,25-OH vitamin D production. The most common malignancies associated with PTHrP mediated hypercalcemia are squamous cell carcinomas and breast cancer. Less often hepatocellular cancer presents with hypercalcemia. We describe the case of a patient presenting with hepatocellular carcinoma presenting with recurrent episodes of severe hypercalcemia due to excessive PTHrP production. Clinical Case: The patient was a 68-year-old male with a past medical history of recurrent hepatocellular carcinoma with liver transplant in the past and type 2 diabetes mellitus who presented to the emergency department (ED) for one day of altered mental status. The patient was noted to be extremely agitated and confused by his home health aide and EMS was called. In the ED the patient’s vital signs were as follows: blood pressure of 196/80 mmHg, heart rate of 82 beats per minute, respiratory rate of 18 breaths per minute and temperature of 36.6 degrees Celsius. Initial lab work showed: calcium 13.5 mg/dL, albumin 4.2 g/dL, ionized calcium of 1.63 mmol/L, creatinine 0.99 mg/dL (baseline 0.5 mg/dL), glucose of 438 mg/dL, bicarbonate 23 mmol/L, anion gap 19, and beta hydroxybutyrate 51 mg/dL. Hypercalcemia workup revealed a suppressed PTH of 5 pg/mL (normal 11-67 pg), normal 25-OH vitamin D 43.6 ng/ml (normal 30-100 ng/ml), normal 1,25-OH vitamin D 38 pg/ml (normal 18-72 pg/ml), and elevated PTHrp 36 pg/ml (normal 11-20 pg/ml). The patient was started on aggressive IV fluid resuscitation with normal saline, administered a one-time dose of zoledronic acid and administered a three-day course of calcitonin. For his significant hyperglycemia the patient was started on an insulin infusion and was eventually transitioned to his home basal bolus insulin regimen. On discharge, the patient was scheduled with his oncologist to begin denosumab as an outpatient; however, he chose a palliative approach due to the terminal nature of his disease and recurrent hospitalizations for hypercalcemia. Conclusion: Hypercalcemia of malignancy is common in many different carcinomas with squamous cell cancer, renal cell cancer, breast cancer and multiple myeloma being commonly associated with this phenomenon. Reports of hepatocellular carcinoma associated with hypercalcemia are less common and occur in only 4-8 % of cases. With this case report, we hope to highlight PTHrP as a potential mechanism of humoral hypercalcemia in patients with hepatocellular carcinoma and propose denosumab as a possible treatment for patients with refractory hypercalcemia of malignancy. Presentation: Friday, June 16, 2023