25-OH Vitamin Research Articles

Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis

Dysmetabolic conditions could drive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), increasing susceptibility to hepatocellular carcinoma (HCC). We therefore aimed to identify novel predictive biomarkers of HCC in patients with and without liver fibrosis. A total of 1,234 patients with putative metabolic conditions and NAFLD were consecutively assessed in our outpatient clinic. Clinical and biochemical data were recorded, and then liver ultrasonography was performed annually for 5 years to detect HCC onset. For the analysis, the population was first divided according to HCC diagnosis; then a further subdivision of those who did not develop HCC was performed based on the presence or absence of liver fibrosis at time0. Sixteen HCC cases were recorded in 5 years. None of our patients had been diagnosed with cirrhosis before HCC was detected. Compared to patients who did not develop HCC, those who did had higher liver transaminases and fibrosis scores at time 0 (p <0.001). In addition, they presented with increased glycated haemoglobin levels and lower 25-OH vitamin D levels (p <0.05). Intriguingly, patients with higher liver fibrosis scores who subsequently developed HCC had lower HDL-cholesterol (HDL-c) levels at time 0 (p <0.001). Furthermore, in the 484 patients presenting with lower HDL-c at baseline, we found that waist circumference, and then vitamin D and glycated haemoglobin levels, were significantly different in those who developed HCC, regardless of liver fibrosis (p <0.05). This study identifies HDL-c as a bona fide novel marker to predict HCC in patients with NAFLD. Increased waist circumference and deranged metabolic pathways represent additional predisposing factors among patients with low HDL-c, highlighting the importance of studying cholesterol metabolism and integrating clinical approaches with dietary regimens and a healthy lifestyle to prevent HCC. Visceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of "good" HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism

BackgroundIt has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. MethodsA total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. ResultsIn the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. ConclusionsVitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Follow-up of Interleukin 6 and Other Blood Markers during the Hospitalization of COVID-19 Patients: A Single-Center Study

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient’s status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia.

ODP079 BCG-Osis, a Rare Cause of 1,25 Hydroxy Vitamin D Mediated Hypercalcemia

Abstract Background Non-parathyroid hormone (PTH) mediated hypercalcemia is mostly related to malignancy and less commonly caused by granulomatous diseases. We report a rare case of severe hypercalcemia caused by systemic granulomatous disease after intravesical Bacillus Calmette-Guerin (BCG) treatment for bladder cancer (BCGosis). Clinical Case 74-year-old male with history of bladder cancer treated with intravesical BCG a year ago, was hospitalized with confusion, weakness, recurrent falls and polyuria for a few days. He had night sweats and 50 lb weight loss over 6 months. Lab evaluation showed hypercalcemia with calcium 10.9 mg/dL, albumin 3.6 g/dL, corrected calcium 11.2 mg/dL, PTH 12 pg/ml, and 25 OH vitamin D 44ng/ml. He had normal thyroid hormone levels, serum electrophoresis and PTHrP &amp;lt;2 pmol/L. CT chest/abdomen/pelvis without contrast revealed sub-cm pulmonary nodules and non-obstructive renal calculi and bone scan showed no evidence of osseous metastases. He was treated with intravenous (IV) hydration and pamidronate 60 mg infusion, and his corrected calcium improved to 9.7 mg/dL. He was admitted again 3 weeks later with hypercalcemia, calcium 11.9 mg/DL, albumin 3.2 g/dL, corrected calcium 12.5 mg/dL, 25 OH vitamin D 24 ng/ml, PTH 14.6 pg/ml, and PTHrP &amp;lt;2 pmol/L. He received IV hydration and zoledronic acid 4 mg infusion. 3 weeks later he was hospitalized for the third time for recurrent hypercalcemia and worsening renal failure, calcium 13.2, albumin 2.6 g/dL, corrected calcium 14.2 mg/dL, PTH 19.2 pg/ml. 1,25 OH vitamin D checked this time was elevated at 113 pg/mL. He received another infusion of zoledronic acid 4 mg infusion and 10 days later required denosumab 120 mg for resistant hypercalcemia. PET CT scan showed multiple hypermetabolic foci in right neck, right anterior 4th rib, scrotum, and around left kidney and aorta. He underwent biopsy of the right rib lesion which demonstrated + AFB on smear and histiocytic inflammation, which led to diagnosis of BCGosis, with subsequent cultures positive for Mycobacterium bovis. He was started on multi drug regimen with rifampin, isoniazid and ethambutol. Follow up labs at 4 weeks showed normalization of calcium 8.9 mg/dL, albumin 3.2 g/dL, corrected calcium 9.78 mg/dL, PTH 54 pg/ml and low 1,25 OH vitamin D 17 pg/mL. Calcium and 1,25 OH vitamin D levels were stable at 4 months follow up. Conclusion Intravesical BCG treatment can be associated with systemic reactions in 1- 5% of patients. Granulomas associated with disseminated BCG infection can lead to hypercalcemia due to increased 1-alpha-hydroxylase activity in macrophages, causing elevated 1,25 OH vitamin D levels. Therefore, evaluation of 1,25 OH vitamin D levels is critical to determine the etiology of hypercalcemia. Treatment of underlying BCGosis with anti-tuberculosis treatment is key in management of hypercalcemia along with supportive treatments that may include IV hydration, bisphosphonates and/or glucocorticoids. Presentation: No date and time listed

PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose

Abstract Introduction Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM. Case 2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml. On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium. Discussion HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF30 | PSAT178 Severe Hyperparathyroidism in a Newborn: Response to Cinacalcet

Abstract Background Neonatal severe hyperparathyroidism (NSHPT) is a rare potentially lethal disorder caused by inactivating mutations in the calcium sensing receptor (CASR) gene. In newborns it presents with multiple bone fractures often confused with forms of osteogenesis imperfecta. Diagnostic and therapeutic experience with this condition is limited, hence here we describe a term baby we identified and treated with this disorder. Case Description A 39-week-old Hispanic female, born small for gestational age (BW 2.38 kg) via vaginal delivery to a 33-year-old G3P2 healthy mother was noted to have relative asymmetry of the thighs/hips. X-rays revealed bone demineralization and multiple fractures including distal femur and proximal tibia bilaterally and rib fractures in various stages of healing. Initially, osteogenesis imperfecta was thought likely and Endocrinology was consulted. Laboratories showed hypercalcemia (calcium 12.1 mg/dL (normal 8.5-11.2), elevated serum PTH 439 pg/mL (12-72). Serum phosphorus (4.2 mg/dL), 25-OH Vitamin D (44 ng/mL) and alkaline phosphatase (232 IU/L) were normal; urine calcium/creatinine ratio was low (0.006 mg/mg). EKG showed non-specific T wave abnormalities and echocardiogram mild pulmonary hypertension. Neck ultrasound and sestamibi scan showed no parathyroid mass. She was placed on oxygen due to desaturations and had poor tone and suck. Father had documented hypercalcemia (calcium 12.6 mg/dL, PTH 53 pg/mL). Paternal aunt and grandmother also had history of hypercalcemia. Serum levels of calcium and PTH remained elevated for 2 weeks despite treatment with IV fluids and furosemide and a low calcium/vitamin D formula. On day 12 we began a trial of cinacalcet, a type 2 calcimimetic, at starting doses of 0.4 mg/kg/day divided BID orally. Over 4 days the patient showed a dramatic reduction in serum levels of calcium and PTH to 8.6 mg/dL and 24 pg/mL, respectively. Over time her clinical course improved with better tone and suck and normal oxygenation. Cinacalcet was titrated up to 2.3 mg/kg/day (2mg PO tid) and baby discharged on day 20. Gene sequencing revealed a known heterozygous pathogenic variant in an exon 4 hotspot of the CASR gene, c.658C&amp;gt;T (p.Arg220Trp), consistent with familial hypocalciuric hypercalcemia. Father was confirmed to have the same pathogenic variant as the child. She has now been followed for 6 months, all fractures are healing with persistently normal PTH and calcium levels. She is thriving, her development appears to be normal, able to eat orally, sit, track and smile. Conclusion Neonatal severe hyperparathyroidism can occur in infants who are heterozygous for a CASR mutation and can manifest as multiple congenital fractures. A family history of asymptomatic parental hypercalcemia/hyperparathyroidism and targeted gene sequencing can be diagnostic of NSHPT. Activators of the CASR are a promising therapy for heterozygous CASR loss-of-function pathogenic variants and can lead to reversal of skeletal demineralization and markedly improved clinical status. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

PSAT226 Management of a Patient with Primary Hyperparathyroidism by Discontinuation of Hydrochlorothiazide: Preventing the Need for Surgical Management

Abstract Introduction Recurrent or persistent primary hyperparathyroidism has been reported in 2-5% of patients after the initial operation. Reoperations have been associated with significant complications. The aim of this presentation is to highlight the importance of medical management prior to proceeding to surgery. Case presentation A 72-year-old man with a past medical history of coronary artery disease and asthma was found to have hypercalcemia and osteoporosis and was diagnosed with primary hyperparathyroidism in 2009. He had no family history of hypercalcemia. Three parathyroid glands were removed in 2010 and his parathyroid hormone normalized immediately after the surgery. About 10 years after the surgery, he developed hypertension and calcium-type kidney stones. He was treated with losartan 50 mg daily and hydrochlorothiazide 12.5 mg daily. One year later his calcium level was 11.1 mg/dL, parathyroid hormone (PTH) 70 pg/mL, 25-OH vitamin D level 44 ng/mL and creatinine was 0.8 mg/dL. A CT scan demonstrated a lesion measuring 1.3×1.1×1.6 cm which was suspicious for an ectopic parathyroid adenoma in the left ascending aorta. He was scheduled for surgical exploration and removal of the parathyroid adenoma for recurrence of primary hyperparathyroidism. Prior to the surgery, the patient was evaluated in our office for a second opinion. Physical exam and review of systems were unremarkable. Thyroid ultrasound showed a heterogeneous thyroid with no thyroid nodules or parathyroid adenoma. Adequate hydration was recommended and since his blood pressure was well-controlled, hydrochlorothiazide was discontinued. Surgery was canceled to confirm that the hypercalcemia was due to hydrochlorothiazide rather than hyperparathyroidism. After 4 months of follow-up, his blood pressure remained controlled on monotherapy with Losartan, and the repeat calcium level was 9.6 mg/dL with a PTH level of 44 pg/mL. Conclusion Post-surgical patients with a history of primary hyperparathyroidism, when presenting with hypercalcemia can get misdiagnosed as recurrent or persistent primary hyperparathyroidism; therefore, other causes of hypercalcemia including medications that may affect the calcium level and its metabolism should be considered and excluded prior to surgical management. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP100 Hypoparathyroidism in the Setting of COVID-19: Increasingly Common Phenomenon

Abstract 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.

ODP106 Mystery of the Calcium: A Case of Exclusive Cutaneous Sarcoidosis presenting with Symptomatic Hypercalcemia

Abstract The skin is the second most involved organ after the lung in sarcoidosis. It could be an early manifestation that may progress to systemic disease later. Exclusive cutaneous disease is more frequently seen in females. Specific lesions include erythema nodosum, skin plaques, subcutaneous nodules, maculopapular rashes, lupus pernio, scar lesions, and psoriasiform lesions. Most with cutaneous sarcoidosis need no treatment unless there is associated cosmetic disfigurement. We present a unique case of cutaneous sarcoidosis presenting with symptomatic hypercalcemia without systemic disease. A 75-year-old African American female was admitted with generalized weakness. She had no other symptoms. On arrival, she was bradycardic with other normal vitals. Physical examination was normal. EKG showed sinus bradycardia with RBBB. She was found to have AKI with creatinine of 4.3 mg/dL (0.6-1.3 mg/dL) and a corrected calcium of 12.2 mg/dL (8.6-10.2 mg/dL). TSH was 4.64 uIU/mL (0.35-5.50 uIU/mL). Chest X-ray showed no abnormalities. Renal ultrasound revealed bilateral medical renal disease, with several non-obstructing calculi in the right kidney. The patient was managed with intravenous fluids. Her creatinine improved to 3.1 mg/dL; however, the calcium remained elevated at 11.8 mg/dL. PTH was 31 pg/mL (12-88 pg/mL) and urine 24-hr calcium was elevated at 470 mg (35-250 mg). 25-OH vitamin D level was 40 ng/mL (30-100 ng/mL). With no response to intravenous hydration, IV bisphosphonates were initiated. Despite that, her calcium remained at 11.9 mg/dL. On obtaining a more detailed history, it was revealed that a skin punch biopsy performed six years prior showed sarcoid granulomatous dermatitis. The 1, 25 dihydroxy vitamin D was 93 pg/mL (20-79 pg/mL). The ACE level was high at 64 U/L (8-52 U/L). CT chest showed no evidence of granulomatous disease, including the absence of hilar adenopathy. The patient was started on prednisone 20 mg/day. Her calcium trended down to 10.7 mg/dL over the next three days. Although cutaneous sarcoidosis may not be life-threatening, it may have substantial psychological and social impacts. Hypercalcemia is a high prevailing complication of systemic sarcoidosis. It occurs due to the uncontrolled synthesis of 1,25-OH D3 by macrophages in the sarcoid granulomata. As a result, there is increased calcium absorption in the intestine and calcium resorption in the bone. Glucocorticosteroids act by inhibiting the 1alpha-hydroxylase activity of macrophages. Prednisone 20 to 40 mg/day followed by a taper is the recommended dose. Other medications that may be used include antimalarials, thalidomide, methotrexate, and other immunomodulatory agents. Hypercalcemia in a patient with cutaneous sarcoidosis and no pulmonary involvement is a rare presentation. It is essential to recognize that long-term follow-up is advised for those with cutaneous sarcoidosis, as some may develop systemic involvement subsequently. Presentation: No date and time listed

OR21-5 Hypocalciuria is Common and Associated with Delayed Parathyroidectomy in Patients with Primary Hyperparathyroidism

Abstract Background A 24-hour urine collection is routinely obtained in the workup of primary hyperparathyroidism (PHPT) to measure calcium and creatinine excretion, rule out familial hypocalciuric hypercalcemia, and guide diagnosis and management. Although hypercalciuria is expected and frequently observed in PHPT, hypocalciuria and/or a low urine calcium (uCa) to creatinine clearance ratio (UCCCR) may occur. Variables including race, age, renal function, and 25-OH vitamin D levels can affect urinary calcium excretion. Given the utility of obtaining urine calcium excretion in patients with PHPT, we performed a retrospective analysis on patients with PHPT to evaluate the effect of clinical variables on urinary calcium excretion, and to test the hypothesis that hypocalciuria may delay parathyroidectomy in PHPT. Methods We retrospectively reviewed charts of patients with PHPT with available 24-hour uCa who underwent successful parathyroidectomy at our institution between 2009 and 2021. We extracted available demographic, clinical, and laboratory data including first available uCa and creatinine excretion prior to parathyroidectomy, age, gender, ethnicity, BMI, eGFR, serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 24-hour sodium excretion. The association between these parameters and uCa and UCCR was assessed in univariate and multivariate models. We compared characteristics of PHPT patients with vs. without hypocalciuria, and duration between uCa measurement and parathyroidectomy. Results 643 PHPT patients were included in this analysis. 8.4% of patients had a 24-hr uCa excretion rate below 100mg/day, and 18.7% had a UCCR&amp;lt;1%.Compared to PHPT patients with UCCCR≥1%, those with UCCCR&amp;lt;1% had a significantly higher proportion of African Americans (22.2% vs 9.1%; p=0.0029), a lower mean serum calcium (p=0.0027), and 25-hydroxyvitamin D (p=0.035). In multivariate analysis, gender, race, serum calcium, serum 25-OH-vitamin D, and 24-hour urine sodium were all significant predictors of UCCCR. The UCCCR&amp;lt;1% group had a significantly longer median time from uCa measurement to parathyroidectomy [8.4 (Interquartile range IQR: 3.3-29.4) vs. 4.2 (IQR: 2.4-8.7) months, p&amp;lt;0.001).Compared to PHPT patients with 24-hr uCa≥100 mg/day, those with 24-hr uCa&amp;lt;100 mg/day had significantly lower mean serum calcium (p=0.002), eGFR (p&amp;lt;0.0001), urine sodium excretion (p=0.036), and significantly greater serum phosphorus (p=0.0085) and PTH (0.0078). In multivariate analysis, race, BMI, serum calcium, eGFR and urine sodium were all significant predictors of 24-hr uCa. The uCa&amp;lt;100 mg/day group had a significantly longer median time from uCa measurement to parathyroidectomy [9.7 (IQR: 3.3-32.2) vs. 4.2 (IQR: 2.4-8.8) months, p&amp;lt;0.001). Conclusions Although elevated uCa is used as a diagnostic marker and indication for parathyroidectomy in PHPT, hypocalciuria and UCCCR&amp;lt;1% are relatively common in PHPT patients, and associated with a significant delay in parathyroidectomy. Intrinsic (race, gender) and extrinsic (vitamin D status, renal function, sodium intake/excretion) factors are all determinants of calcium excretion in PHPT. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.

ODP068 A Case Report of Nivolumab Associated Hypercalcemia

Abstract Introduction Nivolumab is a human immunoglobulin G4 (IgG4) antibody which binds to programmed cell death receptor-1 (PD-1) and blocks the binding of PD-1 to either the PD-ligand 1 (PD-L1) or PD-L2 expressed on the surface of cancer cells. It has been approved for the treatment of melanoma, non-small cell lung cancer, renal cell carcinoma etc. Various endocrine immune-related adverse events including thyroiditis, hyper- and hypothyroidism, hypophysitis and type 1 diabetes has been described. We report a case of Nivolumab associated hypercalcemia. Case presentation 67-year-old female with history of CKD stage 3 with secondary hyperparathyroidism, melanoma of right ankle was admitted after one month of receiving the first dose of Nivolumab for her melanoma. She had altered mentation with elevated corrected calcium of 15.94(8.4-10.2) mg/dl. Prior calcium levels were in low to normal range, eGFR was 13, creatinine elevated at 3.4 (0.57-1.11) mg/dl, PTH 84 (10-65) pg/ml, 25 OH vitamin D 54 (30-74) ng/ml, Phosphorus normal, Magnesium normal, 1,25-OH vitamin D was elevated at 103(18-72) pg/ml, PTHrp normal, normal SPEP, normal TSH, no history of fractures, normal DXA, no history of kidney stones, not on any calcium supplements, not on thiazide or lithium. Chest x ray and NM full body PET CT did not show any evidence of granulomatous disease except for recurrence and metastasis of melanoma in right thigh, calf, and ankle. No family history of kidney stones or hypercalcemia. Patient was treated with IV fluids and Calcitonin. Her calcium quickly improved to 9.9 within 48 hours. Within 3 weeks of discharge, she was readmitted for elevated calcium of 14.4 mg/dl, creatinine 2.29 mg/dl, eGFR 21, PTH 96 pg/ml, Mg 1.8 (1.6-2.6) mg/dl. She was treated with IV fluids and calcitonin and calcium normalized within 48 hours. Parathyroid scan did not show any parathyroid adenoma. She was started on prednisone for possible Nivolumab associated immune adverse reaction. She was also briefly treated with cinacalcet which was discontinued. Prednisone was tapered and then stopped over the course of 6 weeks. Calcium remains normal. PTH remains slightly elevated which is thought to be due to secondary hyperparathyroidism from CKD. Normal cortisol level. Discussion This is likely a case of Nivolumab associated hypercalcemia given the onset soon after immunotherapy initiation and improvement with glucocorticoid therapy. Immunotherapy was not resumed after the first dose due to recurrent severe hypercalcemia. The patient is currently under surveillance for melanoma. Calcium level remains normal. Although it is rare, a few cases of Nivolumab associated hypercalcemia have been reported previously. Exact mechanism is not known but it has been speculated that macrophage activation by Nivolumab can cause increased level of 25(OH) D-hydroxylase with increased conversion of 25-OH vitamin D to 1,25-OH vitamin D resulting in calcitriol mediated hypercalcemia. Presentation: No date and time listed

ODP122 Recurrent Episodes of Hypercalcemia due to Disseminated Mycobacterium Avium Complex Infection-related Immune Reconstitution Inflammatory Syndrome

Abstract Introduction Immune reconstitution inflammatory syndrome (IRIS) may occur in patients with acquired immunodeficiency syndrome (AIDS) following initiation of antiretroviral therapy (ART) due to exacerbation of preexisting infectious process, such as disseminated mycobacterium avium complex (dMAC). This type of inflammatory process may be associated with granuloma formation and 1,25(OH) 2 vitamin D-mediated hypercalcemia. Hypercalcemia typically is controlled with a single dose of intravenous bisphosphonate or a two to four-week course of glucocorticoid, in addition to antibiotics for dMAC and ART. Here we present a case of IRIS-associated hypercalcemia related to dMAC resistant to intravenous bisphosphonate therapy and an extended glucocorticoid course. Case presentation A 30-year-old man with AIDS with CD4 count 4 cells/mm^3 (441-2,156) was admitted with subacute fevers, chills, and cough one month after starting ART. Cultures drawn during admission were positive for MAC and he was started on therapy for dMAC with ethambutol and azithromycin. Seven months after starting ART, he was readmitted with weakness and fatigue and found to have calcium 13.5 mg/dL (8.6-10.4), albumin 3.9 g/dL (3.9-5. 0), creatinine 1.40 mg/dL (0.6-1.3), CD4 count 80 cells/mm3. Further workup revealed intact PTH 2 pg/mL (11-51), 25-OH vitamin D 38 ng/mL (20-50), 1,25(OH) 2 vitamin D 171 pg/mL (19.9-79.3), PTHrP &amp;lt; 2. 0 pmol/L (0. 0-2.3), suggestive of PTH-independent hypercalcemia mediated by 1,25(OH) 2 vitamin D. CT scan of the chest showed multiple cavitary lesions, ground glass nodularity, and diffuse lymphadenopathy. He was treated with intravenous fluids, zoledronic acid 4mg, and continued ART and antibiotics for MAC. On discharge calcium was 9.5 mg/dL. He had recurrence of 1,25(OH) 2 vitamin D-mediated hypercalcemia (calcium 13.6mg/dL) 11 months after starting ART, which was controlled with intravenous fluid and prednisone 60mg tapered over 6 weeks. He then had recurrence of hypercalcemia 13 and 16 months after starting ART, each resolved with intravenous fluids and repeat prolonged prednisone courses. Testing for other infectious causes of granulomatous disease including Cryptococcus, Histoplasma, Mycoplasma tuberculosis was negative during multiple presentations. At 13 months, his CD4 count was 214 cells/mm^3 and repeat CT scan of the chest showed improvement in size of cavitary nodule and ground glass nodularity. Conclusion IRIS related to dMAC is an uncommon cause of 1,25(OH)2 vitamin D-mediated hypercalcemia. Multiple recurrences of hypercalcemia and the need for extended courses of glucocorticoid despite improvement of underlying infectious process has not previously been reported. Presentation: No date and time listed

RF30 | PSAT177 A Case of Hypercalcemia Related to Immune Checkpoint Inhibitor-Induced Sarcoidosis-like Granuloma

Abstract Background Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case. Clinical Case A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia. Conclusion Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

PSAT194 Prolonged Hypercalcemia after Calcium Sulfate Beads Use

Abstract Calcium sulfate beads (CSB) preparations are used for antibiotic release to prevent or treat periprosthetic infections. Transient hypercalcemia in the setting of CSB use have been reported, with most cases being mild. Here we present a case of prolonged hypercalcemia after the use of CSB A 92-year old man with history of CKD stage is admitted to the hospital after sustaining a fall. He underwent a right femur periprosthetic fracture repair. Intraoperatively, he received 30 cc of antibiotic impregnated calcium sulfate beads into the wound. Preoperative labs showed calcium of 9.8 mg/dl, albumin 3.6g/dL, with creatinine of 1.6 mg/dl. 48-hours post-operative, patient developed acute encephalopathy, with laboratory analysis showing a calcium corrected for albumin raising up to 13.2 mg/dL, and creatinine of 1.8 mg/dl in the following days. PTH levels, PTH-rp, 25-OH Vitamin D were normal. He had no history of calcium disorders, kidney stones or pathological fractures. He was started on gentle IV fluids with normal saline, and calcitonin weight based (4 iu/kg) every 12 hours for a total of 6 doses with no improvement of calcium levels. Since he continued with persistent hypercalcemia, we decided to give 1 dose of Zoledronic Acid IV. Patient mental status improved; and calcium levels normalized along with creatinine 11 days after Zoledronic acid. Hypercalcemia secondary to CSB is rare. The use of CSB implantation has increased by orthopedics in the last years. CSB releases 100% of its antibiotic load to improve antibiotic delivery for prevention and treatment of peri-prosthetic infections. There are only two studies evaluating the outcomes of CSB that reported hypercalcemia. In a prospective observational study involving 755 patients receiving CSB implantation, only 5.7% developed mild hypercalcemia, and 2 of them were symptomatic, requiring IV fluids and 1 dose of Bisphosphonates. Hypercalcemia can appear 1 day post-operatively and improve after 5 days. Infrequently, hypercalcemia can be moderate to severe causing symptoms as in our patient. It is important to keep in mind transient hypercalcemia with the use of CSB, especially in high-risk patients. Discussion should include alternate options to prevent peri-prosthetic infections and closer monitoring of calcium and creatinine within the first 24-48 hours of implantation. To our knowledge, this is the second case report of prolonged moderate to severe hypercalcemia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PMON316 Novel Mutation Causing Pseudohypoaldosteronism Type 1 and Transient Hypercalcemia: A Patient Report

Abstract Background Autosomal dominant pseudohypoaldosteronism Type 1 (PHA-1) is a salt-wasting syndrome due to mutation in the renal mineralocorticoid receptor. Here, we report an infant with a novel mutation in NR3C2 causing PHA and associated with transient hypercalcemia. Clinical Case An ex-28 weeks (birth weight 1.35 kg) male infant admitted to the NICU had increased urine output of 6 mL/kg/hr on days of life (DOL) 9-10. Initial laboratory tests showed hyponatremia (121-127 mEq/L), hyperkalemia (5.4-8.4 mEq/L), hypochloremia (89-94 mEq/L), and hypercalcemia (11.2-11.6 mg/dL). Weight had decreased 4% from birth. On exam he was normotensive with no midline defect or hyperpigmentation; he had palpable testes bilaterally and 2 cm penile length. Sodium chloride (NaCl) supplementation 2.5 mEq/day was started on DOL 10. State newborn screen 17-OHP levels were normal. His family history was unremarkable. To further investigate the hyponatremia and hyperkalemia, serum ACTH, cortisol, aldosterone, and renin were obtained. ACTH and cortisol were 33 pg/mL and 11.4 mcg/dL, respectively. While awaiting the results of the aldosterone and renin assays, fludrocortisone was started with minimal improvement in serum sodium and hypercalcemia worsening to 12.0 mg/dL. Laboratory tests obtained to investigate the hypercalcemia included phosphorus 5.5 mg/dL, hypercalciuria (urine calcium to creatinine ratio 0.4), 25-OH vitamin D 21.0 ng/mL (normal 30-100 ng/mL), and PTH 29 pg/mL (normal 10-65 pg/mL). PTH was inappropriately normal, concerning for primary hyperparathyroidism. While awaiting the aldosterone level, it was therefore recommended to decrease fludrocortisone dose. Plasma renin activity resulted at 319 ng/mL/hr (normal 2-37 ng/mL/hr) and aldosterone at 612 ng/dL (normal 5-90 ng/dL), suggesting a diagnosis of PHA. Fludrocortisone was discontinued and NaCl supplementation was increased. A heterozygous pathogenic variant, c.2457C&amp;gt;A (p.Tyr819Ter), was identified in the mineralocorticoid receptor gene, NR3C2, confirming the diagnosis of autosomal dominant PHA-1. This variant has not been previously reported but meets the American College of Medical Genetics and Genomics and the Association for Molecular Pathology's criteria for pathogenicity. At his outpatient follow up at 4 months, sodium was 134 mEq/L and calcium was 10.5 mg/dL. He was continued on 1.5 grams NaCl supplementation. Conclusion We report a patient with a novel mutation in the NR3C2 gene resulting in autosomal dominant PHA-1 and associated with transient hypercalcemia. Further exacerbation of hypercalcemia was seen with addition of fludrocortisone. We suspect the etiology of the transient hypercalcemia to be secondary to excess mineralocorticoids (exogenous or endogenous) that drives PTH to increase serum calcium levels, as previously described by Vaidya et al. (1) Reference (1) Vaidya A, Brown JM, Williams JS. The renin-angiotensin-aldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015 Sep;29(9): 515-21. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP069 A Clinical audit on the diagnosis and management of Vitamin D Deficiency at Scarborough General Hospital, United Kingdom

Abstract 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

PSAT198 Atypical Parathyroid Adenoma is an Unusual Cause of Primary Hyperparathyroidism

Abstract Background Atypical parathyroid adenomas (APA) are considered tumors of uncertain malignant potential and have a biochemical and clinical phenotype that is generally more aggressive than typical parathyroid adenomas (PA). Low incidence as an etiology of primary hyperparathyroidism (PHPT) presents a challenge in understanding the pathological features and natural history of APA. We present a case of PHPT due to an APA and review the published literature for these tumors. Case A 37 year-old male was referred for evaluation of hypercalcemia, with serum calcium level 13.6 mg/dL (8.6-10.3). Repeat serum calcium measurement was 12.7 mg/dL, and two measurements of intact PTH were 870 pg/mL and 919 pg/mL (12-88), respectively. The patient's laboratories raised concern for parathyroid carcinoma (PC), but there was no palpable neck mass and no enlarged parathyroid glands were visualized on ultrasonography. Parathyroid scintigraphy was notable for faint but persistent Tc-99 m sestamibi uptake in the left inferior neck. Additional preoperative evaluation revealed significantly reduced bone mineral density in the distal third of the radius (0.638 g/cm2, Z-score -3.2), silent nephrolithiasis of the right kidney, and vitamin D deficiency (25-OH vitamin D 13.4 ng/dL, 30-100). An unequivocally enlarged (175 mg, 2.5 cm in largest diameter) left inferior parathyroid gland was removed, with the remaining glands unremarkable by inspection. Extensive nuclear atypia and cellular pleomorphism indicated an APA, and invasive features of PC were absent. One month after surgery, serum calcium improved to 10.2 mg/dL and intact PTH was 40 pg/mL. Conclusions APA account for 1-2% of PHPT cases. This patient's case has several features that distinguish it from a PA including degrees of preoperative hypercalcemia and intact PTH elevation, low vitamin D level, significantly reduced bone density in the distal third of the radius, nephrolithiasis, relatively young age, and male gender. Fibrous bands, pseudocapsular invasion, and trabecular growth pattern are the most common histologic features of APA, but nuclear atypia and cellular pleomorphism are well established diagnostic criteria. APA may be biochemically similar to PC but are distinguished from PC by the absence of gross invasion into adjacent anatomic structures, distant metastases, and vascular or perineural invasion. Additionally, CDC73 mutations are present in nearly all cases of PC but not in APA. Over 90% of patients with APA are successfully treated by parathyroidectomy. Careful follow up of APA patients is recommended, though there are no specific guidelines regarding a minimum satisfactory duration of postsurgical monitoring. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT209 A Remission of Hypocalcemia in Idiopathic Hypoparathyroidism

Abstract Background Acquired hypoparathyroidism is known to be transient when caused by surgical trauma but unlikely in idiopathic etiology. Herein we describe a unique presentation of idiopathic hypoparathyroidism that was diagnosed in early adolescence and remitted in adulthood. Clinical Case A male patient was diagnosed with idiopathic hypoparathyroidism at 13 years old after presenting with severe hypocalcemia resulting in generalized convulsive seizure. At diagnosis, his corrected calcium (cCa) was 6.7 (8.5-10.2 mg/dL) and PTH was 8.5 (15-65 pg/mL). Patient was noted to have oral candidiasis raising concerns for autoimmune regulator mutations associated with autoimmune polyendocrinopathy. Adrenal function was normal. Genetic testing was not done due to cost. Calcium citrate of 500 mg twice daily and calcitriol, gradually increased to 1.5 mcg daily, were initiated with normalization of calcium level. At age 24, he presented with altered mental status and was admitted with hypercalcemia and subarachnoid hemorrhage. He had cCa of 12.6 compared with previous calcium levels ∼ 7 (8.5-10.2 mg/dL), ionized calcium of 1.57 mmol/L, magnesium of 1.8 (1.7-2.3mg/dL), hypophosphatemia of 0.4 (2.7-4.8 mg/dL) and undetectable PTH. Further testing showed AKI with creatinine of 2.1, from baseline of 0.8 (0.7-1.22 mg/dL). Vitamin D 25 OH and 1,25 dihydroxy vitamin D, ACE level and PTHrP were all unremarkable. Workup for multiple myeloma was negative. Adrenal and thyroid function tests were normal. CT brain showed diffuse subarachnoid blood with CTA showing an elongated saccular aneurysm measuring 2.57×1.72×1.85 mm.Hypercalcemia and AKI resolved with hydration. Interestingly, corrected calcium remained in the low-normal range between 8.6 - 8.8 (8.5-10.2 mg/dL), throughout 10 days of hospitalization despite holding all calcium citrate and calcitriol supplements, which were also held on discharge. PTH level prior to discharge was 7 (15-65 pg/mL) with cCa of 9.1 and magnesium of 1.7. At one week follow up, a reduced dose of calcium citrate of 250 mg twice a day and calcitriol 0.5 mcg daily were resumed which resulted in recurrent hypercalcemia and AKI with normalization by holding treatment. Repeated testing after one month showed cCa of 8.6, creatinine of 1.3, PTH of 17, magnesium of 1.7, and 25 OH vitamin D of 27.2 (31-80 ng/mL). Calcium citrate of 250 mg daily along with weekly ergocalciferol of 50,000 units and Magnesium Oxide 400 mg TID were initiated. Testing 8 months after the hospitalization revealed cCa of 8.6, creatinine of 1.2, magnesium of 1.6, and a low-normal PTH of 18 which was the highest value ever recorded for this patient. Conclusion To our knowledge, this is the second reported case of spontaneous remission of idiopathic hypoparathyroidism in adulthood. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT222 Muscle Weakness, Bone Pain, and Stress Fractures: When a Fracture is NOT JUST a Fracture: A Case Report

Abstract Case A previously healthy 46-year-old male presented to orthopedic clinic with bilateral hip pain, and progressive weakness without history of trauma requiring cane for ambulation. X-ray and MRI evaluation revealed stress fractures of left subtrochanteric femur and right basicervical femoral neck, both requiring surgery. In hospital blood work revealed elevated total alkaline phosphatase 167 units/L, mild hypocalcemia 8.5 mg/dL, and low 25-hydroxy Vitamin D 18 ng/mL. The patient was started on calcium/vitamin D supplements upon discharge. Initial endocrinology outpatient work-up revealed low phosphorus level of 2.1 mg/dl and low 1, 25 OH vitamin D of 5.9 pg/ml (19.9–79.3). Bone mineral density revealed normal spine bone density, and 1/3 radius osteopenia (T score -1.1). Physical exam revealed profound proximal weakness with inability to rise independently from sitting position. Follow-up of low phosphorous level demonstrated an elevated FGF-23 level of 186 RU/mL (normal &amp;lt; 180) and elevated fractional excretion of phosphorus 16% (expect &amp;lt; 5% with hypophosphatemia), indicating inappropriate renal phosphate wasting. The patient was started on Calcitriol and phosphorus. Before above evaluation was completed the patient had an ED visit with complaint of small mass just below left knee associated with mild pain and warmth. Ultrasound and MRI showed a complex cyst which was aspirated and showed cystic appearing mass suggestive of hematoma. This was treated with antibiotic course. Due to suspicion of tumor-induced osteomalacia, octreotide scan (Indium-111 pentetreotide) performed showed focal increased activity in the medial left knee. MRI showed a 26 mm cystic lesion within the subcutaneous tissue along the inferomedial aspect of the left knee, which correlated with the site of radiotracer uptake on the octreotide scan. The patient underwent left knee soft tissue tumor resection, and pathology demonstrated phosphaturic mesenchymal tumor. Follow-up several weeks postoperatively showed normalization of phosphorus and FGF-23 level. The patient's mobility and weakness improved significantly within a few months. Discussion Tumor-induced osteomalacia is a rare paraneoplastic condition characterized by chronic hypophosphatemia secondary to excessive tumoral FGF 23 production. Typical presenting symptoms are profound muscle weakness, bone pain, and fractures. Diagnosis is often delayed for several years, as phosphorus levels are not included in a routine metabolic panel. Considering high morbidity of this condition including significant mobility limitation requiring use of assistive devices, healthcare provider vigilance is paramount as this condition is potentially curable if the offending tumor is detectable and amenable to surgical resection. This case illustrates the importance of consideration of an underlying metabolic bone disease in patients with unexplained atraumatic fractures and hypophosphatemia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT130 Hypercalcemia In Pregnancy Due To CYP24A1 Mutation

Abstract Background The active form of vitamin D (1,25 OH2 vitamin D) is catabolized by a key enzyme 1,25 OH vitamin D-24 hydroxylase, which is encoded by the CYP24A1 gene. Loss of function mutation in the CYP24A1 leads to elevated levels of active vitamin D, causing PTH independent hypercalcemia with nephrolithiasis and nephrocalcinosis. Two phenotypic variants have been identified: idiopathic infantile hypercalcemia, which is a more severe form presenting in infancy, and a milder form with onset in adulthood as is this case. Pregnancy is known to initiate or worsen the hypercalcemia. Clinical Case A 27-year-old woman presented at 11 weeks gestation with hyperemesis, noted to have hypercalcemia calcium 15.7mg/dl (8.2 to 10.1 pg/ml), low PTH 2pg/ml (24 -85 pg/ml) with high serum 1,25 OHD 309pg/ml (nl 19.9-79.3 pg/ml). She had low PTHrp, normal ACE level, and negative TB testing. Pre-pregnancy calcium was normal (9.8mg/dl). She had a history of hypercalcemia in previous pregnancy (Calcium 13mg/dl) that ended in IUFD. Family history revealed nephrolithiasis in her sister, mother, and paternal aunt as well as a consanguineous marriage in our patient and her parents. Vitamin D metabolites evaluated via liquid chromatography showed low serum 24,25(OH)2D (0.29ng/ml nl N/A) and elevated 25OHD 138 ng/mL (20-80 ng/ml). Ratio of 25 (OH) Vit D to 24,25(OH)2D was 475.86 (values &amp;gt;80 indicate probable bi-allelic CYP24A1 deletion or mutation. Genetic test pending. Conclusion This case highlights the fact that patients with 24 hydroxylase deficiency may be normocalcemic with hypercalcemia unveiled during pregnancy due to increased 1alpha hydroxylase production by the placenta and kidneys as well as intake of prenatal vitamins containing calciferol. An index of suspicion for CYP24A1 mutation is needed in patients with high active vitamin D metabolites, high or normal calcium, low PTH, family history of kidney stones or worsening hypercalcemia in pregnancy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.