Recurrent Hypercalcemia Research Articles

Recurrent Hypercalcemia in a Patient with Hodgkin Lymphoma with Concurrent Elevated Parathyroid Hormone-Related Peptide (PTHrP) and Vitamin D

Recurrent Hypercalcemia in a Patient with Hodgkin Lymphoma with Concurrent Elevated Parathyroid Hormone-Related Peptide (PTHrP) and Vitamin D

Muscle-Limited Sarcoidosis Presenting as Recurrent Hypercalcemia of Unknown Origin

Muscle-Limited Sarcoidosis Presenting as Recurrent Hypercalcemia of Unknown Origin

6859 Recurrent Hypercalcemia Due to Prolonged Immobilization After a Profound Vascular Event

6859 Recurrent Hypercalcemia Due to Prolonged Immobilization After a Profound Vascular Event

#2296 Time to get calciphylaxis on clinicians’ RaDaR?—a multicentre case series

Abstract Background and Aims Calciphylaxis is a rare, severe complication of chronic kidney disease mineral bone disorder. It is hosphorzed by arteriolar calcification of the subcutaneous fat and dermis, and associated with a mortality rate of approximately 50% within a year of diagnosis. The reported prevalence of calciphylaxis in dialysis patients ranges from 1–4%. Between March 2012 and March 2020 the UK calciphylaxis study (UKCS) recruited 139 patients from 36 enrolled renal centres; an average of 1 case every 2.6 years per centre. The multicentre case series presented here includes patients from two NHS Hospital Trusts in the UK. The aim is to raise awareness of i) calciphylaxis and possible risk factors and ii) the role of registry data in rare kidney diseases. Method Patients were included if they had a diagnosis of calciphylaxis between 01.02.2020 and 01.02.2022. Data regarding demographics, dialysis modality, BMI, medications, and mineral bone parameters were collected from clinical databases. A representative sample of results was recorded from initiation of renal replacement therapy through to diagnosis of calciphylaxis. Data regarding calciphylaxis lesions, treatments and current vital status are hosphorz. Results 17 patients with end stage kidney failure (ESKF) and clinical features of calciphylaxis were included; 8 of 17 (47%) had a skin biopsy of which 6 reported evidence of calcification. Median age was 57 years (IQR: 50-74), BMI 26.8 kg/m2 (IQR: 22.9-31.1), 100% were white, 53% female and 59% had diabetes. Median time from onset of ESKF to calciphylaxis diagnosis was 5.5 years (IQR: 1-16). 53% (9 of 17) had history of recurrent hypercalcaemia (corrected calcium >2.55 mmol/L) and 82% (14 of 17) recurrent hyperphosphatemia (phosphate >1.5 mmol/L). 41% (7 of 17) had refractory secondary hyperparathyroidism. Warfarin therapy exposure was recorded in 47% (8 of 17) patients; a finding consistent with the literature. 76% (13 of 17) had received active vitamin D and 76% (13 of 17) a calcium-based phosphate binder. 76% (13 of 17) had lower leg lesions; 2 of whom also had upper leg lesions. 1 patient had a thigh lesion and 2 patients had an abdominal wound. Median follow up time was 8.5 months (range 1-24). 9 of the 17 patients remain alive, of whom lesions have completely healed in 6 patients. All patients received sodium thiosulphate and 1 (transplant patient) received hyperbaric oxygen therapy and sodium thiosulphate. Only 1 patient has been enrolled into the UK registry of rare kidney diseases (RaDaR). Conclusion Calciphylaxis is a devastating condition for which there are no proven treatments. In this case series a history of hyperphosphataemia, calcium-based binder, alfacalcidol, and warfarin use were common. It remains unknown why some patients develop calciphylaxis and others do not. National registry data, such as RaDaR, plays a crucial role in furthering knowledge and understanding of rare diseases; it helps to determine calciphylaxis incidence, and inform possible prevention and treatment strategies. Yet, in reality, few patients maybe being recruited into RaDaR. The opportunity exists for an international calciphylaxis registry; for this to offer maximum impact individual countries need to explore, and where possible address, barriers to recruitment.

SAT240 Recurrent Hypercalcemia Due To 1,25 Dihydroxy Vitamin D Elevation Of Unclear Etiology

Abstract Disclosure: A. Javvaji: None. C. Anastasopoulou: None. Introduction: Recurrent Hypercalcemia is common with primary hyperparathyroidism and malignancy accounting for 90% of cases. Extra renal activation of 1α-hydroxylase with subsequent elevation of 1,25 dihydroxy vitamin D is a relatively uncommon cause of hypercalcemia. Herein, we report an unusual case of recurrent hypercalcemia due to elevated 1,25 dihydroxy vitamin D of unclear etiology, resistant to therapy with denosumab or bisphosphonate that responded to glucocorticoid therapy. Case Presentation: A 68 year old female was admitted to the hospital for worsening calcium with symptoms of polyuria and increased thirst. Review of systems and physical examination were otherwise unremarkable. Initial work-up demonstrated calcium level of 11.7mg/dL (8.7-10.3), creatinine 2.58 mg/dL (0.57-1), PTH 8pg/mL (15-65), Kappa/Lamba ratio 1.82 (0.26-1.6), PTHrP 11pg/mL (11-20), 25 (OH) Vitamin D 14ng/mL (30-100), 24,25 Dihydroxy Vitamin D ratio 25.81 (<25). Bone marrow biopsy, kidney biopsy, and myeloma work up were all unremarkable. Imaging studies including whole body CT and PET CT were also unremarkable. In the acute phase patient was treated with zoledronic acid and later denosumab with only temporary decrease in calcium levels. Ultimately, she responded well to prednisone therapy. Further work-up for finding the underlying cause of elevated 1,25 dihydroxy vitamin D remains ongoing. Discussion: Elevated 1,25 dihydroxy vitamin D level in granulomatous, neoplastic, and certain unusual diseases is well recognized as a cause of hypercalcemia. These levels may be exacerbated by increased intake of calcitriol, or by extra-renal production in granulomatous and lymphoproliferative diseases. Other rare causes of elevated 1,25 dihydroxy vitamin D include granulomatosis with polyangiitis, cat scratch fever, talc granulomatosis, Crohn’s disease, silicone granulomatosis. Patients with all these diseases respond well to steroids and that was another sign that further work-up to find the source of the elevated 1,25 dihydroxy vitamin D in our case is essential. Conclusion: In patients with recurrent hypercalcemia and elevated 1,25 dihydroxy vitamin D levels, a complete work-up for underlying malignancy, granulomatous or other unusual diseases is indicated. Glucocorticoid therapy is the most effective way to control the hypercalcemia related to increased 1,25 dihydroxy vitamin D even in the long-term phase, especially until the main cause of the problem is identified and treated appropriately. Presentation: Saturday, June 17, 2023

SAT207 Parathyroid Carcinoma: A Case Report

Abstract Disclosure: K.T. Sy: None. Background: Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of causes of primary hyperparathyroidism. Case reports have mentioned of parathyroid carcinoma arising in patients with prior neck irradiation, in secondary and tertiary hyperparathyroidism and in patients with history of thyroid cancer and parathyroid adenoma. However, none of these reported associations have been completely established. Clinical Case: The is a case of a 59-year old male presenting with hypercalcemia. He was diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma, underwent parathyroidectomy with resolution of the hypercalcemia. Six years later, patient had recurrence of hypercalcemia with elevated PTH levels. Parathyroid imaging revealed a mild sestamibi-avid focus in the left retrosternal region, suggestive of an ectopic parathyroid gland and radio-guided neck exploration was done with excision of lesion. Histopathological report revealed parathyroid carcinoma. Two years later, there was recurrence of parathyroid carcinoma but mediastinal exploration revealed no lesions consistent with parathyroid carcinoma. Hypercalcemia with hyperparathyroidism persisted, and cinacalet was started but the patient could not tolerate the nausea associated with the medication. Repeat parathyroid imaging revealed sestamibi-avid lesions in the right retroclavicular, left prevascular/retrosternal, and a left paratracheal areas. Surgical exploration was offered but the patient refused. The patient also developed hypertension and low bone density was noted on dual X-ray absorptiometry (DXA) scan. He was started on denosumab 60 mg subcutaneously every 6 months, which was increased to 60mg every month and then 120mg every month to maintain normal calcium levels. The patient also developed chronic kidney disease, eventually requiring hemodialysis for elevated creatinine levels and hypercalcemic crisis. Soon after hemodialysis was started, the patient had a myocardial infarction and eventually expired. Conclusion: Complete surgical resection is the primary mode of therapy in parathyroid carcinoma, although hypercalcemia is the main cause of morbidity and mortality, rather than the tumor burden. The adjuvant use of radiotherapy and chemotherapy are still controversial. Some studies have shown that long term survival is favorable, but recurrences are frequent and patients tend to live a life filled with long-term follow up, multiple laboratory exams and imaging, hospitalizations and frequent reoperations. Mortality is usually due to uncontrollable hypercalcemia, leading to renal failure and cardiac arrhythmias. Presentation: Saturday, June 17, 2023

SAT209 Metastatic Parathyroid Carcinoma And The Challenge Of Maintaining Calcium Balance

Abstract Disclosure: K.M. Tuna: None. S. Badour: None. E.P. Monsour: None. G. Acosta Garcia: None. D. Barb: None. Background: Parathyroid carcinoma is a rare malignancy representing less than 1% of all parathyroid disorders. Presentation is significant for highly elevated calcium (Ca) and parathyroid hormone (PTH) levels, and usually a palpable neck mass (>3cm). Diagnosis is often made after surgery based on histopathology findings. The primary treatment modality remains surgical, but there is no effective approach for metastatic disease. Case presentation: A 51-year-old woman initially presented with multinodular goiter and compressive symptoms in 2008. Workup showed an elevated Ca of 14.4 mg/dl (normal 8.4-10.2 mg/dl) and PTH of 502 pg/ml (normal 12-88 pg/ml) while albumin 4.3 g/dl (normal 3.5-5.2 g/dl) and normal thyroid function tests. Radioactive Iodine uptake scan showed a 4.4 cm cold nodule on the right inferior pole. Sestamibi scan showed increased left upper pole activity. The patient underwent total thyroidectomy with surgical exploration for parathyroid adenoma. Pathology showed right intrathyroidal parathyroid carcinoma with lymphovascular invasion. The patient was lost to follow-up until 2022 when she was admitted with severe hypercalcemic crisis (Ca 15.8 mg/dl, Albumin 3.9 g/dl, and PTH 805 pg/ml). The patient was treated with IV fluids, calcitonin, and multiple rounds of bisphosphonates, and was then maintained on high-dose cinacalcet due to refractory and recurrent hypercalcemia. Repeat Sestamibi and neck US were unremarkable, although CT chest showed a 1.3 cm nodule in the right lower lung lobe. This was not FDG- nor DOTATATE-avid on PET-CT. The patient underwent laparoscopic wedge resection of the right lung nodule, and the pathology was consistent with metastatic parathyroid carcinoma. Her Ca and PTH levels normalized immediately after surgery (PTH decreased from 883 to 27 pg/ml) suggesting possible remission. Prior to discharge, she was started on oral calcium and vitamin D due to dropping Ca levels and clinical signs of hungry bone syndrome. She was readmitted one month later for preexistent heart failure exacerbation and declining renal function. Her PTH was noted to be elevated again, although Ca remained normal, raising concern for recurrent or persistent disease. However, the patient’s renal impairment and lung effusion limited further imaging. Ca and PTH were monitored frequently during hospitalization and weekly after discharge. PTH levels peaked at 634 pg/ml and then dropped to 127 pg/ml without intervention. Ca remained in the normal range while on calcium citrate and calcitriol. Conclusion: Treatment of metastatic parathyroid carcinoma remains a challenge. Mortality is secondary to complications of hypercalcemia; therefore, controlling calcium levels should be the main therapeutic goal. Hungry bone syndrome should be considered after surgery. Metastatic disease may occur even after 20 years; thus, lifelong close monitoring is indicated. Presentation: Saturday, June 17, 2023

#3154 MALIGNANT HYPERCALCEMIA IN A CASE OF SMALL BOWEL GASTROINTESTINAL STROMAL TUMOUR

Abstract Background and Aims Malignant hypercalcemia is the most common cause of hypercalcemia, occurring in 30% of cancer patients and rendering a poor prognosis. Most cases have a humoral cause, the majority mediated by parathyroid hormone related peptide (PTHrP), rarely by 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and very rarely by parathyroid hormone (PTH) ectopic production; other cases are due to local osteolysis. In the literature, there are only 5 reported cases of hypercalcemia associated to gastrointestinal stromal tumour (GIST), only 2 of them due to 1,25(OH)2D overproduction. Method Case report. Results Sixty-two years-old male with small bowel GIST diagnosed in 2014, subjected to enterectomy and on tyrosine kinase inhibitor (TKI) since 2017. TKI was changed from imatinib to sunitinib 25mg since August 2020 to the present date due to disease progression with liver metastasis. In March 2022, a PET scan showed no bone or soft tissue metastasis and there was a finding of right ureteral lithiasis with asymptomatic mild pyelocaliceal dilation. The patient had also subclinical hypothyroidism and several episodes of acute kidney injury (AKI) associated with hypercalcemia and hyperphosphatemia managed in outpatient clinic. He did not take any other medication besides the TKI. In April 2022, symptoms of disequilibrium, confusion, asthenia, and anorexia drove the patient to the Oncology Department. At physical examination the patient had an ECOG 3, was disoriented, cachectic and dehydrated, with no other noticeable findings. Blood lab tests showed a serum creatinine (sCr) of 2,86 mg/dL (baseline 1,10 mg/dL, estimated glomerular filtration rate of 72 mL/min/1,73 m2), a corrected serum total calcium (sCa) of 16,6 mg/dL and a normal serum phosphate of 4,0 mg/dL. The patient was admitted in the oncology ward with the collaboration of the nephrology department and was started on fluid therapy with 3000–4000cc NaCl 0,9%/day for a target urinary output of 75–200 mL/h. Hypercalcemia work-up showed low PTH of 8,8 pg/dL (reference range: 12–65 pg/dL). Measurement of PTHrP and 1,25(OH)2D were requested but took longer. After 3 days, despite the improvement of both sCr (2,23 mg/dL) and sCa (13,6 mg/dL), zoledronic acid was started. Results revealed an increased 1,25(OH)2D of 309 pg/dL (reference range: 10,9-79,3 pg/dL) and negative PTHrP. At the 6th day, a clear improvement of analytical (sCr 1,60 mg/dL; sCa 11,9 mg/dL) and clinical status, so the patient was discharged. The diagnosis was GIST 1,25(OH)2D overproduction causing malignant hypercalcemia and prednisolone on 20mg id was started. In June 2022, the patient had tumour progression, presenting lethargic, disoriented, and dehydrated; blood lab results showed AKI (sCr 1,97 mg/dL) and worsening hypercalcemia (sCa 14,7 mg/dL). He was admitted for fluid therapy and bisphosphonates but, even though there was a recovery of the hypercalcemia and renal function, the patient's clinical status got worse and he had a fatal outcome in the following days. Conclusion Malignant hypercalcemia caused by GIST 1,25(OH)2D overproduction is a rare condition. The work-up of an oncological patient with ureteral lithiasis and recurrent hypercalcemia should prompt us to a more in-depth investigation.

Steroid responsive idiopathic calcitriol induced hypercalcemia: a case report and review of the literature

BackgroundIdiopathic Calcitriol Induced Hypercalcemia is a rare cause of a common condition of hypercalcemia. Hypercalcemia is most commonly the result of hyperparathyroidism and together with hypercalcemia of malignancy accounts for over 95% of cases. Idiopathic Calcitriol Induced Hypercalcemia can mimic hypercalcemia secondary to granulomatous diseases like sarcoidosis, but with apparent absences of both imaging and physical exam findings consistent with the disease. We report here a 51-year-old man who presented with recurrent nephrolithiasis, hypercalcemia, and acute kidney injury.Case presentationA 51-year-old man presented with severe back pain and mild hematuria. He had a history of recurrent nephrolithiasis over the course of a 15-year period. On presentation his calcium was elevated at 13.4 mg/dL, creatinine was 3.1 mg/dL (from baseline of 1.2), and his PTH was reduced at 5 pg/mL. CT abdomen and pelvis showed acute nephrolithiasis which was managed medically. Work up for the hypercalcemia included an SPEP which was normal, Vit D,1,25 (OH)2 was elevated at 80.4 pg/mL, CT chest showed no evidence of sarcoidosis. Management with 10 mg prednisone showed marked improvement in the hypercalcemia and he no longer had any symptoms of hypercalcemia.ConclusionIdiopathic Calcitriol Induced Hypercalcemia is a rare cause of hypercalcemia. All reported cases benefit from more intensive long-term immunosuppression. This report helps consolidate the diagnosis of Idiopathic Calcitriol Induced Hypercalcemia and encourages researchers to better investigate its underlying pathogenesis.

The Case | A 48-year-old man with recurrent hypercalcemia and uremia after parathyroidectomy

The Case | A 48-year-old man with recurrent hypercalcemia and uremia after parathyroidectomy

Persistent and Recurrent Primary Hyperparathyroidism: Etiological Factors and Pre-Operative Evaluation.

Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia and currently the only definitive treatment is surgery. Although the success rate of parathyroidectomy is over 95% in experienced centers, surgical failure is the most common complication today. Persistent HPT (perHPT) is defined as persistence of hypercalcemia after parathyroidectomy or recurrence of hypercalcemia within the first 6 months, and recurrence of hypercalcemia after a normocalcemic period of more than 6 months is defined as recurrent HPT (recHPT). In the literature, perHPT is reported to be 2-22%, and the rate of recHPT is 1-15%. perHPT is often associated with misdiagnosed pathology or inadequate resection of hyperfunctioning parathyroid tissue, recHPT is associated with newly developing pathology from potentially pathologically natural tissue left in situ at the initial surgery. In the pre-operative evaluation, the initial diagnosis of pHPT and the diagnosis of perHPT or rec HPT should be confirmed in patients who are evaluated with a pre-diagnosis (suspect) of perHPT and recHPT. Surgery is recommended if it meets any of the recommendations in surgical guidelines, as in patients with pHPT, and there are no surgical contraindications. The first preoperative localization studies, surgical notes, operation drawings, if any, intraoperative PTH results, pathological results, and post-operative biochemical results of these patients should be examined. Localization studies with preoperative imaging methods should be performed in all patients with perHPT and recHPT with a confirmed diagnosis and surgical indication. The first-stage imaging methods are ultrasonography and Tc99m sestamibi single photon tomography Tc99mMIBI SPECT or hybrid imaging method, which is combined with both single-photon emission computed tomography and computed tomography (SPECT/CT). The combination of USG and sestamibi scintigraphy increases the localization of the pathological gland. In the secondary stage, Four-Dimensional computer tomography (4D-CT) or dynamic 4-dimensional Magnetic Resonance Imaging (4D-MRI) can be applied. It is focused on as a secondary stage imaging method, especially when the lesion cannot be detected by conventional methods. Positron Emission Tomography (PET) and PET/CT examinations with 11C-choline or 18F-fluorocholine are promising imaging modalities. Invasive examinations can rarely be performed in patients in whom suspicious, incompatible or pathological lesion cannot be detected in noninvasive imaging methods. Bilateral jugular vein sampling, selective venous sampling, parathyroid arteriography, imaging-guided fine-needle aspiration biopsy, and parathormone washout are invasive methods.

Abstract 11827: A Case of Rapidly Progressive Aortic Valve Stenosis Secondary to Chronic Hypercalcemia

Introduction: Moderate hypercalcemia may be well-tolerated, but rapid calcium deposition to the aortic valve may have life-threatening consequences. Clinical case: We present a case of a 77-year-old female with a history of retroperitoneal liposarcoma complicated by hypercalcemia. The patient had had recurrent hypercalcemia for the past 6 months, ranging from 12-14 mg/dL. She complained of 4 weeks of progressive dyspnea and orthopnea. Physical exam showed jugular venous distension and bilateral pitting edema. A transthoracic echocardiogram (TTE) showed critical aortic stenosis (AS) with a valve area of 0.4 cm2, peak velocity of 6 m/s, and a mean gradient of 90 mmHg (Figure 1). Her last TTE just 9 months prior showed mildly thickened aortic valve leaflets without evidence of stenosis with a valve area of 2.2 cm2, peak velocity of 1.4 m/s, and mean gradient of 4 mmHg (Figure 2). Discussion: The most common cause of AS is age-related calcification. However, the role of hypercalcemia in AS has not been well-defined. Typically, the valve area is expected to decline by 0.1cm2 per year. Surprisingly, our patient’s valve area decreased from 2.2 cm2 to 0.4 cm2 in just 9 months. Rapid decline is usually associated with typical cardiovascular risk factors, however, studies have begun to recognize hypercalcemia as a potential risk factor for rapid progression. In our case, we believe our patient suffered from rapidly progressive AS secondary to chronic hypercalcemia due to malignancy. Conclusions: The severity of AS should be closely monitored in hypercalcemia and further studies are warranted to develop strategies for secondary prevention.

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.

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.

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

PSAT203 Acquired Resistance to Medical Management in a Patient with Parathyroid Crisis due to a Parathyroid Adenoma

Abstract Introduction Parathyroid crisis is a characterized by severe hypercalcemia associated with multiple organ dysfunction. Case 90 years-old Caucasian man was hospitalized for progressive confusion over 3 days and was noted to have a critically elevated serum calcium (S Ca) 16.8 mg/dl (8.6-10.0) with albumin 4.1 mg/dl. Patient had a good functional status prior to the hospitalization. On further evaluation, patient was diagnosed with primary hyperparathyroidism with a high suspicion for parathyroid cancer, with labs showing a markedly elevated PTH 1183 pg/ml (15-65) and ionized Ca >1.85 mmol/L (1.15-1.35). Of note, S Ca was normal at 9.5 mg/dl (no albumin) approximately 20 months prior to the hospitalization. Parathyroid ultrasound showed a 1.8×1.7×1.1 cm left superior parathyroid mass with ill-defined margins. Sestamibi scan confirmed a left superior parathyroid mass. CT neck/chest/abdomen/pelvis with contrast showed a 1.8×1.1×1.9 cm left superior parathyroid mass with enhancement and punctate non-obstructing right kidney stones. Hypercalcemia responded extremely well to medical management (calcitonin, 4 mg of zoledronic acid infusion and 13 days of cinacalcet 30 mg daily) resulting in normalization of S Ca. However, patient required a prolonged hospitalization for aspiration pneumonia and severe electrolyte disturbances. Since patient was not a good surgical candidate and hypercalcemia resolved on medical management, patient was discharged to a rehab facility with the plan to pursue parathyroidectomy as outpatient. S Ca worsened progressively and was 10.4 mg/dl (albumin 3.6 mg/dl) with PTH 130 pg/ml on day 15 after discharge. Cinacalcet was added when hypercalcemia further worsened to 11.7 mg/dl (albumin 3.6 mg/dl) on day 38. However, patient was hospitalized again for altered mental status, recurrent severe hypercalcemia (S Ca 15.7 mg/dl, albumin 3.8 mg/dl, PTH 1299 pg/ml), hypokalemia and urinary tract infection. In the ED, patient developed complete heart block that responded to atropine. Interestingly, hypercalcemia was recalcitrant to aggressive medical management during this hospitalization (zoledronic acid 4 mg infusion, calcitonin IM- increased up to 6 mg IM q6hr, cinacalcet- increased to 60 mg PO BID and IV fluid resuscitation with furosemide as needed). S Ca was 14.2 mg/dl (albumin 3.4 mg/dl) on day 8 of hospitalization. Therefore, urgent left superior parathyroidectomy was performed. Surgical pathology revealed a 3.1 gm parathyroid adenoma. Post-operative day#1 labs showed normal PTH 17.3 pg/ml, S Ca 12.1 mg/dl and albumin 3.2 mg/dl. S Ca and patient's mental status normalized over next few days. Discussion Urgent parathyroidectomy has shown to have excellent outcomes in patients with parathyroid crisis. Our patient's severe hypercalcemia initially responded excellently to medical management but recurred within few weeks and developed resistance to medical management. Our case highlights the importance of performing surgical exploration as soon as possible after initial medical stabilization in patients with parathyroid crisis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP552 Hypercalcemic Crisis Due to PTH Secretion From a Poorly Differentiated Esophageal Neuroendocrine Tumor

Abstract Background Paraneoplastic secretion of PTH is described in a number of solid organ tumors. Hypercalcemia occurs in up to 30% of patients with malignancy. The most common cause of this phenomenon is PTHrP production. We present a rare case of PTH mediated hypercalcemic crisis from a tumor of presumed esophageal lineage. Clinical Case A 54-year-old man presented with several days of fatigue, lethargy and polyuria. Initial calcium was markedly elevated at 18.4 (8.3-10.1mg/dL). Past medical history included Barrett's esophagus, history of gastric bypass, and prior alcohol abuse. He also had progressive dysphagia and 30lb weight loss over the prior month. On examination, he had tachycardia, cachexia, and encephalopathy. Laboratory testing revealed an elevated PTH of 281 (nl 18.4-80.1pg/mL), creatinine 1.34mg/dL, and low phosphorus at 2.8 (nl 2.7-4.5mg/mL). Hypercalcemia was treated with IV fluids, calcitonin, and pamidronate. The calcium normalized but PTH remained 210pg/mL. Subsequent PTHrP and 1,25 di-hydroxy vitamin D levels were normal. Esophagogastroduodenoscopy (EGD) revealed a friable esophageal mass and biopsy identified a poorly differentiated carcinoma with neuroendocrine features, immunoreactive to synaptophysin and high Ki-67 index of 90%. Immunostains for chromogranin and PTH were negative. A CT of the chest, abdomen, and pelvis revealed diffuse metastases in the liver, lungs, and enlarged mediastinal lymph nodes. The source of primary tumor could not be fully identified from pathology but suspected to be esophageal. Parathyroid scan showed a subtle persistent uptake posterior to right side of trachea suspicious for a parathyroid adenoma, but that could not account for the severity of PTH elevation. He was readmitted in 1 month with recurrent symptomatic severe hypercalcemia to 18mg/dL and PTH to 619.4pg/mL. Again, he received IV fluids, calcitonin, and zoledronic acid. He received 3 cycles of platinum and etoposide based chemotherapy. After chemotherapy, PTH decreased to 123pg/mL and calcium to 9.7mg/dL but he continued to have rapid disease progression including jaundice, pathological bone fractures and orbital metastases. He elected hospice care and passed away in about 4 months from initial diagnosis. Final PTH was 916.8pg/mL. Conclusion PTH is a normally secreted by parathyroid gland chief cells, which are part of the embryonic neural crest cells found in various neuroendocrine tissues. It is plausible that malignancies with neuroendocrine features may secrete neuropeptides including PTHrP and PTH. Few case reports exist describing PTH secretion by neuroendocrine tumors, though most common are tumors of gastroenteropancreatic origin. PTH stain and focal chromogranin tends to be negative with poorly differentiated neuroendocrine tumors. PTH gene is usually intact and upregulation of the regulator sequence of PTH gene promotor is suspected to be the mechanism of elevated PTH levels and hypercalcemia. This case demonstrates the potential for poorly differentiated neuroendocrine malignancies to cause hypercalcemic crises from paraneoplastic secretion of PTH. Presentation: No date and time listed

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 <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 <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

Surgical description and outcome of ultrasound-guided minimally invasive parathyroidectomy in 50 dogs with primary hyperparathyroidism.

To describe the surgical technique and clinical outcome of minimally invasive parathyroidectomy for primary hyperparathyroidism (PHPT) in the dog. Fifty client-owned dogs with PHPT that underwent minimally invasive parathyroidectomy. Retrospective cohort study. An ultrasound-guided mini lateral approach was made via a plane established between the sternocephalicus muscle and sternohyoideus muscles to expose the thyroid gland and enlarged parathyroid gland. Abnormal parathyroid glands were removed en bloc via partial thyroidectomy. The technique for bilateral disease was similar, the skin incision was made on midline and moved laterally to develop the above-mentioned plane of dissection. Age, sex, breed, bodyweight, ultrasound findings, histopathological diagnosis, surgical time, preoperative clinical signs, and clinical outcome were extracted from the records for descriptive statistics. A total of 62 glands were surgically removed, including 17 hyperplastic glands (17/62, 27.4%), 34 adenomas (34/62, 54.8%), and two carcinomas (2/62, 3.2%). Hypercalcemia resolved shortly after surgery in 44 dogs (44/45, 97.8%). One dog had recurrent hypercalcemia (1/45, 2.2%), one dog had persistent hypercalcemia (1/45, 2.2%), two dogs had permanent hypocalcemia requiring life-long calcitriol supplementation (2/45, 4.4%), and one dog died from clinical hypocalcemia (1/45, 2.2%). Minimally invasive parathyroidectomy was associated with a low morbidity and led to favorable outcomes in 44/45 dogs in this series. The results of this study supports the use of minimally invasive parathyroidectomy to treat PHPT in dogs.

S3016 Hepatocellular Carcinoma as an Uncommon Cause of PTHrP-Mediated Hypercalcemia

Introduction: Humoral hypercalcemia of malignancy driven by PTHrP is a syndrome frequently associated with squamous cell carcinoma. We present a case of humoral hypercalcemia as a rare manifestation of hepatocellular carcinoma and describe the impact of early diagnosis on patient care. Case Description/Methods: A 67-year-old male with HCC presented to the emergency department with subacute confusion, constipation, and lower extremity weakness. Physical exam revealed tangential thinking and no asterixis. Serum calcium was 14.8 (corrected to 15.3), creatinine 1.36 (baseline 0.8), AST 141, ALT 32, and AFP 135 (all previously normal). Imaging revealed new liver lesions in multiple segments, enlarged lymph nodes in the porta hepatis, widespread lytic lesions in the spine, calvarium, and facial bones with a 3.4 cm x 2.4 cm left orbital wall mass consistent with metastatic disease. Serum calcium levels normalized with IV fluids, calcitonin, and zolendronic acid. The PTHrP was elevated at 79. Vitamin D levels, SPEP and UPEP were normal. He returned one week later with recurrent severe hypercalcemia. No further cancer treatment options were available so the patient elected for hospice services and died at home. Discussion: Malignancy is the most common cause of hypercalcemia in the inpatient setting. Malignancy-associated hypercalcemia occurs through three distinct mechanisms – humoral (PTHrP mediated), lytic bone lesions, and increased absorption due to excess 1,25 vitamin D production by the cancer. Most cases of HCC-associated hypercalcemia are due to metastatic lytic bone lesions. Less than 10% of cases are attributable to PTHrP, which is severe and often refractory. The mechanism for this is unknown but may be related to an underlying paraneoplastic syndrome and downstream metabolic derangements. Humoral hypercalcemia in patients with HCC is associated with a more advanced TNM stage and higher tumor burden. In a study of 534 patients with HCC, 6.3% had humoral hypercalcemia and had worse prognoses by Child-Pugh scores. Another study of 165 patients with HCC and PTHrP-mediated hypercalcemia found a median survival time of 15 days. Early recognition of humoral hypercalcemia in patients with HCC is essential given its association with higher mortality. Doing so can help providers expedite locoregional therapy or guide goals of care discussions with their patients.