Management Of Hypercalcemia Research Articles

Treatment Outcomes and Survival in Hypercalcemia of Malignancy: A Grave Metabolic Emergency.

Management of hypercalcemia is based on the manifestation of symptoms and serum calcium levels. It is considered an oncological emergency; therefore, management has to be done on an urgent basis. In the present study, we analyzed the clinicopathological profile, treatment, and outcome of patients with hypercalcemia in solid malignancies at our institute. We retrospectively analyzed the medical records of patients diagnosed with cancer and admitted to the department of radiation oncology with hypercalcemia. The parameters studied were age, gender, performance status, date of diagnosis, the primary site of cancer, stage, histopathology, time of presentation of hypercalcemia since initial cancer diagnosis, clinical symptoms, parathyroid hormone levels, liver and renal function tests, bone metastases, management, outcome, and present status. In the present study, 47 patients of hypercalcemia from various solid malignancies were admitted during the study period between 1st January 2018 and 30th April 2022. Head and neck cancer (14, 29.7%) was the most common site of the primary malignancy. Twelve patients had incidental hypercalcemia and were asymptomatic. Management of hypercalcemia included intravenous saline hydration, bisphosphonates, and supportive medication. At the time of analysis, 17 patients were lost to follow-up, 23 patients died, and seven were alive and on follow-up. Median survival was 68.0 days (95% CI: 1.7-134.3 days). Hypercalcemia of malignancy is considered a metabolic oncological emergency and requires urgent and aggressive management. It gets complicated by a deranged kidney function test. Despite available treatment, it portends an abysmal prognosis.

Parathyroid carcinoma: lessons from a rare malignancy of head and neck-a case series.

Parathyroid carcinoma (PC) is a very rare head-neck malignancy. Because the symptoms of parathyroid carcinoma are similar to those of benign causes of hyperparathyroidism, it may be not easy to detect it before surgery. The management of PC after initial surgery will be perplexing because of the adequacy of surgery. We wish to describe the difficulties encountered throughout treatment using a literature review. We conducted a retrospective analysis of individuals with parathyroid carcinoma who had treatment at our department between 2017 and 2022. We gathered data on the clinical profile, investigations, management of hypercalcemia, surgical techniques, histopathological features, adjuvant therapy, and outcomes. We treated three patients with parathyroid carcinoma: Two patients with inferior parathyroid carcinoma and one with superior parathyroid carcinoma. Generalized weakness and bony pain are the predominant symptoms. In all cases, the tumor was located using 99Tc MIBI / SPECT scintigraphy and Ultrasonography. Hemithyroidectomy and tumor excision were done as the surgery of choice. All are disease-free at the 12th-month follow-up. We suggested that parathyroid hormone testing be performed in all bony fibrous lesions to rule out hyperparathyroidism. PC is a likely diagnosis when there is noticeable throat swelling, elevated PTH levels greater than 400IU/L, and serum calcium levels greater than 15mg/dL.

ODP564 Hypercalcemia in the Setting of HTLV-1 Infection and Normal PTHrP Levels

Abstract A 53 year old male with history of HTLV-1 infection associated myelopathy but with unknown mode of transmission, presented with acute on chronic bilateral lower extremity weakness and numbness with no other deficits. Examination revealed decreased strength (grade 1/5) in lower extremities with normal bulk, tone and sensations. Initial blood work revealed hypercalcemia with corrected Calcium of 16.2mg/dl(8.5-11.5), Phosphorus of 2.7mg/dl (2.5- 4.5) and Alkaline Phosphatase of 126mg/dl(20-140). Workup for hypercalcemia revealed Parathyroid hormone (PTH) level of 14pg/ml (10-65), 25 hydroxy vitamin D at 19.6 ng/ml(30-100), 1,25 dihydroxy vitamin D at 6.7pg/ml(19.9-79.3) and TSH of 1.265 microIU/ml(0.5-5). The Parathyroid hormone related protein(PTHrP) level was low at < 2pmol/L while Lactate Dehydrogenase (LDH) was 433U/L(100-220). Urine calcium creatinine ratio was 0.388. Reverse Transcriptase PCR was positive for HTLV-1 but negative for HTLV-2. Smudge cells and atypical lymphocytes were noted on peripheral smear. Imaging revealed generalized lymphadenopathy with splenomegaly but no spinal cord compression. Flow cytometry showed 7.8% atypical helper T cells, positive for CD3, CD4, CD5 and CD45. Clonal T cell receptor gene rearrangements were found, suggesting an underlying T cell neoplasm. Lymph node biopsy confirmed ATLL. He received treatment with fluids, Calcitonin and Denosumab after which serum Calcium levels fell (nadir 7.7mg/dl) and then normalized. He developed another episode of hypercalcemia 5 weeks later which was treated similarly. Discussion Human T cell Lymphotropic Virus-1 (HTLV-1) is a retrovirus causing asymptomatic infections, symptomatic systemic disorders and adult T cell Leukemia and lymphoma(ATLL). HTLV-1 infections, whether in asymptomatic or symptomatic patients, and ATLL are rare but important causes of hypercalcemia and hypercalcemic crises. Individuals with ATLL have the highest incidence of hypercalcemia(50-70%) among all hematologic malignancies. Hypercalcemia is a poor prognostic factor and predicts lower overall survival. It is caused by increased bone resorption, mediated by various factors with the largest role being played by Receptor Activator of Nuclear Factor Kappa B ligand (RANKL), followed by PTHrP, Interleukins, Macrophage Inflammatory Protein 1 alpha and gp 46. RANKL expression is increased upon transactivation by the viral TAX gene product and mediates conversion of osteoclast precursors to mature osteoclasts engaging in bone resorption. PTHrP expression is variable among patients, relating to levels of the TAX gene product that transactivates the PTHrP gene promoter. Thus, a low level, like in our patient, does not rule out HTLV infection as the cause of hypercalcemia. Management of hypercalcemia is in keeping with guidelines for management of other causes of hypercalcemia but may be better responsive to monoclonal antibodies against RANKL than bisphosphonates given the role of the ligand in mediating hypercalcemia in these cases. It can also be used in the setting of poor renal function, which is commonly encountered in hypercalcemic patients. 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

PSAT208 A Case of Hypercalcemia From PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy

Abstract Background Parathyroid hormone-related protein (PTHrP) is a major cause of humoral hypercalcemia of malignancy. PTHrP-induced hypercalcemia can also occur in benign disorders including pneumonia, SLE, HIV, sarcoidosis, and mammary hyperplasia. Treatment for PTHrP-induced hypercalcemia includes treating the underlying disorder and general management of hypercalcemia. Clinical Case A 70-year-old male with a chronic left thigh mass following trauma 12 years prior diagnosed as myositis ossificans, presented with worsening pain and swelling over the mass. Evaluation revealed serum calcium 18.6 mg/dl, PTH 10 ng/L (18-90), 25(OH)D 7 ng/ml (20-50), 1,25(OH)2D 15 pg/ml (20-79), PTHrP 9.3 pmol/L (≤ 4.2), negative SPEP, UPEP, serum light chains and immunofixation, and no bony lesions. MRI showed a large heterogenous mass centered in the left adductor muscle compatible with chronic hematoma with myositis ossificans. FDG PET/CT scan showed FDG avidity and calcification of the left thigh without any other site of uptake. Combination of IV hydration, denosumab and zoledronic acid lowered his calcium to 9.5 mg/dl, but levels increased again within 10 days. Repeated treatments with zoledronic acid initially led to modest lowering of calcium to 10.5 mg/dl, but he became refractory to treatment after 6 weeks, with calcium increasing to 12.3 mg/dl.Two biopsies of the mass were performed, including an open biopsy. The pathology showed nonpolarizable crystalline material with foreign giant cell reaction, without evidence for malignancy. It was concluded therefore that the patient's PTHrP-induced hypercalcemia was secondary to an inflammatory granulomatous condition. Since it had been reported that PTHrP-induced hypercalcemia in SLE and sarcoidosis responded to glucocorticoids, we initiated treatment with methylprednisolone 24 mg daily. After 7 days, the calcium declined from 12.3 to 10.5 mg/dl and PTHrP declined to 2.5 pmol/L. When the methylprednisolone dose was reduced to 12 mg daily, calcium increased to 11.4 mg/dl and PTHrP to 5 pmol/L. Increasing the methylprednisolone briefly back to 24 mg daily, and then 20 mg daily, lowered calcium to 9.0 mg/dl, increased PTH to 74 ng/L, and normalized PTHrP to 1.3 pmol/L. As long-term management with high-dose steroids was not a tenable option, a decision was made to resect the mass. The pathological diagnosis of the surgical mass was low-grade fibromyxoid sarcoma (LGFMS). Immunohistochemical studies identified PTHrP in surrounding vasculature, suggesting possible tumor-vessel interaction. Conclusion PTHrP-mediated hypercalcemia is rarely seen in sarcomas and treatments include coadministration of bisphosphonates, chemotherapy and surgery. We report here the first case of PTHrP-induced hypercalcemia from LGFMS with sustained lowering of calcium and PTHrP levels with glucocorticoid treatment. Further studies are needed to elucidate the mechanism of glucocorticoids in the treatment of PTHrP-induced hypercalcemia and could include lowering levels of inflammatory cytokines that stimulate PTHrP production from tumor cells, or by directly suppressing PTHrP gene expression. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP133 Rare Case of Primary Hyperparathyroidism Causing Hypercalcemic crisis in Systemic Lupus Erythematosus (SLE)

Abstract Introduction Hyperparathyroid crisis is a rare endocrine emergency with a high mortality. Primary hyperparathyroidism (PHP) can present as severe hypercalcemia. There are very few cases documented in literature of patients with concomitant SLE and PHP. We present a case of hypercalcemic crisis in a patient with untreated primary hyperparathyroidism with a history of SLE. Case description A 46 year old woman was found to have hypercalcemia of 12.9 mg/dl on routine lab work. Her medical history is significant for SLE (diagnosed 9 years prior) and osteoarthritis. She had no physical complaints. Further workup confirmed primary hyperparathyroidism with PTH of 322.8 pg/ml and findings consistent with parathyroid adenoma on Sestamibi scintigraphy. Parathyroidectomy was strongly recommended however the patient refused. She was then offered medical management but did not show up for any follow up appointments. Two years later, she presented to the emergency department with altered mentation, lethargy, poor oral intake and abdominal pain for 2 days. She was found to have severe hypercalcemia with a serum calcium of > 24.8 mg/dl and was in acute renal failure. On admission, EKG changes suggestive of pseudoinfarct pattern from severe hypercalcemia were present. She was managed in the intensive care unit with intravenous hydration, calcitonin, zoledronic acid and hemodialysis. Shortly after initiation of hemodialysis, the patient succumbed to a cardiac arrest. Conclusion Hyperparathyroid crisis when untreated has a 100% mortality rate. Early management with surgical intervention is the only confirmed cure for PHP. There are only 18 cases reported in literature of hypercalcemia in SLE. Mechanisms involved are believed to be stimulatory PTH antibodies, PTHrP and osteoclastic activity due to inflammatory cytokines. To our best knowledge this is the 6th case report of a patient with concomitant SLE and PHP. A prospective study by Norman et. al 1 done in 10000 PHP patients demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/ml . Her baseline calcium at diagnosis was 13mg/dl and intact PTH was 322.8 pg/ml which is higher than seen in the normograms as per the study. In our patient, we believe SLE could have exacerbated the hypercalcemia caused by PHP. It is important to perform further studies to identify if any association exists between the two conditions. Physicians must recognize their concomitant occurrence as prompt management of hypercalcemia becomes even more crucial in these cases.

LBODP069 Parathyroid Crisis And Recalcitrant Hypercalcemia From Double Parathyroid Adenomas

Abstract Parathyroid crisis is a rare and life-threatening manifestation of hyperparathyroidism. Patients present with severe hypercalcemia and associated symptoms of bone disease, nephrolithiasis, abdominal pain, and fatigue. Multi-organ dysfunction in the form of encephalopathy, cardiac dysrhythmias, and renal failure is often present. There have also been reports of bleeding duodenal ulcers secondary to marked elevated parathyroid hormone. The most common etiology is a single parathyroid adenoma (85%) followed by hyperplasia (10%), double adenomas (4%), and carcinoma (1%). Parathyroid crisis requires immediate medical management of hypercalcemia and in recalcitrant cases, urgent parathyroidectomy. A 67-year-old female presented to the hospital with weakness and intermittent hematochezia. She was found to have acute renal failure, new onset anemia, and profound hypercalcemia of 17.1 mg/dl. On exam, she was slow to respond and exhibited diffuse muscle weakness. EKG showed sinus tachycardia, a right bundle branch block, and normal QTc. She received aggressive intravenous fluids and calcitonin. Bisphosphonate was not given due to renal failure. Due to refractory hypercalcemia, she was initiated on cinacalcet. She ultimately required hemodialysis due to failure of medical therapy. Further work-up showed a PTH of 2627 pg/ml. Vitamin D levels, TSH, and serum and urine protein electrophoresis were unremarkable. Renal ultrasound did not show nephrolithiasis. Given hematochezia and anemia in the setting of parathyroid crisis, endoscopy was done and was unrevealing of ulcers. A parathyroid ultrasound and nuclear medicine CT scan showed bilateral parathyroid adenomas. She underwent left superior and right inferior parathyroidectomy with biopsies revealing hypercellular parathyroid tissue with no features of malignancy. Following surgery, calcium levels gradually normalized. However, she remained dialysis dependent. This case exhibits a rare presentation of parathyroid crisis from double adenomas, requiring urgent double parathyroidectomy due to refractory hypercalcemia. This patient had an astoundingly elevated PTH level of 2627 pg/dl, one of the highest values documented in literature, which may attribute to the recalcitrant nature of hypercalcemia. Prompt diagnosis and treatment of parathyroid crisis is critical in preventing life-threatening complications. Presentation: No date and time listed

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation – a case report

BackgroundParathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy.Case presentationTwenty-four – Year – old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was – 15 mg/dl (8.5 – 10.3), serum phosphate – 2.3 mg/dl (2.5 – 4.5), intact PTH – 118 pg/ml (20 – 80), Vitamin D – 15 ng/ml and Urine Ca/Cr ratio – 2.1 (0.1 – 0.2). Her CECT–neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid – 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful.One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease.ConclusionThis case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Hypercalcemia: Is Dialysis Still an Option?

Hypercalcemia is a common disorder that can cause acute kidney failure, neurological damage up to coma, arrhythmia and cardiac arrest. The management of hypercalcemia is based on intravenous hydration with normal saline, when insufficient, bisphosphonate treatment is used. More recently, denosumab has shown significant benefit. Hemodialysis is an additional option in the treatment of severe refractory hypercalcemia when medical treatment is deemed ineffective or unavailable. It allows rapid correction of calcium levels, especially in patients with renal failure or cardiac co-morbidities, where hydration cannot be performed safely. The aim of our study was to compare hemodialysis as a therapeutic tool, to more conservative treatments. Our study is retrospective, descriptive, analytical and comparative, sprawling from January 2015 to June 2019 at the university hospital Hassan II in Fez. 78 patients with hypercalcemia were studied. The mean age was 55 ± 15 years and sex ratio M/F of 1.1. The mean corrected serum calcium at admission was 144 mg/l ± 23 mg/l. Malignancies represented 72.7% of all etiologies. Kidney injury was observed in 50 of our patients (64%). Mortality was noted in 16.6% of all cases. When comparing the 2 groups (patient on dialysis versus patient under other treatments), electrocardiogram abnormalities, patient who had high levels of calcium and those who had hyperparathyroidism were more likely to be on dialysis rate. In our study, even though we used relatively high calcium dialysate, we were able to achieve a decrease of 39% in patient’s calcemia in the hemodialysis group versus 27% decrease when using a combination of forced saline dieresis and bisphosphonate without a difference in term of mortality.

Evaluation of the Therapeutic Management of Hypercalcemia in Myeloma at the Nephrology Department of Louis Pasteur Hospital of Chartres: About 8 Cases

Introduction: Hypercalcemia is the most common metabolic complication in myeloma. The aim of this study was to evaluate the management strategy of hypercalcemia in myeloma at the nephrology department of Louis Pasteur hospital of Chartres. Patients and Methods: We carried a retrospective study of patients treated for myeloma-related hypercalcemia between January 1, 2019 to December 31, 2021. The clinical, paraclinical, therapeutic and evolutive characteristics were studied. Results: Eight patients were included in this study with a median age of 67 years [41 - 85] and a sex ratio (M/F) of 1. A quarter of patients were known with chronic kidney disease. Four patients (50%) had symptoms of hypercalcemia. Biologically, the mean hemoglobin was 9.8 ± 2.7 g/dl, all patients had an acute kidney injury with a mean creatinine level of 364.1 ± 173.3 mmol/l, a mean serum calcium of 3.42 ± 0.59 mmol/l and three quarter of patients had bone lesions. Five patients (62.5%) were rehydrated with a mean volume of saline of 2700 ± 836.7 ml/24h. Seven patients (87.5%) received biphosphonates and none received diuretics. The mean normalization time of the serum calcium was 5 days. Conclusion: Hypercalcemia is frequent in malignancy and represents a poor prognosis factor of the disease. A well-conducted therapeutic strategy allows rapid normalization.

Parathyroid Carcinoma: a Review.

Parathyroid cancer is a rare endocrine malignancy with only a few thousand cases reported worldwide. As a result, there exists considerable controversy regarding the various aspects of this disease, viz., etiology, diagnosis, and management. We hereby attempt to review the literature on parathyroid carcinoma (PC) and summarize the practices based on the current evidence available. The majority of the PC are sporadic although an association with hyperparathyroidism-jaw tumor syndrome, multiple endocrine neoplasia (MEN) 1 and 2, and isolated familial hyperparathyroidism has been shown. As preoperative diagnosis is challenging, PC should be suspected in patients presenting with a neck mass with signs and symptoms of invasion to surrounding structures. Skeletal and renal symptoms are often associated with PC as presenting complaints. The biochemical parameters are more pronounced in the case of PC compared with benign countpart. Due to its rarity, the American Joint Committee of cancer control (AJCC) acknowledges that as yet a clear distinct staging system to prognosticate the disease would be premature. Complete excision with negative margins at first surgery offers the best chance of cure. The role of radiotherapy (RT) is still unclear; however few series have suggested a better locoregional control with adjuvant RT. Recurrences are common and are most significantly associated with an incomplete clearance at initial surgery. Surgical salvage of recurrent/metastatic disease with medical management of hypercalcemia is the treatment of choice. Large prospective studies and trials need to be conducted to understand the pathology better and improve management protocols; however this is a challenge due to rarity of cases.

Assessment of Hypercalcemia Management at an Academic Institution

Abstract Background: Currently, there is no widely accepted clinical practice guideline for the management of severe hypercalcemia in hospitalized patients. Objective: The purpose of this project was to analyze management of hypercalcemia in hospitalized patients at an academic medical center, then establish and implement a clinical practice guideline for hypercalcemia treatment. Design: Retrospective chart review of all patients admitted for management of hypercalcemia over 37 consecutive months. Setting: Urban academic tertiary referral center Measurements: We examined which calcium- lowering medications were used, how often 2 medications were needed, average time to normocalcemia, incidence of hypocalcemia post treatment, serum phosphorus nadir and serum creatinine peak. We also assessed medication appropriateness (dose and frequency). Results: Seventy-two patients were included; 58 patients with hypercalcemia of malignancy and 14 patients with hypercalcemia of other diagnoses. In the malignancy group the most common treatment was a combination of calcitonin + bisphosphonate (43%), followed by bisphosphonate alone (29%) and calcitonin alone (24%). In the non-malignancy group, calcitonin alone was used in 50%, calcitonin + bisphosphonate in 21% and a bisphosphonate alone in 14%. Denosumab was rarely used in both groups. The median time to normocalcemia was 3.0 days irrespective of diagnostic group. Seventy two percent of the patients with malignancy and 86% of the non-malignancy group achieved normocalcemia. The incidence of hypocalcemia was 21% (12/58) in the malignancy subgroup and 29% (4/14) in the others after treatment. Serum creatinine did not change from baseline to post-treatment in either population. Median serum phosphorus dropped from 2.9 mg/dL to 1.8 mg/dL in the malignancy group and 4.2 mg/dL to 2.1 mg/dL in the non-malignancy group. Only 41% of patients that received calcitonin, were given recommended dose, route, and frequency. Conclusion: Based on the results of this study, a hypercalcemia treatment guideline was developed, highlighting appropriate medication dose and frequency. This guideline recommends zoledronic acid alone for asymptomatic malignancy patients, and in combination with calcitonin for symptomatic patients. In contrast, calcitonin alone is considered first line for non-malignant conditions.

Maffucci Syndrome, Calcium Homeostasis, and Endocrine Challenges in Management

Maffucci syndrome is a rare disorder characterized by enchondromatosis and hemangiomata. It can occur due to sporadic, de novo, mosaic pathogenic variants in the gene encoding isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). IDH1 variants are associated with endocrine manifestations, such as pituitary adenomas. However, literature is limited in describing other clinical features and available treatments in severe phenotypes. We report a pediatric patient with uniquely complex and severe Maffucci syndrome. Case: A 5-year-old boy was evaluated by pediatric endocrinology for chronic hypercalcemia as part of a multidisciplinary evaluation of his severe Maffucci syndrome. Past medical history included prematurity, restrictive lung disease, developmental delay, seizures, 2-OH glutaric aciduria, angiomas, and bicytopenia. Physical exam revealed angiomas, scoliosis, and severe bony deformities throughout the entire skeleton. During admission, laboratory assays revealed normal parathyroid hormone, phosphorus, 1,25-OH2D, and C-telopeptide; elevated serum calcium and PTH-related peptide; and low 25-OHD, alkaline phosphatase, and osteocalcin. Low-dose ACTH stimulation test yielded a peak cortisol level of 16.8. A 24-hour urine study confirmed hypercalciuria. Renal ultrasound demonstrated nephrocalcinosis. Skeletal survey revealed diffuse and chondromatous changes of nearly every bone. Whole-exome sequencing detected a presumed, mosaic de novo IDH1 variant. DEXA scan revealed total body BMD z-score of -3.8. Discussion: Hypercalcemia in Maffucci syndrome is a rare phenomenon. The most likely etiology was due to the severe and chronic bony breakdown from the underlying progressive enchondromatosis. Subsequently, the body attempted to adapt to these chronic processes with abnormal mineral homeostasis, as seen in his laboratory assays. Chronic primary hyperparathyroidism was not likely, as his PTH, phosphorus, and 1,25 OH2D levels were not congruent with that diagnosis. Familial hypocalciuric hypercalcemia was not likely, as his urine calcium clearance ratio was >0.01. Finally, his slightly elevated PTHrP level was not due to PTHrP-mediated hypercalcemia of malignancy, as his bone marrow biopsy was negative. The options for short-term hypercalcemia management had their own inherent risks and were not suitable for long-term management. Although there is a lack of pediatric data to guide therapy in Maffucci syndrome, decision was made to proceed with bisphosphonate infusion given the benefits in the setting of his nephrocalcinosis, chronic hypercalcemia, and results of his DEXA scan. Given the rarity of Maffucci syndrome, few characteristics are well-described in the pediatric population. A multidisciplinary approach is necessary to review the severity of the disease and to determine the best treatment approach based on this information.

Complexities surrounding the diagnosis and management of hypercalcaemia in pregnancy.

SummaryHypercalcaemia in pregnancy is uncommon, with associated adverse obstetric and perinatal outcomes for both the mother and the fetus. Determination of causality is central to its management. Diagnostic imaging techniques are limited during pregnancy and the diagnosis is made more complex by physiological changes in calcium and vitamin D homeostasis in pregnancy. Further, therapeutic options are limited due to safety considerations for the pregnant woman and the developing foetus. Three cases of hypercalcaemia in pregnancy will be presented, highlighting the distinct aetiologies and management strategies for hypercalcaemia in pregnancy and the importance of early measurement of serum calcium in pregnancy screening.Learning pointsThere are complex physiological changes in calcium balance in pregnancy, including increased calcium intestinal absorption and renal excretion.Hypercalcaemia in pregnancy is uncommon but has important potential maternal and foetal complications, making a compelling argument for routine antenatal, calcium screening.Identifying the cause of hypercalcaemia in pregnancy can be challenging due to the complex placental interplay in biochemical test interpretation and due to safety constraints restricting imaging and surgery.Acute medical management of hypercalcaemia must be considered in the context of both maternal and foetal well-being, along with gestational age and specific consideration for the safety of the developing fetus in late gestation.

A Case Report and Anesthetic Considerations in Subcutaneous Fat Necrosis of the Newborn

Subcutaneous fat necrosis of the newborn (SCFN) is an uncommon, self-limiting panniculitis generally diagnosed in the first few weeks of extrauterine life in term or postterm infants subjected to perinatal physiologic stress. Hallmarks of the process include dramatic hypercalcemia without identifiable cause that may be associated with renal disease, seizures, and death. Herein, we describe the anesthetic approach in an 11-week-old infant, including perioperative laboratory testing, management of hypercalcemia, and intraoperative considerations.

Management of hypercalcemia in critically ill patients

Management of hypercalcemia in critically ill patients

Severe hypercalcemia and a pelvic brown tumor in an adolescent with primary hyperparathyroidism: a case report

BackgroundPrimary hyperparathyroidism may present in a myriad of manners, varying from an incidental asymptomatic biochemical finding to gastrointestinal, psychiatric, renal, and bone manifestations. While hyperparathyroidism remains a rare diagnosis in the pediatric population, the initial approach to diagnosis and management of hypercalcemia in children is imperative for the general pediatrician. Herein, we describe an adolescent who presented with a lytic bone lesion and severe, symptomatic hypercalcemia due to primary hyperparathyroidism.Case presentationA 14-year-old male presented with vomiting, constipation, abdominal pain, and lethargy. He had an elevated total corrected calcium of 4.3 mmol/L. He was found to have a large pelvic lytic tumor consistent with a brown tumor due to primary hyperparathyroidism. He received pharmacologic therapy for stabilization of his hypercalcemia, including intravenous saline, intravenous bisphosphonates, and calcitonin. He subsequently received definitive therapy via parathyroidectomy and his post-operative course was complicated by hungry bone syndrome. Long-term follow-up has found full resolution of the lytic lesion and restored calcium homeostasis.Conclusions We present this case to highlight the possible presentations of hypercalcemia and hyperparathyroidism that are essential for a general pediatrician to recognize to ensure prompt diagnosis and management. Evaluation for hypercalcemia should be considered in patients with suggestive symptoms and physical exam findings. To our knowledge, this patient represents the first reported pediatric case of a pelvic brown tumor in an adolescent. While the multi-systemic complications of hyperparathyroidism may be quite severe, swift and appropriate management may mitigate these clinical outcomes.

When CKD-MBD is not just CKD-MBD, a case of humoral hypercalcemia of malignancy in a dialysis patient

Patients on maintenance hemodialysis have dysregulations of calcium and phosphorus homeostasis which results in a plethora of mineral and bone pathologies. Management is typically focused on maintenance eucalcemia and limiting hyperphosphatemia while avoiding extremes of intact parathyroid hormone. Hypercalcemia in this setting is often iatrogenic. We present a case of humoral hypercalcemia of malignancy initially thought to be iatrogenic due to mineral bone management and discuss the overlap of management of hypercalcemia and management of mineral bone disease in end stage kidney disease. We highlight the relationship between malignancy and end stage kidney disease and the increased risk of hypercalcemia associated with malignancy.

Safety of Intravenous Bisphosphonates for the Treatment of Hypercalcemia in Patients With Preexisting Renal Dysfunction.

Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited. The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction. A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30. A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function. The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.