Symptomatic Hypercalcemia Research Articles

Clinical Presentation and Management Approach in a Case of Familial Hypocalciuric Hypercalcemia Type 3 Due to APS21 Gene Mutation

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder caused by dysfunctional calcium homeostasis. Thus far, three types of FHH are known to be caused by mutations inCASR (FHH1), GNA11 (FHH2), and AP2S1 (FHH3). The patient in this case report is a 36-year old male that initially presented for a second opinion after being diagnosed with Primary Hyperparathyroidism(PHPT) with subsequent parathyroidectomy done at another institute, and developed recurrent symptomatic hypercalcemia. Prior to considering this patient for further surgical options, he underwent genetic testing, which revealed he had c.43C>T (p.Arg15Cys) mutation in the AP2S1 gene diagnostic of Familial Hypocalciuric Hypercalcemia Type 3 (FHH3). The patient’s father and sister also have hypercalcemia, and have been offered genetic testing. There have been cases reported of patients with FHH3 that have symptomatic hypercalcemia and that have associated cognitive issues. Many patients with FHH can be misdiagnosed and may undergo unnecessary parathyroidectomy. This case report further elucidates the need to raise awareness of FHH.

Paraneoplastic Hypercalcemia as the Initial Presenting Sign of Metastatic Renal Cell Carcinoma

Introduction: Malignant hypercalcemia can occur in patients with renal cell carcinoma as part of a paraneoplastic syndrome. The suggested mechanisms of malignant hypercalcemia include overproduction of parathyroid hormone-related peptide (PTHrP), interleukin-6 (IL-6), prostaglandins, and tumor necrosis factor-alpha (TNF-α). This report describes an unusual case of paraneoplastic hypercalcemia as the initial manifestation of metastatic renal cell carcinoma (RCC). Case presentation: A 44-year-old Caucasian male with no past medical history who presented to his PCP complaining of unintentional weight loss of 25 lbs, increasing fatigue, occasional right flank pain, and nausea. His family history is significant for multiple myeloma of his mother. The physical exam was unremarkable. Labs were remarkable for serum calcium of 11.5 mg/dL, Albumin of 4.5 g/dL, intact parathyroid hormone (PTH) of 9 pg/mL, undetectable PTHrP, 25 hydroxy VitD of 26.4 ng/mL, and 1, 25 hydroxy VitD of 18 pg/mL. Serum and urine protein electrophoresis and PSA were unremarkable. CXR revealed the right lower lobe noncalcified nodule of 15×11×7 mm. CT abdomen/Pelvis revealed a right renal mass of 13×14×12 cm without lymphadenopathy or local metastasis. The patient was referred to a medical oncologist and further workup including PET/CT scan that demonstrated increased uptake in right lung nodule of SUV 6, right renal mass uptake of SUV 72, and MRI brain without metastasis. The patient treated with right total nephrectomy that revealed a sarcomatoid renal cell carcinoma. Right lung nodule biopsy revealed a clear cell renal carcinoma. The patient further treated with two cycles of Gemcitabine/oxaliplatin and four cycles of nivolumab/ipilimumab. A repeated PET/CT scan showed a complete resolution of a right lung nodule. Repeated labs were unremarkable, including serum calcium of 8.7 mg/dL. Discussion: Hypercalcemia is a frequent occurrence in patients with RCC, but it is an unusual presenting symptom. The initial evaluation should focus on whether the hypercalcemia is parathyroid-dependent or medication-related. Basic laboratory investigations for hypercalcemia include PTH, PTHrP, and 1, 25(OH)2D. Bone-resorbing cytokines may be present in those patients in which the cause of the hypercalcemia is unclear. In our case, we could not determine the specific cytokine that caused hypercalcemia, as IL-6 and TNF-α were unavailable. If laboratory tests are unavailable, bone scan, CT scan, or PET-CT should be considered to evaluate for lytic bone lesions or underlying malignancy. Evaluation for carcinoma should be persistently pursued in a patient who has symptoms suggestive of paraneoplastic hypercalcemia. Finally, symptomatic malignant hypercalcemia can be treated with IV fluids and bisphosphonates. Approximately 50% of patients who undergo nephrectomy and/or tumor debulking will revert to normocalcemia.

Hypercalcemia in a Patient Treated With Abaloparatide

Abstract Introduction: The antifracture efficacy of newer agents like PTHrP analogues is promising but knowledge about the mechanism of action and safety profile is needed in order to use these agents effectively. The reported incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL was 3.4% in Abaloparitide. Case Presentation: A 59 year-old female with past medical history significant for diabetes mellitus type 2, hypothyroidism, necrotizing autoimmune myositis, osteoporosis and renal stones presented with complaints of generalized body aches and pains with swelling and redness of the left leg. The patient was diagnosed with osteoporosis based on atraumatic L4 compressive injury involving superior end plate. Her only DXA scan was 8 years ago which showed osteopenia, with the lowest T score of -1.2 at lumbar spine. Subsequent evaluation with DXA scan was unable to be performed due to physical disabilities. She was intolerant to oral bisphosphonates and was started on abaloparatide subcutaneous injections 2 weeks prior to her current admission. Her physical examination was positive for obesity, proximal muscle weakness and bilateral leg edema with bruises and left leg erythema. Laboratory findings showed hypercalcemia with corrected calcium levels of 12.48 mg/dl, suppressed intact PTH 4 pg/ml. Evaluations for secondary causes of hypercalcemia were negative. Her last dose of abaloparatide injection was the morning prior to her presentation to the emergency room. The patient was treated with IV fluids and her calcium level improved within 24 hours with normalization of intact PTH level in 72hrs. Abaloparatide injection was suspended on admission. Hypercalcemia with suppressed PTH was most likely secondary to abaloparatide given the timing of the hypercalcemia after the injection and resolution of hypercalcemia and normalization of PTH. Conclusions: Abaloparatide is a peptide that selectively binds to the RG conformation of the parathyroid hormone type 1 receptor. Abaloparatide is increasingly used following the results from the ACTIVE and ACTIVExtend trials which demonstrate significant increase in bone mineral density and risk reduction of vertebral, nonvertebral, clinical, and major osteoporotic fractures. Hypercalcemia was reported as a side effect, but there is no guidance on further evaluation or management of these patients. The incidence of hypercalcemia defined as albumin-adjusted serum calcium ≥10.7mg/dL is 3.4 % and risk is increased in patients with renal impairment. As in our case, transient hypercalcemia and PTH suppression may be associated with abaloparatide. Efficacy of abaloparatide and impact on bone density with delay or interrupted treatment are not available. Further studies are needed to guide monitoring and treatment of clinically symptomatic transient hypercalcemia in patients taking abaloparatide.

Isolated Hepatic Sarcoidosis Presenting With Severe Hypercalcemia

Introduction: Sarcoidosis is an inflammatory disorder of unknown etiology that can affect various organs. Lungs, intra thoracic lymph nodes and skin are the most commonly affected organs. The prevalence of hepatic sarcoidosis ranges between 5 to 30%. However, isolated hepatic sarcoidosis is rare. Hypercalcemia in sarcoidosis varies considerably due to the varying disease course and is reported to occur between 2 to 63% cases. We report a unique care of isolated liver sarcoidosis that presented with severe parathyroid hormone (PTH) independent hypercalcemia.Case: A 58 years old woman of Asian ethnicity with a past medical history of type 1 diabetes, hypothyroidism and chronic kidney disease presented to emergency department with headaches and altered mental status. The headaches were present since 4 weeks and was associated with polyuria and polydipsia. Non contrast CT scan of brain was negative for acute intracranial process. Physical examination revealed unremarkable vital signs and physical findings except for the altered mental status on neurological exam (orientation to self only). Initial laboratory testing revealed high corrected serum calcium 12.2 (8.0- 10.1 mg/dl), acute renal failure with high serum creatinine 2.90 (0.57–1.0 mg/dl), abnormal liver panel with elevated AST 84 (5-32U/L), ALT 85 (5–33 U/L), Alkaline Phosphatase 151 (35-104U/L). Repeat corrected serum calcium was still high at 12.4 mg/dl which prompted further evaluation to search for the etiology of hypercalcemia and testing revealed 1, 25 dihydroxy vitamin D (1, 25 vit D) mediated hypercalcemia. Labs showed low PTH 14.6 (15–65 pg/ml), normal serum protein electrophoresis, low PTH-related peptide <2.0 pmol/L, low 25 hydroxy vitamin D 20 (30–100 ng/ml) and high 1, 25 vit D 96.5 (19.9–79.3 pg/ml). Imaging evaluation revealed multiple hypodense nodules in both lobes of the liver seen on ultrasound, and CT scan of chest, abdomen and pelvis was unremarkable except for the similar liver findings. Biopsy of the liver lesion revealed non-caseating granulomas with no evidence for lymphoma and negative for acid fast bacteria and fungal organisms. Patient was treated with intravenous fluids, zoledronic acid and initiated on a course on oral prednisone that was tapered over a period of 6 months. There was a tremendous improvement in overall clinical condition. Serum calcium and 1, 25 vit D levels normalized. CT scan performed 3 months later showed complete resolution of all liver lesions.Conclusion: While most cases of hepatic sarcoidosis are asymptomatic and are incidentally found due to abnormal liver function tests or imaging done for other causes, we present a case of isolated hepatic sarcoidosis diagnosed due to symptomatic severe PTH independent hypercalcemia. Even though rare, extra-pulmonary sarcoidosis should be in differentials for 1, 25 vit D mediated hypercalcemia even if thoracic imaging are unremarkable.

1-25OH2D Mediated Hypercalcemia Secondary to DISR From Immune Checkpoint Inhibitors

Background: Drug induced sarcoid like reactions (DISR) have recently been described as a potential consequence of immune checkpoint inhibitor therapy. However, hypercalcemia associated with DISR has not been reported.Clinical Case: A 72 year old male presented with metastatic melanoma. He initiated therapy with Ipilimumab/Nivolumab (Ipi/Nivo). Three weeks after his first cycle he developed symptomatic hypercalcemia (calcium 14.4 mg/dL), and acute kidney injury (creatinine 3.45mg/dL), PTH 12 pg/mL, 25OHD 51, and PTHrp 0.5. He received IV fluids and IV bisphosphonates and calcium normalized to 9.1 mg/dL and creatinine 1.85 mg/dL. His Ipi/Nivo were stopped due to concern for neurotoxicity. He subsequently switched to Q3week Pembrolizumab (Pembro) and after 2 infusions, he again developed hypercalcemia (calcium 11.8 mg/dL). FDG PET demonstrated a complete radiographic response. Labs showed a 1,25OH2D of 103 pg/mL (reference range 19.9–79.3 pg/mL), PTH of 4 pg/mL and calcium of 11.4 mg/dL. He was treated with prednisone 20 mg QD. After 9 days on prednisone, 1,25OH2D was 26 pg/mL and calcium 9.4 mg/dL. He took prednisone for 3 weeks total. Repeat labs off prednisone for one week were 1,25OH2D of 38 pg/mL and calcium 9.1 mg/dL. He continued on Pembro. After being off steroids for 5 weeks, he developed body aches and swelling of the hands. 1,25OH2D increased to 100 pg/mL and calcium to 10 mg/dL. He restarted prednisone and stopped Pembro. Labs one month later showed a 1,25OH2D of 45 pg/dL while still on prednisone 10 mg qd and a normal calcium in the mid 9’s. Follow up FDG PET showed hypermetabolic bilateral hilar and mediastinal lymphadenopathy not seen on previous imaging. Ultrasound-guided lymph node biopsy revealed granulomatous lymphadenitis. He was diagnosed with DISR, secondary to immunotherapy with checkpoint inhibitors. He continues on prednisone 10 mg per day and calcium and 1,25OH2D levels have remained normal.Conclusion: This is the first case of 1,25OH2D mediated hypercalcemia as a consequence of DISR induced by immune checkpoint inhibitor therapy. Hypercalcemia in the setting of malignancy is more commonly due to humoral hypercalcemia of malignancy from PTHrp or bone metastasis, but DISR needs to be a consideration in persons with hypercalcemia on immune checkpoint inhibitor therapy, with elevated 1,25OH2D levels and low PTH and PTHrp levels.

Single Dose of Denosumab Effective for Management of Bisphosphonate-Refractory Hypercalcemia of Malignancy Related to Non-Small Cell Lung Cancer

Background: First line therapy for hypercalcemia of malignancy (HCM) includes cancer directed treatment and bisphosphonate therapy. Denosumab is effective in bisphosphonate-refractory HCM (BR-HCM), approved for treatment with dosing schedule at 1, 8, 15, and 29 days and then monthly.Clinical Case: We present the case of a 64 year-old man with Stage IIIA squamous cell lung carcinoma diagnosed 5/2019 with corrected serum calcium (CSC) of 11.2 mg/dL (8.4–10.2) at presentation. Prior to treatment, he developed symptomatic CSC 14.0 mg/dL, treated with IV pamidronate 90mg and IV fluids (IVF) 6/28/2019 with improvement to CSC 9.7 mg/dL. Hypercalcemia recurred 8/2019 while undergoing radiation therapy with CSC 14.7 mg/dL, phosphorus 2.5 mg/dL (2.7–4.5), PTH 7 pg/mL (15–65), PTHrP 2.2 pmol/L (<2.0), 25-OH vitamin D 30.16 ng/mL (30–100), and 1,25-OH2 vitamin D 98.7 pg/mL (19.9–79.3). He was treated with IVF and 4mg zoledronic acid (ZA) on 8/20 and 8/29/2019. CSC normalized 9/30/2019 and he subsequently received three cycles of pembrolizumab 11/25/2019 to 1/6/2020, discontinued for associated pneumonitis He again developed HCM 6/5/2020 with CSC 12.6 mg/dL. He was treated with ZA 4mg on 6/16 and 6/29/2020 with persistent, symptomatic hypercalcemia to 13.7 mg/dL 7/9/2020 with ongoing confusion, constipation, and lethargy. Endocrinology was consulted 7/9/2020 and initiated IVF, calcitonin SQ 4U/kg q12h for 48 hours, and prednisone 30mg daily for 5 days. Chemotherapy was initiated 7/14/2020. CSC remained stable <11.5 mg/dL until 8/3/2020 with recurrent calcium to 13.0 mg/dL despite cancer-directed therapy. He was then given 120mg SQ denosumab on 8/7/2020. CSC improved to 10.6 mg/dL on 8/11/2020 and has remained <11 mg/dL at 70 days after a single dose of denosumab.Conclusion: Denosumab was approved for BR-HCM with a complex treatment schedule based on a single-arm study of 33 patients, of whom 39% had treatment-related adverse events.1 We present a case of successful management of BR-HCM with a single dose of 120mg denosumab with CSC <11.5 mg/dL at day 4 after treatment and persistent control of calcium at day 70 without further treatment. Further investigation is warranted to determine the most effective treatment schedule of denosumab for BR-HCM to reduce adverse events including hypocalcemia and overtreatment.

Intracranial tumour detected on routine parathyroid technetium sestamibi scan

A 63-year-old woman presented with symptomatic hypercalcaemia, with a calcium level of 2.83 mmol/L (normal range 2.2–2.6 mmol/L) and an inappropriately elevated parathyroid hormone level of 14.6 pmol/L (normal range...

Primary Hyperparathyroidism: A Narrative Review of Diagnosis and Medical Management.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient setting. Symptomatic presentation includes non-specific signs and symptoms of hypercalcemia, skeletal fragility, nephrolithiasis and nephrocalcinosis. The majority of individuals present at an asymptomatic stage following routine biochemical screening, without any signs or symptoms of calcium or parathyroid hormone (PTH) excess or target organ damage. Indications for surgery have recently been revised as published in recent guidelines and consensus statements. Parathyroidectomy is advised in patients younger than 50 years old and in the presence of either significant hypercalcemia, impaired renal function, renal stones or osteoporosis. Surgery is always appropriate in suitable surgical candidates, however, medical management may be considered in those with mild asymptomatic disease, contraindications to surgery or failed previous surgical intervention. We summarized the optimal medical interventions available in the care of PHPT patients not undergoing parathyroidectomy. Calcium and vitamin D intake should be optimized. Antiresorptive therapy may be used for skeletal protection in patients with an increased fracture risk. Cinacalcet, a calcimimetic agent, has been shown to effectively lower serum calcium and PTH levels. The effect of medical treatment on the reduction in fracture risk is unknown and should be the focus of future research.

Unmasking normocalcaemic hyperparathyroidism (nPHPT) resulting in severe hypercalcaemia from lack of monitoring during in the COVID pandemic

Primary hyperparathyroidism (PHPT) is a common endocrine disorder in the older person although the incidence of normocalcaemic primary hyperparathyroidism (nPHPT) remains largely unknown. Whilst the majority of patients with PHPT asymptomatic, we describe a case of severe symptomatic hypercalcaemia from undiagnosed nPHPT whilst on calcium and vitamin D supplements. This is an important reminder to clinicians that serum calcium should be monitored before and after initiation of calcium and vitamin D supplementation in the older person.

An update on parathyroid carcinoma

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Management of Parathyroid Disease during the COVID-19 Pandemic.

The coronavirus disease, COVID-19, has caused widespread and sustained disruption to healthcare, not only in the delivery of emergency care, but knock-on consequences have resulted in major delays to the delivery of elective care, including surgery. COVID-19 has accelerated novel pathways for delivering clinical services, many of which have an increased reliance on technology. COVID-19 has impacted care for patients with both hypoparathyroidism and hyperparathyroidism. The role of vitamin D in the prevention of severe COVID-19 infection has also been widely debated. Severe hypocalcemia can be precipitated by infection in patients with hypoparathyroidism. With this in mind, compliance with medical management, including calcium and vitamin D supplementation, is crucial. Technology in the form of text message reminders and smartphone apps may have a key role in ensuring this. Furthermore, clinicians should ensure that patients are educated on the symptoms of hypocalcemia and the steps needing to be taken should these symptoms be experienced. Patients with primary hyperparathyroidism (PHPT) should be educated on the symptoms of hypercalcemia, as well as the importance of remaining adequately hydrated. In addition, patients should be reassured that the postponement of parathyroidectomy is likely to have negligible impact on their condition; for those with symptomatic hypercalcemia, cinacalcet can be considered as an interim measure.

High-dose versus low-dose ergocalciferol for correcting hypovitaminosis D after fragility hip fracture: a randomized controlled trial

BackgroundHypovitaminosis D can be observed in most fragility hip fracture patients. However, measurement of 25-hydroxyvitamin D (25(OH)D) level is costly and may not be available in some centers. Without the baseline serum 25(OH)D level, the appropriate dose of vitamin D supplementation is not known. The aim of this study was to evaluate the effectiveness and safety of vitamin D supplementation in fragility hip fracture patients compared between high- and low-dose vitamin D supplementation.MethodsA total of 140 patients diagnosed with fragility hip fracture were randomly allocated to either the high-dose (60,000 IU/week) or low-dose (20,000 IU/week) vitamin D2 supplementation group for 12 weeks. The number of patients who achieved optimal vitamin D level (serum 25(OH)D > 30 ng/mL), the proportion of patients who developed hypercalcemia, and the functional outcome were compared between groups.ResultsOf the 140 patients who were enrolled, 21 patients were lost to follow-up during the study period. The remaining 119 patients (58 and 61 in the high- and low-dose groups, respectively) were included in the final analysis. The high-dose group had a higher rate of serum 25(OH)D restoration to optimal level than the low-dose group (82.8% vs 52.5%, respectively; p < 0.001). Approximately 3.4 and 1.6% of patients in the high- and low-dose groups, respectively, had mild transient hypercalcemia, but none developed moderate, severe, or symptomatic hypercalcemia. There were no differences in functional outcome scores between groups.ConclusionsIn treatment settings where baseline serum 25(OH)D level can’t be evaluated in older adults with fragility hip fracture, we recommend high-dose vitamin D2 of approximately 60,000 IU/week for 12 weeks, with subsequent switch to a maintenance dose. This regimen effectively restored serum vitamin D to an optimal level in 82.8% of patients without causing symptomatic hypercalcemia.Trial registrationThe protocol of this study was retrospectively registered in the Thai Clinical Trials Registry database no. TCTR20180302007 on 20 February 2018.

Case Series: Hypercalcemia From Granulomatous Silicosis Developing After COVID-19 Infection.

Hypercalcemia is one of the most commonly encountered laboratory abnormalities in clinical medicine. Various causes have been well established. However, it is likely that the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be a newly found cause of this frequent finding, especially amongst those with a history of cosmetic surgery, specifically by means of silicone injection. In this case series, we describe 2 patients presenting with symptomatic hypercalcemia likely from their prior silicone injections. Interestingly, each patient only developed symptoms of hypercalcemia following infection with SARS-CoV-2.

An unusual cause of hypercalcaemia in a home haemodialysis patient: Peritoneal tuberculosis

A 36-year-old patient of North African origin (lived in Belgium since childhood) who had been on home haemodialysis (HD) for 24 months for end-stage kidney disease secondary to diabetic nephropathy presented with progressive symptomatic hypercalcaemia.

Initial Assessment and Monitoring of Patients with Chronic Hypoparathyroidism: A Systematic Current Practice Survey.

Chronic hypoparathyroidism (HypoPT) is associated with significant morbidity and impaired quality of life (QoL). The goals of management for chronic HypoPT include improvement in QoL and the prevention of both hypo- and hypercalcemia symptoms and long-term complications. Several groups have provided consensus statements and guidelines on the management of HypoPT; however, due to limited evidence, these recommendations have largely been based on literature reviews, expert opinion, and consensus statements. The objective of this study was to use a systematic approach to describe current practice for the initial assessment and follow-up of patients with chronic HypoPT. We developed a survey asking experts in the field to select the responses that best reflect their current practice. The survey found no differences in responses between nonsurgical and postsurgical patient assessment. For new patients, respondents usually performed an assessment of serum lab profile (calcium [either albumin-adjusted or ionized], magnesium, creatinine, phosphate, 25-hydroxyvitamin D), 24-hour urine (creatinine,calcium), and a renal ultrasound to evaluate for the presence of nephrocalcinosis or nephrolithiasis. For follow-up patients, most respondents perform blood tests and urine tests every 6 months or less frequently. The reported clinical practice patterns for monitoring for complications of chronic HypoPT vary considerably among respondents. Based on the responses in this systematic expert practice survey, we provide practice suggestions for initial assessment and follow-up of patients with chronic HypoPT. In addition, we highlight areas with significant variation in practice and identify important areas for future research. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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.

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features.

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004-2018. The study cohort comprised twenty cases of PC. The median age was 49years (range 21-73years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4cm (range 0.8-3.5cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months).Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.

Causes of hypercalcemia in people living with HIV in the HAART era

Background Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV. Methods We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia. Results A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (p < 0.05, all). Logistic regression identified solid organ malignancy as the only factor associated with moderate to severe hypercalcemia (odds ratio 12.72, 95% confidence interval 3.11–52.08; p < 0.001). Conclusions Hypercalcemia in PLHIV is associated with solid organ malignancy, hematologic malignancy, and infection. Most PLHIV with hypercalcemia are asymptomatic. Solid organ malignancy is associated with moderate to severe hypercalcemia, and as such PLHIV presenting with moderate to severe hypercalcemia should be investigated for solid organ malignancy.

O09 Isolated muscular sarcoidosis revealed by calcitriol-mediated hypercalcaemia and fluorodeoxyglucose positron emission tomography

Case report - IntroductionSarcoidosis, a multisystem disorder of unknown aetiology, commonly presents with bilateral hilar adenopathy, pulmonary infiltrates, skin and/or eye lesions. Musculoskeletal and neuromuscular manifestations occur less commonly.Calcitriol-mediated hypercalcaemia is a known complication of sarcoidosis. Severe hypercalcaemia, however, is detected in ˂5% of patients and pseudo-malignant hypercalcaemia (>3.5 mmol/L) is very unusual.There are limited reports of isolated granulomatous myositis causing hypercalcaemia. Our patient uniquely presented with symptoms of hypercalcaemia and PET-scan incidentally revealed sarcoid-like myositis. This case reports an unusual presentation of life-threatening hypercalcaemia revealing sarcoid myositis that rheumatologists and physicians should be aware of.Case report - Case descriptionThe patient, a 69-year old Caucasian female, was referred to Rheumatology after a PET-scan identified features of sarcoid myositis. She was initially admitted due to hypercalcaemia and 2 months of tiredness, lethargy, generalised weakness, and nausea. She had difficulty in climbing stairs but was independently mobile with no difficulty standing from sitting. History included biopsy-proven cutaneous lupus (on Hydroxychloroquine, which she stopped weeks prior to admission), chronic interstitial cystitis and CKD stage 3A without proteinuria.Clinical examination was unremarkable. Bloods showed hypercalcaemia (3.62 mmol/L) with inappropriately normal PTH (1.8 qmol/L) and a raised ACE (72 U/L). PET-scan showed symmetric, diffuse, and heterogeneous muscular activity within the posterior thighs, anterior to the hips and psoas muscles, reported as possible sarcoid-like myositis. PET-scan findings were discussed with nuclear medicine team and deemed non-specific. Remaining results included phosphate 1.28, ALP 78, vitamin D3 64, urea 8.6, creatinine 97, e-GFR 49, ESR 10 and CK 30. Normal CXR, CT head and MIBI NM parathyroid scan. CT thorax, abdomen and pelvis showed bladder calcification. Calcium level and symptoms resolved with IV fluid, IV pamidronate and zoledronic acid. She was discharged with follow up arranged.Follow-up bloods revealed high 1,25 vitamin D of 259 (43-144pmol/L) raising the possibility of calcitriol-mediated hypercalcaemia from granulomatous myositis. EMG showed borderline myopathic results. Calcium levels and symptoms remained stable, so no treatment was initiated until 6 months following initial presentation, when she was readmitted with severe hypercalcaemia, similar symptomatology, and normal examination. MRI thighs showed changes consistent with myositis and muscle biopsy revealed granulomatous inflammation consistent with sarcoid. Myositis autoantibodies (anti Ro-52) came back positive. After 10 months of multiple investigations and monitoring, a diagnosis of sarcoid myositis has been made and patient initiated on a Prednisolone tapering regimen; her response is yet to be assessed. Case report - DiscussionIn patients with granulomatous disease, such as sarcoidosis, hypercalcaemia occurs because of ectopic 25(OH)D-1-hydroxylase expression in macrophages and formation of excessive amounts of 1,25(OH)2D. In a review of 101 adult cases of calcitriol-mediated hypercalcaemia, 48% were eventually diagnosed with sarcoidosis.Sarcoid myositis, as described by Aubart et all, has four patterns: nodular; smouldering phenotype; acute, subacute, or progressive myopathic; and combined myopathic/neurogenic type. In all patterns, sarcoidosis was multi-visceral with a median of 3 extra muscular organs involved (mostly lungs, lymph nodes, eyes, and skin). Our patient, however, did not fit into one of these patterns given her single-organ involvement which is clearly challenging. Furthermore, rather uniquely, our patient had no respiratory symptoms and chest imaging did not reveal hilar lymphadenopathy. It was the PET-scan, performed as part of malignancy screen for resistant hypercalcaemia, which highlighted the diagnosis. However, due to lack of objective weakness on examination and normal CK the significance of this incidental nonspecific finding was deemed low.A literature review has highlighted 12 similar cases where PET-scan, performed as malignancy screening for hypercalcaemia, incidentally, revealed intense, diffuse, and isolated muscular FDG uptake consistent with granulomatous myositis. CK was normal in all cases and no patients displayed the usual thoracic features of sarcoidosis. All patients were treated with high-dose steroids and achieved rapid, complete, and sustained remission.Case report - Key learning pointsSarcoidosis should be considered in patients presenting with symptomatic hypercalcaemia with no apparent causes and negative routine workup. The absence of proximal weakness or elevated muscle enzymes do not preclude the diagnosis of granulomatous myositis.Severe hypercalcaemia revealing a diffuse granulomatous disorder limited to muscles might be life threatening and following literature review appears highly steroid-sensitive.We describe a rare case where PET-scan incidentally revealed sarcoid-like myositis features which were subsequently demonstrated by muscle biopsy. Rheumatologists and physicians should be aware of this potential cause of markedly elevated calcium, even with normal CK and CXR and no prior sarcoidosis diagnosis. Earlier recognition of this disease phenotype can avoid unnecessary investigations, diagnosis delay and added stress to patients.

S2006 Hypercalcemia as a Cause of Dysphagia

INTRODUCTION: Severe hypercalcemia, (levels greater than 12 or 13 mg/dL) can manifest with gastrointestinal symptoms such as nausea, anorexia, constipation and pancreatitis. Hypercalcemia inhibits neuromuscular depolarization, and is associated with decreased smooth muscle tone and autonomic dysfunction. Even though hypercalcemia-induced dysphagia has been rarely described in the literature, this might be one of the mechanisms by which dysphagia may occur. CASE DESCRIPTION/METHODS: A 70-year-old male with a past medical history of diabetes mellitus, Hepatitis C, chronic kidney disease and multiple myeloma with metastases to spine, presented to the hospital due to progressive dysphagia to solids and liquids. He had a hospitalization for symptomatic hypercalcemia about a month prior, when his corrected calcium (Ca) level was 13.6 mg/dL. He had noticed resolution of his dysphagia after being treated for hypercalcemia, but had recurrence of symptoms a couple of weeks prior to this presentation. He denied odynophagia, but reported regurgitation. His corrected Ca level during this admission was 12.1 mg/dL, with ionized Ca of 1.44 mmol/L. A chest x-ray was normal. Further workup with a barium swallow did not show any evidence of mechanical obstruction (Figure 1). An MRI of the spine did not show evidence of esophageal compression, but revealed known osteolytic lesions in spine. He was treated with intravenous fluids and Pamidronate with normalization of Ca level and complete resolution of dysphagia. DISCUSSION: There have been few case reports of patients with dysphagia and hypercalcemia of malignancy (HCM), in which symptoms resolved with treatment of hypercalcemia. The reason why dysphagia only affects some patients with elevated Ca remains unknown. It could be an under recognized or a rare complication. The heterogeneity of skeletal and smooth muscle distribution in the esophagus could also explain variability in presentation. There is not enough data about dysphagia and hypercalcemia from benign etiologies. This is possibly due to lower levels of Ca in these cases compared to cases with HCM. Furthermore, contribution of hypercalcemia towards dysphagia in cases with external compression of the esophagus by a benign tumor cannot be entirely ruled out. Due to a possible causal relationship between HCM and dysphagia, it might be reasonable to treat hypercalcemia prior to attempting invasive diagnostic procedures such as endoscopy.Figure 1.: Normal barium swallow in patient with dysphagia and corrected calcium level of 12.1 mg/dL.Table 1.: Corrected Calcium Level and Work-Up in Patients with Dysphagia and Hypercalcemia. Case 1 shows calcium level and diagnostic work-up from patient admitted to our hospital (a). Cases 2 and 3 were previously reported by Grieve et al. Case 4 was previously reported by Balcombe et al. N/A = not applicable.