Cause Of Hypercalcemia Research Articles

Primary hyperparathyroidism, presenting with acute kidney injury in the first trimester of pregnancy; a case report

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia. Total serum calcium level >3.5 mmol/L is associated with a high risk of a hypercalcemic crisis, manifesting with nausea, vomiting, dehydration, myalgia’s, abdominal pain, acute pancreatitis, acute kidney injury (AKI), cardiac rhythm disorders and disturbances of consciousness. We report here a case of PHPT, manifested with hypercalcemic crisis during pregnancy. A 30-year-old woman in the first trimester of pregnancy admitted complaining on loss of appetite, nausea, vomiting, lower abdomen pain, weakness, and leg pain during the last 10 days. She had a history of two uncomplicated pregnancies, and two episodes of renal colic, her kidney function was normal 2 weeks prior to admission. Work-up showed hypochloremia, hypokalemia, hyponatremia, total serum calcium was 5.34 mmol/L, and serum creatinine 226 µmol/L, and she underwent urgent hemodialysis (HD). Her parathyroid hormone (PTH) was 948 pg/mL, and imaging revealed missed miscarriage 9-10 weeks, soft tissue mass 30x20x33mm near the lower pole of the left lobe of the thyroid gland, small stones in renal calices, and polysegmental pneumonia. She received antibiotics, calcimimetics, and every-day hemodiafiltration (HDF), and underwent vacuum aspiration of uterine cavity and surgical removal of the parathyroidoma. Her PTH shortly returned to the reference level, and serum creatinine dropped to 140 µmol/L after kidney replacement therapy (KRT) secession. Pathology confirmed the diagnosis of parathyroid adenoma. PHPT should be included in the diagnostic algorithm of AKI in pregnancy along with vomiting of pregnant, sepsis, pre-eclampsia and other causes. Successful management of PHPT complications in pregnancy demands multidisciplinary team.

Malignant hypercalcemia: clinical case and minireview

Malignant hypercalcemia is defined as the presence of high serum calcium concentrations in the context of tumor pathology. It is the most common cause of hypercalcemia in hospitalized patients with solid tumors or hematological neoplasms where the postulated mechanisms are the presence of bone metastases and / or the secretion of factors that activate resorption by tumor cells. It can be detected as a finding in the study of asymptomatic patients or be associated with severe clinical manifestations that require urgent treatment. The therapeutic approach must be carried out in an interdisciplinary way aimed at normalizing calcemia, being important the etiological diagnosis to adapt the therapeutic behavior in the long term avoiding future complications. This article presents the case of a 43-year-old female patient immunosuppressed by HIV with a diagnosis of symptomatic hypercalcemia in the context of tumor pathology and bone metastases, her multidisciplinary diagnostic and therapeutic approach with a brief review of the topic.

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.

What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature.

Background: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature. Methods: We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN. Results: The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome. Discussion: The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth.

Hypercalcemia in the setting of HTLV-1 infection and a normal PTHrP level

SummaryHuman T-cell lymphotropic virus-1 (HTLV-1) causes adult T-cell leukemia and lymphoma (ATLL) and is a rare but important cause of hypercalcemia. A 53-year-old male with HTLV-1-associated myelopathy presented with acute on chronic bilateral lower extremity weakness and numbness. Initial blood work revealed hypercalcemia with corrected calcium of 16.2 mg/dL (8.5–11.5) with normal levels of phosphorus and alkaline phosphatase. Workup for hypercalcemia revealed parathyroid hormone (PTH) of 14 pg/mL (10–65), 25 hydroxy vitamin D at 19.6 ng/mL (30–100), 1,25 dihydroxy vitamin D at 6.7 pg/mL (19.9–79.3), thyroid-stimulating hormone of 1.265 μIU/mL (0.5–5), undetectable PTH-related protein (PTHrP) and lactate dehydrogenase of 433 U/L (100–220). The urine calcium creatinine ratio was 0.388. Reverse transcriptase PCR was positive for HTLV-1 and negative for HTLV-2. Peripheral blood flow cytometry and lymph node biopsy confirmed ATLL. He received treatment with fluids, calcitonin and denosumab after which serum calcium levels fell (nadir: 7.7 mg/dL) and then normalized. Humoral hypercalcemia in this setting is mediated by receptor activator of nuclear factor-kappa B ligand (RANKL), PTHrP and other cytokines. PTHrP levels depend on levels of the TAX gene product, cell type and lymphocyte-specific factors. Thus, a low level, like in our patient, does not rule out HTLV-1 infection/ATLL as the cause of hypercalcemia. Hypercalcemia is known to be responsive to monoclonal antibodies against RANKL given the compound’s role in mediating hypercalcemia in these cases.Learning pointsHuman T-cell lymphotropic virus-1 infection and adult T-cell leukemia and lymphoma are associated with high rates of hypercalcemia and hypercalcemic crises.Hypercalcemia in these cases is mediated by osteoclastic bone resorption carried out by several agents including receptor activator of nuclear factor-kappa B ligand, parathyroid hormone-related protein (PTHrP), macrophage inflammatory protein 1 alpha, interleukins, etc. A normal PTHRrP does not rule out humoral hypercalcemia of malignancy in this setting, as indicated by this case.Hypercalcemia in such settings is highly responsive to monoclonal antibodies against RANKL given the role the ligand plays in resorptive hypercalcemia.

A CASE SERIES ON HYPERCALCEMIA

Hypercalcemia in adults arises from a myriad of underlying causes. Etiology of hypercalcemia varies from causes like Vitamin D toxicity to hyperparathyroidism, hyperthyroidism, chronic kidney disease, granulomatous diseases, and malignant diseases .Though not an uncommon metabolic problem, hypercalcemia can easily be missed due to the diverse clinical presentations. Primary hyperparathyroidism and malignancy are the most common causes, accounting for 90% of the cases. Clinical manifestation varies depending on the ionized calcium levels. Symptoms manifest when calcium levels exceed 12 mg/dl. We report four different cases that illustrate the need for a focused workup of hypercalcemia. Routine hypercalcemia workup includes serum Parathormone (PTH), Vitamin D, ionized calcium, phosphorus, magnesium, alkaline phosphatase levels, renal functions, and urinary calcium-creatinine ratio. Prognosis depends on the cause of hypercalcemia. The clinical diagnosis needs a high index of suspicion. Denitive management requires focused workup for etiological diagnosis and treatment of underlying cause. Treatment for hypercalcemia is required in all symptomatic patients or if the calcium level exceeds more than 15 mg/dL, even if asymptomatic. Immediate management includes restoring intravascular volume and promoting diuresis. Calcitonin, Bisphosphonates and steroids play a role in medical management. For patient's refractory to medical treatment, hemodialysis is required.

Asymptomatic Hypercalcemia Due to Bilateral Parathyroid Adenoma: A Case Report

Hyperparathyroidism caused by parathyroid adenoma is one of causes of hypercalcemia. Majority of parathyroid adenoma cases are found incidentally. We report a male patient aged 40 years, asymptomatic, who is undergoing routine laboratory examinations to extend his work contract. On examination we found an increase in calcium levels and parathyroid hormone levels. Then MSCT examination showed bilateral parathyroid adenoma. The diagnosis pathway and proper treatment for parathyroid adenoma can be challenging and problematic owing to inability of standard imaging to detect small enlargement of parathyroid glands. MSCT has the advantage of being able to detect small parathyroid lesions that cannot be detected by simple imaging modalities. Parathyroidectomy is the definitive treatment for adenoma parathyroid. Keywords: Hypercalcemia, parathyroid, asymptomatic.

Common electrolyte abnormalities in primary care: Hypercalcemia.

Hypercalcemia is a frequent and often incidental finding in primary care. The most common causes for hypercalcemia are primary hyperparathyroidism and malignancy. Providers should feel confident in progressing through an initial evaluation with appropriate diagnostics, interventions, and suitable and timely specialty referrals.

Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease

ObjectiveHypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality. MethodsA systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality. ResultsThirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes. ConclusionIn patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.

Atypical parathyroid adenoma: Series of two consecutive cases from a tertiary care hospital in Qatar.

IntroductionAtypical parathyroid adenomas (APA) are an uncommon cause of hypercalcemia and comprise a minority of parathyroid adenomas.Presentation of casesCase 1 - Egyptian male, 48 years old with history of type 2 diabetes mellitus, incidentally discovered increased serum of calcium level on routine investigation, was diagnosed as PHPT, US and MIBI scan showed large left inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA. Case 2 - Egyptian male, 60 years old, cardiac patient with history of diabetes, hypertension and multiple cardiac interventions, had nausea, vomiting, constipation abdominal pain, polyuria, polydipsia, and history of passing renal stones, hypercalcemia workup showed primary hyperparathyroidism (PHPT), MIBI was negative and SPECT scan suggested right inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA.DiscussionAPA are an uncommon cause of hypercalcemia and are responsible for a minority of parathyroid adenomas. Combined US and MIBI and SPECT scans can detect APA. Focused exploration and excision of the APA under general anaesthesia can completely remove the APA.ConclusionAwareness of the physician and a high index of suspicion to symptoms or signs that could reflect an underlying PHPT is essential. Yearly biochemical and neck US follow up are required to detect any risk of recurrence or malignancy in the long term.

Primary hyperparathyroidism in Saudi Arabia revisited: a multi-centre observational study.

PurposePrimary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and remains understudied within the Arabian population. The present study, the largest of its kind within the Gulf Cooperation Council (GCC) countries, aims to determine the demographics and clinical presentation of PHPT in Saudi Arabia.MethodsIn this multi-center retrospective study involving three tertiary hospitals in different geographic locations of Saudi Arabia namely, Riyadh, Al Ahsa and Jeddah, a total of 205 out of 243 confirmed PHPT cases aged 16 to 93 years old were included (N = 96 from Riyadh; N = 59 from Al Ahsa and N = 50 from Jeddah). Demographics, clinical manifestations and surgical outcomes were recorded as well as laboratory and radiologic investigations including serum parathyroid hormone (PTH), 25(OH)D, adjusted calcium, estimated glomerular filtration rate (eGFR) and nuclear scan outcome.ResultsPHPT cases appeared to increase over time when compared to other local studies published so far, with 12.8 cases per 100,000 hospital population. Females outnumber males (3:1) with 86% seen as out-patients. The average age was 59.8 ± 15.5 years. Abnormal PTH scan was seen in 171 patients (83.4%). Kidney stones was the most common renal manifestation (32 cases, 15.6%) and osteoporosis was the most common skeletal manifestation (67 cases, 32.7%). Al Ahsa had the highest prevalence of multiple comorbidities at 54% and the highest prevalence of obesity as a single comorbidity (17%) compared to other regions (p < 0.05). Jeddah recorded the highest prevalence of osteoporosis with bone and joint pains (30%) (p < 0.05).ConclusionComparison of present data with previous local studies suggest an increasing trend in PHPT cases in Saudi Arabia. Regional variations in the clinical presentation of PHPT were observed and warrant further investigation.

Fine-tuned continuous renal replacement therapy with calcium-free dialysate to manage severe hypercalcemia refractory to medical and intermittent hemodialysis.

Malignancy-related hypercalcemia is a leading cause of hypercalcemia among hospitalized patients that carries poor prognosis. Parathyroid carcinoma is a rare form of primary hyperparathyroidism that may be associated with PTH dependent hypercalcemia. Severe hypercalcemia is life-threatening and may require management in an intensive care unit by means of medical therapy consisting of volume expansion, loop diuretics, cinacalcet, calcitonin and bisphosphonates. Renal replacement therapy such as intermittent hemodialysis has been successfully used among patients with severe hypercalcemia who become refractory to medical treatment. However, little data are available for cases of severe refractory hypercalcemia that fail to respond to both optimal medical therapy and hemodialysis. Our present case illustrates the successful use of continuous veno-venous hemodiafiltration (CVVHDF) with calcium-free dialysate calcium and markedly increased dialysate flow rate, to restore normal calcemia in a patient with metastatic parathyroid carcinoma with severe refractory hypercalcemia.

Prevalence, causes and associated mortality of hypercalcaemia in modern hospital care.

Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in the prevalence of the underlying causes such as malignancy. To explore the epidemiology of hypercalcaemia in a modern tertiary hospital setting in Australia and evaluate the risk of mortality associated with hypercalcaemia. A retrospective study was performed in all inpatients with elevated blood calcium levels admitted from July 2013 to June 2018. ICD coding data identified primary diagnoses and mortality. Electronic medical records were reviewed in n = 292 patients admitted across 12 months from January to December 2017, to determine the causes of hypercalcaemia. Hypercalcaemia occurred in 1819 admissions (0.93% of all hospital admissions), during the 5-year period. The admission primary diagnoses were: malignancy (20% of cases), cardiovascular disease (17%) and gastrointestinal disease (11%). The top causes of hypercalcaemia among the 292 cases where electronic records were reviewed were malignancy (26%), primary hyperparathyroidism (25%) and hyperparathyroidism in the setting of chronic kidney disease (12%). Mortality occurred in 17% of these admissions. Non-survivors had significantly higher calcium levels, phosphate and white cell count, and had lower haemoglobin and albumin levels. Hypercalcaemia occurred in ~1% of admissions with main causes being malignancy and primary hyperparathyroidism, similar to historical studies. Hypercalcaemia in hospitalised patients is associated with high mortality and higher levels may be a marker for more severe underlying disease.

Immobilisation hypercalcaemia.

Hypercalcaemia is a common metabolic abnormality and its differential diagnosis is vast. Immobility is an uncommon cause of hypercalcaemia. Immobilisation hypercalcaemia is independent of parathyroid hormone and is associated with low levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. In addition, it is characterised by elevated levels of markers of bone resorption and low levels of bone-specific alkaline phosphatase, highlighting an imbalance of bone remodelling favouring osteoclastic bone resorption. Although immobilisation hypercalcaemia is a diagnosis of exclusion, physicians need to be aware of this condition to avoid excessive and invasive investigations when all other causes of parathyroid hormone-independent hypercalcaemia have been excluded. Management of immobilisation hypercalcaemia revolves around early mobilisation and rehabilitation together with pharmacotherapeutic agents such as intravenous isotonic saline, calcitonin and bisphosphonates. Denosumab may be a potential alternative yet off-label treatment for immobility hypercalcaemia in patients with renal insufficiency.

Systemic lupus erythematosus as a rare cause of hypercalcemia: A case report

Hypercalcemia is a rare manifestation in systemic lupus erythematosus (SLE) patients. In this case report, a thirty-five-year-old woman with a 3-year-old history of lupus was reported. Our case had symptoms of SLE flare, including joint pain, hair loss, photosensitivity, high level of calcium and creatinine, and lymphadenopathy. In her brain magnetic resonance imaging, intracranial hemorrhage was detected. Given her high serum level of calcium and phosphorus, reduced parathyroid hormone, and normal level of vitamin D, her hypercalcemia was attributed to the presence of stimulating parathyroid hormone receptor autoantibody. Regarding the findings of this study, it is suggested to consider SLE as a rare but possiblecause of severe hypercalcemia.

Too much of a good thing: A case series of rare yet pertinent causes of hypercalcaemia and acute kidney injury.

Calcium compounds and vitamin D supplements are readily available as over-the-counter preparations. Whilst integral in maintaining calcium homeostasis in certain patients, excess exogenous intake of these preparations can have deleterious effects, particularly in terms of renal function. We look at the cases of two patients, aged 52 and 34, who were referred into hospital with hypercalcaemia and acute kidney injury (AKI). Both individuals reported regular and prolonged self-medication with unregulated over-the-counter supplements containing calcium carbonate and vitamin D, respectively. Prompt investigation and treatment enabled an element of reversibility of the AKI in both the cases, with further improvement in renal function over time. We emphasise the importance of recognising the overuse of exogenous vitamin D supplements and calcium compounds as rare yet treatable causes of AKI associated with hypercalcaemia and discuss how raising public awareness into the risks posed by self-medication of over-the-counter medicines is paramount.

Abstract #1182278: Hyperthyroidism-induced hypercalcemia: Timing of response to treatment in the acute setting

Hyperthyroidism is an uncommon cause of hypercalcemia (HYPERCA). There is little information to guide the clinician on calcium (CA) response in relation to thyroid hormone control. This knowledge may be important when HYPERCA needs to be quickly treated due to its severity or to underlying patient co-morbidities. We describe a patient with HYPERCA of moderate severity due to Graves’ disease (GD) hyperthyroidism in whom normalization of CA level was a priority. Changes in CA levels in response to improvement in thyroid function and the role of anti-resorptive agents in this setting are discussed.

Abstract #1174395: Calcium Balance in Rhabdomyolysis and Acute Kidney Injury. A biphasic disease

Calcium homeostasis is closely regulated mainly by the parathyroid hormone (PTH) and to a lesser degree by the activated form of vitamin D. Primary hyperparathyroidism and underlying malignancy are the two most common causes of hypercalcemia. Few cases of rebound hypercalcemia have been reported in the recovery period of rhabdomyolysis-induced acute kidney injury (AKI) despite the relatively high incidence from up to one third of cases. Here we report a case of severe and symptomatic hypercalcemia in the recovery period of rhabdomyolysis and AKI with low PTH, PTH-related peptide (PTHrP) and 1,25-dihydroxycholecalciferol levels, and normal 25-hydroxycholecalciferol.

Abstract #1154108: Severe Hypercalcemia with a normal PTHrP level treated with Denosumab in the setting of ATLL

Asymptomatic and symptomatic Human T cell Lymphotropic Virus-1 (HTLV-1) infections and Adult T cell Leukemia and Lymphoma (ATLL) are rare but important causes of hypercalcemia. Here, we describe a case of severe hypercalcemia due to ATLL from HTLV-1 infection treated with denosumab, a monoclonal antibody that inhibits Receptor Activator of Nuclear Factor Kappa B ligand (RANKL).

Hypercalcaemia - A Rare Manifestation of Tuberculosis - A Case Report

Hypercalcaemia is defined as a serum calcium level of more than 10.50 mg/dl. Although there are several causative factors for hypercalcaemia, primary hyperparathyroidism and malignancy are the two most common causes encountered in clinical practice. Other causes include vitamin D intoxication, granulomatous diseases like sarcoidosis, tuberculosis and some fungal infections, thyrotoxicosis, Addison’s disease, milk-alkali syndrome, vitamin A intoxication, therapy with thiazide diuretics and lithium, familial hypocalciuric hypercalcaemia and prolonged immobilization. All these account for fewer than 10 % of all causes of hypercalcaemia. These rare causes of hypercalcaemia are important to consider in certain clinical situations when the underlying cause of hypercalcaemia cannot be attributed to primary hyperparathyroidism or overt malignancy.[1]