Materiały źródłowe

• #1 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  Hypercalcemia is diagnosed by a serum calcium concentration 10.4 mg/dL (2.60 mmol/L) or ionized serum calcium 5.2 mg/dL (1.30 mmol/L). […] Diagnosis is by measuring serum ionized calcium and parathyroid hormone concentrations. […] Hypercalcemia can be classified by severity based on serum calcium concentration: Mild 10.5 to 11.9 mg/dL (2.60 to 2.97mmol/L), Moderate 12.0 to 13.9 mg/dL (2.99 to 3.47 mmol/L), Severe 14.0 mg/dL (3.49 mmol/L). […] The cause is apparent from clinical data and results of these tests in 95% of patients. […] Patients without an obvious cause of hypercalcemia after this evaluation should undergo measurement of intact parathyroid hormone and 24-hour urinary calcium. […] Measurement of intact PTH levels help differentiate PTH-mediated hypercalcemia (eg, caused by hyperparathyroidism or familial hypocalciuric hypercalcemia), in which PTH levels are high or high-normal, from most other (PTH-independent) causes.

• #2 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Identify signs and symptoms of hypercalcemia. […] Interpret laboratory and imaging results accurately to determine the underlying cause of hypercalcemia. […] Evaluate differentials to determine the etiology of hypercalcemia. […] Determine appropriate treatment options for hypercalcemia. […] Hypercalcemia is often an incidental finding detected on labwork completed for other reasons. […] When calcium levels rise above 12 mg/dL, patients typically present with clinical signs and symptoms, including polyuria, polydipsia, constipation, weakness, neuropsychiatric effects, nausea, vomiting, fatigue, anorexia, and confusion. […] Hypercalcemia can be classified into the following categories: Mild hypercalcemia: 10.5 to 11.9 mg/dL, Moderate hypercalcemia: 12.0 to 13.9 mg/dL, Hypercalcemic crisis: 14.0 to 16.0 mg/dL.

• #3 Hypercalcemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/240681-overview

  Hypercalcemia may be classified based on total serum and ionized calcium levels, as follows: […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. Hypercalcemia from hyperparathyroidism is usually mild, asymptomatic, and sustained for years. Immunoreactive parathyroid hormone (PTH) and ionized calcium should be simultaneously measured. […] Mild cases of hypercalcemia can be asymptomatic and are more often diagnosed incidentally from routine blood tests. Because calcium metabolism normally is tightly controlled by the body, even mild persistent elevations above normal signal disease and should be investigated. […] Hypercalcemia is relatively common and often is mild but of long duration. The incidence of hyperparathyroidism alone is approximately 1-2 cases per 1000 adults. Mild cases are often not diagnosed.

• #4 A Practical Approach to Hypercalcemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0501/p1959.html

  Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. The diagnosis of hypercalcemia most often is made incidentally when a high calcium level is detected in blood samples. It is essential that physicians know how to evaluate and optimally manage patients with hypercalcemia, because treatment and prognosis vary according to the underlying disorder. […] Primary hyperparathyroidism and malignancy account for more than 90 percent of hypercalcemia cases. These conditions must be differentiated early to provide the patient with optimal treatment and accurate prognosis. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g., kidney stones).

• #5 Hypercalcemia: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14597-hypercalcemia

  Hypercalcemia is a fairly common finding on routine blood tests such as a comprehensive metabolic panel (CMP) or basic metabolic panel (BMP), which include a calcium blood test. These tests allow healthcare providers to detect abnormally high calcium levels early. […] If you have symptoms of hypercalcemia or are at risk for developing hypercalcemia due to having a certain kind of cancer, your provider will order different blood tests to determine if you have hypercalcemia. If your blood calcium level is elevated, your provider will review your medications and medical history and conduct a physical exam. […] If there’s no obvious cause to your elevated levels, your provider may ask you to see an endocrinologist, a provider who specializes in hormone-related conditions, who will provide further evaluation and testing.

• #6 Hypercalcemia – Endocrinology Advisor

  https://www.endocrinologyadvisor.com/ddi/hypercalcemia/

  Hypercalcemia is a condition in which the calcium level in your blood is above normal. […] Diagnostic workup includes laboratory tests and imaging, to determine the cause and severity of the condition. […] Patients presenting with signs of hypercalcemia should have the following labs drawn: Serum parathyroid hormone, Vitamin D, Calcitonin, Ionized calcium, Phosphorous, Magnesium, Alkaline phosphatase, Urinary calcium-creatinine ratio, Renal function. […] Laboratory values and presentation of symptoms aid in determining a diagnosis of hypocalcemia vs hypercalcemia. […] Imaging, including X-ray, MRI, and ultrasound should be done to rule out kidney stones, sarcoidosis, malignancies. […] Other diagnoses to consider during the hypercalcemia workup include hypermagnesemia, hyperparathyroidism, hyperphosphatemia, familial hypocalciuric hypercalcemia, Williams or Murk Jansen syndrome.

• #7 Hypercalcemia and Hypocalcemia – Vitamin D Testing | Choose the Right Test

  https://arupconsult.com/content/hypercalcemia-hypocalcemia

  Calcium imbalance (hyper- or hypocalcemia) is a metabolic abnormality with widespread effects that may be acute or chronic. […] Given the complex regulation of calcium homeostasis in the body, when evaluating for hyper- or hypocalcemia, laboratory testing for albumin, phosphorous, magnesium, creatinine, parathyroid hormone (PTH), and vitamin D (25-hydroxyvitamin D) should also be performed. […] Malignancy is a common cause of hypercalcemia, particularly in those with multiple myeloma or solid tumors such as lung, breast, and renal cancers. Hypercalcemia in these cases is due to the production of parathyroid hormone-related peptide (PTHrP), 1,25(OH)D2, or metastases to the bone inducing the release of osteoclast-activating factors. […] If hypo- or hypercalcemia is confirmed, and/or if the patient is symptomatic, intact PTH should be tested. In addition to PTH testing, phosphorous, magnesium, creatinine, vitamin D, and 24-hour urinary calcium and creatinine should be measured to aid in the diagnostic workup.

• #8 Hypercalcaemia of malignancy (HCM)

  https://www.eviq.org.au/clinical-resources/oncological-emergencies/486-hypercalcaemia-of-malignancy-hcm

  Hypercalcaemia of malignancy (HCM) is a condition which occurs in cancer patients and can be defined when the serum calcium level (corrected for albumin) is greater than 2.6 mmol/L or greater than the upper limit of normal (ULN) for a given reference value used in a lab. […] Therapy for hypercalcaemia should be initiated for symptomatic patients and those who have serum calcium concentrations 3.0 mmol/L. […] Severe hypercalcaemia is considered to be a medical emergency and must be treated aggressively. […] To confirm a diagnosis of hypercalcaemia: Check calcium level, corrected for serum albumin (as serum calcium is bound to albumin), which gives an indication of the amount of ionised (active) calcium. […] Additional laboratory evaluations include: serum creatinine, urea and electrolytes, phosphate and magnesium level, parathyroid hormone (PTH) to rule out primary hyperparathyroidism, PTHrP to rule out humoral hypercalcaemia of malignancy, 1,25-dihydroxy vitamin D (1,25(OH)2D), 25-hydroxy vitamin D (25(OH)D) to rule out vitamin D intoxication, TSH, Vitamin A, ECG to look for shortened QT interval or other conduction abnormalities.

• #9 A Practical Approach to Hypercalcemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0501/p1959.html

  Increased screening of calcium levels and wide availability of reliable assays for intact PTH levels have led to more frequent and earlier diagnoses of primary hyperparathyroidism. In primary or tertiary hyperparathyroidism, PTH levels are normal or high in the setting of hypercalcemia. Patients should be considered for parathyroidectomy only if they meet criteria recommended by the National Institutes of Health Consensus Development Conference. […] In cases of hypercalcemic crisis resulting from primary hyperparathyroidism, urgent parathyroidectomy is potentially curative.

• #10 Approach to Hypercalcemia – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279129/

  Nevertheless, although algorithms to adjust for albumin levels are widely used, their accuracy may be poor. […] Consequently, when major shifts in serum protein or pH are present it is most prudent to directly measure the ionized calcium level in order to determine the presence of hypercalcemia. […] Consequently, decreased levels of PTH and decreased levels of 1,25(OH)2D should accompany hypercalcemia unless the PTH or 1,25(OH)2D is the cause of the hypercalcemia. […] Hypercalcemic disorders can be broadly grouped into Endocrine Disorders, Malignant Disorders, Inflammatory Disorders, Pediatric Syndromes, Medication-Induced Hypercalcemia, and Immobilization. […] Approximately 90% of patients with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy-associated hypercalcemia (MAH).

• #11 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Hyperparathyroidism is the most common cause of hypercalcemia in the population at large and usually is mild, asymptomatic, and sustained for years. Immunoreactive parathyroid hormone (PTH) and ionized calcium should be simultaneously measured. PTH levels should be suppressed in hypercalcemia; thus, the combination of normal PTH levels and elevated calcium levels suggests mild hyperparathyroidism. Hyperparathyroidism may be part of multiple endocrine neoplasia type 1, (ie, Wermer syndrome). […] Other causes of hypercalcemia usually can be distinguished or at least considered on the basis of history and physical examination findings. Measurement of serum phosphate, alkaline phosphatase, serum chloride, serum bicarbonate, and urinary calcium may be useful in some cases. Renal function should be evaluated and thyroid-stimulating hormone should be checked to help rule out hyperthyroidism. In rare cases, measurement of vitamin D and its metabolites and measurement of parathyroid hormone-related peptide (PTHrP) may be necessary.

• #12 Hypercalcemia – Endocrinology Advisor

  https://www.endocrinologyadvisor.com/ddi/hypercalcemia/

  Patients with hyperparathyroidism will have high calcium and parathyroid hormone levels with low phosphorus. […] Parathyroid hormone related peptide levels are high in patients with hypercalcemia due to malignancy. […] Hypercalcemia treatment should be started in patients who present with hypercalcemia symptoms or have a serum calcium level of more than 14 mg/dl. […] Hypercalcemia treatment goals include eliminating excess calcium from the extracellular fluid, decreasing absorption of calcium in the digestive tract, and decreasing resorption of calcium in the bones. […] Patients with high parathyroid hormone levels should be evaluated for possible surgery to remove the source of increased parathyroid hormone secretion. […] Hypercalcemia of malignancy is treated with bisphosphonates, such as etidronate, pamidronate, and alendronate.

• #13 Hypercalcemia in Dogs and Cats – Endocrine System – Merck Veterinary Manual

  https://www.merckvetmanual.com/endocrine-system/the-parathyroid-glands-and-disorders-of-calcium-regulation-in-dogs-and-cats/hypercalcemia-in-dogs-and-cats

  Vitamin D status can be assessed by measuring calcidiol and calcitriol concentrations. Because vitamin D metabolites play a role in calcium homeostasis, assessing vitamin D status should be considered when creating a diagnostic plan. […] Imaging of the abdomen and thorax is warranted in patients with hypercalcemia. Abdominal radiographs or ultrasound examination should be performed to rule out urolithiasis. Thoracic radiographs are used to evaluate the lungs for evidence of masses or metastasis, thoracic lymph nodes, the cranial mediastinum, and bones in the field of view for osteolytic lesions. […] Once a diagnosis of PHPT is suspected, localization tests can be used to detect the abnormal gland(s) as well as help prepare for surgery. Cervical ultrasonography is the localization technique most commonly used but requires an experienced ultrasonographer because abnormal glands can be as small as 4 mm.

• #14 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  Hypercalcemia is diagnosed by a serum calcium concentration 10.4 mg/dL (2.60 mmol/L) or ionized serum calcium 5.2 mg/dL (1.30 mmol/L). […] Diagnosis is by measuring serum ionized calcium and parathyroid hormone concentrations. […] Hypercalcemia can be classified by severity based on serum calcium concentration: Mild 10.5 to 11.9 mg/dL (2.60 to 2.97mmol/L), Moderate 12.0 to 13.9 mg/dL (2.99 to 3.47 mmol/L), Severe 14.0 mg/dL (3.49 mmol/L). […] The cause is apparent from clinical data and results of these tests in 95% of patients. […] Patients without an obvious cause of hypercalcemia after this evaluation should undergo measurement of intact parathyroid hormone and 24-hour urinary calcium. […] Measurement of intact PTH levels help differentiate PTH-mediated hypercalcemia (eg, caused by hyperparathyroidism or familial hypocalciuric hypercalcemia), in which PTH levels are high or high-normal, from most other (PTH-independent) causes.

• #15 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Identify signs and symptoms of hypercalcemia. […] Interpret laboratory and imaging results accurately to determine the underlying cause of hypercalcemia. […] Evaluate differentials to determine the etiology of hypercalcemia. […] Determine appropriate treatment options for hypercalcemia. […] Hypercalcemia is often an incidental finding detected on labwork completed for other reasons. […] When calcium levels rise above 12 mg/dL, patients typically present with clinical signs and symptoms, including polyuria, polydipsia, constipation, weakness, neuropsychiatric effects, nausea, vomiting, fatigue, anorexia, and confusion. […] Hypercalcemia can be classified into the following categories: Mild hypercalcemia: 10.5 to 11.9 mg/dL, Moderate hypercalcemia: 12.0 to 13.9 mg/dL, Hypercalcemic crisis: 14.0 to 16.0 mg/dL.

• #16 Evaluation of hypercalcemia – Differential diagnosis of symptoms | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/159

  Hypercalcemia is diagnosed when the concentration of serum calcium is two standard deviations above the mean value found in people with normal calcium levels, in at least two samples taken at least 1 week apart. […] Normal serum or plasma total calcium should be 8.5 to 10.5 mg/dL and ionized calcium should be 4.6 to 5.1 mg/dL. […] Hypercalcemia may be mild and occur without symptoms. History may also identify symptoms of high calcium such as renal stones (typical of hyperparathyroidism), lethargy, easy fatigue, confusion, depression, irritability, constipation, and polyuria and polydipsia. […] Severe hypercalcemia is a life-threatening electrolyte emergency requiring prompt recognition and urgent response. […] Patients with asymptomatic primary hyperparathyroidism (mild hypercalcemia, generally within 1 mg/dL of the upper limit of the normal range), may undergo parathyroid surgery in the absence of medical contraindications. […] Surgery is not, however, mandatory in all patients with asymptomatic disease; recommendations for monitoring those who do not undergo parathyroid surgery should be followed.

• #17 Hypercalcemia: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14597-hypercalcemia

  Your healthcare provider may order any of the following tests to help diagnose hypercalcemia and its cause: Calcium blood test, Parathyroid hormone (PTH) blood test, PTH-related protein (PTHrP) blood test, Vitamin D blood test, Calcium urine test. […] If your provider suspects primary hyperparathyroidism is causing hypercalcemia, they’ll likely recommend an imaging test to see if there are any growths on your parathyroid gland(s) or if they’re enlarged. Different imaging tests for this purpose include: Ultrasound test, Nuclear medicine imaging, specifically a parathyroid scan, CT (computed tomography) scan.

• #18 Hypercalcemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypercalcemia/symptoms-causes/syc-20355523

  Hypercalcemia is a condition in which the calcium level in the blood becomes too high. […] Most often, hypercalcemia happens after one or more of the parathyroid glands make too much hormone. […] We utilize multimodal imaging, meaning various types of imaging to identify where the abnormal parathyroid is located. […] Patients can come into the office feeling a variety of symptoms that are generally nonspecific but rather debilitating for them. […] Call your healthcare professional if you think you have any symptoms of hypercalcemia. […] Hypercalcemia can be caused by: Overactive parathyroid glands. This also is called hyperparathyroidism. […] Hypercalcemia can lead to medical conditions that include: Osteoporosis.

• #19 Hypercalcemia in Dogs and Cats – Endocrine System – Merck Veterinary Manual

  https://www.merckvetmanual.com/endocrine-system/the-parathyroid-glands-and-disorders-of-calcium-regulation-in-dogs-and-cats/hypercalcemia-in-dogs-and-cats

  Vitamin D status can be assessed by measuring calcidiol and calcitriol concentrations. Because vitamin D metabolites play a role in calcium homeostasis, assessing vitamin D status should be considered when creating a diagnostic plan. […] Imaging of the abdomen and thorax is warranted in patients with hypercalcemia. Abdominal radiographs or ultrasound examination should be performed to rule out urolithiasis. Thoracic radiographs are used to evaluate the lungs for evidence of masses or metastasis, thoracic lymph nodes, the cranial mediastinum, and bones in the field of view for osteolytic lesions. […] Once a diagnosis of PHPT is suspected, localization tests can be used to detect the abnormal gland(s) as well as help prepare for surgery. Cervical ultrasonography is the localization technique most commonly used but requires an experienced ultrasonographer because abnormal glands can be as small as 4 mm.

• #20 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Chest radiographs always should be performed to help rule out lung cancer or sarcoidosis. Other radiographs should be considered to help evaluate for possible malignancies, metastases, or Paget disease. […] Mammograms should be considered to help rule out breast cancer. Computed tomography (CT) and ultrasound should be considered to help rule out renal cancer. […] When a biochemical diagnosis of primary hyperparathyroidism is made, CT scan, ultrasound, magnetic resonance imaging (MRI), and radionuclide imaging of the parathyroid gland may be helpful to assist with preoperative localization. […] On electrocardiography (ECG), characteristic changes in patients with hypercalcemia include shortening of the QT interval. ECG changes in patients with very high serum calcium levels include the following: slight prolongation of the PR and QRS intervals, T wave flattening or inversion, a J wave at the end of the QRS complex, ST elevation mimicking acute myocardial infarction.

• #21 Hyperparathyroidism: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14454-hyperparathyroidism

  Hyperparathyroidism is a condition where one or more of your parathyroid glands is overactive and releases (secretes) too much parathyroid hormone (PTH). This can cause hypercalcemia, or high levels of calcium in your blood. […] Healthcare providers diagnose hyperparathyroidism by measuring your calcium, vitamin D and parathyroid hormone levels. Theyll also check your kidney function. […] Primary hyperparathyroidism causes high levels of calcium in your blood and pee, and low levels of phosphate in your blood. Secondary hyperparathyroidism causes low levels of vitamin D, normal or low levels of calcium and high levels of phosphate in your blood. Providers often find hyperparathyroidism during routine tests before you have symptoms. […] Tests providers use to diagnose and monitor hyperparathyroidism include: Blood tests. 24-hour urine test. For this test, you collect your pee for 24 hours and then bring it to a lab for testing. Your provider will give you instructions on how to complete a 24-hour urine test. Parathyroid scan. Also called a sestamibi scan, providers can use a parathyroid scan to help locate which gland or glands are producing too much PTH. Before surgery, they may use the scan to locate specific areas to remove. Ultrasounds or other imaging of your kidneys or parathyroid glands. Bone density scans.

• #22 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Chest radiographs always should be performed to help rule out lung cancer or sarcoidosis. Other radiographs should be considered to help evaluate for possible malignancies, metastases, or Paget disease. […] Mammograms should be considered to help rule out breast cancer. Computed tomography (CT) and ultrasound should be considered to help rule out renal cancer. […] When a biochemical diagnosis of primary hyperparathyroidism is made, CT scan, ultrasound, magnetic resonance imaging (MRI), and radionuclide imaging of the parathyroid gland may be helpful to assist with preoperative localization. […] On electrocardiography (ECG), characteristic changes in patients with hypercalcemia include shortening of the QT interval. ECG changes in patients with very high serum calcium levels include the following: slight prolongation of the PR and QRS intervals, T wave flattening or inversion, a J wave at the end of the QRS complex, ST elevation mimicking acute myocardial infarction.

• #23 Disease Management: Hypercalcemia

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypercalcemia/default.htm

  Hypercalcemia is usually detected initially as an elevation of total plasma calcium levels rather than ionized calcium levels. Approximately 90% of all cases of hypercalcemia in the outpatient setting are caused by either primary HPT or hypercalcemia of malignancy. […] The diagnosis of primary HPT requires an elevated serum calcium level either with a simultaneous elevation of PTH levels (in 80% to 90% of patients) or normal PTH levels (10% to 20% of patients). […] The PTH elevation should be determined by an assay that measures the intact PTH molecule. […] Urinary calcium excretion is measured by a 24-hour urine collection, which should also specify total volume and urine creatinine levels. Hypercalciuria is defined as urinary calcium excretion higher than 400 mg/day. […] In some cases, a less invasive surgical approach can be used in which the abnormal parathyroid glands are localized preoperatively using ultrasound, Tc-99m sestamibi scintigraphy, or magnetic resonance imaging.

• #24 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #25 Hypercalcemia: High calcium levels and what to do

  https://www.medicalnewstoday.com/articles/322012

  Hypercalcemia or high calcium levels may not cause any symptoms. […] In this article, we explore the symptoms, causes, and complications of hypercalcemia. We also describe how doctors diagnose and treat hypercalcemia. […] If calcium levels become too high, a person may receive a diagnosis of hypercalcemia. […] Anyone experiencing symptoms of hypercalcemia should speak with a doctor, who will order a blood test and make a diagnosis based on the results. […] A person with mild hypercalcemia may have no symptoms, and doctors might only diagnose the condition after carrying out a routine blood test. […] The test will check the blood levels of calcium and parathyroid hormone. […] After diagnosing hypercalcemia, a doctor may perform further tests, such as: an electrocardiogram (EKG) to record the electrical activity of the heart, a chest X-ray to check for lung cancer or infections, a mammogram to check for breast cancer, a CT or MRI scan to examine the body’s structure and organs, dual-energy X-ray absorptiometry, commonly known as a DEXA scan, to measure bone density. […] If calcium levels continue to rise or do not improve on their own, doctors may recommend further testing. […] For people with more severe hypercalcemia, it is important to discover the cause. […] The treatment options for hypercalcemia will depend on its severity and cause.

• #26 Hypercalcemia | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/hypercalcemia

  The diagnosis of hypercalcemia requires a simple blood test for measurement of the serum calcium level. […] In order to determine the cause of hypercalcemia, a child will need additional laboratory tests, including measurement of serum levels of phosphorus, PTH and vitamin D metabolites. […] Hypercalcemia with increased PTH suggests a parathyroid cause, such as primary hyperparathyroidism. […] If this is suspected, imaging of the parathyroid glands may be done. […] Your child may also have skeletal X-rays and bone densitometry (DXA scan) to look for bone thinning and erosions that are sometimes associated with hyperparathyroidism. […] A kidney ultrasound can identify calcium deposits in the kidneys. […] Genetic testing may also be performed depending on the cause of hypercalcemia.

• #27 Hypercalcemia Causes, Symptoms, Diagnosis and Treatment – Cura4U

  https://cura4u.com/conditions/hypercalcemia

  Blood Tests: Hypercalcemia has few, if any, symptoms you may not realize you have until routine blood tests detect a high level of calcium in your blood. Blood testing can also show whether you have hyperparathyroidism if your parathyroid hormone level is high. Granulomatous disease, iatrogenic causes (e.g., kidney dialysis), adrenal insufficiency, thyrotoxicosis, and vitamin D intoxication all cause low PTH levels. […] Your doctor may order imaging studies of your bones or lungs to see if a disease like cancer or sarcoidosis causes your hypercalcemia. Bone abnormalities such as demineralization, bone cysts, pathological fractures, and bony metastases may be visible on plain X-rays. To detect abnormalities of the urogenital tract, such as calcification or stones, an ultrasound scan, computerized tomography (CT) scan, or intravenous pyelogram (IVP) may be required. If hypertrophy or adenoma of the parathyroid glands is suspected, an ultrasound or technetium scan of the glands may be recommended.

• #28 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Chest radiographs always should be performed to help rule out lung cancer or sarcoidosis. Other radiographs should be considered to help evaluate for possible malignancies, metastases, or Paget disease. […] Mammograms should be considered to help rule out breast cancer. Computed tomography (CT) and ultrasound should be considered to help rule out renal cancer. […] When a biochemical diagnosis of primary hyperparathyroidism is made, CT scan, ultrasound, magnetic resonance imaging (MRI), and radionuclide imaging of the parathyroid gland may be helpful to assist with preoperative localization. […] On electrocardiography (ECG), characteristic changes in patients with hypercalcemia include shortening of the QT interval. ECG changes in patients with very high serum calcium levels include the following: slight prolongation of the PR and QRS intervals, T wave flattening or inversion, a J wave at the end of the QRS complex, ST elevation mimicking acute myocardial infarction.

• #29 Hypercalcaemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypercalcaemia

  Elevated PTHrP is suggestive of malignancy. […] The normal range is 2.12.6 mmol/L (8.810.7 mg/dL, 4.35.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcaemia. […] Moderate hypercalcaemia is a level of 2.883.5 mmol/L (11.514 mg/dL) while severe hypercalcaemia is 3.5 mmol/L (14 mg/dL). […] Abnormal heart rhythms can also result, and ECG findings of a short QT interval suggest hypercalcaemia. […] Significant hypercalcaemia can cause ECG changes mimicking an acute myocardial infarction.

• #30 A Practical Approach to Hypercalcemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0501/p1959.html

  Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. The diagnosis of hypercalcemia most often is made incidentally when a high calcium level is detected in blood samples. It is essential that physicians know how to evaluate and optimally manage patients with hypercalcemia, because treatment and prognosis vary according to the underlying disorder. […] Primary hyperparathyroidism and malignancy account for more than 90 percent of hypercalcemia cases. These conditions must be differentiated early to provide the patient with optimal treatment and accurate prognosis. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g., kidney stones).

• #31 Diagnostic approach to hypercalcemia – UpToDate

  https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia

  Diagnostic approach to hypercalcemia. Hypercalcemia is a relatively common clinical problem. Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases. Therefore, the diagnostic approach to hypercalcemia typically involves distinguishing between the two. It is usually not difficult to differentiate between them. Malignancy is often evident clinically by the time it causes hypercalcemia, and patients with hypercalcemia of malignancy usually have higher calcium concentrations and are more symptomatic from hypercalcemia than individuals with primary hyperparathyroidism. Although hypercalcemia in otherwise healthy outpatients is usually due to primary hyperparathyroidism and malignancy is more often responsible for hypercalcemia in hospitalized patients, other potential causes of hypercalcemia must be considered. This topic will review the diagnostic approach to hypercalcemia. The clinical manifestations, etiology, and treatment are reviewed separately.

• #32 The diagnosis and management of hypercalcaemia | The BMJ

  https://www.bmj.com/content/350/bmj.h2723

  Primary hyperparathyroidism and malignancy are the two most common causes of increased serum calcium levels. […] The diagnosis of hypercalcaemia is made when the corrected serum calcium concentration is 2 standard deviations above the mean of values found in people with normal calcium levels, in at least two samples at least one week apart over a period of three months. […] The presence of high or not adequately suppressed serum parathyroid hormone levels should point the diagnosis towards hypercalcaemia of parathyroid origins. […] Mild hypercalcaemia is usually caused by primary hyperparathyroidism, the treatment for which is typically surgery; those aged 50 or more with serum calcium levels 0.25 mmol/L above the upper limit of normal and without end organ damage may be followed up conservatively. Treatment with a calcimimetic agent, cinacalcet, is an option in selected cases. […] Severe hypercalcaemia requires admission to hospital and treatment with aggressive intravenous hydration and bisphosphonates along with treatment of the underlying disease.

• #33 Approach to Hypercalcemia – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279129/

  A reduction in serum calcium can stimulate parathyroid hormone (PTH) release which may then increase bone resorption, enhance renal calcium reabsorption, and stimulate renal conversion of 25-hydroxyvitamin D, to the active moiety 1,25-dihydroxyvitamin D [1,25(OH)2D] which then will enhance intestinal calcium absorption. […] Normal serum concentrations of total calcium generally range between 8.5 and 10.5 mg/dL (2.12 to 2.62 mM) and ionized calcium between 4.65-5.30 mg/dL (1.16-1.31 mM). […] Decreased PTH and decreased 1,25(OH)2D should accompany hypercalcemia unless PTH or 1,25(OH)2D is causal. […] Hypercalcemia can be defined as a serum calcium greater than 2 standard deviations above the normal mean in a reference laboratory. […] Concentrations of total calcium in normal serum generally range between 8.5 and 10.5 mg/dL (2.12 to 2.62 mM) and levels above this are considered to be consistent with hypercalcemia.

• #34 Hypercalcemia – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hypercalcemia/

  Hypercalcemia refers to high serum calcium levels (total Ca 10.5 mg/dL or ionized Ca2+ 5.25 mg/dL). The most important initial diagnostic steps are ruling out factitious hypercalcemia (by measuring ionized calcium or calculating the corrected calcium) and measuring intact PTH levels (to differentiate between PTH-mediated hypercalcemia and non-PTH-mediated hypercalcemia). […] Confirm true hypercalcemia: measure ionized calcium OR calculate corrected calcium using total calcium and serum albumin. […] Measure serum intact PTH: initial study to determine the etiology of hypercalcemia and to differentiate PTH-mediated hypercalcemia from non-PTH-mediated hypercalcemia. […] Measurement of serum intact PTH level is the key initial study for confirmed hypercalcemia with no immediately evident etiology.

• #35 Approach to Hypercalcemia – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279129/

  Nevertheless, although algorithms to adjust for albumin levels are widely used, their accuracy may be poor. […] Consequently, when major shifts in serum protein or pH are present it is most prudent to directly measure the ionized calcium level in order to determine the presence of hypercalcemia. […] Consequently, decreased levels of PTH and decreased levels of 1,25(OH)2D should accompany hypercalcemia unless the PTH or 1,25(OH)2D is the cause of the hypercalcemia. […] Hypercalcemic disorders can be broadly grouped into Endocrine Disorders, Malignant Disorders, Inflammatory Disorders, Pediatric Syndromes, Medication-Induced Hypercalcemia, and Immobilization. […] Approximately 90% of patients with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy-associated hypercalcemia (MAH).

• #36 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  Hypercalcemia is diagnosed by a serum calcium concentration 10.4 mg/dL (2.60 mmol/L) or ionized serum calcium 5.2 mg/dL (1.30 mmol/L). […] Diagnosis is by measuring serum ionized calcium and parathyroid hormone concentrations. […] Hypercalcemia can be classified by severity based on serum calcium concentration: Mild 10.5 to 11.9 mg/dL (2.60 to 2.97mmol/L), Moderate 12.0 to 13.9 mg/dL (2.99 to 3.47 mmol/L), Severe 14.0 mg/dL (3.49 mmol/L). […] The cause is apparent from clinical data and results of these tests in 95% of patients. […] Patients without an obvious cause of hypercalcemia after this evaluation should undergo measurement of intact parathyroid hormone and 24-hour urinary calcium. […] Measurement of intact PTH levels help differentiate PTH-mediated hypercalcemia (eg, caused by hyperparathyroidism or familial hypocalciuric hypercalcemia), in which PTH levels are high or high-normal, from most other (PTH-independent) causes.

• #37 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  A key diagnostic step is checking a parathyroid hormone level to clarify if hypercalcemia is parathyroid hormone-mediated or not. […] Hypercalcemia is easily diagnosed through laboratory tests, but further diagnostics often guide etiology and treatment options. […] The goals of treating hypercalcemia include increased elimination from the extracellular fluid, reduced gastrointestinal absorption, and decreased bone resorption. […] Treatment options differ based on the etiology and severity of hypercalcemia. […] Patients with hypercalcemia can become volume-depleted and require intravenous (IV) hydration. […] Obtaining a detailed history and performing a thorough physical examination, including reviewing all medications, are crucial to determining the etiology of hypercalcemia. […] The prognosis of hypercalcemia is largely dependent on its etiology.

• #38 Hypercalcemia – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hypercalcemia/

  Hypercalcemia refers to high serum calcium levels (total Ca 10.5 mg/dL or ionized Ca2+ 5.25 mg/dL). The most important initial diagnostic steps are ruling out factitious hypercalcemia (by measuring ionized calcium or calculating the corrected calcium) and measuring intact PTH levels (to differentiate between PTH-mediated hypercalcemia and non-PTH-mediated hypercalcemia). […] Confirm true hypercalcemia: measure ionized calcium OR calculate corrected calcium using total calcium and serum albumin. […] Measure serum intact PTH: initial study to determine the etiology of hypercalcemia and to differentiate PTH-mediated hypercalcemia from non-PTH-mediated hypercalcemia. […] Measurement of serum intact PTH level is the key initial study for confirmed hypercalcemia with no immediately evident etiology.

• #39 Calcium Disorders | College of Veterinary Medicine at MSU

  https://cvm.msu.edu/vdl/laboratory-sections/endocrinology/calcium-disorders-1

  The combination of a clinically significant ionized hypercalcemia and a parathyroid hormone (PTH) concentration above the upper limit of the reference interval is consistent with a diagnosis of primary hyperparathyroidism. […] The combination of a clinically significant ionized hypercalcemia and a parathyroid hormone (PTH) concentration below the lower limit of the reference interval, or low-normal, is consistent with parathyroid independent hypercalcemia. […] An increased (positive) parathyroid hormone-related protein (PTHrP) result with ionized hypercalcemia and concurrent suppression of parathyroid hormone (PTH) adds support for humoral hypercalcemia of malignancy. […] The combination of ionized hypercalcemia and a parathyroid hormone (PTH) concentration that is between low- and mid-normal is equivocal with regard to distinguishing between primary hyperparathyroidism and parathyroid independent causes of hypercalcemia.

• #40 Diagnosing a disorder with few symptoms | I.M. Matters from ACP

  https://immattersacp.org/archives/2012/03/hypercalcemia.htm

  According to a May 2003 article in American Family Physician, primary hyperparathyroidism is the most common cause of hypercalcemia, and about one in every 500 patients treated by primary care physicians has undiagnosed primary hyperparathyroidism. […] PTH-independent hypercalcemia is diagnosed when the serum calcium is elevated and the PTH is low or suppressed. […] This type of hypercalcemia can indicate a malignancy and is a secondary effect of cancer or of a paraneoplastic syndrome that develops in 10% to 20% of patients with certain types of cancer. […] Diagnosing hypercalcemia requires a high index of suspicion, particularly since the symptoms can be nonspecific or subtle. […] Recognition of the condition often occurs with an incidental finding of elevated calcium on a blood test.

• #41 Hypercalcemia – EMCrit Project

  https://emcrit.org/ibcc/hypercalcemia/

  evaluation of hypercalcemia: Ionized calcium level. Electrolytes including Mg/Phos. Parathyroid hormone (PTH). PTH-related peptide (PTHrp). 25-OH vitamin D and 1,25-OH vitamin D. Thyroid stimulating hormone (TSH). […] Overall, ~90% of hypercalcemia is due to hyperparathyroidism or malignancy. Among critically ill patients (especially those with severe hypercalcemia), malignancy is the most likely cause. […] basic hypercalcemia lab panel: Ionized calcium level. Complete electrolytes (including Ca/Mg/Phos): Hypophosphatemia suggests: hyperparathyroidism, humoral hypercalcemia of malignancy (due to PTH-related peptide), or sometimes milk-alkali syndrome. Hyperphosphatemia suggests: everything else (myriad disorders in which endogenous PTH is suppressed). Parathyroid hormone (PTH): Elevated or inappropriately normal in primary or tertiary hyperparathyroidism. Low in all other causes of hypercalcemia.

• #42 Hypercalcaemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypercalcaemia

  Diagnosis should generally include either a calculation of corrected calcium or direct measurement of ionized calcium level and be confirmed after a week. […] Once calcium is confirmed to be elevated, a detailed history taken from the subject, including review of medications, any vitamin supplementations, herbal preparations, and previous calcium values. […] If detailed history and examination does not narrow down the differential diagnoses, further laboratory investigations are performed. […] Elevated (or high-normal) iPTH with high urine calcium/creatinine ratio (more than 0.03) is suggestive of primary hyperparathyroidism, usually accompanied by low serum phosphate. […] High iPTH with low urine calcium/creatinine ratio is suggestive of familial hypocalciuric hypercalcemia. […] Low iPTH should be followed up with Parathyroid hormone-related protein (PTHrP) measurements (though not available in all labs).

• #43 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  A key diagnostic step is checking a parathyroid hormone level to clarify if hypercalcemia is parathyroid hormone-mediated or not. […] Hypercalcemia is easily diagnosed through laboratory tests, but further diagnostics often guide etiology and treatment options. […] The goals of treating hypercalcemia include increased elimination from the extracellular fluid, reduced gastrointestinal absorption, and decreased bone resorption. […] Treatment options differ based on the etiology and severity of hypercalcemia. […] Patients with hypercalcemia can become volume-depleted and require intravenous (IV) hydration. […] Obtaining a detailed history and performing a thorough physical examination, including reviewing all medications, are crucial to determining the etiology of hypercalcemia. […] The prognosis of hypercalcemia is largely dependent on its etiology.

• #44 Approach to Hypercalcemia – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279129/

  Nevertheless, although algorithms to adjust for albumin levels are widely used, their accuracy may be poor. […] Consequently, when major shifts in serum protein or pH are present it is most prudent to directly measure the ionized calcium level in order to determine the presence of hypercalcemia. […] Consequently, decreased levels of PTH and decreased levels of 1,25(OH)2D should accompany hypercalcemia unless the PTH or 1,25(OH)2D is the cause of the hypercalcemia. […] Hypercalcemic disorders can be broadly grouped into Endocrine Disorders, Malignant Disorders, Inflammatory Disorders, Pediatric Syndromes, Medication-Induced Hypercalcemia, and Immobilization. […] Approximately 90% of patients with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy-associated hypercalcemia (MAH).

• #45 Hyperparathyroidism | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0115/p333.html

  Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. […] Persistent hypercalcemia and an elevated serum parathyroid hormone level are the diagnostic criteria for primary hyperparathyroidism. […] Laboratory measurements of the mediators of calcium metabolism are reliable and facilitate determination of etiologic factors in almost all patients with hypercalcemia. […] Persistent hypercalcemia and an elevated serum PTH level confirm the diagnosis of primary hyperparathyroidism. […] Further laboratory testing is unnecessary because other causes of hypercalcemia rarely are associated with elevated PTH levels. […] Hypercalcemia should be confirmed by repeated measurements of serum calcium concentrations, because all patients with primary hyperparathyroidism do not have demonstrable hypercalcemia every time the serum calcium level is measured.

• #46 Hypercalcemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/240681-overview

  Some studies suggest that up to 20% of patients who present to the ED with hypercalcemia are ultimately diagnosed with hyperparathyroidism. […] Hypercalcemia caused by a neoplasm tends to be much more serious. The mechanism of hypercalcemia in malignancy can be from the ectopic production of a PTH-like factor, PTH-related protein (PTHrP), or osteolytic metastases. […] Cancer-related hypercalcemia most often occurs in later-stage malignancies and it predicts a poor prognosis for patients with it.

• #47 Diagnose and Treat Hypercalcemia of Malignancy | Oncology Nursing Society

  https://www.ons.org/publications-research/voice/news-views/07-2021/diagnose-and-treat-hypercalcemia-malignancy

  Hypercalcemia of malignancy (HCM) is a common paraneoplastic syndrome associated with poor prognosis that affects approximately 20%30% of patients with cancer. […] Elevated calcium levels can result in life-threatening outcomes, but HCM is typically manageable with early diagnosis. Regularly monitoring calcium levels is critical, but practitioners must recognize that it may fluctuate with albumin levels because 40%45% of serum calcium is bound to albumin, so measure serum albumin or ionized calcium levels as well. […] HCM can affect multiple organ systems through several clinical manifestations. Kidney involvement can lead to nephrolithiasis and chronic renal insufficiency. […] Because an incidental finding of hypercalcemia may be the first sign of an undiagnosed cancer, the work-up should not stop after HCM diagnosis. […] PTH lab values are critical to guide treatment. Although palliative IV fluids and bisphosphonate therapy is the mainstay of initial treatment, addressing the underlying malignancy is the best chance at long-term management.

• #48 Hypercalcemia | VCA Animal Hospitals

  https://vcahospitals.com/know-your-pet/hypercalcemia

  Hypercalcemia occurs when the level of calcium in the blood is higher than normal (hyper = above; -emia = blood). […] High calcium levels may signal the presence of serious underlying disease, including kidney failure, adrenal gland failure (called Addison’s disease), a parathyroid gland tumor, and some types of cancer. […] If preliminary testing reveals hypercalcemia, then it is often recommended to measure ionized calcium to confirm the finding. […] If there is no evidence of a disease that might explain the high calcium (e.g., renal failure, Addisons disease etc.), then total calcium should be re-measured on a fresh blood sample to confirm the result. […] Once hypercalcemia is confirmed, the challenge is to identify the underlying cause. Further testing will be needed to assess the health of the kidneys, adrenal glands, and parathyroid glands.

• #49

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=8708&catId=18057&id=3843801

  Glucocorticosteroids can contribute significantly in reducing the magnitude of persistent hypercalcemia in patients with lymphosarcoma (cytolysis), multiple myeloma, hypoadrenocorticism, hypervitaminosis D, or granulomatous disease, but they have little effect on other causes of hypercalcemia. Steroids exert their effect mainly by reducing bone resorption, decreasing intestinal calcium absorption, and increasing renal calcium excretion. Steroids should be withheld if a definitive diagnosis has not been established. […] Recently, chemical ablation of the parathyroid gland has been reported as an effective means of reducing serum calcium concentrations in dogs with primary hyperparathyroidism. Guided by ultrasound, ethanol is injected into the parathyroid mass. Both total and ionized calcium concentrations return to normal within 24 hours in most dogs. Transient hypocalcemia may develop, and may require treatment.

• #50 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #51 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #52 Familial Hypocalciuric Hypercalcemia (FHH) | Dr. Babak Larian

  https://www.hyperparathyroidmd.com/familial-hypocalciuric-hypercalcemia/

  A medical evaluation is key for those who display symptoms of FHH and/or PHPT. After getting an evaluation, people can find out if either of these conditions are causing their symptoms and receive appropriate treatment. […] Measuring the PTH level is a great first step to determine if a patient is dealing with hypercalcemia. If the PTH level is higher than normal, a patient may be dealing with PHPT. If the PTH level is close to normal or in the normal range then FHH should also be considered. […] Diagnosis of FHH can be confirmed by doing genetic testing.

• #53 Hypercalcemia: A Practice Overview of Its Diagnosis and Causes

  https://www.mdpi.com/2673-8236/5/1/7

  Hypercalcemia is defined as a serum calcium concentration higher than 10.5 mg/gL or 2.6 mmol/L. […] Thus, to discriminate true hypercalcemia from pseudo hypercalcemia, an ionized calcium concentration higher than 1.3 mmol/L might be more appropriate. […] For this condition, the correct diagnostic algorithm should be followed. In this review, we summarize the diagnostic steps to follow and detail each clinical pathway is involved in hypercalcemia. […] Before the diagnostic management of hypercalcemia, iatrogenic causes should be excluded. […] In keeping with Murray et al. and their diagnostic algorithm of genuine hypercalcemia, the differential diagnosis should start with the PTH dosage. […] After detecting PTH-mediated or non-PTH-mediated hypercalcemia, PTHrP, vitamin D in two forms, and oncological screening should be performed.

• #54

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=8708&catId=18057&id=3843801

  Diseases result in hypercalcemia by causing increased bone resorption of calcium, decreased renal excretion of calcium, increased GI absorption of calcium, increased serum binding of calcium to proteins/complexes, or a combination of these processes. The causes of hypercalcemia noted in referral hospitals may not reflect the same frequency of diagnosis encountered in primary care facilities. Observations from a primary care biochemistry laboratory indicate that renal failure is most commonly associated with hypercalcemia in the dog. […] Hypercalcemia can be transient and inconsequential (common), persistent and inconsequential (occasionally), or persistent and pathologic. The differential diagnoses for persistent pathologic hypercalcemia are heavily biased toward malignancy. Nonpathologic conditions associated with hypercalcemia include non-fasting (minimal increase), physiologic growth of young animals, laboratory error, and spurious as a result of lipemia or detergent contamination of the sample/tube. Transient/inconsequential causes associated with hypercalcemia include hemoconcentration, hyperproteinemia, hypoadrenocorticism, and severe environmental hypothermia. Diseases result in pathologic, persistent hypercalcemia by causing increased bone resorption, decreased renal excretion of calcium, increased GI absorption of calcium, increased serum binding of calcium to proteins/complexes, or combinations of these processes. HARDIONS is an eponym technique used to remind us of several categories of disease that may result in hypercalcemia: H = Hyperparathyroidism (primary and tertiary), HHM (humoral hypercalcemia of malignancy); A = Addisons Disease; R = Renal Disease; D = Vitamin D toxicosis (includes granulomatous disease); I = Idiopathic (mostly cats); O = Osteolytic (osteomyelitis, immobilization), N = Neoplasia (HHM and local osteolytic hypercalcemia); S = Spurious.

• #55 Etiology of hypercalcemia – UpToDate

  https://www.uptodate.com/contents/etiology-of-hypercalcemia

  Patients with severe chronic kidney disease often develop frankly low or low-normal serum calcium concentrations due to decreased renal synthesis of 1,25-dihydroxyvitamin D. Prolonged chronic hypocalcemia causes compensatory increases in serum PTH (secondary hyperparathyroidism) and leads to parathyroid gland hyperplasia over time.

• #56 Diagnostic approach to hypercalcemia – UpToDate

  https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia

  Diagnostic approach to hypercalcemia. Hypercalcemia is a relatively common clinical problem. Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases. Therefore, the diagnostic approach to hypercalcemia typically involves distinguishing between the two. It is usually not difficult to differentiate between them. Malignancy is often evident clinically by the time it causes hypercalcemia, and patients with hypercalcemia of malignancy usually have higher calcium concentrations and are more symptomatic from hypercalcemia than individuals with primary hyperparathyroidism. Although hypercalcemia in otherwise healthy outpatients is usually due to primary hyperparathyroidism and malignancy is more often responsible for hypercalcemia in hospitalized patients, other potential causes of hypercalcemia must be considered. This topic will review the diagnostic approach to hypercalcemia. The clinical manifestations, etiology, and treatment are reviewed separately.

• #57 A Practical Approach to Hypercalcemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0501/p1959.html

  Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. The diagnosis of hypercalcemia most often is made incidentally when a high calcium level is detected in blood samples. It is essential that physicians know how to evaluate and optimally manage patients with hypercalcemia, because treatment and prognosis vary according to the underlying disorder. […] Primary hyperparathyroidism and malignancy account for more than 90 percent of hypercalcemia cases. These conditions must be differentiated early to provide the patient with optimal treatment and accurate prognosis. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g., kidney stones).

• #58 Hypercalcemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/240681-overview

  Hypercalcemia may be classified based on total serum and ionized calcium levels, as follows: […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. Hypercalcemia from hyperparathyroidism is usually mild, asymptomatic, and sustained for years. Immunoreactive parathyroid hormone (PTH) and ionized calcium should be simultaneously measured. […] Mild cases of hypercalcemia can be asymptomatic and are more often diagnosed incidentally from routine blood tests. Because calcium metabolism normally is tightly controlled by the body, even mild persistent elevations above normal signal disease and should be investigated. […] Hypercalcemia is relatively common and often is mild but of long duration. The incidence of hyperparathyroidism alone is approximately 1-2 cases per 1000 adults. Mild cases are often not diagnosed.

• #59 Etiology of hypercalcemia – UpToDate

  https://www.uptodate.com/contents/etiology-of-hypercalcemia

  Hypercalcemia is a relatively common clinical problem. It results when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in bone. This occurs when there is accelerated bone resorption, excessive gastrointestinal absorption, or decreased renal excretion of calcium. Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases. This topic will review the etiology of hypercalcemia. The clinical manifestations, diagnostic approach, and treatment are reviewed separately. […] Hypercalcemia in primary hyperparathyroidism is due to parathyroid hormone (PTH)-mediated osteoclast activation, leading to increased bone resorption. Elevated intestinal calcium absorption due to PTH-mediated increases in renal synthesis of 1,25-dihydroxyvitamin D is also important. Primary hyperparathyroidism is most often due to a parathyroid adenoma. Patients typically have relatively minor elevations in serum calcium concentrations (less than 11 mg/dL or 2.75 mmol/L), and some patients have mostly high-normal values with intermittent hypercalcemia. Occasionally, however, patients have more severe hypercalcemia with levels over 12 mg/dL. When one suspects primary hyperparathyroidism (eg, patient with calcium nephrolithiasis), and the serum calcium is high-normal, it may be necessary to obtain serial measurements of serum calcium to detect intermittent hypercalcemia.

• #60 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #61 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #62 Hypercalcemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/240681-overview

  Hypercalcemia may be classified based on total serum and ionized calcium levels, as follows: […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. Hypercalcemia from hyperparathyroidism is usually mild, asymptomatic, and sustained for years. Immunoreactive parathyroid hormone (PTH) and ionized calcium should be simultaneously measured. […] Mild cases of hypercalcemia can be asymptomatic and are more often diagnosed incidentally from routine blood tests. Because calcium metabolism normally is tightly controlled by the body, even mild persistent elevations above normal signal disease and should be investigated. […] Hypercalcemia is relatively common and often is mild but of long duration. The incidence of hyperparathyroidism alone is approximately 1-2 cases per 1000 adults. Mild cases are often not diagnosed.

• #63 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Malignancy is one of the most common causes and must be excluded. Hyperparathyroidism and other causes of hypercalcemia can coexist with malignancy. If calcium levels have been mildly elevated for months or years, malignancy is an unlikely cause. […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. If calcium levels have been elevated for an unknown duration, the patient should be evaluated for the presence of malignancy. Breast, lung, and kidney cancers should be considered, as should multiple myeloma, lymphoma, and leukemia. Testing in such cases might include a peripheral blood smear and/or serum and urine immunofixation electrophoresis. Biopsy samples may be taken from a solid tumor or from bone marrow for tissue histology studies.

• #64 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #65 Hypercalcaemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypercalcaemia

  Diagnosis should generally include either a calculation of corrected calcium or direct measurement of ionized calcium level and be confirmed after a week. […] Once calcium is confirmed to be elevated, a detailed history taken from the subject, including review of medications, any vitamin supplementations, herbal preparations, and previous calcium values. […] If detailed history and examination does not narrow down the differential diagnoses, further laboratory investigations are performed. […] Elevated (or high-normal) iPTH with high urine calcium/creatinine ratio (more than 0.03) is suggestive of primary hyperparathyroidism, usually accompanied by low serum phosphate. […] High iPTH with low urine calcium/creatinine ratio is suggestive of familial hypocalciuric hypercalcemia. […] Low iPTH should be followed up with Parathyroid hormone-related protein (PTHrP) measurements (though not available in all labs).

• #66 Hypercalcaemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypercalcaemia

  Diagnosis should generally include either a calculation of corrected calcium or direct measurement of ionized calcium level and be confirmed after a week. […] Once calcium is confirmed to be elevated, a detailed history taken from the subject, including review of medications, any vitamin supplementations, herbal preparations, and previous calcium values. […] If detailed history and examination does not narrow down the differential diagnoses, further laboratory investigations are performed. […] Elevated (or high-normal) iPTH with high urine calcium/creatinine ratio (more than 0.03) is suggestive of primary hyperparathyroidism, usually accompanied by low serum phosphate. […] High iPTH with low urine calcium/creatinine ratio is suggestive of familial hypocalciuric hypercalcemia. […] Low iPTH should be followed up with Parathyroid hormone-related protein (PTHrP) measurements (though not available in all labs).

• #67 Familial Hypocalciuric Hypercalcemia (FHH) | Dr. Babak Larian

  https://www.hyperparathyroidmd.com/familial-hypocalciuric-hypercalcemia/

  A medical evaluation is key for those who display symptoms of FHH and/or PHPT. After getting an evaluation, people can find out if either of these conditions are causing their symptoms and receive appropriate treatment. […] Measuring the PTH level is a great first step to determine if a patient is dealing with hypercalcemia. If the PTH level is higher than normal, a patient may be dealing with PHPT. If the PTH level is close to normal or in the normal range then FHH should also be considered. […] Diagnosis of FHH can be confirmed by doing genetic testing.

• #68 Hypercalcemia – EMCrit Project

  https://emcrit.org/ibcc/hypercalcemia/

  The initial diagnosis of milk-alkali syndrome is typically based upon a combination of: Alkalosis. Renal impairment. Ingestion of calcium and absorbable alkali. (Diagnosis is especially supported by a history of aggressively over-ingesting calcium.) Exclusion of other causes. Diagnosis is confirmed by resolution of hypercalcemia with basic supportive measures, and subsequent ongoing normocalcemia (following discontinuation of oral calcium).

• #69 Hypercalcemia – EMCrit Project

  https://emcrit.org/ibcc/hypercalcemia/

  The initial diagnosis of milk-alkali syndrome is typically based upon a combination of: Alkalosis. Renal impairment. Ingestion of calcium and absorbable alkali. (Diagnosis is especially supported by a history of aggressively over-ingesting calcium.) Exclusion of other causes. Diagnosis is confirmed by resolution of hypercalcemia with basic supportive measures, and subsequent ongoing normocalcemia (following discontinuation of oral calcium).

• #70 Hypercalcemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia

  The chest x-ray is particularly helpful, revealing most granulomatous disorders, such as tuberculosis, sarcoidosis, and silicosis, as well as primary lung cancer and lytic and Paget lesions in bones of the shoulder, ribs, and thoracic spine. […] In hyperparathyroidism, the serum calcium is rarely 12 mg/dL (3 mmol/L), but the ionized serum calcium is almost always elevated. […] Increased intact PTH, particularly inappropriate elevation (ie, a high concentration in the absence of hypocalcemia) or an inappropriate high-normal concentration (ie, despite hypercalcemia), is diagnostic. […] A serum calcium measurement 13 mg/dL (3.25 mmol/L) suggests some cause of hypercalcemia other than hyperparathyroidism. […] FHH is very rare but should be considered in patients with hypercalcemia and elevated or high-normal intact PTH levels. […] The diagnosis can be confirmed when the serum calcium concentration rapidly returns to normal when calcium and alkali ingestion stops, although renal insufficiency can persist when nephrocalcinosis is present.

• #71 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  A key diagnostic step is checking a parathyroid hormone level to clarify if hypercalcemia is parathyroid hormone-mediated or not. […] Hypercalcemia is easily diagnosed through laboratory tests, but further diagnostics often guide etiology and treatment options. […] The goals of treating hypercalcemia include increased elimination from the extracellular fluid, reduced gastrointestinal absorption, and decreased bone resorption. […] Treatment options differ based on the etiology and severity of hypercalcemia. […] Patients with hypercalcemia can become volume-depleted and require intravenous (IV) hydration. […] Obtaining a detailed history and performing a thorough physical examination, including reviewing all medications, are crucial to determining the etiology of hypercalcemia. […] The prognosis of hypercalcemia is largely dependent on its etiology.

• #72 A Practical Approach to Hypercalcemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0501/p1959.html

  Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. The diagnosis of hypercalcemia most often is made incidentally when a high calcium level is detected in blood samples. It is essential that physicians know how to evaluate and optimally manage patients with hypercalcemia, because treatment and prognosis vary according to the underlying disorder. […] Primary hyperparathyroidism and malignancy account for more than 90 percent of hypercalcemia cases. These conditions must be differentiated early to provide the patient with optimal treatment and accurate prognosis. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g., kidney stones).

• #73 Hypercalcaemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypercalcaemia

  Diagnosis should generally include either a calculation of corrected calcium or direct measurement of ionized calcium level and be confirmed after a week. […] Once calcium is confirmed to be elevated, a detailed history taken from the subject, including review of medications, any vitamin supplementations, herbal preparations, and previous calcium values. […] If detailed history and examination does not narrow down the differential diagnoses, further laboratory investigations are performed. […] Elevated (or high-normal) iPTH with high urine calcium/creatinine ratio (more than 0.03) is suggestive of primary hyperparathyroidism, usually accompanied by low serum phosphate. […] High iPTH with low urine calcium/creatinine ratio is suggestive of familial hypocalciuric hypercalcemia. […] Low iPTH should be followed up with Parathyroid hormone-related protein (PTHrP) measurements (though not available in all labs).

• #74 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  A key diagnostic step is checking a parathyroid hormone level to clarify if hypercalcemia is parathyroid hormone-mediated or not. […] Hypercalcemia is easily diagnosed through laboratory tests, but further diagnostics often guide etiology and treatment options. […] The goals of treating hypercalcemia include increased elimination from the extracellular fluid, reduced gastrointestinal absorption, and decreased bone resorption. […] Treatment options differ based on the etiology and severity of hypercalcemia. […] Patients with hypercalcemia can become volume-depleted and require intravenous (IV) hydration. […] Obtaining a detailed history and performing a thorough physical examination, including reviewing all medications, are crucial to determining the etiology of hypercalcemia. […] The prognosis of hypercalcemia is largely dependent on its etiology.

• #75 Hypercalcemia: A Practice Overview of Its Diagnosis and Causes

  https://www.mdpi.com/2673-8236/5/1/7

  Hypercalcemia is defined as a serum calcium concentration higher than 10.5 mg/gL or 2.6 mmol/L. […] Thus, to discriminate true hypercalcemia from pseudo hypercalcemia, an ionized calcium concentration higher than 1.3 mmol/L might be more appropriate. […] For this condition, the correct diagnostic algorithm should be followed. In this review, we summarize the diagnostic steps to follow and detail each clinical pathway is involved in hypercalcemia. […] Before the diagnostic management of hypercalcemia, iatrogenic causes should be excluded. […] In keeping with Murray et al. and their diagnostic algorithm of genuine hypercalcemia, the differential diagnosis should start with the PTH dosage. […] After detecting PTH-mediated or non-PTH-mediated hypercalcemia, PTHrP, vitamin D in two forms, and oncological screening should be performed.

• #76 A Practical Approach to Hypercalcemia | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/internal-medicine/a-practical-approach-to-hypercalcemia/

  If the cause of hypercalcemia remains elusive, calcium hormone levels should be measured to ascertain whether the hypercalcemia is parathyroid dependent or independent. […] Initial treatment is symptomatic and supportive, aimed at diluting the iCa concentration through volume expansion with intravenous fluids and encouraging calciuresis. […] No single treatment protocol effectively reduces serum ionized calcium concentrations, and each patient requires an individualized protocol until the cause of hypercalcemia can be determined. […] Hypercalcemia is defined as an elevation of serum total calcium (tCa) and/or iCa above the following normal physiological ranges: […] The concept of corrected calcium has been proven unhelpful. […] Failure to identify an underlying cause from history and physical examination should prompt collection of blood and urine for a complete blood count, serum biochemistry panel, urinalysis, and urine culture.

• #77 Evaluation of hypercalcemia – Differential diagnosis of symptoms | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/159

  Hypercalcemia is diagnosed when the concentration of serum calcium is two standard deviations above the mean value found in people with normal calcium levels, in at least two samples taken at least 1 week apart. […] Normal serum or plasma total calcium should be 8.5 to 10.5 mg/dL and ionized calcium should be 4.6 to 5.1 mg/dL. […] Hypercalcemia may be mild and occur without symptoms. History may also identify symptoms of high calcium such as renal stones (typical of hyperparathyroidism), lethargy, easy fatigue, confusion, depression, irritability, constipation, and polyuria and polydipsia. […] Severe hypercalcemia is a life-threatening electrolyte emergency requiring prompt recognition and urgent response. […] Patients with asymptomatic primary hyperparathyroidism (mild hypercalcemia, generally within 1 mg/dL of the upper limit of the normal range), may undergo parathyroid surgery in the absence of medical contraindications. […] Surgery is not, however, mandatory in all patients with asymptomatic disease; recommendations for monitoring those who do not undergo parathyroid surgery should be followed.

• #78 Hypercalcaemia of malignancy (HCM)

  https://www.eviq.org.au/clinical-resources/oncological-emergencies/486-hypercalcaemia-of-malignancy-hcm

  Hypercalcaemia of malignancy (HCM) is a condition which occurs in cancer patients and can be defined when the serum calcium level (corrected for albumin) is greater than 2.6 mmol/L or greater than the upper limit of normal (ULN) for a given reference value used in a lab. […] Therapy for hypercalcaemia should be initiated for symptomatic patients and those who have serum calcium concentrations 3.0 mmol/L. […] Severe hypercalcaemia is considered to be a medical emergency and must be treated aggressively. […] To confirm a diagnosis of hypercalcaemia: Check calcium level, corrected for serum albumin (as serum calcium is bound to albumin), which gives an indication of the amount of ionised (active) calcium. […] Additional laboratory evaluations include: serum creatinine, urea and electrolytes, phosphate and magnesium level, parathyroid hormone (PTH) to rule out primary hyperparathyroidism, PTHrP to rule out humoral hypercalcaemia of malignancy, 1,25-dihydroxy vitamin D (1,25(OH)2D), 25-hydroxy vitamin D (25(OH)D) to rule out vitamin D intoxication, TSH, Vitamin A, ECG to look for shortened QT interval or other conduction abnormalities.

• #79

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=8708&catId=18057&id=3843801

  Parenteral fluids, furosemide, sodium bicarbonate, glucocorticosteroids, or combinations of these treatments will effectively reduce serum calcium concentrations in most animals with hypercalcemia. The first goal of fluid therapy is to correct dehydration, because hemoconcentration contributes to increased serum ionized calcium concentration. Physiologic saline (0.9% NaCl) is the solution of choice for correction of intravascular volume deficit, and for further mild volume expansion. Potassium supplementation is often necessary to maintain normal serum potassium during extended periods of fluid treatment. […] Furosemide (Lasix) follows rehydration and fluid volume expansion in importance for treatment of persistent hypercalcemia. Furosemide (5 mg/kg IV initial bolus dose followed by 5 mg/kg/hr infusion) can be helpful in acutely decreasing serum calcium concentration by a maximum of about 3 mg/dL. Less aggressive regimens of furosemide administration may be effective in combination with other treatments, or for chronic management of hypercalcemia.

• #80 Disease Management: Hypercalcemia

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypercalcemia/default.htm

  The success of these approaches in curing HPT and minimizing complications is relatively unknown because clinical follow-up periods are short. […] The need to treat hypercalcemia depends on the degree of hypercalcemia and the presence or absence of clinical symptoms. If calcium levels are lower than 12 mg/dL and a patient has no symptoms, it is unnecessary to treat the hypercalcemia. […] Medical treatment of hypercalcemia can include increasing renal calcium excretion and decreasing intestinal absorption of calcium, slowing bone resorption, directly removing calcium from circulation, and controlling the underlying diseases causing hypercalcemia. […] Calcium excretion can be achieved by inhibiting proximal tubular and loop sodium reabsorption. […] Medications primarily used for this purpose include calcitonin and bisphosphonates.

• #81 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Therefore, this is another reason why not only diagnosing hypercalcemia but also determining its etiology is crucial for its proper management. […] The complications of hypercalcemia include the following: Depression, Kidney stones, Bone pain, Constipation, Pancreatitis, Renal failure, Gastric ulcers, Paresthesias, Syncope and arrhythmias, Altered mental status. […] In addition to treatment, follow-up becomes equally important and care must be coordinated to ensure effective long-term management of the patient’s condition. […] Key information to keep in mind when dealing with hypercalcemia is to determine the etiology. […] It is imperative that cases of persistent hypercalcemia, even if mild, be investigated further. […] Early identification and subsequent management can result in decreased morbidity and mortality associated with hypercalcemia.

• #82 Hyperparathyroidism | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0115/p333.html

  Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. […] Persistent hypercalcemia and an elevated serum parathyroid hormone level are the diagnostic criteria for primary hyperparathyroidism. […] Laboratory measurements of the mediators of calcium metabolism are reliable and facilitate determination of etiologic factors in almost all patients with hypercalcemia. […] Persistent hypercalcemia and an elevated serum PTH level confirm the diagnosis of primary hyperparathyroidism. […] Further laboratory testing is unnecessary because other causes of hypercalcemia rarely are associated with elevated PTH levels. […] Hypercalcemia should be confirmed by repeated measurements of serum calcium concentrations, because all patients with primary hyperparathyroidism do not have demonstrable hypercalcemia every time the serum calcium level is measured.

• #83 Hyperparathyroidism | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0115/p333.html

  Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. […] Persistent hypercalcemia and an elevated serum parathyroid hormone level are the diagnostic criteria for primary hyperparathyroidism. […] Laboratory measurements of the mediators of calcium metabolism are reliable and facilitate determination of etiologic factors in almost all patients with hypercalcemia. […] Persistent hypercalcemia and an elevated serum PTH level confirm the diagnosis of primary hyperparathyroidism. […] Further laboratory testing is unnecessary because other causes of hypercalcemia rarely are associated with elevated PTH levels. […] Hypercalcemia should be confirmed by repeated measurements of serum calcium concentrations, because all patients with primary hyperparathyroidism do not have demonstrable hypercalcemia every time the serum calcium level is measured.

• #84 Hyperparathyroidism | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0115/p333.html

  Primary hyperparathyroidism is the most frequent cause of hypercalcemia in ambulatory patients. […] Persistent hypercalcemia and an elevated serum parathyroid hormone level are the diagnostic criteria for primary hyperparathyroidism. […] Laboratory measurements of the mediators of calcium metabolism are reliable and facilitate determination of etiologic factors in almost all patients with hypercalcemia. […] Persistent hypercalcemia and an elevated serum PTH level confirm the diagnosis of primary hyperparathyroidism. […] Further laboratory testing is unnecessary because other causes of hypercalcemia rarely are associated with elevated PTH levels. […] Hypercalcemia should be confirmed by repeated measurements of serum calcium concentrations, because all patients with primary hyperparathyroidism do not have demonstrable hypercalcemia every time the serum calcium level is measured.

• #85 Diagnosing a disorder with few symptoms | I.M. Matters from ACP

  https://immattersacp.org/archives/2012/03/hypercalcemia.htm

  According to Dr. Whitaker, a 24-hour urine calcium test should be ordered for patients who have PTH-dependent hypercalcemia. […] An elevated 24-hour urine calcium level can indicate hyperparathyroidism, which should prompt a referral to a surgeon or an endocrinologist. […] Patients with hypercalcemia should also be referred to an endocrinologist if the corrected serum calcium level indicates hypercalcemia but the PTH level is normal, if the etiology remains unclear, or if further diagnostic help is needed. […] Hypercalcemia is much more common in patients with cancer than in the general population. […] Even though patients with cancer will most likely be treated by an oncologist, a primary care physician may first identify the malignancy through elevated calcium. […] Myeloma can initially present with hypercalcemia, and the patient may also have some back pain. […] However, if you see a hypercalcemic patient who also has back pain, you would start to think cancer. […] Dr. LeGrand also advised that a primary care physician should do additional testing to identify the cause of the condition if a patient presents with hypercalcemia and a low PTH.

• #86 Diagnose and Treat Hypercalcemia of Malignancy | Oncology Nursing Society

  https://www.ons.org/publications-research/voice/news-views/07-2021/diagnose-and-treat-hypercalcemia-malignancy

  Hypercalcemia of malignancy (HCM) is a common paraneoplastic syndrome associated with poor prognosis that affects approximately 20%30% of patients with cancer. […] Elevated calcium levels can result in life-threatening outcomes, but HCM is typically manageable with early diagnosis. Regularly monitoring calcium levels is critical, but practitioners must recognize that it may fluctuate with albumin levels because 40%45% of serum calcium is bound to albumin, so measure serum albumin or ionized calcium levels as well. […] HCM can affect multiple organ systems through several clinical manifestations. Kidney involvement can lead to nephrolithiasis and chronic renal insufficiency. […] Because an incidental finding of hypercalcemia may be the first sign of an undiagnosed cancer, the work-up should not stop after HCM diagnosis. […] PTH lab values are critical to guide treatment. Although palliative IV fluids and bisphosphonate therapy is the mainstay of initial treatment, addressing the underlying malignancy is the best chance at long-term management.

• #87 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Malignancy is one of the most common causes and must be excluded. Hyperparathyroidism and other causes of hypercalcemia can coexist with malignancy. If calcium levels have been mildly elevated for months or years, malignancy is an unlikely cause. […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. If calcium levels have been elevated for an unknown duration, the patient should be evaluated for the presence of malignancy. Breast, lung, and kidney cancers should be considered, as should multiple myeloma, lymphoma, and leukemia. Testing in such cases might include a peripheral blood smear and/or serum and urine immunofixation electrophoresis. Biopsy samples may be taken from a solid tumor or from bone marrow for tissue histology studies.

• #88 Diagnose and Treat Hypercalcemia of Malignancy | Oncology Nursing Society

  https://www.ons.org/publications-research/voice/news-views/07-2021/diagnose-and-treat-hypercalcemia-malignancy

  Hypercalcemia of malignancy (HCM) is a common paraneoplastic syndrome associated with poor prognosis that affects approximately 20%30% of patients with cancer. […] Elevated calcium levels can result in life-threatening outcomes, but HCM is typically manageable with early diagnosis. Regularly monitoring calcium levels is critical, but practitioners must recognize that it may fluctuate with albumin levels because 40%45% of serum calcium is bound to albumin, so measure serum albumin or ionized calcium levels as well. […] HCM can affect multiple organ systems through several clinical manifestations. Kidney involvement can lead to nephrolithiasis and chronic renal insufficiency. […] Because an incidental finding of hypercalcemia may be the first sign of an undiagnosed cancer, the work-up should not stop after HCM diagnosis. […] PTH lab values are critical to guide treatment. Although palliative IV fluids and bisphosphonate therapy is the mainstay of initial treatment, addressing the underlying malignancy is the best chance at long-term management.

• #89 Hypercalcemia Workup: Approach Considerations, Imaging Studies, Electrocardiography

  https://emedicine.medscape.com/article/240681-workup

  Malignancy is one of the most common causes and must be excluded. Hyperparathyroidism and other causes of hypercalcemia can coexist with malignancy. If calcium levels have been mildly elevated for months or years, malignancy is an unlikely cause. […] Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. If calcium levels have been elevated for an unknown duration, the patient should be evaluated for the presence of malignancy. Breast, lung, and kidney cancers should be considered, as should multiple myeloma, lymphoma, and leukemia. Testing in such cases might include a peripheral blood smear and/or serum and urine immunofixation electrophoresis. Biopsy samples may be taken from a solid tumor or from bone marrow for tissue histology studies.

• #90 Approach to Hypercalcemia – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279129/

  Nevertheless, although algorithms to adjust for albumin levels are widely used, their accuracy may be poor. […] Consequently, when major shifts in serum protein or pH are present it is most prudent to directly measure the ionized calcium level in order to determine the presence of hypercalcemia. […] Consequently, decreased levels of PTH and decreased levels of 1,25(OH)2D should accompany hypercalcemia unless the PTH or 1,25(OH)2D is the cause of the hypercalcemia. […] Hypercalcemic disorders can be broadly grouped into Endocrine Disorders, Malignant Disorders, Inflammatory Disorders, Pediatric Syndromes, Medication-Induced Hypercalcemia, and Immobilization. […] Approximately 90% of patients with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy-associated hypercalcemia (MAH).

• #91 Hypercalcemia | VCA Animal Hospitals

  https://vcahospitals.com/know-your-pet/hypercalcemia

  PTH levels may also provide clues about what is causing hypercalcemia. […] If a pet has both hypercalcemia and high levels of parathyroid hormone, then a diagnosis of hyperparathyroidism can be made. […] If a pet has hypercalcemia but has low levels of parathyroid hormone, then it suggests there has been a breakdown in the normal mechanism that controls calcium levels, and may mean there is an underlying cancer. […] If cancer is suspected, then a specialized blood test can be performed that measures a substance called parathyroid hormone-related protein (PTH-rP). […] In some pets, no cause can be found for elevated calcium, despite extensive testing. It is then termed idiopathic hypercalcemia, which is a diagnosis of exclusion.

• #92 A Practical Approach to Hypercalcemia | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/internal-medicine/a-practical-approach-to-hypercalcemia/

  Successful definitive therapy for hypercalcemia depends on the identification and reversibility of the underlying disease, with clinical signs and prognosis depending on the cause and severity of hypercalcemia. […] In patients with elevated total calcium, the first step in diagnosis is to verify hypercalcemia by measuring ionized calcium. […] Concurrent measurement and evaluation of serum phosphorus may provide further insight into the cause of hypercalcemia. […] If the cause of hypercalcemia remains elusive after a thorough history and physical examination, calcium hormone levels should be measured to ascertain whether the hypercalcemia is parathyroid dependent or independent. […] The clinical workup for hypercalcemia initially encompasses a repeat confirmatory calcium measurement, thorough history, and meticulous physical examination.

• #93 Challenges in the differential diagnosis of hypercalcemia: A case of hypercalcemia with normal PTH level

  https://www.wjgnet.com/2218-4333/full/v3/i1/7.htm

  Challenges in the differential diagnosis of hypercalcemia: A case of hypercalcemia with normal PTH level. The hypercalcemias are a common and heterogeneous group of disorders, ranging from the occasional detection of a high level of serum calcium to a life-treating condition. In a patient presenting with hypercalcemia, a differential diagnosis can be established easily by measuring serum calcium and parathyroid hormone (PTH) concentrations. The finding of an increased serum calcium level in the presence of an inappropriately elevated PTH concentration should suggest a PTH-dependent HCa (primary hyperparathyroidism), while the observation of HCa with suppressed or low-normal PTH values should suggest a PTH-independent hypercalcemia (e.g., granulomatous disorders or malignancy-associated hypercalcemia, MAH). In the acute clinical setting, the management of severe HCa is independent of the underlying cause, being based on life-treating interventions such as hydration and the prescription of calcium lowering agents (e.g., bisphosphonates). Therefore, a correct differential diagnosis is crucial to maximize the outcome and improve quality of life. The coexistence of severe symptomatic hypercalcemia with a PTH level within the reference range suggested the presence of two different conditions producing an increase in serum calcium, but opposite effects on PTH (PTH-dependent and PTH-independent hypercalcemia). In summary, the case described has some clinical implications: in patients with primary hyperparathyroidism, the coexistence of severe hypercalcemia which is not PTH-mediated, represents a challenge in the differential diagnosis of HCa; therefore, the presence of very high calcium concentrations with normal PTH values should suggest the coexistence of more than one disease producing hypercalcemia.

• #94 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Calcium is an essential cation that regulates myocardial activity, nerve transmission, vascular health, intracellular signaling, hormonal secretion, and other physiological functions and requires very tight regulation and homeostasis, which is accomplished mainly by the kidneys, bones, and gastrointestinal tract. […] Although often asymptomatic and typically discovered on routine blood work, hypercalcemia can lead to acute and chronic effects on cardiac tissue, the renal system, and bone health. […] This activity helps the reader obtain a focused history and physical examination followed by a comprehensive targeted laboratory and imaging investigations to manage the condition properly, empowering healthcare professionals to treat hypercalcemia through various approaches and interdisciplinary teams.

• #95 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Therefore, this is another reason why not only diagnosing hypercalcemia but also determining its etiology is crucial for its proper management. […] The complications of hypercalcemia include the following: Depression, Kidney stones, Bone pain, Constipation, Pancreatitis, Renal failure, Gastric ulcers, Paresthesias, Syncope and arrhythmias, Altered mental status. […] In addition to treatment, follow-up becomes equally important and care must be coordinated to ensure effective long-term management of the patient’s condition. […] Key information to keep in mind when dealing with hypercalcemia is to determine the etiology. […] It is imperative that cases of persistent hypercalcemia, even if mild, be investigated further. […] Early identification and subsequent management can result in decreased morbidity and mortality associated with hypercalcemia.

• #96 Hypercalcemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypercalcemia/symptoms-causes/syc-20355523

  Hypercalcemia is a condition in which the calcium level in the blood becomes too high. […] Most often, hypercalcemia happens after one or more of the parathyroid glands make too much hormone. […] We utilize multimodal imaging, meaning various types of imaging to identify where the abnormal parathyroid is located. […] Patients can come into the office feeling a variety of symptoms that are generally nonspecific but rather debilitating for them. […] Call your healthcare professional if you think you have any symptoms of hypercalcemia. […] Hypercalcemia can be caused by: Overactive parathyroid glands. This also is called hyperparathyroidism. […] Hypercalcemia can lead to medical conditions that include: Osteoporosis.

• #97 Hypercalcemia | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/hypercalcemia

  The diagnosis of hypercalcemia requires a simple blood test for measurement of the serum calcium level. […] In order to determine the cause of hypercalcemia, a child will need additional laboratory tests, including measurement of serum levels of phosphorus, PTH and vitamin D metabolites. […] Hypercalcemia with increased PTH suggests a parathyroid cause, such as primary hyperparathyroidism. […] If this is suspected, imaging of the parathyroid glands may be done. […] Your child may also have skeletal X-rays and bone densitometry (DXA scan) to look for bone thinning and erosions that are sometimes associated with hyperparathyroidism. […] A kidney ultrasound can identify calcium deposits in the kidneys. […] Genetic testing may also be performed depending on the cause of hypercalcemia.

• #98 Hypercalcemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430714/

  Therefore, this is another reason why not only diagnosing hypercalcemia but also determining its etiology is crucial for its proper management. […] The complications of hypercalcemia include the following: Depression, Kidney stones, Bone pain, Constipation, Pancreatitis, Renal failure, Gastric ulcers, Paresthesias, Syncope and arrhythmias, Altered mental status. […] In addition to treatment, follow-up becomes equally important and care must be coordinated to ensure effective long-term management of the patient’s condition. […] Key information to keep in mind when dealing with hypercalcemia is to determine the etiology. […] It is imperative that cases of persistent hypercalcemia, even if mild, be investigated further. […] Early identification and subsequent management can result in decreased morbidity and mortality associated with hypercalcemia.

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