Indications for Testing

  • Fatigue, weakness, recurrent nephrolithiasis, coincidental discovery of elevated calcium on laboratory testing

Laboratory Testing

  • Initial laboratory testing 
    • Electrolytes – including BUN and creatinine
    • Phosphorus
    • Calcium
      • For level >10.3 but <11.0 mg/dL, repeat with albumin measurement or ionized calcium – correct value if albumin decreased without using the ionized value
      • Confirmed calcium elevation of >11.0 mg/dL – order intact PTH 
  • PTH (intact)

Differential Diagnosis

  • See Etiology for differential diagnoses

Clinical Background

Hypercalcemia is a metabolic abnormality frequently related to primary hyperparathyroidism and cancer.


  • Incidence – 8/100,000
  • Age – 40s-50s; mean is 55 years
  • Sex – M<F for primary hyperparathyroidism



  • ~80% of hypercalcemia is caused by hyperparathyroidism or malignancy (Charg, 2014)
  • Hyperparathyroidism – usually causes mild hypercalcemia
    • Four parathyroid glands found within the thyroid gland secrete PTH
    • PTH acts directly on bone and kidney and induces calcium resorption with a tight negative feedback loop
    • Pathology for hyperparathyroidism and excess secretion of PTH
    • Most patients are asymptomatic when hypercalcemia is discovered due to frequent use of screening chemistries
  • Cancer – several etiologies for hypercalcemia in malignancy and may cause severe hypercalcemia
    • Presence of humoral factors mimicking parathyroid hormone (PTH) action
      • Secretion of PTHrP by tumor tissue or tumor metastasis
    • Osteolytic or nonosteolytic activity related to bone metastases
    • Ectopic secretion of 1-alpha hydroxylase by tumor tissue
    • Impaired renal function caused by tumor or treatment
    • Increased production of calcitrol – stimulates gastrointestinal calcium absorption

Clinical Presentation

  • Clinical symptoms progress slowly in hyperparathyroid related disease
    •  Rate of increase causes symptoms
  •  Systems involved
    • Renal – nephrolithiasis, nephrocalcinosis, polyuria
    • Cardiovascular – arrhythmias, bradycardia, short QT interval with prolonged PR and QRS intervals
      • Can develop atrioventricular block or complete heart block with severe hypercalcemia
    • Skeletal – bone pain, arthralgias; classic finding is osteitis fibrosa (rare)
    • Neurologic – easy fatigability, proximal muscle weakness, muscle atrophy, lethargy, confusion
      • Can progress to seizures, coma
    • Gastrointestinal – nausea, bloating, constipation, anorexia
  • Syndromic diseases associated with hypercalcemia
    • Multiple endocrine neoplasia (MEN)
    • Familial hypocalciuric hypercalcemia
      • Hypercalcemia with subnormal urine calcium excretion
      • Removal of parathyroids does not correct hypercalcemia
    • Neonatal severe primary hyperparathyroidism
      • Rare, potentially lethal
      • Enlargement of all 4 parathyroids with very high parathyroid hormone (PTH)
    • Hyperparathyroidism – jaw tumor syndrome
      • Hyperparathyroidism with cemento-ossifying tumors of the jaw, Wilms tumor, and renal cysts
    • Medications (eg, thiazides, lithium, antacids)

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Calcium, Ionized, Serum 0020135
Method: Ion-Selective Electrode/pH Electrode

Diagnose disorders of calcium metabolism

Parathyroid Hormone, Intact with Calcium 0070172
Method: Quantitative Electrochemiluminescent Immunoassay
Preferred test to diagnose calcium disorders suspected to be a result of parathyroid dysfunction    
Parathyroid Hormone-Related Peptide (PTHrP) by LC-MS/MS, Plasma 2010677
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Aid in the diagnosis and monitoring of treatment for hypercalcemia

Highly specific test for PTHrP

Amino (N)- and carboxy (C )-terminus PTHrP fragments, such as those produced by some patients with renal insufficiency, do not interfere with this assay

Results should not be interpreted as absolute evidence for the presence of hypercalcemia

Calcium, Urine 0020472
Method: Quantitative Spectrophotometry

Distinguish between primary hyperparathyroidism and familial benign hypercalcemia

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Renal Function Panel 0020144
Method: Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay

Screen kidney function

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and BUN

Vitamin D, 1, 25-Dihydroxy 0080385
Method: Quantitative Chemiluminescent Immunoassay

Preferred test for individuals with hypercalcemia or renal failure in addition to Vitamin D, 25-Hydroxy testing

Normal result does not rule out deficiency

Vitamin D, 25-Hydroxy 0080379
Method: Quantitative Chemiluminescent Immunoassay

Preferred screening test for vitamin D deficiency

Preferred test to monitor response to supplementation

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry
Calcium, Ionized, Whole Blood 0020140
Method: Ion-Selective Electrode/pH Electrode
Parathyroid Hormone, Intact 0070346
Method: Quantitative Electrochemiluminescent Immunoassay
Parathyroid Hormone, CAP 0095611
Method: Immunoradiometry
Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry
Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic
Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic
Albumin by Nephelometry 0050671
Method: Quantitative Nephelometry
Phosphorus, Inorganic, Plasma or Serum 0020028
Method: Quantitative Spectrophotometry
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic
Potassium, Plasma or Serum 0020002
Method: Quantitative Ion-Selective Electrode
Sodium, Plasma or Serum 0020001
Method: Quantitative Ion-Selective Electrode
Chloride, Serum or Plasma 0020003
Method: Quantitative Ion-Selective Electrode
Carbon Dioxide, Serum or Plasma 0020004
Method: Quantitative Enzymatic
Albumin, Serum or Plasma by Spectrophotometry 0020030
Method: Quantitative Spectrophotometry