Hypercalcemia

Diagnosis

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.

Epidemiology

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

Etiology

Risk Factors

  • 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
  • Most common cancers – squamous cell subtypes

Pathophysiology

  • Hyperparathyroidism
    • 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
    • Most patients are asymptomatic when hypercalcemia is discovered due to frequent use of screening chemistries
  • Cancer – causes of hypercalcemia of malignancy
    • Presence of humoral factors mimicking parathyroid hormone (PTH) action
      • Commonly, 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 a tumor or a treatment

Clinical Presentation

  • Clinical symptoms progress slowly
    • Renal – nephrolithiasis, nephrocalcinosis, polyuria
    • Cardiovascular – arrhythmias, bradycardia, short QT interval
    • Skeletal – bone pain, arthralgias; classic finding is osteitis fibrosa (rare)
    • Neurologic – easy fatigability, proximal muscle weakness, muscle atrophy, lethargy, confusion
    • Gastrointestinal – nausea, bloating, constipation, anorexia
    • Cancer – usually fatigue, weakness

Treatment

  • Based on etiology of hypercalcemia

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 hyperparathyroidism    
Parathyroid Hormone, Intact with Calcium 0070172
Method: Quantitative Electrochemiluminescent Immunoassay
Preferred test to diagnose hypercalcemia, hyperparathyroidism    
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

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 Radioimmunoassay

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