Hypocalcemia

Hypocalcemia can occur either acutely or chronically in hospitalized patients and outpatients. Testing includes calcium, albumin, phosphate, magnesium, creatinine, 25-hydroxy vitamin D, and parathyroid hormone (PTH).

Quick Answers for Clinicians

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Diagnosis

Indications for Testing

  • Neurologic signs
    • Perioral numbness or other paresthesias
    • Muscle spasms/cramps
    • Neuromuscular irritability
  • Thyroid or parathyroid resection or other neck surgery, irradiation to neck
  • Chronic kidney disease
  • Prolongation of QT interval on electrocardiogram (ECG)
  • Malnutrition or malabsorption

Laboratory Testing

  • Initial testing
    • Serum calcium and albumin 
      • Corrected calcium = measured total calcium + 0.8 (4.0 - serum albumin)
    • Phosphate
    • Magnesium
    • Creatinine
  • If calcium is low, consider repeat testing with ionized calcium
    • Ionized calcium needs no correction for hypoalbuminemia but should be corrected for pH
  • If hypocalcemia is confirmed, order intact PTH
    • Elevated PTH, normal or high phosphate, normal magnesium, high creatinine – consider renal failure/pseudohypoparathyroidism
    • Elevated PTH, normal or low phosphate, normal magnesium, normal creatinine – consider vitamin D testing
    • Low PTH, normal or high phosphate, normal creatinine, low or normal magnesium – consider hypoparathyroidism or hypomagnesemia
    • Normal PTH, normal or low phosphate, normal creatinine, normal magnesium, low albumin – consider hypoalbuminemia (pseudohypocalcemia)

Differential Diagnosis

Refer to Etiology in Background

Monitoring

  • Serum calcium, phosphate, and creatinine – measure weekly during initial therapy, then monthly
  • Once stabilized on therapy, measure values one to two times/year

Background

Epidemiology

Prevalence – occurs in 12-80% of critically ill patients

Etiology

  • Acute severe illness – patients in intensive care unit (acute pancreatitissepsis, burns)
  • Hypoparathyroidism
    • Acquired
      • Surgical removal of parathyroid glands (eg, head and neck surgery)
      • Radiation-induced parathyroid destruction
      • Metastatic infiltration of glands (rare)
      • Other infiltrative disorders (eg, hemochromatosis)
    • Autoimmune
      • Associated with autoimmune polyglandular syndrome 1
        • Autosomal recessive inheritance
        • Symptoms – chronic mucocutaneous candidiasis, alopecia, vitiligo
    • Pseudohypoparathyroidism
      • Resistance to PTH (eg, chronic renal failure)
    • Genetic syndromes
      • DiGeorge (22q11.2 deletion) syndrome and velocardiofacial syndrome
      • Familial hypocalcemias (eg, Bartter syndrome subtype V and Gitelman syndrome)
      • X-linked hypoparathyroidism
      • Mitochondrial disorders with hypoparathyroidism (eg, Kearns-Sayre syndrome)
      • Hypoparathyroidism, sensorineural deafness, and renal disease (HDR) syndrome
      • Sanjad-Sakati and Kenny-Caffey type 1 syndromes
  • Chronic kidney disease
  • Vitamin D deficiency
  • Magnesium deficiency
  • Medications
    • Chemotherapy drugs
    • Anticonvulsants
    • Foscarnet
    • Histamine 2 (H2) receptor blockers
    • Proton pump inhibitors
    • Bisphosphonates

Pathophysiology

  • Serum calcium concentration is normally maintained within a narrow physiologic range
  • Calcium is controlled by PTH, vitamin D (1,25), calcium, and phosphate
  • Calcium is bound to albumin
    • Low levels may reflect hypoalbuminemia, not level of ionized calcium

Clinical Presentation

  • Symptom severity is related to the rate of change and absolute calcium levels
    • Most patients with mild hypocalcemia are asymptomatic
  • Acute
    • Neuromuscular – tetany, paresthesias, muscle spasms (Chvostek and Trousseau signs), perioral numbness
    • Neuropsychiatric – anxiety, hallucinations, confusion, irritability
    • Cardiovascular – bradycardia, ventricular arrhythmias, congestive heart failure, cardiac collapse
    • Pulmonary – laryngeal stridor, bronchospasm
  • Chronic
    • Neuropsychiatric – cognitive deficits, extrapyramidal symptoms
    • Dermatologic – dermatitis, dry skin, brittle nails
    • Dental – enamel hypoplasia
    • Ophthalmologic – cataracts

ARUP Laboratory Tests

Diagnose disorders of calcium metabolism

Order concurrent with calcium to assess for hypoalbuminemia

Diagnose disorders of calcium metabolism

Abnormal pH will alter results

No correction necessary for hypoalbuminemia

Evaluate renal function

Diagnose disorders of the parathyroid glands

May help to determine etiology of hypocalcemia

Preferred test to diagnose vitamin D insufficiency and monitor response to therapy

Testing is recommended only for patients at risk for vitamin D insufficiency

Related Tests

Screening test to evaluate kidney function

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only with concentrations at or above those expected during acetaminophen overdose

Use to evaluate calcium dysregulation

Investigate potential autoimmune disorders involving the parathyroid gland

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer: Medical Director, Automated Core Laboratory, ARUP Laboratories
Contributor

Pearson

Lauren N. Pearson, DO, MPH
Assistant Professor of Clinical Pathology, University of Utah
Laboratory Director for ARUP at University of Utah Health and Huntsman Cancer Institute
Laboratory Director, South Jordan and Sugarhouse Health Center Clinical Laboratories
Contributor

References

Additional Resources