Hypocalcemia

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 vitamin D 25(OH) – vitamin D deficiency confirmed
  • 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 pancreatitis, sepsis, 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
      • Rare congenital disorder
      • Symptoms – cardiac, facial, thymic, thyroid abnormalities
        • Severe early childhood infections
      • Learning disorders
      • Genetics – rearrangements on chromosome 22 (TBX1 gene)
    • 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
  • Malabsorption
  • Inadequate diet/sunlight
• Magnesium deficiency
  • Malabsorption
  • Inadequate diet
  • Alcohol misuse
• 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