Hypocalcemia: Causes and Treatment
Causes of Hypocalcemia
The most common causes of hypocalcemia are hypoparathyroidism (75% postsurgical, 25% primary) and vitamin D deficiency. 1
PTH-Mediated Causes
- Hypoparathyroidism is the classic cause of chronic hypocalcemia, characterized by impaired secretion of parathyroid hormone, which is essential for maintaining calcium homeostasis 2
- Postsurgical hypoparathyroidism is the most frequent cause overall, particularly following thyroid or parathyroid surgery 3
- In patients with 22q11.2 deletion syndrome (DiGeorge syndrome), 80% have a lifetime history of hypocalcemia due to relative or absolute hypoparathyroidism, which may arise or recur at any age despite apparent childhood resolution 4, 5
Non-PTH-Mediated Causes
- Vitamin D deficiency disrupts calcium homeostasis by reducing gut absorption of dietary calcium 2
- Hypomagnesemia can contribute to hypocalcemia and must be corrected concurrently 4, 6
- Acute causes include citrate toxicity from massive transfusion (citrate in blood products binds calcium), tumor lysis syndrome, and medications 6
- Biological stressors such as surgery, fracture, injury, childbirth, or infection can precipitate hypocalcemia, especially in predisposed patients 4
Exacerbating Factors
- Alcohol and carbonated beverages (especially colas) can worsen hypocalcemia 4, 5
- Hypothyroidism may be an associated or contributory condition 4
Treatment of Hypocalcemia
Acute Symptomatic Hypocalcemia (Severe: ≤7.5 mg/dL or ionized <0.9 mmol/L)
For severe or symptomatic hypocalcemia, administer intravenous calcium chloride immediately, as it is three times more potent than calcium gluconate and is the preferred agent in emergencies. 7, 5, 6
Immediate IV Calcium Administration
- Calcium chloride is preferred over calcium gluconate: 10 mL of 10% calcium chloride contains 270 mg elemental calcium versus only 90 mg in 10 mL of 10% calcium gluconate 7, 5, 6
- Calcium chloride is particularly preferred in patients with liver dysfunction due to faster release of ionized calcium 7
- Administer slowly with continuous ECG monitoring to detect cardiac arrhythmias 5, 6
- Monitor ionized calcium levels frequently, especially during massive transfusion 5, 6
Critical Safety Considerations
- Never administer calcium and sodium bicarbonate through the same IV line due to precipitation risk 5, 6
- Use caution when phosphate levels are high due to risk of calcium phosphate precipitation in tissues 6
- Symptoms requiring immediate treatment include neuromuscular irritability, tetany, seizures, cardiac arrhythmias, and prolonged QT interval 4, 2
Chronic Hypocalcemia Management
Daily calcium and vitamin D supplementation are the cornerstone of chronic hypocalcemia management, with treatment individualized based on severity and underlying cause. 7, 5, 6
Standard Supplementation Approach
- Daily vitamin D supplementation is recommended for all adults with chronic hypocalcemia 4, 7
- Calcium carbonate is commonly used as it contains the highest percentage of elemental calcium 7
- For vitamin D deficiency (25-hydroxyvitamin D <30 ng/mL), supplement with ergocalciferol (vitamin D2) 7
- Magnesium supplementation is essential when concurrent hypomagnesemia is present 5, 6
Severe or Refractory Cases
- Hormonally active vitamin D metabolites (calcitriol) are reserved for more severe or refractory cases, typically requiring endocrinologist consultation 4, 7, 5
- In hypoparathyroidism specifically, calcium and vitamin D must be carefully titrated to keep serum calcium in the low-normal range to minimize hypercalciuria and prevent renal dysfunction 2, 3
- Recombinant human PTH(1-84) has been approved by FDA and EMA for hypoparathyroidism, though high cost necessitates strict patient selection 3
Monitoring and Follow-Up
Regular monitoring of pH-corrected ionized calcium, magnesium, parathyroid hormone, and creatinine is essential for chronic management. 7, 6
Routine Monitoring
- Assess calcium, parathyroid hormone, magnesium, thyroid-stimulating hormone, and creatinine concentrations regularly 4
- Thyroid function should be assessed annually in at-risk populations 4
Targeted Monitoring During Vulnerable Periods
- Perioperatively, perinatally, during pregnancy, and during acute illness, targeted calcium monitoring is critical 4, 7, 6
- Patients with 22q11.2 deletion syndrome require heightened surveillance during stress periods including surgery, childbirth, and infection 4, 6
Critical Pitfalls to Avoid
Overcorrection can result in iatrogenic hypercalcemia, renal calculi, and renal failure and must be carefully avoided. 4, 7, 5, 6
Common Causes of Overcorrection
- Dehydration can inadvertently cause overcorrection 4
- Changes in treatment compliance (particularly with calcitriol) can lead to unexpected hypercalcemia 4, 5
- In CKD patients, total elemental calcium intake (including dietary calcium and calcium-based phosphate binders) should not exceed 2,000 mg/day 7
Hidden Hypocalcemia
- Corrected calcium frequently overestimates ionized calcium levels, leading to "hidden hypocalcemia" where patients have low ionized calcium despite normal corrected calcium 8
- Patients with hidden hypocalcemia are less likely to receive appropriate interventions and have worse cardiovascular outcomes 8
- Measuring ionized calcium is important when clinical suspicion exists despite normal corrected calcium 8
Special Population Considerations
22q11.2 Deletion Syndrome
- Daily calcium and vitamin D supplementation are recommended for all adults with this condition 4, 5, 6
- Hypocalcemia may induce or worsen movement disorders, seizures, and neuropsychiatric symptoms in these patients 4
- Increased risk exists with any biological stress throughout life 4
CKD and Dialysis Patients
- Use an individualized approach rather than routine correction of all hypocalcemia 6
- In patients on calcimimetics, mild to moderate hypocalcemia may not require aggressive correction 5
- Maintain dialysate calcium concentration between 1.25 and 1.50 mmol/L 5