What is Hypocalcemia?

Hypocalcemia is abnormally low calcium levels in the blood. Normal serum calcium is 8.5-10.5 mg/dL (total) or 4.6-5.3 mg/dL (ionized). Hypocalcemia is defined as total calcium <8.5 mg/dL or ionized calcium <4.6 mg/dL.

Common Causes:

1. Hypoparathyroidism (Low or Absent PTH):

• Post-Surgical: Most common cause; after thyroid or parathyroid surgery
• Autoimmune
• Congenital/Genetic: DiGeorge syndrome, familial hypoparathyroidism
• Infiltrative Diseases, Radiation

2. Vitamin D Deficiency or Resistance:

• Nutritional Deficiency: Inadequate sun exposure, dietary insufficiency
• Malabsorption: Celiac disease, Crohn's, gastric bypass
• Chronic Kidney Disease: Kidneys cannot convert Vitamin D to active form (calcitriol)
• Liver Disease: Impairs Vitamin D activation
• Vitamin D-Dependent Rickets: Genetic defects in Vitamin D metabolism or receptor

3. Hypomagnesemia (Low Magnesium):

• Magnesium is required for PTH secretion and action
• Low magnesium → functional hypoparathyroidism
• Causes: Alcoholism, diuretics, diarrhea, malnutrition, PPI use

4. Chronic Kidney Disease (CKD):

• Decreased calcitriol production
• Hyperphosphatemia (high phosphorus binds calcium)
• Secondary hyperparathyroidism (elevated PTH trying to compensate)

5. Acute Pancreatitis:

• Calcium binds to fatty acids released from necrotic pancreatic tissue (saponification)

6. Medications:

• Bisphosphonates, Denosumab: Especially with Vitamin D deficiency
• Calcitonin
• Chemotherapy (Cisplatin)
• Foscarnet (antiviral)
• Proton Pump Inhibitors (PPIs): Chronic use can impair calcium absorption and cause hypomagnesemia

7. Pseudohypoparathyroidism:

• Resistance to PTH (high PTH, low calcium)

8. Hungry Bone Syndrome:

• Rapid uptake of calcium into bones after parathyroidectomy (for hyperparathyroidism)

9. Sepsis, Critical Illness:

• Multifactorial; common in ICU patients

10. Hyperphosphatemia:

• Tumor lysis syndrome, rhabdomyolysis, kidney failure
• Excess phosphate binds calcium, forming calcium-phosphate complexes

11. Massive Blood Transfusions:

• Citrate in stored blood binds calcium

Symptoms:

Mild Hypocalcemia: Often asymptomatic

Moderate to Severe Hypocalcemia:

• Neuromuscular Irritability:
  • Paresthesias: Tingling/numbness around mouth, fingers, toes
  • Muscle Cramps, Spasms
  • Tetany: Involuntary muscle contractions (hands, feet, face)
  • Carpopedal Spasm: "Trousseau's Sign"—hand/wrist spasm when BP cuff inflated
  • Chvostek's Sign: Facial twitching when tapping facial nerve
  • Laryngospasm: Throat spasm—can be life-threatening
  • Seizures (if severe)
• Cardiac:
  • Prolonged QT interval on ECG (risk of arrhythmias, Torsades de Pointes)
  • Heart failure (chronic hypocalcemia)
• Neuropsychiatric:
  • Anxiety, irritability, depression
  • Confusion, cognitive impairment
  • Psychosis (rare)
• Chronic Hypocalcemia:
  • Cataracts
  • Dry skin, brittle nails, hair loss
  • Dental abnormalities (enamel hypoplasia)
  • Basal ganglia calcifications (movement disorders)

Diagnosis:

Confirm Low Calcium:

• Total Serum Calcium: <8.5 mg/dL (correct for low albumin if present: corrected calcium=measured calcium + 0.8 × [4.0 - albumin])
• Ionized Calcium: <4.6 mg/dL (most accurate; not affected by albumin)

Find the Cause:

• PTH (Parathyroid Hormone): KEY TEST
  • PTH Low or Inappropriately Normal: Hypoparathyroidism
  • PTH Elevated: Vitamin D deficiency, CKD, pseudohypoparathyroidism
• Magnesium: Check and correct if low
• Phosphorus:
  • High in hypoparathyroidism, CKD
  • Low in Vitamin D deficiency, malabsorption
• 25-OH Vitamin D: Assess Vitamin D status
• Kidney Function (Creatinine, eGFR): Rule out CKD
• Alkaline Phosphatase: Elevated in rickets/osteomalacia
• Albumin: Correct calcium if hypoalbuminemia present
• ECG: Check for prolonged QT interval

Treatment:

Depends on Severity and Cause

1. Acute Symptomatic Hypocalcemia (Tetany, Seizures, QT Prolongation):

• IV Calcium Gluconate (FIRST-LINE EMERGENCY):
  • 1-2 grams (10-20 mL of 10% solution) IV over 10-20 minutes
  • Follow with continuous IV infusion if needed
• Monitor ECG, Calcium Levels
• Correct Hypomagnesemia: Magnesium sulfate IV if magnesium low

2. Chronic or Mild Hypocalcemia:

• Oral Calcium Supplementation:
  • 1500-3000 mg/day (divided doses)
  • Calcium carbonate (take with food) or calcium citrate
• Vitamin D Supplementation:
  • If Vitamin D Deficient: Cholecalciferol (D3) 50,000 IU weekly for 6-8 weeks, then maintenance
  • If Hypoparathyroidism: Active Vitamin D (Calcitriol 0.25-2 mcg/day)
  • If CKD: Active Vitamin D (calcitriol or analogs)
• Magnesium Replacement (if low): Magnesium oxide 400-800 mg/day

3. Treat Underlying Cause:

• Hyperphosphatemia: Phosphate binders, dialysis (if CKD)
• Medications: Stop or adjust offending drugs
• Malabsorption: Treat underlying GI condition

Monitoring:

• Acute Setting: Check calcium frequently (every 4-6 hours) until stable
• Chronic Management: Calcium, phosphorus, magnesium, PTH every 3-6 months
• Goal: Maintain calcium in low-normal range (8.0-9.0 mg/dL) for hypoparathyroidism (to avoid hypercalciuria)
• 24-Hour Urine Calcium: Monitor for hypercalciuria (kidney stone risk)
• Kidney Function: Monitor creatinine

Complications:

• Seizures, arrhythmias (if untreated)
• Laryngospasm (life-threatening)
• Cataracts, basal ganglia calcifications (chronic)
• Kidney stones, nephrocalcinosis (from over-treatment)