What is the appropriate management of hypercalcemia in an infant?

Management of Hypercalcemia in Infants

Infants with hypercalcemia should be treated immediately with a low-calcium diet and increased water intake under medical supervision, with more frequent calcium monitoring every 4-6 months until 2 years of age. 1

Initial Assessment and Diagnostic Workup

When evaluating an infant with suspected hypercalcemia, measure the following laboratory parameters to determine the underlying cause:

• Serum calcium (total and ionized) 2
• Albumin to calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium + 0.8 × [4.0 - Serum albumin] 3
• Intact parathyroid hormone (iPTH) - the single most critical test that determines the diagnostic pathway 4
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D - must be measured together 4
• Serum phosphorus, magnesium, blood urea nitrogen, and creatinine 1, 4

Look specifically for: extreme irritability, vomiting, constipation, muscle cramps, hypotonia, anorexia, failure to thrive, dehydration, and lethargy 1, 5, 6. These symptoms are most common in the first 2 years of life 1.

Treatment Algorithm

Step 1: Immediate Dietary and Hydration Management

For infants with confirmed hypercalcemia:

• Implement a low-calcium diet immediately under medical and nutritional supervision 1
• Increase water intake to promote calciuresis and prevent dehydration 1
• Discontinue all vitamin D supplements immediately, even if 25-OH vitamin D levels are low 2
• Stop any calcium-based supplements 2

Step 2: Pharmacologic Treatment Based on Severity

For symptomatic or severe hypercalcemia (>14 mg/dL):

• Administer IV normal saline to correct hypovolemia and promote calciuresis, targeting urine output of 3 mL/kg/hour in infants <10 kg 2
• Calcitonin-salmon 100 IU subcutaneously or intramuscularly provides rapid onset within hours for immediate short-term management 2, 7, 8. This normalizes serum calcium within 4 days in idiopathic infantile hypercalcemia 8
• Glucocorticoids (prednisone 1 mg/kg/day orally or methylprednisolone IV equivalent) are effective for hypercalcemia due to vitamin D intoxication or when other causes are ruled out 2, 5, 6
• Furosemide (loop diuretic) should be added after adequate hydration is achieved, particularly useful in idiopathic infantile hypercalcemia 5, 6

Important caveat: Loop diuretics must only be used after complete volume repletion, as premature use worsens dehydration and can aggravate hypercalcemia 2.

Step 3: Consider Bisphosphonates for Refractory Cases

• Pamidronate IV can be used in severe cases that do not respond to initial measures 6
• Bisphosphonates are typically reserved for more severe or refractory hypercalcemia in infants 6

Step 4: Dialysis for Severe Cases with Renal Failure

• Hemodialysis with calcium-free or low-calcium dialysate is reserved for severe hypercalcemia complicated by renal insufficiency or oliguria 2, 9

Specific Etiologies in Infants

Idiopathic Infantile Hypercalcemia

This is the most common cause of hypercalcemia in otherwise healthy infants and usually resolves during childhood, though lifelong abnormalities of calcium and vitamin D metabolism may persist 1. The condition is characterized by increased calcium absorption from the gut, with the exact mechanism unknown 1.

Treatment approach:

• Low-calcium diet + increased water intake 1
• Glucocorticoids + furosemide 5
• Calcitonin for rapid control 7, 8

Williams Syndrome

Symptomatic hypercalcemia is most common in the first 2 years and usually resolves during childhood 1.

Key management points:

• Monitor calcium every 4-6 months until 2 years of age, then every 2 years thereafter 1
• Educate parents regarding signs and symptoms of hypercalcemia 1
• Children with normocalcemia should receive the reference daily intake of calcium, and parents should be cautioned not to restrict calcium without medical supervision 1

Vitamin D Intoxication

This is an increasingly recognized cause, particularly in immigrant families who fear rickets and may purchase high-dose vitamin D preparations online 6.

Treatment approach:

• Hyperhydration + loop diuretics 6
• Bisphosphonate infusion (pamidronate) often allows control of hypercalcemia 6
• In severe cases with neurological impairment and EKG abnormalities (shortened QTc), hemodialysis may be required 6

Monitoring and Follow-Up

Frequency of calcium monitoring:

• Every 4-6 months until 2 years of age for infants with hypercalcemia 1
• More frequent surveillance (weekly to monthly) for infants on active treatment 3
• Every 2 years after age 2 for conditions like Williams syndrome 1

Additional monitoring parameters:

• Serum blood urea nitrogen, creatinine, vitamin D concentrations (both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D), and intact parathyroid hormone 1
• Renal ultrasound to assess for nephrocalcinosis, which is a common complication 1, 5, 7

Critical Pitfalls to Avoid

• Do not delay treatment while waiting for complete diagnostic workup in symptomatic infants 5
• Do not use loop diuretics before adequate hydration, as this worsens dehydration 2
• Do not restrict calcium intake without medical supervision in normocalcemic infants with conditions like Williams syndrome 1
• Do not overlook vitamin D intoxication as a cause, especially in immigrant families - always ask about vitamin D supplementation practices 6
• Do not assume hypercalcemia will resolve without intervention - complications include dehydration, hypercalciuria, nephrocalcinosis, and renal tubular acidosis 1, 7

Complications to Monitor

Problems associated with infantile hypercalcemia include:

• Dehydration 1
• Hypercalciuria 1, 8
• Nephrocalcinosis - correlates with chronic administration 1, 5, 7, 6
• Distal renal tubular acidosis 7
• Renal failure (if untreated) 7