Dr Ira Shah
MD, DCH (Gold Medalist), FCPS, DNB

A 3 1/2 months old male child presented with failure to thrive and polyuria. He was a full term normal vertex vaginal delivery with birth weight of 3 kg. He was on exclusive breast feeding. On day 8 of life, he had generalized tonic clonic convulsions for which he was admitted in hospital for 9 days and treated with intravenous calcium gluconate. His septic workup at that time was negative (Hb = 13.9 gm/dl, WBC = 13,420 cells/cu mm, CRP = negative) and S. calcium levels were not done at that time. At the age of 1 month, he was given Vitamin D supplementation along with calcium.

On examination, he was malnourished (weight = 2.4 kg, height = 53 cm) and had pallor. There were no signs of rickets. He was suspected to have hypercalcemia due to Hypervitaminosis D. On investigations, his hemogram showed leucocytosis with positive CRP. His liver enzymes were deranged (SGOT = 110 IU/L, SGPT = 72 IU/L) and S. creatinine was also elevated (1.2 mg %). His serum calcium was normal (9.9 mg %) though ionic calcium was elevated [(2.78 mmol/L (Normal = 1.0-1.3 mmol/L)] and S. albumin was normal. Serum phosphorus and alkaline phosphatase were normal. His electrolytes and blood sugar was normal and there was no evidence of acidosis. An ultrasound of the kidneys revealed normal sized kidneys with medullary calcifications though ultrasound of skull revealed no intracranial calcifications. Echocardiography of the heart showed no valvular calcification and there was no keratitis in the eye. X Ray of the body showed no metastatic calcifications. His 24 hours urinary excretion of calcium was elevated to 5.9 mg/kg/day. He was treated with IV antibiotics, double maintenance fluids and diuresis with IV Furosemide and alkali therapy following which his ionic calcium dropped to 1.11 mmol/Lit and the polyuria subsided. On follow up after 15 days, the child showed significant weight gain.

Thus, we have an infant who has been treated for hypocalcaemia and vitamin D deficiency following which he develops problems due to hypercalcemia, one of the avoidable problems in this child. This child is left behind with nephrocalcinosis.

Causes of Hypercalcemia in children :

Hypervitaminosis of Vit. D
1. Nutritional
   
2. Inflammatory / Granulomatous / Neoplastic diseases
   
Hyperparathyroidism
1. Sporadic (Adenoma, Hyperplasia)
   
2. Familial (Isolated, MEN I & IIa)
   
Familial Hypocalciuric hypercalcemia


Immobilization

Others
1. Hypophosphatemia
   
2. Drugs (Thiazides, Vitamin A, Calcium, alkali, aluminium excess)
   
3. Hyperthyroidism
   
4. Adrenal insufficiency
   
5. Pheochromocytoma
   
William's syndrome

Evaluation of a child with hypercalcemia : A history for excessive exposure to Vitamin D, Vitamin A or calcium or thiazide diuretics should be taken. Examination for neoplasms should be undertaken.

Many patients with slight hypercalcemia (<12 mg/dl) are asymptomatic. In moderately hypercalcemic subjects (12-13.5 mg/dl), patients have weakness, anorexia, impaired concentration, constipation, polyuria and polydipsia as calcium acts as an osmotic diuretic. Severely hypercalcemic child (calcium >13.5 mg/dl) presents with nausea, vomiting, dehydration and altered consciousness. Infants also have failure to thrive. Some patients may have pancreatitis, peptic ulcer and nephrolithiasis.

A child with hypercalcemia should have a baseline total and ionic calcium, phosphorus and urine calcium excretion tests. If urine calcium is less, it suggests Familial Hypocalciuric hypercalcemia. If urine calcium is elevated, one should do serum PTH levels. If PTH levels are high, it suggest Primary hyperparathyroidism. If it is low, it suggests hypophosphatemia or Vitamin D excess.

Management of hypercalcemia : When total calcium concentration is more than 13.5 to 14 mg/dl, emergency intervention is often necessary due to the adverse effects of hypercalcemia on cardiac, CNS, renal and GI functions. Hydration with isotonic saline (twice maintenance volume) restores intravascular volume, dilutes and decreases serum Ca2+ levels and increases glomerular filtration of ionic calcium. After hydration, IV furosemide (1 mg/kg) inhibits renal tubular reabsorption of Ca++, further increasing calciuresis.

If hypercalcemia does not respond to the above measures, calcitonin (4U/kg SC every 12 hourly), osteoclast inhibitors - bisphosphonates may be used. In patients with hematological malignancies or excessive Vitamin D, glucocorticoids may also be useful. When hypercalcemia is moderate, aggressive medical therapy is usually not indicated unless the patient is symptomatic.

Treatment of specific cause: Hypercalcemia due to Vitamin D intoxication responds to the withdrawal of Vitamin D or administration of corticosteroids by impairing intestinal absorption of calcium and depressing expression of 25 hydroxy Vitamin D3 hydroxylase.

Hypercalcemia due to granulomatous disorder may respond to ketoconazole.

In children or adolescents with parathyroid adenoma, surgical removal of the adenoma is recommended. In patients with non-familial hyperplasia of parathyroid gland, subtotal parathyroidectomy is recommended.

For children and adolescents with familial hypocalciuric hypercalcemia, no aggressive therapy to required. However, neonates with severe life-threatening hypercalcemia may require emergency parathyroidectomy for survival.