Pediatric Hypercalcemia Treatment & Management

Initial treatment of hypercalcemia involves hydration to improve urinary calcium output. Isotonic sodium chloride solution is used, because increasing sodium excretion increases calcium excretion. Addition of a loop diuretic inhibits tubular reabsorption of calcium, with furosemide having been used up to every 2 hours. Attention should be paid to other electrolytes (eg, magnesium, potassium) during saline diuresis. These treatments work within hours and can lower serum calcium levels by 1-3 mg/dL within a day.

Bisphosphonates serve to block bone resorption over the next 24-48 hours by absorbance into the hydroxyapatite and by shortening the life span of osteoclasts. Administered intravenously (IV), they decrease serum calcium in 2-4 days with a nadir at 4-7 days. These medications have been studied more in adults than in children; however, many studies have established safety and efficacy in children, particularly with etidronate and pamidronate. ^[13]

• Etidronate (Didronel), a first-generation bisphosphonate, may result in hyperphosphatemia and a transient increase in creatinine. It is given as 7.5 mg/kg/d IV over 2 hours for 3-7 days and lowers serum calcium in 2 days; maximal action is reached in 7 days. Oral etidronate doses are 5-20 mg/kg/d. Oral dosing of etidronate for 3-12 months can inhibit bone mineralization, leading to bony pain and fractures, and occasionally nephrotic syndrome.

• Clodronate (Bonefos), is an orphan drug in the United States and is used for increased bone resorption or hypercalcemia of malignancy. It acts similarly to etidronate.

• Pamidronate (Aredia) in IV and oral formulation has been used successfully in children. To lower serum calcium levels over a period of days to months, intravenous doses of 1-1.5 mg/kg (to an adult dose of 90 mg) are administered. Redosing is based on a rise in serum calcium levels and should not be done more than once a month. Oral doses are 4-8 mg/kg/d. Fever, musculoskeletal discomfort, and vomiting are common side effects.

• Alendronate (Fosamax), tiludronate (Skelid), and risedronate (Actonel) are newer, more potent bisphosphonates that carry the uncommon but potential toxicities of lowering serum phosphorus, acute phase response with low grade fever, myalgia, lymphopenia, increased cAMP receptor protein (CRP), GI upset, gastritis, bone pain, and reversible hepatotoxicity. Additionally, some believe that the tensile strength of bones formed while on these medications may be less than that of native bone. Mineralization defects may occur, particularly in pediatric patients before growth plates are fused. Ibandronate (Boniva) and zoledronate (Zometa) are believed to be even more potent medications. Adult literature contains the preponderance of studies involving these medications.

• Neridronic acid is an IV/intramuscular (IM) bisphosphonate currently licensed in Europe; some pediatric data are available, including some in neonates. ^[14]

Calcitonin at subcutaneous (SC) or IM doses of 3-6 mcg/kg every 6 hours, works within hours to decrease skeletal reabsorption of calcium and inhibit renal reabsorption, but it lowers serum calcium concentration only for 2-3 days because of tachyphylaxis. It can be expected to lower serum calcium only 0.5 mmol/L. Adverse effects include nausea, cramping, abdominal pain, and flushing. One benefit of calcitonin is that it has analgesic properties.

Other options include 200 mg/m²/d of gallium nitrate for 5 days as a continuous infusion. Gallium nitrate inhibits bone resorption by reducing the solubility of hydroxyapatite, but it is potentially nephrotoxic.

Plicamycin (ie, mithramycin) lowers calcium by inhibiting RNA synthesis to kill osteoclasts. The manufacture and distribution of plicamycin was discontinued in the United States in 2000. A dose of 25 mcg/kg/d is given IV over 3-4 days; the onset of action is within 24-48 hours. Mithramycin is associated with many reversible adverse effects, such as thrombocytopenia, hepatocellular necrosis with increased lactate dehydrogenase (LDH) and aspartate aminotransferase (AST), decreased clotting factors with resultant bleeding, azotemia, proteinuria, hypokalemia, hypophosphatemia, nausea, vomiting, and facial swelling. These adverse effects are more common with repeated dosing.

Peritoneal dialysis or hemodialysis can be used in extreme situations, particularly in patients with renal failure; careful attention must be given to the phosphorus level following dialysis.

Cinacalcet hydrochloride (Sensipar) is the first medication approved from the calcimimetic class. It changes the configuration of the transmembranal calcium-sensing receptor in a manner that makes it more sensitive to serum calcium. It is primarily indicated for chronic renal disease and secondary hyperparathyroidism. No large pediatric studies have been done to date, but its efficacy has been substantiated in adults.

Several newer medications that do not acutely lower serum calcium levels and may raise them have been developed for hyperparathyroidism. These include calcitriol and its more potent forms (eg, DN-101) and other vitamin D analogues, such as paricalcitol (Zemplar). By binding to vitamin D receptors, they chronically inhibit the secretion of parathyroid hormone (PTH). However, their use in patients with severe or symptomatic hypercalcemia is limited by their ability to increase serum calcium and the calcium x phosphate product. One report of a long-acting depot form of octreotide demonstrated efficacy in patients with multiple endocrine neoplasia (MEN) 1 who also had hyperparathyroidism. ^[15]

Surgical intervention may be needed in patients with hyperparathyroidism, particularly with recurrent renal stones or persistent serum calcium levels higher than 12.5 mg/dL.

Subtotal parathyroidectomy can be performed, or complete parathyroidectomy can be chosen with reimplantation of a small amount of tissue in the forearm.

Consultations include the following:

• Endocrinologist

• Nephrologist

• Oncologist

A low-calcium diet is indicated. Restriction of vitamin D (sunlight, dairy) may be warranted in some disorders.