Pediatric Hypercalcemia Treatment & Management

  • Author: Ilene A Claudius, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Apr 3, 2012
 

Medical Care

  • 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 medication have been studied more in adults than in children; however, many studies have established safety and efficacy in children, particularly with etidronate and pamidronate.
    • 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.[7]
  • 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 affects 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 new 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.[8]
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Surgical Care

  • 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.
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Consultations

  • Endocrinologist
  • Nephrologist
  • Oncologist
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Diet

  • A low-calcium diet is indicated. Restriction of vitamin D (sunlight, dairy) may be warranted in some disorders.
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Contributor Information and Disclosures
Author

Ilene A Claudius, MD  Assistant Professor of Pediatrics, Division of Emergency Medicine, Children's Hospital, Los Angeles

Ilene A Claudius, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Coauthor(s)

Oved Fattal, MD  Staff Physician, Department of Pediatrics, Kaiser Permanente Medical Group

Oved Fattal, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Jon Nakamoto, MD  Consulting Staff, Department of Pediatric Endocrinology, Quest Diagnostics

Jon Nakamoto, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Pisit (Duke) Pitukcheewanont, MD  Associate Professor of Clinical Pediatrics, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles

Pisit (Duke) Pitukcheewanont, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, American Society for Bone and Mineral Research, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Thomas A Wilson, MD  Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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Investigations flowchart.
Table 1
Laboratory Test Reference Range Normal Response to Increased Calcium
Serum calcium8.5-10.2 mg/dLNA
Ionized calcium1-1.3 mmol/LNA
PTH (intact)10-55 pg/mL*Decrease
Serum phosphateAge-dependentIncrease
1,25-dihydroxyvitamin D36-108 pmol/LDecrease
Alkaline phosphatase68-217 U/LNormal
Urine calcium4 mg/kg/dIncrease
Urine Ca/Cr ratioSee note†Increase
Urine cAMP‡< 5 molDecrease
*Note that 1 mmol/L equals 4 mg/dL. †In infants younger than 7 months, the reference range is less than 0.86; in infants aged 7-18 months, the reference range is less than 0.6. By age 6-7 years, the adult reference range of less than 0.21 is reached.‡The urine cAMP level generally parallels the PTH level.
Table 2
Condition Serum Phosphorus Serum Alkaline Phosphatase Urine Calcium Urine Phosphate PTH
HyperparathyroidismLowNormal-highHigh*HighHigh
Vitamin D excessNormal-highLowHighHigh
MalignancyOften lowHigh † VariableHigh
Granulomatous diseaseNormal-highNormal-highHighNormal
Milk alkali syndromeNormal-highNormalNormalNormal
FHHNormal or lowNormalLow (< 200mg/d)NormalLow
*67% of the time



† Except hematologic malignancies, in which alkaline phosphatase is normal



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