What Causes Hypercalcemia?

Patient Presentation
A 19-month-old male was referred to a regional children’s hospital for mild hypercalcemia that was noted when routine laboratories were drawn in an emergency room when he presented with bronchiolitis. He was otherwise well with normal growth parameters and development. The parents denied any medication, vitamins or herbal use including topical medications. There was some blood pressure medication and oral contraceptives in the parents and grandparents homes but the family denied that the child had access to the medications. He had been well with no fatigue, nervousness, changes in skin, hair, sleep or weight. A record review from the emergency room showed a normal saline bolus and albuterol were given but no calcium. The family history had no cancers, bone, kidney, or hearing problems.

The pertinent physical exam showed a mildly tachypneic male with otherwise normal vital signs and growth parameters in the 10-50% range. Pulse oximeter was 90% on room air. HEENT showed mild rhinorrhea with wet mucosa. Thyroid was normal. Lungs were coarse with mild end expiratory wheezing. There was normal skin except for mild shin bruising bilaterally. The laboratory evaluation at the outside hospital found normal electrolyes, BUN, creatinine, phosphorus, magnesium, albumin, T4, TSH, and parathyroid hormone. His ionized calcium was 5.73 mg/dL (normal up to 5.52), 25-OH Vitamin D was normal and spot urine calcium/creatinine ratio was .65 (normal up to .6 for age). Chest radiograph showed mild hyperexpansion with patchy areas of atelectesis. The diagnosis of bronchiolitis and idiopathic hypercalcemia were found. As there was no obvious malignancy, parathyroid hormone or Vitamin D abnormalities, and the patient was asymptomatic, it was felt that this was most consistent with a transient abnormality or familial hypercalciuric hypercalcemia. A pediatric endocrinologist recommended to recheck both 1,25-OH Vitamin D, and an ionized calcium in 1-2 weeks. If these were abnormal then additional studies may be indicated. At 2 weeks, the repeat lab tests were normal on the infant, but the mother had a spot calcium/creatinine ratio which was elevated, and the mother was now being evaluated further.

Discussion
Calcium homeostasis is regulated by mechanisms involving the absorption from the gastrointestinal tract, bone deposition and resorption, and renal excretion. To review Vitamin D homeostasis click here.

Serum calcium is found in three forms: free (47%), protein bound (43%) and diffusable calcium complexes (10%). The protein binding proteins are albumin (80%) and globulin (20%). The free calcium is the most important biologically. Acidosis also increases free calcium and alkalosis decreases free calcium.

Problems associated with hypercalcemia include nausea, emesis, abdominal pain, constipation, polyuria, dehydration, mental status changes and coma.

Learning Point
The differential diagnosis of hypercalcemia includes:

  • Hyperparathyroidism
    • Primary
    • Familial isolated
    • Familial hypercalciuria hypercalcemia
    • MEN I and II
  • Vitamin D excess
    • Chronic granulomatous disorders
  • Drugs
    • Catecholamines
    • Lithium
    • Teriparatide
    • Theophylline
    • Thiazides
    • Vitamin A excess
  • Malignancies
    • Ectopic PTH-producing tumors
    • Pheochromocytoma
  • Other
    • Acromegaly
    • Aluminum excess
    • Adrenal insufficiency
    • Hypophosphatemia
    • Hyperthyroidism
    • Immobilization
    • Idiopathic infantile hypercalcemia
    • Milk alkali syndrome
    • Parenteral nutrition
    • Renal failure
    • Williams syndrome

Questions for Further Discussion
1. What are treatments for hypercalcemia?
2. What is included in the differential diagnosis of hypocalcemia?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: fluid and Electrolyte Balance and Calcium.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Bakerman’s ABC’s of Interpretative Laboratory Data. Fourth Edit. Interpretative Laboratory Data Inc. Scottsdale, AZ. 2002;123-125.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:163-64,2152-56.

Shane E. Diagnostic Approach to Hypercalcemia. UptoDate.
Available from the Internet at http://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia?source=search_result&search=diagnostic+approach+to+hypercalcemia&selectedTitle=1%7E150 (rev. 1/25/2013, cited 2/8/13).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital