Hypercalcemia

Hypercalcemia: Excerpt from In a Page: Signs and Symptoms

Calcium is the most abundant mineral in the body, with 99% stored in bone. Calcium in the plasma is either protein-bound (mostly to albumin) or is ionized and readily available for use. Serum calcium is regulated by parathyroid hormone (PTH) and vitamin D metabolites (1,25-dihydroxyvitamin D, 25-hydroxyvitamin D). 90% of cases of hypercalcemia are secondary to an underlying malignancy (via bone metastases or PTH-related peptide secretion) or hyperparathyroidism (especially parathyroid adenoma).

Differential Diagnosis

• Primary hyperparathyroidism
  –Most commonly caused by an adenoma of one of the parathyroid glands (90% of cases of primary hyperparathyroidism)
  –Less commonly caused by parathyroid hyperplasia or carcinoma (may be associated with multiple endocrine neoplasia syndromes)
  –Symptoms may include weakness, confusion, polyuria, renal stones, nausea, and anorexia
  –Symptoms are usually only present when calcium rises over 12 mg/dL
• Drugs (e.g., thiazides, lithium)
• Malignancy (e.g., multiple myeloma, leukemia; lymphoma; breast, lung, and kidney cancers)
  –Most common cause in hospitalized patients
  –Hypercalcemia occurs due to stimulation of bone resorption by cytokines released from tumor cells or to the release of PTH-related peptide produced by the tumor
  –Symptoms are identical to primary hyperparathyroidism

• Renal failure
• Hyperthyroidism
• Addison's disease
• Familial hypocalciuric hypercalcemia
• Vitamin A or D intoxication
• Granulomatous disease (e.g., sarcoidosis, tuberculosis)
• Adrenal insufficiency
• Paget's disease
• Immobilization
• Hypophosphatemia
• Acromegaly
• Milk-alkali syndrome (due to excessive ingestion of milk or calcium supplements)

Workup and Diagnosis

• Complete history and physical examination
  –Most cases are relatively asymptomatic (fatigue and other nonspecific symptoms present)
  –“Stones, bones, abdominal groans, and psychic overtones” is the classic presentation; however, these are not common clinically

  *

  Stones: Renal stones in 50%

  *

  Bones: Bone pain, weakness, osteoporosis

  *

  Groans: Abdominal pain, nausea/vomiting, constipation, peptic ulcer disease, pancreatitis

  *

  Psychic overtones: Psychosis, depression, anxiety

  
  –Evaluate for increased urination or renal stones, GI upset, confusion, tiredness, mental status changes, hyporeflexia, hypertension, arrhythmias, and coma
• Initial laboratory studies include serum and urinary calcium, electrolytes, BUN/creatinine, parathyroid hormone, PTH-related peptide, CBC, albumin, magnesium, phosphate, alkaline phosphatase, vitamin D
  –The higher the plasma Ca²⁺, the more likely it is due to a malignancy; it is generally more difficult to correct
  –Be sure to correct calcium level for serum albumin
  –Corrected calcium level =[0.8 ×(normal albumin - serum albumin) +serum Ca^₂+]

• ECG may show ST depression, wide T waves, short ST segment, QT shortening, bradyarrhythmias, heart block
• Further lab tests and/or imaging modalities may be indicated to evaluate for specific etiologies (e.g., CT scan to rule out nephrolithiasis, amylase/lipase)

Treatment

• Patients are often dehydrated; repletion of blood volume with normal saline may correct calcium level
• Severe hypercalcemia (calcium >13 mg/dL or symptoms) requires immediate intervention
  –IV rehydration with large volumes of normal saline
  –Loop diuretics to prevent volume overload and to augment renal calcium excretion
  –Bisphosphonates (e.g., IV pamidronate) inhibit bone resorption; full effect may not occur for 1–5 days
  –Calcitonin and mithramycin decrease bone resorption by osteoclast inhibition (note that mithramycin is cytotoxic and causes renal toxicity)
  –IV steroids may be used in vitamin D disorders, granulomatous diseases, and malignancy
  –Correct other electrolyte abnormalities as necessary

• Parathyroidectomy for primary hyperparathyroidism
• Treat malignancy according to established protocols

Book Source Details

• Book Title: In a Page: Signs and Symptoms
• Author(s): Scott Kahan, Ellen G. Smith
• Year of Publication: 2004
• Copyright Details: In a Page: Signs and Symptoms, Copyright © 2004 Lippincott Williams & Wilkins.

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: In a Page: Signs and Symptoms Authors: Scott Kahan, Ellen G. Smith Publisher: Lippincott Williams & Wilkins Copyright: 2004 ISBN: 1-4051-0368-X

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