Rosen & Barkin's 5-Minute Emergency Medicine Consult (367 page)

Stones, bones, abdominal groans, and psychiatric moans

Depends on the severity and rapidity of hypercalcemia

• Neonate:
  
  • Hypotonia, weakness, and listlessness
    
  • Following delivery to hypoparathyroid mothers
    
• Hypercalcemic infants:
  
  • Broad forehead
    
  • Epicanthal folds
    
  • Underdeveloped nasal bridge
    
  • Prominent upper lip
    

• Dehydration
  
• Cardiac:
  
  • Hypertension (even in the face of dehydration)
    
  • Cardiac conduction abnormalities (
    not
    proportional to degree of hypercalcemia)
    
  • Bradydysrhythmia
    
  • Bundle branch blocks
    
  • Complete heart block
    
  • Asystole
    
  • Short QT interval (shortened ST segment)
    
  • Potentiation of digitalis effects (Hypercalcemia +digoxin = digitalis toxicity)
    
• Neurologic:
  
  • Headaches
    
  • Decreased reflexes
    
  • Proximal muscle weakness
    
  • Dementia
    
  • Lethargy
    
  • Coma
    
• Psychiatric:
  
  • Personality changes
    
  • Depression
    
  • Inability to concentrate
    
  • Anxiety
    
  • Psychosis
    
• GI:
  
  • Anorexia, nausea, vomiting
    
  • Constipation
    
  • Peptic ulcer disease
    
  • Pancreatitis
    
• General:
  
  • Fatigue
    
  • Weight loss
    
  • Polyuria and polydipsia
    
• Musculoskeletal:
  
  • Gout/pseudogout
    
  • Bone pain, bone cysts (osteitis cystica)
    
  • Arthralgias
    
  • Chondrocalcinosis
    
• Renal:
  
  • Kidney stones
    
  • Nephrocalcinosis
    
  • Decreased renal concentrating ability
    

• Calcium level
  
• Albumin:
  
  • Elevated albumin—falsely elevated calcium level
    
  • Low albumin—falsely lowered calcium level
    
• Evaluate for symptoms of hypercalcemia, especially impending parathyroid storm (hypercalcemic crisis—anorexia, nausea, vomiting, obtundation progressing to coma).
  
• Review history for medication ingestion (see Differential Diagnosis below)
  
• No further ED workup if:
  
  • Asymptomatic
    
  • Normal ECG
    
  • Calcium level <14 mg/dL when corrected for albumin
    
• If symptomatic with Ca
  ²⁺
  <14 mg/dL or any patient with Ca
  ²⁺
  ≥14 mg/dL, check:
  
  • Ionized calcium
    
  • Chest radiograph (for CHF/malignancy)
    
  • Phosphorus
    
  • Electrolytes, BUN, creatinine
    
  • Sedimentation rate
    
  • Alkaline phosphatase
    
  • Magnesium
    
  • Thyroid-stimulating hormone (TSH)
    
  • CBC
    

• Calcium correction for albumin:
  
  • Corrected Ca
    ²⁺
    (mg/dL) = measured Ca
    ²⁺
    (mg/dL) + 0.8 [4 – albumin (g/dL)]
    
  • Acidosis:
    
    • Decreases affinity to albumin—increases ionized (metabolically active) Ca
      ²⁺
      
    • Decrease of 0.1 pH unit increases the ionized Ca
      ²⁺
      by 3–8%
      
• Phosphorus:
  
  • Low in primary hyperparathyroidism
    
  • Usually high in secondary hyperparathyroidism
    
  • Normal or high in malignancy-related hypercalcemia
    
• Chloride/PO
  ₄
  ²⁻
  ratio:
  
  • >33—hyperparathyroidism
    
  • <30—malignancy
    
• Alkaline phosphatase:
  
  • Increased in 50% of patients with hyperparathyroidism
    
  • Normal with vitamin D excess
    
• Erythrocyte sedimentation rate (ESR):
  
  • Normal in hyperparathyroidism
    
  • Elevated in malignancy or granulomatous diseases
    
• Anemia:
  
  • Present with malignancy or granulomatous disease
    
  • Absent in hyperparathyroidism
    
• Magnesium:
  
  • Low or low normal
    
• PTH:
  
  • Elevated in primary and secondary hyperparathyroidism
    
• PTH-related peptide:
  
  • Secreted by squamous cell carcinomas of lung, head, neck; renal carcinomas, bladder carcinomas, adenocarcinomas, and lymphomas
    

• Chest radiograph:
  
  • To assess CHF risk during IV hydration
    
  • Granulomatous disease or malignancy if cause of hypercalcemia is uncertain
    

Definitive treatment is parathyroidectomy to treat and establish cause of hyperparathyroidism

• PTH related:
  
  • Primary or secondary hyperparathyroidism
    
  • Familial hypocalciuric hypercalcemia
    
• Malignancy related:
  
  • PTH-related peptide or Ca
    ²⁺
    release from osteolytic tumor
    
• Vitamin D related:
  
  • Excess vitamin D intake or vitamin D production by granulomas
    
• Immobilization:
  
  • Associated with Paget disease
    
• Drug induced:
  
  • Thiazide diuretics
    
  • Lithium
    
  • Aluminum-containing antacids
    
  • Tamoxifen
    
  • Estrogens
    
  • Androgens
    
  • Vitamin A
    

TREATMENT

May present as a primarily psychiatric disorder

• Cardiac monitor if:
  
  • Symptomatic hypercalcemia
    
  • Ca
    ²⁺
    level >14 mg/dL
    
• Hydrate with IV 0.9% NS.
  
• Correct acidosis
  

• Treat hypercalcemia:
  
  • Vigorous hydration with 0.9% NS at minimum of 250 mL/hr unless CHF:
    
    • Lowers calcium 1.5–2 mg/dL in 24 hr
      
    • Achieve urine output 100 mL/hr
      
  • Administer furosemide or other loop diuretic (calciuric) after adequate volume replacement or in the presence of CHF:
    
    • Common error: Administration of furosemide before adequate hydration
      
    • If urinary sodium losses exceed replacement sodium, then renal conservation measures impede calcium excretion
      
  • Avoid thiazide diuretics (impede calcium excretion)
    
  • Consider glucocorticoid administration (decreases gut absorption and increases renal excretion of Ca
    ²⁺
    ); most effective with vitamin D intoxication or granulomatous diseases
    
  • Start bisphosphonates (pamidronate or etidronate) in conjunction with primary physician (inhibits calcium mobilization from bone)
    
• Treat cardiac dysrhythmias in standard fashion:
  
  • Correct acidosis
    
• Determine the cause of the hypercalcemia.
  
• Stop all medications that may contribute to hypercalcemia
  
• Exercise extreme caution in the use of digoxin.
  
• Anticipate CHF and electrolyte imbalance with frequent reassessment of patient and monitoring of serum electrolytes and magnesium levels
  
• Calcitonin if unable to use hydration
  
• Emergent dialysis with renal failure
  

• NS hydration: Initial 250–300 mL/h depending on patient’s propensity to CHF
  
• Furosemide: 40 mg IV q2–4h after assurance of adequate hydration
  
• Prednisone: 40–60 mg PO OR Hydrocortisone: 100 mg (peds: 1–2 mg/kg) IV
  

• IN CONSULTATION WITH ENDOCRINOLOGIST
  
• Calcitonin salmon 4 U/kg SC if saline hydration contraindicated
  
  • Test dose: Intradermal 0.1 mL of 10 U/mL solution recommended
    
  • Initial dose: 4 U/kg SC q12h
    
• Pamidronate:
  
  • If albumin-corrected Ca
    ²⁺
    level 12–13.5 mg/dL: 60 mg IV infused over 2 hr
    
  • If albumin-corrected Ca
    ²⁺
    level > 13.5 mg/dL: 90 mg IV over 4 hr
    
  • Dosage should be reduced in renal impairment and infusion time may be extended to reduce nephrotoxic potential but no formal recommendations exist (pregnancy category D – maternal benefit may outweigh fetal risk)
    
• Zoledronic acid: 4 mg IV over 15–30 min (first-line agent due to efficacy and convenience, but less preferred due to lack of less expensive available generic)
  
• Cinacalcet (Sensipar): 30 mg PO daily or BID (calcimimetic for secondary hyperparathyroidism or parathyroid carcinoma)
  

FOLLOW-UP

• Corrected calcium >14 mg/dL
  
• Symptomatic hypercalcemia
  
• Evidence of abnormal cardiac rhythm or conduction
  

• Not meeting admission criteria
  
• Able to maintain adequate hydration
  

If diagnosis is suspected, referral to check PTH levels and response to therapy

• If hyperparathyroidism is suspected arrange follow-up and send a PTH level
  
• Patient needs to be instructed to maintain hydration and stop medications associated with hypercalcemia (see the list in Differential Diagnosis)
  

• The hypercalcemia of hyperparathyroidism is rarely symptomatic and Ca
  ²⁺
  level rarely >14. (Higher levels are most frequently attributable to neoplastic disease)
  
• The importance of diagnosis is to prevent long-term complications
  
• Calcium level should be measured as ionized Ca
  ²⁺
  , or corrected for albumin level
  
• Administration of loop diuretics prior to adequate saline hydration will worsen hypercalcemia; some experts suggest that loop diuretics may be no longer warranted for this indication
  

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  Cecil’s Textbook of Medicine
  . 23rd ed. Philadelphia, PA: Saunders-Elsevier; 2008.
  
• Jamal SA, Miller PD. Secondary and tertiary hyperparathyroidism.
  J Clin Densitom.
  2013;16(1):64–68.
  
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  J Densitom.
  2013;16(1):60–63.
  
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  N Engl J Med.
  2011;365:2389–2397.