Hyper (Ca)

Also See Other bone disorder (Labs)Hyperparathyroidism

THE CALL

Overview

  • Hypercalcemia:
    • Corrected calcium > 2.6 mmol/L (10.5 mg/dL) or
    • Ionized calcium > 1.32 mmol/L (5.3 mg/dL): The values used in this vignette refer to the total serum calcium (corrected).
  • Hypercalcemic patients are usually volume-depleted 2ndto hypercalcemia-induced urinary salt wasting.

Etiology

  • Over supplementation:
    • Calcium or vitamin D
  • Hyperparathyroidism
  • Neoplasm
    • Squamous cell Carcinoma Lung = PTHrP
    • Breast cancer
    • Renal Cell Carcinoma
    • Lymphomas
    • Multiple myeloma
  • Medication:
    • Thiazides,
    • Lithium,
    • Antacids (milk-alkali syndrome)
  • Immobilization
  • Granulomatous disease
  • Renal diseases

History/Symptoms

  • Suspect in all known cancer patients presenting with nonspecific complaints
  • Weakness, nausea, vomiting, anorexia, mental status changes, constipation, or polyuria, polydypsia, natriuresis
  • Apathy, depression, malaise, obtundation, psychosis, seizure, coma
  • Muscle weakness, anorexia, nausea, abdominal pain, constipation
  • Pancreatitis
    • Calcium deposition in pancreatic duct, activating trypsinogen
    • Elevated amylase
  • Peptic Ulcer Disease
    • Due to primary hyperparathyroidism
    • By calcium-induced increases in gastrin secretion
  • Nephrolithiasis, acute/chronic renal insufficiency
     

Physical Exam/Signs

  • General Appearance, Vitals
    • Nonspecific physical examination findings
    • May present with signs of underlying malignancy
    • Dehydration, anorexia, lethargy
    • High blood pressure
  • HEENT
    • Tongue fasciculations
    • Band keratopathy (band of calcium across central cornea; very rare)
  • Cardiovascular
    • Hypertension
    • Bradycardia
  • Abd/GI/GU
    • Abdominal discomfort
    • Polyuria
  • Neuro/Musculoskeletal
    • Lower extremity muscle weakness
    • Bony tenderness to palpation
    • Confusion, stupor, coma

Labs/Tests

  • Measure total and ionized (free) Ca2+
    • 40-45% of serum calcium bound to protein (albumin)
      • Hypoalbuminemia can cause normal total calcium levels and elevated ionized levels
      • Hyperalbuminemia can cause increased total calcium levels and normal ionized levels
        • Due to increased protein binding (i.e. dehydration)
      • Corrected Ca2+ = [0.8 x (normal albumin - patient's albumin)] + serum Ca2+
    • Usually > 12 mg/dL [3 mmol/L] causes symptoms
    • Mild hypercalcemia: < 12 mg/dL
    • Calcium 12-14 mg/dL [3.0- 3.5 mmol/L] can be tolerated chronically, but will cause symptoms acutely
    • Severe hypercalcemia: > 14 mg/dL [3.5 mmol/L]
  • PTH
    • Reference range: 2-6 mmol/L
    • Elevated: primary hyperparathyroidism
  • Mg2+, phosphate, chloride, alk. phosphatase, creatinine
    • Elevated phosphate in vitamin D disorders or thyrotoxicosis
    • Chloride > 103 meq/L, suspect primary hyperparathyroidism
    • Low chloride and metabolic alkalosis, suspect milk alkali syndrome
  • Consider T4, TSH
     
  • Other Tests/Criteria
    • EKG
      • QT interval shortening
      • Osborn waves (J waves)
    • PTHrP assay, vitamin D metabolites

Imaging

  • Chest X-ray
    • Consider malignancy or granulomatous disease
  • Consider CT, MRI, ultrasound if suspecting primary hyperparathyroidism or malignancy

Differential Diagnosis

  • Hyperparathyroidism
  • Malignancy
  • Sarcoidosis
  • Granulomatous disease
  • Familial
  • Tuberculosis
  • HIV/AIDS
  • Drug Toxicity
    • Lithium
    • Theophylline
    • Vitamins
    • Salicylates
    • Thyroid hormone

Treatment

  1. Mild (10.5 - 12 mg/dL), asymptomatic
    • Observation; increase IV fluid rate PRN
       
  2. Moderate (12 - 14 mg/dL), Asymptomatic or mildly symptomatic
    • Correct hypovolemia/induce diuresis:
      • Bolus 500 mL NS, then 3 - 6 L in 24h.
      • Careful if known CHF.
      • Repeat lytes q8h; aim for a diuresis of around 2.5 L/day.
    • Furosemide 20 - 80 mg IV PRN (usually q4h) in the presence of volume overload
    • Consider a Foley catheter for the patient's comfort (and security at night).
       
    • Bisphosphonate:
      • Pamidronate 60 mg IV (Ca < 3.5 mmol/L; 14 mg/dL) or
      • Pamidronate 90 mg IV (Ca > 3.5 mmol/L; 14mg/dL) weekly or
      • Zoledronic acid 4 mg IV.
      • Pamidronate is less expensive but takes longer to administer. Both have been associated with osteonecrosis of the jaw. (< than 1%, long term) Effect in 1 - 2 days
         
  3. Severe (> 14 mg/dL), No response to previous Tx, Trending up, symptomatic
    • As with moderate  PLUS
    • Calcitonin 4 IU/kg IM or subQ q6 - 12h, max 48h. Rapid but short-effect duration. Risk of allergy; a test dose is recommended: dilute 10 IU (0.05 mL) in 1 mL NS, inject 0.1 mL IM in the flexor surface of the forearm, wait 15 min; look for "more than mild" erythema. Do not administer calcitonin if +.
    • Consider corticosteroids for patients with granulomatous disease, lymphoma, myeloma.
      • Prednisone 20 - 40 mg PO daily
      • +/- Hydrocortisone 500 mg IVP q8h
         
  4. Severe (> 18 mg/dL), neuro symptoms
    • Urgent hemodialysis referral: call a senior resident/fellow/attending physician

Disposition

  • Admission criteria
    • Symptomatic
    • Heart failure
    • Renal insufficiency
    • Ca2+ > 12.5 mg/dL [> 3.1 mmol/L]
    • ICU or monitored bed for:
      •  Ca2+ > 14 mg/dL [> 3.5 mmol/L] or serious symptoms
         
  • Discharge/Follow-up instructions
    • Asymptomatic without severe underlying disease may be discharged with early follow-up
    • Stop thiazide diuretics, drink plenty of fluids and avoid Ca2+
 

Admission Order Set

1. Admit to:
2. Diagnosis: Hypercalcemia
3. Condition:
4. Vital Signs: q4h. Call physician if BP >160/90, <90/60; P >120, <50; R>25, <10; T >38.5°C.
5. Activity: Encourage ambulation.
6. Nursing: Measure inputs and outputs.
7. Diet: Restrict dietary calcium to 400 mg/d, push PO fluids.
8. Special Medications:

  • 500 mL 0.9% saline boluses over 1-4 hours until no longer hypotensive, then saline diuresis with 0.9% saline infused at 125 cc/h AND
  • Furosemide (Lasix) 20-80 mg IV q4-12h. Maintain urine output of 200 mL/h; monitor serum sodium, potassium, magnesium.
  • Calcitonin (Calcimar) 4-8 IU/kg IM q12h or SQ q6-12h.
  • Etidronate (Didronel) 7.5 mg/kg/day in 250 mL of normal saline IV infusion over 2 hours. May repeat in 3 days.
  • Pamidronate (Aredia) 60 mg in 500 mL of NS infused over 4 hours or 90 mg in 1 liter of NS infused over 24 hours x one dose.

9. Extras: CXR, ECG, mammogram.
10. Labs: Ionized calcium, parathyroid hormone, chem 7&12, phosphate, Mg, carcinoembryonic antigen. 24h urine calcium, phosphate.

 

ITE 2014 Q17 .
Which one of the following intravenous agents is the best INITIAL management for hypercalcemic crisis?

A) Furosemide
B) Pamidronate
C) Hydrocortisone
D) Saline

ANSWER: D

  • The initial management of hypercalcemic crisis involves volume repletion and hydration. The combination of inadequate fluid intake and the inability of hypercalcemic patients to conserve free water can lead to calcium levels >14–15 mg/dL. Because patients often have a fluid deficiency of 4–5 liters, delivering 1000 mL of normal saline during the first hour, followed by 250–300 mL/hour, may decrease the hypercalcemia to less than critical levels (<13 mg/dL).
  • If the clinical status is not satisfactory after hydration alone, then renal excretion of calcium can be enhanced by saline diuresis using furosemide.
     
  • Intravenous pamidronate, a bisphosphonate, reduces the hypercalcemia of malignancy and is best used in the semi-acute setting, since calcium levels do not start to fall for 24 hours.
  • Glucocorticoids are useful in the treatment of hypercalcemia associated with certain malignancies (multiple myeloma, leukemia, several lymphomas, and breast cancer) or with vitamin D intoxication. The onset of action, however, takes several days, with the effect lasting days to weeks.

    Ref: Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, ed 18. McGraw-Hill, 2012, pp 3111-3113.