Hypercalcemia of malignancy: Difference between revisions

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==Background==
==Background==
4 categories:
===Causes===
#Local osteolysis associated primarily with bone mets (20%)
*PTHrP release
##Breast, MM, lymphoma
**[[squamous cell carcinoma|SCC]] (particularly of the head and neck), breast renal, endometrial cancer
#PTHrP release
*Local osteolysis
##Squamous cell carcinoma (particularly of the head and neck); renal, endometrial, and breast cancers, HTLV-lymphoma
**Associated primarily with bone mets
#Lymphoma-associated secretion of calcitriol (increases intestinal ca absorption and bone resorption by osteoclasts (1%)
**[[Multiple myeloma]], lung, breast cancer
##Hodgkin-associated hypercalcemia and 30% to 40% of non-Hodgkin lymphoma–associated hypercalcemia
*Production of vitamin D analogues
# Ectopic secretion of PTH, which is extremely rare (usually with parathyroid carcinomas)
**[[Lymphoma]] (Hodgkin)
##ovary, lung, and primitive neuroectoderm


==Diagnosis==
==Clinical Features==
Signs & Symptoms
{{Hypercalcemia clinical features}}
#Consistent with degree of hypercalcemia and rate of increase (see Hypercalcemia)
#Polydipsia, polyuria
#Bone pain
#Gastrointestinal symptoms (anorexia, nausea, vomiting, and constipation)
#Psychiatric symptoms (memory loss, apathy)
#Lethargy, and fatigue
#Bony tenderness over sites of osteolysis
#Dehydration
#Look for signs of CHF, renal failure to avoid vol overload


==Work-Up==
==Differential Diagnosis==
#Chem10
{{Hypercalcemia DDX}}
#ionized Ca
#CBC
#LFTs (alk phos, albumin)
#PTH
#PTH-rP (non emergent)
#EKG (prolonged PR interval, widened QRS complex, shortened QT interval, bundle branch block, or bradydysrhythmia and even cardiac arrest (typically with calcium levels > 15 mg/dL)


===Categorization===
{{Oncologic emergencies DDX}}
#Mild (total calcium level, 10.5-11.9 mg/dL)
#Moderate (total calcium level, 12.0-13.9 mg/dL)
#Severe (total calcium level ≥ 14.0 mg/dL)


==Treatment==
==Evaluation==
Address volume losses and reduce bone resorption
*Chemistry
*Ionized Ca
*CBC
*[[LFTs]] (alk phos, albumin)
*[[ECG]]


===Calcium level < 12 mg/dL (mild or chronic)===
==Management==
#Oral hydration
{{Hypercalcemia treatment}}
#High-salt diet
#Avoid medications that cause hypercalcemia
#No treatment at all may be an option
 
===Calcium level ≥ 12 mg/dL (severe or symptomatic)===
#Normal saline
##initially 200-300 mL/h until patient is euvolemic
##then adjust to maintain urine output of 100-150 mL/h
#IV Bisphosphonate (pyrophosphate analogues bind to hydroxyapatite and inhibit bone crystal dissolution and therefore osteoclastic resorption)
##Zoledronic acid: 4 mg over 15 minutes; 8 mg if second dose is required (not FDA approved)
##Pamidronate: given over 2-24 hours, either as 60 mg (calcium level, 12-13.5 mg/dL) or 90 mg (calcium level >13.5 mg/dL)
##Calcium levels begin to decrease 2 to 4 days after administration of IV bisphosphonates, reach a nadir between 4 and 7 days, and typically remain within the reference range for 1 to 4 weeks
##In a head-to-head comparison of zoledronate (4 mg) versus pamidronate (90 mg), zoledronate had the benefit of a shorter administration time (15 minutes vs 2 hours, respectively) and a statistically significant difference (p 0.001) of 0.7 mg/dL in the calcium level at its nadir (9.8 mg/dL vs 10.5 mg/dL, respectively)
#Calcitonin 4 IU/kg SQ or IM; repeat every 6-12 hours only if patient is responsive
##Calcitonin exerts this effect by inhibiting osteoclastic resorption and inducing calciuresis
##peak activity within 12-24h
##lowers Ca ~1.0mg/dL
#Loop diuretics only after volume repletion in patients with congestive heart failure or chronic kidney disease
#Hemodialysis for patients with any of the following:
##Neurologic symptoms
##Calcium level ≥ 18 mg/dL
##Acute or chronic kidney disease (GFR < 10-20 mL/min)
##Congestive heart failure


==Disposition==
==Disposition==
#Ca <12: home with f/u after d/w onc
*Ca <12
#Ca>12: admit ward
**Home with follow up if oncology concurs
#EKG changes: tele
*Ca>12
**Admit
*[[ECG]] changes
**Admit with telemetry


==See Also==
==See Also==
Hypercalcemia
*[[Hypercalcemia]]
 
==Source==
EM Practice 3/10


==References==
<references/>
[[Category:FEN]]
[[Category:FEN]]
[[Category:Heme/Onc]]
[[Category:Heme/Onc]]

Latest revision as of 00:59, 29 September 2019

Background

Causes

  • PTHrP release
    • SCC (particularly of the head and neck), breast renal, endometrial cancer
  • Local osteolysis
  • Production of vitamin D analogues

Clinical Features

Symptoms of hypercalcemia

Mnemonic: Stones, Bones, Groans, Moans, Thrones, Psychic Overtones

Differential Diagnosis

Causes of Hypercalcemia

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

Evaluation

  • Chemistry
  • Ionized Ca
  • CBC
  • LFTs (alk phos, albumin)
  • ECG

Management

Asymptomatic or Ca <12 mg/dL

  • Does not require immediate treatment
  • Advise to avoid factors that can aggravate hypercalcemia (thiazide diuretics, Li, volume depletion, prolonged inactivity, high Ca diet)

Mildly symptomatic Ca 12-14 mg/dL

  • May not require immediate therapy; however, an acute rise may cause symptoms necessitating treatment as described for severe hypercalcemia (see below)

Symptomatic or Severe hypercalcemia (Ca >14 mg/dL)

  • Patients are likely dehydrated and require saline hydration as initial therapy

Hydration

  • Isotonic saline at 200-300 mL/hour; adjust to maintain urine output at 100-150 mL/hour

Calcitonin

  • Consider adding calcitonin 4 units/kg SC or IV q12hr in patients w/ Ca >14 mg/dL (3.5 mmol/L) who are also symptomatic (lowers Ca w/in 2-4hr)
  • Tachyphylaxis limits use long term, but is a great choice for emergent cases

Bisphosphonates

Give for severe hypercalcemia due to excessive bone resorption (lowers Ca within 12-48hr)[≥12 mg/dL][≥3 mmol/L][1]

  • Pamidronate 90mg IV over 24 hours OR
  • Zoledronate 4mg IV over 15 minutes
  • Caution in renal failure, though bisphosphonates have been safely used in pts with pre-existing renal failure[2]

Electrolyte Repletion

Diuresis

  • Furosemide is NOT routinely recommended
  • Only consider in patients with renal insufficiency or heart failure and volume overload

Dialysis

Consider if patient:

  • Anuric with renal failure
  • Failing all other therapy
  • Severe hypervolemia not amenable to diuresis
  • Serum Calcium level >18mg/dL
  • Neurologic symptoms
  • Heart failure with reduced ejection fraction (unable to provide fluids)

Corticosteroids

Decrease Ca mobilization from bone and are helpful with steroid-sensitive tumors (e.g. lymphoma, MM)

Disposition

  • Ca <12
    • Home with follow up if oncology concurs
  • Ca>12
    • Admit
  • ECG changes
    • Admit with telemetry

See Also

References

  1. ↑ Shane et al. Uptodate: Treatment of Hypercalcemia. https://www.uptodate.com/contents/treatment-of-hypercalcemia#disclaimerContent
  2. ↑ LeGrand SB et al. Narrative Review: Furosemide for Hypercalcemia: An Unproven yet Common Practice. Ann Intern Med. 2008;149:259-263.
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