Hypercalcemia of malignancy: Difference between revisions

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==Etiology==
==Background==
===Causes===
*PTHrP release
**[[squamous cell carcinoma|SCC]] (particularly of the head and neck), breast renal, endometrial cancer
*Local osteolysis
**Associated primarily with bone mets
**[[Multiple myeloma]], lung, breast cancer
*Production of vitamin D analogues
**[[Lymphoma]] (Hodgkin)


==Clinical Features==
{{Hypercalcemia clinical features}}


In the setting of cancer, hypercalcemia falls into the following 4 categories:
==Differential Diagnosis==
{{Hypercalcemia DDX}}


1. Local osteolysis associated primarily with bone metastasis (20%)
{{Oncologic emergencies DDX}}


-breast, MM, lymphoma
==Evaluation==
*Chemistry
*Ionized Ca
*CBC
*[[LFTs]] (alk phos, albumin)
*[[ECG]]


2. Humoral hypercalcemia of malignancy (HHM) associated with PTHrP
==Management==
 
{{Hypercalcemia treatment}}
-Squamous cell carcinoma (particularly of the head and neck); renal, endometrial, and breast cancers, HTLV-lymphoma
 
3. Lymphoma-associated secretion of calcitriol, which increases intestinal calcium absorption and bone resorption by osteoclasts (1%)
 
-Hodgkin-associated hypercalcemia and 30% to 40% of non-Hodgkin lymphoma–associated hypercalcemia
 
4. Ectopic secretion of PTH, which is extremely rare (usually with parathyroid carcinomas)
 
-ovary, lung, and primitive neuroectoderm
 
 
==Si/Sy==
 
 
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
 
 
==W/U==
 
 
Chem10
 
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==
 
 
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==
 
 
Address volume losses and reduce bone resorption
 
 
Calcium level < 12 mg/dL (mild or chronic)•Oral hydration
 
•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 follow up if oncology concurs
*Ca>12
**Admit
*[[ECG]] changes
**Admit with telemetry


==See Also==
*[[Hypercalcemia]]


Ca <12: home with f/u after d/w onc
==References==
 
<references/>
Ca>12: admit ward
[[Category:FEN]]
 
EKG changes: tele
 
 
==Source==
 
 
EM Practice 3/10
 
 
 
 
 
[[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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