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Hypercalcemia, Emergency Medicine

Basics

Description

- Renal: - Polyuria, polydipsia - Complaints related to oliguric renal failure - Chronic, complaints related to: - Renal calculi - Nephrocalcinosis - Interstitial nephritis

- Dermatologic: - Pruritus - Mnemonic: "Stones, Bones, Groans, Thrones and Psychiatric Overtones, " "bones " refers to bone pain and "thrones " refers to polyuria.

- Renal: - Dermatologic: - Band keratopathy - Ectopic calcification

- ECG: - Shortening of QT interval - Prolongation of PR interval - QRS widening - Accentuated side effects of digoxin - Sinus bradycardia, bundle branch block, AV block, cardiac arrest with severe hypercalcemia (rare) - Can cause Osborn J-wave at the end of QRS complex that is usually associated with hypothermia

- Malignancy: - Most common cause in hospitalized patients - Usually a rapid rise in serum calcium - Patients are more often symptomatic - Higher serum calcium concentrations - Most common paraneoplastic complication of cancer - Common tumors causing hypercalcemia: Breast, lung, colon, stomach, cervix, uterus, ovary, kidney, bladder, head and neck, multiple myeloma, and lymphoma - Most commonly from production of PTH-related protein with similar actions - May result from production of other bone-resorbing substances by tumor - May result from local effects of osteolytic skeletal metastasis

- Miscellaneous: - Hypercalcemia associated with granulomatous diseases - Excessive calcium supplements - Thiazide diuretics causing increased renal reabsorption - Familial hypocalciuric hypercalcemia - Acute vitamin A intoxication - Exogenous vitamin D intake - Milk-alkali syndrome from excessive ingestion of calcium and nonabsorbable antacids, such as milk or calcium carbonate - Long-term lithium therapy - Renal transplantation - Hyperthyroidism - Acute tubular necrosis

- Immobilization hypercalcemia: - Typically adolescent who is growing rapidly - Prolonged immobilization, especially in traction, leads to hypercalciuria and then hypercalcemia - Presumably from increased bone resorption with decreased or arrested bone mineralization

- Often need 2 " 5 L/day - Bedside vigilance necessary to prevent fluid overload - Correct other electrolyte abnormalities - Cardiovascular status of patient may necessitate central venous pressure monitoring to adjust fluid administration rates

  • Severity depends on serum calcium level and rate of increase
  • 0.1 " 1% of patients on routine screening
  • Most cases mild (<12 mg/dL) and asymptomatic
  • Hypercalcemic crisis, usually >14 mg/dL, causes serious signs and symptoms
  • Calcium in bloodstream in 3 forms:Ionized: 45%Bound to protein (primarily albumin): 40%Bound to other anions: 15%
  • Ionized calcium " only physiologically active form

Etiology

  • Primary hyperparathyroidism
  • Malignancy
  • Miscellaneous

Diagnosis

Signs and Symptoms

History

  • Neurologic:HeadacheFatigue, lethargyWeaknessDifficulty concentratingConfusionDepression, paranoia
  • Renal:Polyuria, polydipsiaComplaints related to oliguric renal failureChronic, complaints related to:Renal calculiNephrocalcinosisInterstitial nephritis
  • GI:AnorexiaNausea, vomitingAbdominal painConstipationChronic, complaints related to:Peptic ulcer diseasePancreatitis
  • Dermatologic:PruritusMnemonic: "Stones, Bones, Groans, Thrones and Psychiatric Overtones, " "bones " refers to bone pain and "thrones " refers to polyuria.
  • Failure to thrive
  • Slow development
  • Mental retardation may ensue

Physical Exam

  • Neurologic:IrritabilityLethargyStuporComaHyporeflexia
  • Cardiovascular:Hypotension, if severely volume depleted, or HTNSinus bradycardiaCardiac arrest with severe hypercalcemia (rare)
  • Renal:
  • Dermatologic:Band keratopathyEctopic calcification
  • Characteristic facies: Pug nose, fat nasal bridge, "cupids bow " upper lip
  • Hypotonia

Essential Workup

  • Ionized and total serum calcium levels, albumin levels:Normal total calcium level is <10.5 mg/dLMust correct for calcium that is protein bound, primarily to albuminCorrected total calcium (mg/dL) = measured total calcium (mg/dL) + 0.8 [4.0 " albumin concentration (g/dL)]
  • Electrolytes, BUN/creatinine, glucosePossible oliguric renal failure
  • ECG:Shortening of QT intervalProlongation of PR intervalQRS wideningAccentuated side effects of digoxinSinus bradycardia, bundle branch block, AV block, cardiac arrest with severe hypercalcemia (rare)Can cause Osborn J-wave at the end of QRS complex that is usually associated with hypothermia

Diagnosis Tests & Interpretation

Lab

  • Phosphate
  • Protein
  • Urinalysis
  • Parathyroid hormone (PTH) level:If elevated or high normal, likely primary hyperparathyroidism.If <20 pg/mL, consider testing PTH-related peptide and vitamin D metabolites.
  • Vitamin D metabolites, if suspected25-hydroxy vitamin D (calcidiol):If elevated, consider exogenous source (i.e., meds, vitamins, supplements).1,25-dihydroxy vitamin D (calcitriol):If elevated, consider lymphoma or sarcoid
  • Digoxin level, if taking
  • Thyroid function tests

Imaging

  • CT head for altered mental status
  • Chest x-ray and workup for occult malignancy, if no other cause for hypercalcemia

Diagnostic Procedures/Surgery

Parathyroidectomy:

  • For primary hyperparathyroidism resulting in symptomatic or severe hypercalcemia
  • Some patients require urgent parathyroidectomy.

Differential Diagnosis

  • Primary hyperparathyroidism:Most common cause among outpatientsParathyroid adenoma 80%; hyperplasia 15%; carcinoma 5%Usually mild, <11.2 mg/dLPatients can be asymptomatic or have chronically elevated calciumIncreased bone resorption, relative decrease in calcium excretion, increased intestinal calcium absorption
  • Malignancy:Most common cause in hospitalized patientsUsually a rapid rise in serum calciumPatients are more often symptomaticHigher serum calcium concentrationsMost common paraneoplastic complication of cancerCommon tumors causing hypercalcemia: Breast, lung, colon, stomach, cervix, uterus, ovary, kidney, bladder, head and neck, multiple myeloma, and lymphomaMost commonly from production of PTH-related protein with similar actionsMay result from production of other bone-resorbing substances by tumorMay result from local effects of osteolytic skeletal metastasis
  • Miscellaneous:Hypercalcemia associated with granulomatous diseasesExcessive calcium supplementsThiazide diuretics causing increased renal reabsorptionFamilial hypocalciuric hypercalcemiaAcute vitamin A intoxicationExogenous vitamin D intakeMilk-alkali syndrome from excessive ingestion of calcium and nonabsorbable antacids, such as milk or calcium carbonateLong-term lithium therapyRenal transplantationHyperthyroidismAcute tubular necrosis

Differential diagnosis: Differences from adults:

  • Primary hyperparathyroidism:Less common than in adults
  • Infantile hypercalcemia:Uncertain causePossibly hypersensitivity and in utero excessive exposure to vitamin D
  • Immobilization hypercalcemia:Typically adolescent who is growing rapidlyProlonged immobilization, especially in traction, leads to hypercalciuria and then hypercalcemiaPresumably from increased bone resorption with decreased or arrested bone mineralization

Treatment

Pre-Hospital

Routine stabilization techniques

Initial Stabilization/Therapy

  • ABCs, IV access, oxygen, cardiac monitor
  • 0.9% NS 1 L bolus (20 mL/kg) for hypotension or severe dehydration
  • Naloxone, thiamine, D50W (or stat serum glucose measurement) for altered mental status

Ed Treatment/Procedures

  • General:Immediate therapy for severe hypercalcemia (corrected total >14 mg/dL) regardless of symptoms, or for symptomatic hypercalcemiaAsymptomatic, mild hypercalcemia does not require emergency treatment
  • Restoration of IV volume:Isotonic saline:200 " 300 mL/hr adjusted to maintain urine output 100 " 150 mL/hrOften need 2 " 5 L/dayBedside vigilance necessary to prevent fluid overloadCorrect other electrolyte abnormalitiesCardiovascular status of patient may necessitate central venous pressure monitoring to adjust fluid administration rates
  • Renal elimination:After volume expansion and if needed to avoid overload, administer loop diuretics (furosemide)Avoid thiazide diureticsMay need peritoneal or hemodialysis against a low calcium dialysate in renal failure
  • Inhibition of osteoclastic activity:Reduce mobilization of calcium from boneAdminister drug therapy when corrected calcium level >14 mg/dL or signs or symptomsFirst-line drug therapy:Bisphosphonates: Pamidronate (more potent and possibly less toxic), etidronateCalcitonin: Rapid onset but modest decrease in levelsOther potential drug therapy:Plicamycin: Efficacious but numerous side effectsHydrocortisone: Especially useful with malignancies, granulomatous disorders, or vitamin D intoxicationEncourage ambulation in appropriate patients
  • Treat underlying disorder:Parathyroidectomy for primary hyperparathyroidism resulting in symptomatic or severe hypercalcemiaDiscontinue medication if cause of hypercalcemia

Medication

First Line

  • Calcitonin: 4 IU/kg IM/SC q12h
  • Etidronate: 7.5 mg/kg over 4 hr daily for 3 " 7 days IV
  • Furosemide: 10 " 40 mg q6 " 8h (peds: 1 " 2 mg/kg) IV
  • Pamidronate: Single 2 " 24 hr infusion of 60 " 90 mg IV (peds: Consult pediatrician)

Second Line

  • Gallium nitrate: Continuous infusion of 200 mg/m2/d for 5 days IV
  • Hydrocortisone: 200 " 400 mg/d IV for 3 " 5 days (peds: Consult pediatrician)
  • Plicamycin: 25 Όg/kg/d over 4 " 6 hr IV for 3 " 8 doses
  • In infants, loop diuretics are rarely necessary and possibly harmful as they may decrease glomerular filtration rate and worsen hypercalcemia
  • Bisphosphonates have not been extensively studied in pediatrics but do appear to be safe

Follow-Up

Disposition

Admission Criteria

  • Corrected total calcium level >13 mg/dL
  • Signs or symptoms attributed to hypercalcemia, especially EKG changes
  • Monitored bed or ICU for corrected level >14 or serious signs and symptoms

Discharge Criteria

Corrected calcium level <13 mg/dL and no signs or symptoms of hypercalcemia

Issues for Referral

  • Rapid follow-up arranged to determine cause and long-term therapy
  • Consultation with endocrinologist should be considered

Follow-Up Recommendations

  • Fluid hydration
  • Watch for mental status changes

Pearls and Pitfalls

  • Make decisions based on symptoms or corrected Ca levels
  • All patients with serum Ca >14 mg/dL require treatment regardless of symptoms
  • Pay careful attention to EKG changes
  • Careful monitoring is required for patients receiving IV volume repletion:They often require a large volume of fluid but care must be taken to avoid volume overload

Additional Reading

  • Ariyan CE, Sosa JA. Assessment and management of patients with abnormal calcium. Crit Care Med. 2004;32(suppl 4):S146 " S154.
  • Inzucchi SE. Management of hypercalcemia. Diagnostic workup, therapeutic options for hyperparathyroidism and other common causes. Postgrad Med. 2004;115:27 " 36.
  • Lietman SA, Germain-Lee EL, Levine MA. Hypercalcemia in children and adolescents. Curr Opin Pediatr. 2010;22(4):508 " 515.
  • Marx JA, Hockberger RS, Walls RM, eds. Rosens Emergency Medicine. Philadelphia, PA: Elsevier; 2009.

See Also (Topic, Algorithm, Electronic Media Element)

  • Hyperparathyroidism
  • Hypocalcemia
  • Hypoparathyroidism

Codes

ICD9

  • 275.42 Hypercalcemia
  • 275.49 Other disorders of calcium metabolism
  • 588.89 Other specified disorders resulting from impaired renal function
  • 592.0 Calculus of kidney

ICD10

  • E83.52 Hypercalcemia
  • E83.59 Other disorders of calcium metabolism
  • N25.89 Oth disorders resulting from impaired renal tubular function
  • N20.0 Calculus of kidney

SNOMED

  • 66931009 Hypercalcemia (disorder)
  • 33763006 Hypercalcemic nephropathy (disorder)
  • 48638002 nephrocalcinosis (disorder)
  • 95570007 Kidney stone (disorder)