Hypercalcemia

Question 1

Hypercalcemia symptoms

Answer 1

• sx correlate with Ca level and rapidity of rise
• GI
  
  • nausea
  • constipation/ileus
  • anorexia
• Neuro
  
  • confusion
  • delirium
  • weakness
  • somnolence
  • HYPOreflexia
• Cardiac
  
  • Arrythmias
  • SHORT Qtc
  • LONG PR
• Other
  
  • polydipsia
  • polyuria

Question 2

Symptoms of hypercalcemia

Answer 2

Bones : Osteolysis, fractures

Stones : Renal colic, hypercalcemic bones

Groans : Abdominal sx, anorexia, n/v, constipation, PUD, pancreatitis

(Psychic) Moans: depression, delirium, coma

Question 3

Prognosis of hypercalcemia

Answer 3

• 80% die within 1 year
• 50% die within 30 days
• median survival is 3-4 months

Question 4

List cancers commonly associated with hypercalcemia

Answer 4

• MM
• breast
• lung
• RCC
• head and neck
• esophagus
• lymphoma

usually with bony mets.

Question 5

Pathophysiology of Hypercalcemia in malignancy

Answer 5

• Increased osteoclastic bone resportion
  
  • RANKL - osteoclast activity
  • OPG (osteoprogeterin) is decoy receptor for RANKL
  • OPG reduces RANKL activity in bone
  • Tumours release RANKL, stimulate bone cells to produce RANKL
  • Cytokines release RANKL, decrease OPG
• Decreased renal clearance of calcium
  
  • d/t increased PTHrp
  • low GFR
• Enhanced calcium absorption from gut
  
  • rare

Question 6

Corrected serum calcium

Answer 6

Corrected calcium =

measured Ca + (40-albumin x 0.02)

Question 7

Normal serum calcium

Answer 7

< 2.65 mmol/L

Question 8

Best way to measure serum calcium

Answer 8

• IONIZED CA
• preferred especially in MM
• Myeloma paraproteins bind calcium and artificially elevate Ca

Question 9

Treatment of MILD hypercalcemia

(< 3, mild symptoms)

Answer 9

• hydration
• avoid lithium, thiazide diuretics
• supp Vit A and D

Question 10

Treatment of MODERATE hyperkalemia

(3.0-3.5)

Answer 10

• Moderate symptoms
• IV hydration 2-3L/day
• Bisphosphonate
• Zolendronic acid 4 mg in 100 ml NS over 15 minutes

Question 11

Treatment of SEVERE Hyperkalemia

(> 3.5)

Answer 11

• Hydration, volume expansion to urine outputr of 150 ml/hour
• Calcitonin 100 IU sc tid until bisphosphonate takes effect
  
  • short duration
  • tachyphylaxis
• Bisphosphonate Zometa 4 mg
  
  • takes 2-7 days
  • repeat levels in 1 week
• Steroids in hematologic malignancies
  
  • cytostatic effects
  • 4-10 days to lower calcium

Question 12

Calcitonin

Answer 12

• 100 IU sc tid x 1-2 days
• Reduces osteoclast bone resportion, increases calciuresis
• Onset in 4 hours, duration 8 hours
• SE: nausea, allergy
• Check calcium several hours level to ensure working
• Temporary effect–> tachyphlaxis
• give with bisphosphonate

Question 13

Bisphosphonates

Answer 13

• Clodronate
• Pamidronate 90 mg IV, repeat after 1 week prn
• Zoledronic Acid, can repeat after 1 week prn

Onset 3-7 days

Effect for 4-6 weeks

Regular dosing q4 weeks

MOA

• bind hydroxyapatite crystals
• inhibit osteoclast function
• often dont work if no bony mets

AE:

• caution in renal failure
• osteonecrosis of the jaw (dental check up, abx, debridement prn)

Question 14

Denosumab

Answer 14

• Monoclonal Antibody to RANKL
• used for post menopausal women with OP
• used to prevent SRE in MM
• May be used if severe RF and bisphosphonates are CI
• 120 mg IV/sc q weekly x 4, then q4weeks

Question 15

More pathophysiology

Answer 15

• local osteoclastic hypercalcemia due to direct effect of bone mets
• Humoral Hypercalcemia of Malignancy
  
  • secretion of parathyroid hormone related protein (PTHrP)
  • Vit D secreting lymphomas
  • ectopic secretion of PTH (very rare)

Question 16

Treatment principles

Answer 16

• explore goals of care
• Treat malignancy
• Saline hydration
• Loop diuretics (furosemide) block calcium resorption in Loop of Henle
• Discontinue meds that increased Ca
  
  • lithium, vit D, thiazides, calcium antacids
• Increas mobility if possible
• Bisphosphonates
• Steroids in Vit D secreting Lymphoma