Hypercalcemia Flashcards
What is hypercalcemia?
Corrected total serum calcium > upper limit of normal or elevated ionized calcium.
What is the distribution of calcium in the body?
- 50% free (ionized)
- 40% protein-bound (80% to albumin, 20% to globulins)
- 10% complexed to anions (phosphate, citrate, etc.)
How does albumin affect calcium levels?
Albumin changes: ±1 g/dL → ±0.8 mg/dL calcium.
How does globulin affect calcium levels?
Globulin changes: ±1 g/dL → ±0.16 mg/dL calcium.
What determines symptoms of hypercalcemia?
Free calcium (ionized).
What is the prevalence of hypercalcemia in the general population?
0.5–1%.
What is the prevalence of hypercalcemia in postmenopausal women?
Up to 3%.
What are the main causes of hypercalcemia?
- Primary Hyperparathyroidism (PHPT): 70% of outpatient cases
- Cancer: Majority of inpatient cases (10–30% of cancer patients)
What percentage of hypercalcemia cases are caused by PHPT and cancer?
90%.
What levels classify mild hypercalcemia?
<12 mg/dL.
What levels classify moderate hypercalcemia?
12–14 mg/dL.
What levels classify severe hypercalcemia?
> 14 mg/dL.
What is the correction formula for calcium levels?
Corrected Ca = Observed Ca + [(4.0 – Albumin) × 0.8].
What are common symptoms of moderate/severe hypercalcemia?
- CNS: Lethargy, stupor, coma, psychosis
- GI: Anorexia, nausea, constipation, pancreatitis
- Renal: Polyuria, nephrolithiasis
- Musculoskeletal: Arthralgias, myalgias, weakness
- Cardiac: Short QT interval, dysrhythmias, ST elevation
What are the primary sources of calcium in the body?
- Bone (99% of body calcium)
- Gut (absorption)
- Kidney (reabsorption)
- Bone (resorption)
What is the daily calcium intake and absorption?
- Intake: 1000 mg
- Absorption: 300 mg
- Excretion: 200 mg (urine), 800 mg (feces)
What are the dietary sources of vitamin D?
- Fish oils
- Fortified foods
- Sunlight (UV activation of 7-dehydrocholesterol → vitamin D3)
What are the stages of vitamin D metabolism?
- Liver: 25-hydroxylation → 25-OH vitamin D
- Kidney: 1-alpha-hydroxylation → 1,25(OH)2 vitamin D (calcitriol)
What regulates the production of 1,25(OH)2 vitamin D?
- High PTH, low phosphate, low calcium → ↑1,25(OH)2 vitamin D
- Low PTH, high phosphate, high calcium → ↑24,25(OH)2 vitamin D
What is the function of FGF23?
Reduces serum phosphate, 1,25(OH)2 vitamin D, and PTH.
What stimulates FGF23 production?
Produced by osteocytes in response to high phosphate, 1,25(OH)2 vitamin D, PTH.
What are the classic effects of vitamin D?
- Intestine: ↑ calcium and phosphate absorption
- Bone: ↑ calcium and phosphate resorption
- Kidney: ↑ calcium and phosphate reabsorption
What are the nonclassic effects of vitamin D?
- Antiproliferative effects
- Prodifferentiating effects on various cells
- Enhances insulin secretion, neuronal function, immune response
What is the function of the calcium-sensing receptor (CaSR)?
Maintains extracellular calcium levels.
Where is the calcium-sensing receptor (CaSR) located?
- Parathyroid glands
- Kidneys
- Other tissues
What do calcimimetics do?
Bind CaSR → ↓ PTH, ↓ calcium.
What mnemonic helps remember the causes of hypercalcemia?
VITAMINS TRAP.
What does the ‘V’ in VITAMINS TRAP stand for?
Vitamins (excess vitamin D).
What does the ‘I’ in VITAMINS TRAP stand for?
Immobilization.
What does the ‘T’ in VITAMINS TRAP stand for?
Thyrotoxicosis.
What does the ‘A’ in VITAMINS TRAP stand for?
Addison’s disease.
What does the ‘M’ in VITAMINS TRAP stand for?
Milk-alkali syndrome.
What does the ‘N’ in VITAMINS TRAP stand for?
Neoplasms.
What does the ‘S’ in VITAMINS TRAP stand for?
Sarcoidosis.
What does the ‘R’ in VITAMINS TRAP stand for?
Rhabdomyolysis.
What does the ‘P’ in VITAMINS TRAP stand for?
Paget’s disease, parenteral nutrition, pheochromocytoma, parathyroid disease.
What are mechanisms of hypercalcemia related to increased bone resorption?
- PHPT
- Malignancy
- Immobilization
What causes increased renal reabsorption in hypercalcemia?
- Thiazides
- Familial hypocalciuric hypercalcemia (FHH)
What causes increased gut absorption in hypercalcemia?
- Excess vitamin D
- Milk-alkali syndrome
What is the acute management for hypercalcemia?
- Saline hydration
- Furosemide
- Calcitonin
- Bisphosphonates
- Glucocorticoids
What is the chronic management for hypercalcemia?
- Cinacalcet
- Denosumab
When is dialysis indicated in hypercalcemia?
For severe, refractory hypercalcemia.
What is the most potent bisphosphonate for hypercalcemia?
Zoledronic acid.
What is cinacalcet effective for?
PHPT and secondary hyperparathyroidism.
