Causes & Mechanisms
Most common cause of hypercalcemia in the outpatient setting
Primary hyperparathyroidism
This gland produces PTH
Parathyroid gland (specifically chief cells)
Classic mnemonic for hypercalcemia symptoms
"Stones, bones, groans, and psychiatric overtones"
First test to order after confirming elevated calcium
Intact PTH level
First-line initial treatment for symptomatic hypercalcemia
IV isotonic saline
Most common cause of hypercalcemia in hospitalized patients
Malignancy
This lab value must be checked alongside total calcium since it affects the result
Albumin
This EKG finding is associated with hypercalcemia
Shortened QT interval
This corrects total calcium for low albumin
Corrected calcium = measured Ca + 0.8 × (4 − albumin)
This drug class works within hours by inhibiting osteoclasts (fast but short-acting)
Calcitonin
PTHrP is secreted by this cancer type most classically
Squamous cell carcinoma (lung, head/neck) — via PTHrP
PTH does this to renal calcium and phosphate handling
PTH increases renal calcium reabsorption and phosphate excretion, and stimulates bone resorption and renal 1-alpha-hydroxylase activity
This describes bone pain, kidney stones, abdominal pain, and confusion together
"Stones, bones, abdominal groans, and psychic moans" (classic tetrad)
Elevated PTH + elevated calcium points to this category of causes
PTH-dependent causes (primary or tertiary hyperparathyroidism)
This IV bisphosphonate is first-line for malignancy-associated hypercalcemia
IV zoledronic acid (zoledronate)
This granulomatous disease causes hypercalcemia via extrarenal 1-alpha-hydroxylase activity
Sarcoidosis
This vitamin D metabolite is measured to diagnose granulomatous disease-related hypercalcemia
1,25-dihydroxyvitamin D (calcitriol) — elevated in granulomatous disease
This condition presents with hypercalcemia, band keratopathy, and normal-to-high PTH after years of untreated primary hyperparathyroidism
Hypercalcemic (parathyroid) crisis from long-standing untreated primary hyperparathyroidism
Low PTH + high calcium should prompt evaluation for these two categories of causes
PTH-independent causes: malignancy (PTHrP, osteolytic mets, calcitriol from lymphoma) and non-malignant causes (vitamin D toxicity, milk-alkali, granulomatous disease, thyrotoxicosis, immobilization)
This monoclonal antibody is used for bisphosphonate-refractory malignant hypercalcemia
Denosumab
This benign genetic condition mimics primary hyperparathyroidism but should NOT be treated surgically
Familial hypocalciuric hypercalcemia (FHH)
This urine study distinguishes FHH from primary hyperparathyroidism
24-hour urine calcium/creatinine clearance ratio (low in FHH, typically <0.01; higher in primary hyperparathyroidism)
This life-threatening calcium level requires emergent treatment regardless of symptoms
>14 mg/dL (or any level with severe symptoms — seizure, arrhythmia, coma) = hypercalcemic crisis
This imaging study localizes a parathyroid adenoma preoperatively
Sestamibi scan (parathyroid scintigraphy), often combined with neck ultrasound
This is the definitive treatment for severe, refractory hypercalcemia, especially with renal failure
Hemodialysis (with low/no-calcium dialysate)