惡性腫瘤相關高血鈣

Buzzwords → Dx

Diagnostic Criteria

• Total Ca corrected for albumin: total Ca + 0.8 × (4 - albumin).
• Ionized Ca >1.32 mmol/L (or corrected total >10.5 mg/dL) = hypercalcemia.
• Severity:
  • Mild: Ca 10.5–12 mg/dL
  • Moderate: Ca 12–14 mg/dL
  • Severe: Ca >14 mg/dL — symptomatic; emergent treatment

Workup

• Total + ionized Ca + albumin (calculate corrected).
• PTH (suppressed in malignancy hyperCa, except primary HPT or rare ectopic PTH).
• PTHrP (elevated in HHM).
• 25-OH vit D + 1,25(OH)₂ vit D (elevated 1,25 in lymphoma / granulomatous).
• Phosphate, Cr, BUN, magnesium.
• SPE/IFE/sFLC for MM workup.
• Imaging for skeletal mets (skeletal survey, PET-CT, MRI).
• TSH (rule out thyrotoxicosis hypercalcemia).
• 24-hour urine Ca / Cr / urine Ca-Cr ratio for FHH (familial hypocalciuric hypercalcemia).
• ECG for QT shortening, arrhythmia.

Treatment Algorithm

flowchart TD
  A[Hypercalcemia of malignancy] --> B{Severity}
  B -- mild Ca 10.5-12 --> C[Treat underlying disease<br>oral hydration + monitor<br>avoid lithium, thiazides]
  B -- moderate / severe / symptomatic --> D[Aggressive IV NS 200-300 mL/h<br>goal UO 100-150 mL/h]
  D --> E{Adequate UO?}
  E -- yes --> F[Add bisphosphonate:<br>zoledronic acid 4 mg IV over 15 min<br>pamidronate 60-90 mg IV over 2-4 h<br>onset 24-72 h, lasts 1-3 wk]
  E -- volume overload risk --> G[Loop diuretic AFTER rehydration<br>furosemide selectively]
  F --> H[Add calcitonin 4 IU/kg SC q6-12h × 24-48 h<br>rapid bridge while bisphosphonate works]
  F --> I{Refractory or renal failure?}
  I -- yes --> J[Denosumab 120 mg SC<br>no renal dose adjustment]
  I -- severe Ca >18 / oliguric --> K[Hemodialysis with low-Ca dialysate]
  H --> L{Calcitriol-mediated?}
  L -- yes --> M[Steroids prednisone 20-40 mg/d<br>+ underlying lymphoma / granulomatous tx]

Pearls / Pitfalls

• Hydration FIRST + bisphosphonate is the standard combo. Loop diuretics only AFTER adequate hydration (to avoid worsening dehydration).
• Zoledronic acid > pamidronate (more potent, faster, longer-lasting). Onset 24–72 h — use calcitonin as bridge for rapid Ca lowering in 4–6 h.
• Denosumab is bisphosphonate-refractory option + safer in renal failure (no dose adjustment, no nephrotoxicity); risk: hypocalcemia, ONJ.
• Calcitonin tachyphylaxis within 24–48 h — limited as monotherapy.
• Steroids work for calcitriol-mediated hypercalcemia (lymphoma, granulomatous disease) — block 1α-hydroxylase activity.
• MM hypercalcemia responds to dexamethasone + chemotherapy + bisphosphonates / denosumab. Don't use rasburicase for MM hyperCa (no role).
• ATLL + hypercalcemia + lytic bone = classic. PTHrP-mediated.
• Avoid thiazides + lithium + vitamin D supplements during hypercalcemia.
• Bisphosphonate adverse effects: nephrotoxicity (avoid in CrCl <30 with zoledronic acid), osteonecrosis of jaw (ONJ — dental clearance before therapy), atypical femoral fractures (long-term).
• Hemodialysis with low-Ca dialysate for refractory severe hypercalcemia (Ca >18) or oliguric AKI.
• Familial hypocalciuric hypercalcemia (FHH) — DDx pitfall: low urinary Ca, normal/high PTH, autosomal dominant — don't treat, no malignancy.
• Hungry bone syndrome post-parathyroidectomy mimics inadequate Ca correction — distinct entity.
• Don't routinely give Ca during HCT-related TLS — calcium phosphate precipitation.

Cross-references

• MM — most common cause + bisphosphonate / denosumab
• ATLL — PTHrP-mediated
• Hodgkin — calcitriol-mediated
• TLS — concurrent emergency, opposite Ca
• Drug Regimens — bisphosphonates, denosumab, calcitonin

相關題目

• Q-053 — T-cell — adult T-cell leukemia/lymphoma (ATLL) recognition
• Q-190 — Hypercalcemia of malignancy — first-line therapy
• Q-191 — Hypercalcemia — denosumab in renal failure
• Q-192 — Calcitriol-mediated hypercalcemia in lymphoma

Sources