Corticosteroids in Hypercalcemia
Corticosteroids are effective first-line treatment for hypercalcemia caused by excessive intestinal calcium absorption, specifically in vitamin D intoxication, granulomatous diseases (particularly sarcoidosis), and certain lymphomas, but should NOT be used as primary therapy for malignancy-related hypercalcemia where bisphosphonates are preferred. 1, 2
When to Use Corticosteroids
Primary Indications (Corticosteroids as First-Line)
- Vitamin D-mediated hypercalcemia: Use glucocorticoids when hypercalcemia results from elevated 1,25-dihydroxyvitamin D levels, as corticosteroids inhibit the conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D 1, 2, 3
- Sarcoidosis with hypercalcemia: Initiate prednisone 1 mg/kg/day (or IV methylprednisolone equivalent) when corrected total calcium exceeds 3 mmol/L (12 mg/dL) or at lower levels if symptomatic 4, 5
- Granulomatous diseases: Glucocorticoids work by inhibiting the overactive 1-alpha-hydroxylase activity in macrophages that produce excessive 1,25-dihydroxyvitamin D 5, 6
- Select lymphomas: Consider corticosteroids in lymphomas producing 1,25-dihydroxyvitamin D, particularly in combination with other therapies 1, 3
Secondary Role (Adjunctive Therapy)
- Multiple myeloma: Use as part of combination therapy with hydration, bisphosphonates (zoledronic acid preferred), and/or calcitonin 1, 7
- Immune checkpoint inhibitor-related sarcoidosis: Prednisone 1 mg/kg for grade 2 or higher sarcoidosis with hypercalcemia, tapering over 2-4 months 4
When NOT to Use Corticosteroids as Primary Therapy
- Malignancy-related hypercalcemia (non-lymphoma): Bisphosphonates (zoledronic acid 4 mg IV) are first-line, not corticosteroids 1, 7, 2
- Primary hyperparathyroidism: Corticosteroids have no role; parathyroidectomy or observation is appropriate 1, 2
- PTH-related protein (PTHrP)-mediated hypercalcemia: Requires bisphosphonates, not corticosteroids 7, 2
Dosing and Duration
- Standard dose: Prednisone 1 mg/kg/day orally or methylprednisolone IV equivalent 4
- Sarcoidosis-specific: Taper over 2-4 months depending on response 4
- Vitamin D intoxication: Continue until 25-hydroxyvitamin D levels normalize, which may take weeks to months depending on the vitamin D preparation involved 8, 6
Critical Monitoring and Prophylaxis
- Pneumocystis pneumonia prophylaxis: Required for patients receiving ≥20 mg methylprednisolone equivalent for ≥4 weeks 4
- GI prophylaxis: Proton pump inhibitor therapy for all patients on corticosteroids 4
- Calcium and vitamin D supplementation: Paradoxically needed with prolonged steroid use to prevent bone loss, but carefully monitored in hypercalcemia context 4
- Tuberculosis screening: T-spot testing before initiating corticosteroids in granulomatous disease 4
Mechanism of Action
Corticosteroids reduce hypercalcemia through two mechanisms:
- Decreased intestinal calcium absorption: By inhibiting the effects of 1,25-dihydroxyvitamin D on the gut 2, 3
- Reduced bone resorption: Though this is a secondary effect compared to bisphosphonates 8, 6
Common Pitfalls to Avoid
- Do not delay bisphosphonates in malignancy-related hypercalcemia: Even if lymphoma is suspected, initiate bisphosphonates first while awaiting diagnostic confirmation 1, 7
- Response time varies: Corticosteroids have a more delayed calcium-lowering effect (days) compared to calcitonin (hours) but faster than bisphosphonates alone 3, 8
- Vitamin D preparation matters: Hypercalcemia from vitamin D2 or D3 persists for months, while 1-alpha-hydroxyvitamin D3 or calcitriol-induced hypercalcemia resolves within a week 6
- Always combine with hydration: IV normal saline to correct hypovolemia and promote calciuresis should accompany corticosteroid therapy 1, 7, 2