What is the appropriate management for a patient with symptomatic hypercalcemia due to vitamin D intoxication, accompanied by dehydration‑related polycythemia, excessive thirst, light‑headedness, and nausea?

Management of Symptomatic Hypercalcemia Due to Vitamin D Intoxication

Immediately discontinue all vitamin D and calcium supplements, initiate aggressive IV normal saline hydration targeting urine output of 100-150 mL/hour, and administer corticosteroids (prednisone 20-40 mg/day orally or IV methylprednisolone equivalent) as primary therapy for vitamin D-mediated hypercalcemia. 1, 2, 3

Immediate Interventions (First 24 Hours)

Stop All Exogenous Sources

• Discontinue all vitamin D supplements immediately, even if 25-OH vitamin D levels appear low, as supplementation will worsen calcium elevation 1
• Stop all calcium-based supplements and phosphate binders to eliminate additional calcium load 1, 2
• The effects of vitamin D toxicity persist for 2+ months after cessation due to fat tissue storage, so early discontinuation is critical 2, 4

Aggressive Hydration Protocol

• Administer IV normal saline aggressively to correct hypovolemia and promote calciuresis, targeting urine output of 100-150 mL/hour 1, 5, 2
• Give boluses of 250-500 mL crystalloids every 15 minutes until rehydration is achieved 1
• Avoid loop diuretics (furosemide) until complete volume repletion is achieved; only use in patients with cardiac or renal insufficiency to prevent fluid overload 1, 2
• Dehydration creates a vicious cycle: it causes mild hypercalcemia by reducing renal calcium excretion, which then impairs the kidney's ability to concentrate urine, worsening both dehydration and hypercalcemia 6

Primary Pharmacologic Therapy for Vitamin D Intoxication

• Corticosteroids are the primary treatment for vitamin D-mediated hypercalcemia because they reduce excessive intestinal calcium absorption 1, 7, 3
• Dose: Prednisone 20-40 mg/day orally or IV methylprednisolone equivalent 1
• Corticosteroids work by reducing intestinal calcium absorption and are specifically indicated for vitamin D intoxication, granulomatous diseases, some lymphomas, and multiple myeloma 1, 3
• Response typically occurs within 3-6 days, but allow 3-6 months to demonstrate full responsiveness before considering escalation 1

Monitoring Parameters

Frequent Laboratory Assessment

• Measure ionized calcium every 4-6 hours during the first 48-72 hours, then twice daily until stable 1
• Monitor serum calcium, creatinine, and electrolytes (especially potassium and magnesium) every 6-12 hours during the acute phase 1
• Check serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels; vitamin D intoxication is defined as 25-OH vitamin D >150 ng/mL 7, 4
• Measure intact PTH, which will be suppressed (<20 pg/mL) in vitamin D intoxication, confirming a PTH-independent mechanism 1, 7, 3

Target Calcium Levels

• Aim for corrected calcium of 8.4-9.5 mg/dL, preferably at the lower end of this range 1
• Use the formula: Corrected calcium (mg/dL) = Total calcium + 0.8 × [4.0 - Serum albumin] 1

Additional Therapeutic Options

Bisphosphonates (Adjunctive Therapy)

• Bisphosphonates are NOT first-line for vitamin D intoxication but may be added if corticosteroids alone are insufficient 1, 3
• Vitamin D intoxication causes hypercalcemia primarily through increased bone resorption, making bisphosphonates mechanistically rational as adjunctive therapy 8
• If used: Zoledronic acid 4 mg IV over ≥15 minutes is preferred over pamidronate (normalizes calcium in 50% by day 4 vs. 33% for pamidronate) 1, 5, 3
• Check serum creatinine before each bisphosphonate dose; withhold if creatinine increases >0.5 mg/dL from normal baseline or >1.0 mg/dL from abnormal baseline 1
• Pamidronate provides more delayed calcium reduction compared to the brisk response seen with bisphosphonates in other causes of hypercalcemia 8

Calcitonin (Bridge Therapy Only)

• Calcitonin 100 IU subcutaneously or intramuscularly provides rapid onset (within hours) but limited efficacy with tachyphylaxis 1, 3
• Use only as a bridge until corticosteroids and bisphosphonates take effect (1-4 hours of benefit) 1

Denosumab (Refractory Cases or Renal Impairment)

• Denosumab 60-120 mg subcutaneously is an alternative in patients with acute kidney injury who cannot receive bisphosphonates 9
• Two case reports demonstrate successful treatment of vitamin D intoxication with denosumab, with prompt calcium reduction and renal function improvement within 7 days 9
• Higher risk of hypocalcemia with denosumab; monitor calcium closely and provide calcium supplementation (500 mg) plus vitamin D (400 IU) daily during treatment 1

Dialysis (Severe Cases with Renal Failure)

• Hemodialysis with calcium-free or low-calcium dialysate (1.25-1.50 mmol/L) is reserved for severe hypercalcemia (≥14 mg/dL) complicated by renal insufficiency or oliguria 1, 5, 2

Symptomatic Management

Address Presenting Symptoms

• Nausea/vomiting: Antiemetics as needed; symptoms will improve as calcium normalizes 7, 3
• Lightheadedness/dehydration: Corrected by aggressive IV hydration 5, 6
• Polydipsia/polyuria: Result from hypercalcemia interfering with renal concentrating ability; resolve with calcium normalization 10, 7
• Polycythemia: Secondary to dehydration-induced hemoconcentration; resolves with rehydration 6

Severe Hypercalcemia (≥14 mg/dL) Requires Emergency Intervention

• Severe hypercalcemia causes altered mental status, bradycardia, hypotension, and can progress to stupor, coma, and azotemia 2, 3
• Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment with immediate hydration as the first step 2

Critical Pitfalls to Avoid

• Do not delay corticosteroid therapy in vitamin D-mediated hypercalcemia; they are the primary treatment, not adjunctive 1, 3
• Do not use NSAIDs or IV contrast in patients with renal impairment, as they worsen kidney function 1
• Do not restrict dietary calcium excessively without medical supervision, as this can worsen bone disease long-term 1
• Do not rely on corrected calcium alone; measure ionized calcium to avoid pseudo-hypercalcemia from hemolysis or improper sampling 1
• Avoid overhydration in patients with cardiac or renal insufficiency; use loop diuretics after volume repletion 1, 2
• Do not assume asymptomatic hypocalcemia after treatment requires intervention; only treat symptomatic hypocalcemia (tetany, seizures) with calcium gluconate 50-100 mg/kg 1

Expected Clinical Course

• Corticosteroids typically show response within 3-6 days but full effect may take weeks to months 1
• Vitamin D effects persist for 2+ months after discontinuation due to fat storage, requiring prolonged monitoring 2, 4
• Recovery is the usual outcome when no permanent renal or cardiovascular damage has occurred 2
• Deaths from renal or cardiovascular failure have been reported in severe cases 2

Follow-Up Strategy

• Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 1, 7
• Taper corticosteroids over 2-4 months depending on response, targeting the lowest effective dose ≤10 mg/day to minimize toxicity 1
• If unable to wean below 10 mg/day after 3-6 months, consider adding methotrexate as a steroid-sparing agent 1
• Serial questioning about supplement use is required during and after treatment to prevent recurrence 4