Treatment of Vitamin D Toxicity
The primary treatment for vitamin D toxicity is immediate discontinuation of all vitamin D supplementation combined with aggressive management of hypercalcemia through intravenous saline hydration, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates when calcium exceeds 14 mg/dL. 1
Diagnostic Confirmation
- Vitamin D toxicity typically occurs at 25(OH)D levels >150 ng/mL (>375 nmol/L), with levels >200 ng/mL (>500 nmol/L) associated with acute toxicity. 1
- Laboratory findings include hypercalcemia, suppressed parathyroid hormone (PTH), normal or high serum phosphorus, normal or low alkaline phosphatase, and elevated urine calcium/creatinine ratio. 1, 2
- The upper safety limit for 25(OH)D is 100 ng/mL, beyond which toxicity risk increases substantially. 3, 4
Immediate Management Algorithm
When Calcium >14 mg/dL (3.5 mmol/L):
- Emergency intervention is mandatory due to adverse effects on cardiac, central nervous system, renal, and gastrointestinal function. 2
- Initiate aggressive intravenous hydration with normal saline. 1, 2
- Administer loop diuretics (after adequate hydration). 1, 2
- Give glucocorticoids to reduce intestinal calcium absorption. 1, 2
- Administer calcitonin for rapid calcium reduction. 1, 2, 5
- Use bisphosphonates (such as pamidronate) for sustained calcium control, particularly effective in achieving normocalcemia within approximately 6 days. 5, 6
When Calcium 11.1-14 mg/dL:
- Discontinue all vitamin D supplementation immediately. 1, 2
- Implement a low calcium and phosphorus diet. 2, 5
- Initiate intravenous saline hydration. 1, 2
- Consider loop diuretics and calcitonin based on clinical severity. 1, 2
Critical Clinical Considerations
- Vitamin D is stored in adipose tissue, so effects of toxicity may persist for months (up to 18 months) despite removal of the exogenous source. 2, 7
- Patients typically require low-calcium diets and serial laboratory monitoring for months after initial presentation. 5
- Normocalcemia is usually achieved within approximately 6 days with appropriate treatment, but 25(OH)D levels may take 6-18 months to normalize. 7, 6
- Acute kidney injury is common and may require months to resolve. 5, 7
Common Causes to Investigate
- Prescription errors with mega-doses of vitamin D (cumulative doses of 2-6 million IU have been reported). 8
- Manufacturing errors in supplements not claiming to contain vitamin D (cases with up to 425,000 IU per serving documented). 5
- Overzealous correction of vitamin D deficiency by healthcare providers. 8
- Contaminated nutritional supplements including fish oil and creatine products. 5, 6
Monitoring During Recovery
- Check serum calcium levels daily until normocalcemia is achieved. 2, 6
- Monitor renal function (creatinine, eGFR) as acute kidney injury is common. 5, 7
- Assess for nephrocalcinosis with renal ultrasound, present in approximately 40% of cases. 6
- Continue monitoring 25(OH)D levels every 3-6 months until normalization. 7
- Serial questioning about all supplements and medications is essential to identify the source. 2, 5
Prevention Pitfalls
- Always measure baseline 25(OH)D levels before initiating high-dose vitamin D therapy. 2
- Avoid single very large doses (>300,000 IU) as they may be inefficient or harmful. 3
- Toxicity rarely occurs with standard supplementation doses up to 4,000 IU daily. 3, 4
- Take detailed history of all dietary supplements, not just those claiming vitamin D content. 5