What are the manifestations and management of vitamin D (Vit D) overdose?

Vitamin D Overdose: Clinical Manifestations and Management

Clinical Manifestations

Vitamin D toxicity manifests primarily through hypercalcemia-related symptoms, with severity directly correlating to serum calcium levels and duration of exposure. 1

Biochemical Findings

• Serum 25(OH)D levels above 150 ng/mL (375 nmol/L) indicate vitamin D toxicity, with levels exceeding 200 ng/mL (500 nmol/L) associated with acute toxicity. 2
• Typical laboratory abnormalities include hypercalcemia, normal or elevated serum phosphorus, normal or low alkaline phosphatase, suppressed parathyroid hormone (PTH), and elevated urinary calcium/creatinine ratio. 1
• Hypercalcemia severity determines clinical urgency, with calcium levels exceeding 14 mg/dL requiring emergency intervention due to life-threatening cardiac, neurological, renal, and gastrointestinal complications. 2, 1

Clinical Symptoms by System

Gastrointestinal manifestations include nausea, vomiting, anorexia, constipation, weight loss, and potentially pancreatitis. 3, 4

Neurological symptoms present as altered sensorium, lethargy, weakness, muscle hypotonia, and in severe cases, seizures or coma. 3, 4

Renal complications include acute kidney injury, polyuria, nephrocalcinosis (especially with chronic exposure), and progressive renal dysfunction that may persist for months. 3, 5, 4

Cardiovascular effects manifest as shortened QT interval on ECG, with severe dysrhythmias being rare but potentially fatal when calcium exceeds 14 mg/dL. 4

Important Clinical Context

• Symptoms persist for months despite discontinuation of vitamin D supplementation because vitamin D is stored in adipose tissue, creating a prolonged reservoir effect. 1
• The most common cause in recent case series is iatrogenic overdose from prescription of mega-doses (cumulative doses of 2-6 million IU or higher), often prescribed for correction of deficiency without appropriate monitoring. 3
• One documented case involved 78 million IU cumulative dose over 20 months (mean 130,000 IU daily), resulting in severe toxicity with 25(OH)D levels of 920 nmol/L. 5

Management Protocol

Immediate Interventions for Severe Hypercalcemia (Calcium >14 mg/dL)

The primary treatment goal is aggressive correction of hypercalcemia through immediate discontinuation of vitamin D supplementation combined with multi-modal therapy. 2, 1

1. Discontinue all vitamin D supplementation immediately and implement a low calcium and phosphorus diet. 1

2. Intravenous hydration with normal saline to promote calciuresis and restore intravascular volume. 2, 1

3. Loop diuretics (after adequate hydration) to enhance urinary calcium excretion. 2, 1, 4

4. Glucocorticoids to reduce intestinal calcium absorption and enhance vitamin D metabolism, though response may be delayed. 2, 1, 6

5. Calcitonin for rapid but temporary reduction in serum calcium. 2, 1

6. Bisphosphonates (such as pamidronate or clodronate) are highly effective for controlling hypercalcemia by inhibiting bone resorption, which is a prominent feature of vitamin D toxicity. 2, 6

   • Bisphosphonates demonstrate superior efficacy compared to prednisone therapy alone in correcting both hypercalcemia and hypercalciuria. 6
   • Enhanced bone resorption persists even after plasma calcium normalizes, making bisphosphonates particularly valuable. 6

7. Hemodialysis should be considered for life-threatening hypercalcemia with neurological impairment or cardiac complications, particularly when calcium exceeds 15-16 mg/dL. 4

Monitoring and Follow-Up

• Serial calcium measurements are essential initially (every 4-6 hours in severe cases) until stabilization occurs. 1
• Renal function monitoring is critical as acute kidney injury is common and may take 6 months or longer to normalize. 5
• 25(OH)D levels should be monitored but may take 18 months to return to normal range due to adipose tissue storage. 5
• Nephrocalcinosis screening with renal ultrasound is warranted, as this complication correlates with chronic administration and may cause permanent renal impairment. 4

Critical Pitfalls to Avoid

• Do not underestimate the duration of toxicity: Effects persist for months after discontinuation due to fat tissue storage, requiring prolonged monitoring and treatment. 1, 5
• Do not rely solely on glucocorticoids: While commonly used, bisphosphonates are more effective for controlling the enhanced bone resorption that drives hypercalcemia in vitamin D toxicity. 6
• Do not overlook cardiovascular monitoring: EKG should be performed urgently when calcium exceeds 14 mg/dL to assess for shortened QT interval and arrhythmia risk. 4
• Do not miss the diagnosis in high-risk populations: Turkish and other immigrant families may administer excessive vitamin D due to fear of rickets, facilitated by internet purchase of high-dose formulations. 4

Prevention Strategies

• Always measure baseline 25(OH)D levels before initiating vitamin D therapy to avoid redundant treatment leading to toxicity. 1
• Question all patients about dietary supplements and over-the-counter vitamin D use before prescribing additional supplementation. 1
• Avoid mega-dose prescriptions: The documented toxic cases involved cumulative doses of 2-6 million IU or higher, far exceeding standard replacement protocols. 3
• Serial questioning during supplementation is necessary to detect excessive intake, particularly in infants and children. 1