Signs and Symptoms of Vitamin D Toxicity
Vitamin D toxicity occurs when serum 25-hydroxyvitamin D [25(OH)D] levels exceed 150 ng/mL (375 nmol/L), causing hypercalcemia and a constellation of symptoms affecting multiple organ systems. 1
Clinical Manifestations
Generalized Symptoms
- Fatigue
- Weakness
- Confusion
Neurological Symptoms
- Altered mental status
- Irritability
- Headache
- Vertigo
- Blurred vision
- Muscular incoordination
- Apathy
- In severe cases: encephalopathy 2
Gastrointestinal Symptoms
- Nausea
- Vomiting
- Constipation
- Abdominal pain
- Weight loss 3
Endocrinological Symptoms
- Polyuria
- Polydipsia
Renal Manifestations
- Kidney injury
- Kidney stones
- Nephrocalcinosis 4
Cardiovascular Effects
- Potential arrhythmias in severe cases
- Short QTc interval on ECG 4
- Increased risk of cardiovascular calcification 5
Other Manifestations
- Bone abnormalities (with chronic toxicity)
- Dermatitis
- Alopecia
- Muscle pain
- Cheilitis
- Skin disorders
- Pseudotumor cerebri
- Hepatocellular necrosis
- Hyperlipidemia 5, 1
Laboratory Findings
- Elevated serum 25(OH)D levels >150 ng/mL (375 nmol/L) 6
- Hypercalcemia (serum calcium >10.2 mg/dL, often >13 mg/dL) 3
- Normal or high serum phosphorus levels
- Normal or low levels of alkaline phosphatase
- Low serum parathyroid hormone (PTH) - typically suppressed
- High urinary calcium excretion 7
Risk Factors for Toxicity
- Excessive supplementation with daily doses >10,000 IU for prolonged periods
- Accidental overdose with single extremely high doses
- Manufacturing errors in supplement production
- Increased vitamin D sensitivity due to genetic factors (e.g., CYP24A1 mutations)
- Liver or renal disorders 1
Clinical Pearls
- Vitamin D toxicity is increasingly common due to overzealous correction of vitamin D deficiency 3
- Effects may persist for months after discontinuation due to vitamin D storage in adipose tissue 1
- Severity of symptoms correlates with both serum calcium concentration and duration of hypercalcemia 7
- When calcium concentration exceeds 14 mg/dL, emergency intervention is necessary due to potential life-threatening effects on cardiac, neurological, renal, and gastrointestinal systems 7
- Children may present with developmental regression and hypotonia 2
Understanding these signs and symptoms is crucial for early recognition and prompt management of vitamin D toxicity, which can be life-threatening if not identified and treated appropriately.