Common causes of vitamin D toxicity include:
- Repeated administration of high doses of vitamin D for the treatment of rickets over a short period.
- Excessive preventive doses of vitamin D, including daily intake of an overly large amount or repeated intramuscular injections of high doses over several months.
- Misdiagnosis of other metabolic bone diseases or endocrine disorders as rickets, leading to prolonged intake of high doses of vitamin D.
The toxic dose of vitamin D varies significantly among individuals. Generally, in children, taking 20,000–50,000 IU (500–1,250 μg) per day or 2,000 IU (50 μg) per kg of body weight per day for several weeks or months can result in toxicity.
Mechanism
Excessive intake of vitamin D disrupts feedback regulation, causing an increase in serum 1,25-(OH)2D3 levels. This leads to enhanced intestinal absorption of calcium and phosphorus, resulting in hypercalcemia. Calcitonin regulation promotes deposition of calcium in bones and other tissues, impairing their function. If calcium salts accumulate in the kidneys, they can cause tubular necrosis and renal calcification, potentially leading to renal atrophy and chronic renal impairment in severe cases. Deposition in small bronchi and alveoli may damage respiratory epithelial cells, causing ulcers or calcified lesions. Extensive calcification in critical organs such as the central nervous system and cardiovascular tissues may result in severe, irreversible damage.
Clinical Manifestations
Early symptoms include anorexia, nausea, lethargy, irritability, low-grade fever, vomiting, persistent constipation, and weight loss. Severe cases may present with seizures, hypertension, arrhythmias, excessive thirst, frequent urination, nocturia, dehydration, and metabolic acidosis. Urinary abnormalities such as proteinuria, red blood cells, and casts may occur. In severe cases, acute or chronic renal failure may develop.
Diagnosis
A history of excessive vitamin D intake is an essential diagnostic clue. Early symptoms are nonspecific and overlap with early signs of rickets, such as irritability and excessive sweating, necessitating careful history-taking for differentiation. A serum 25-(OH)D3 concentration exceeding 100 ng/mL (>250 nmol/L) confirms the diagnosis. Early hypercalcemia (>3 mmol/L or >12 mg/dL), strongly positive urinary calcium (Sulkowitch test), and proteinuria are often observed. In severe cases, red and white blood cells and casts may be found in urinalysis.
X-ray findings may show widening (>1 mm) and increased density of the calcification zone in the metaphysis of long bones, cortical thickening, osteoporosis, or osteosclerosis. Skull thickening with ring-like areas of increased density is also observed. Calcified lesions in the brain, heart, kidneys, major blood vessels, or skin may occur in severe cases. Additionally, azotemia, dehydration, and electrolyte imbalances may be present. Renal ultrasound may indicate kidney atrophy.
Treatment
Suspected vitamin D toxicity necessitates the immediate cessation of vitamin D intake. If hypercalcemia is present, calcium intake should be restricted, including reducing the consumption of calcium-rich foods. Measures to accelerate calcium excretion may include oral administration of aluminum hydroxide or disodium EDTA to reduce intestinal calcium absorption and promote calcium elimination via the gastrointestinal tract. Prednisone may be taken orally to suppress the production of intestinal calcium-binding proteins, thereby decreasing calcium absorption. Calcitonin can also be considered. Maintaining fluid and electrolyte balance is essential.