Vitamin D intoxication is one of the iatrogenic diseases. Vitamin D poisoning is mainly caused by misdiagnosis and outdated use of vitamin D preparations in the prevention and treatment of rickets, such as cod liver oil, vitamin D₂ (calciferol), vitamin D₂ (cholecalciferol or cholecalciferol), and calciferol colloidal calcium.

bubble_chart Etiology

The causes of poisoning in cases observed at Beijing Children's Hospital include the following situations: ① Failure to thoroughly understand the previous vitamin D doses used by the child, simply advising to "eat more" or "take frequently" cod liver oil, while neglecting to inform parents about the correct dosage and treatment course of D preparations. Some parents also believe that vitamins are all nutritional supplements and that the more taken, the better, leading to long-term administration to their children. ② Not comprehensively analyzing the diagnosis and severity of the child's rickets, or even prescribing high-dose shock therapy based solely on a single symptom like profuse sweating or signs such as pillow baldness or Harrison's groove. ③ Partially catering to parents' demands, thinking that "injections are more convenient" or "injections are more effective," leading to multiple consecutive injections of D₂ or D₃. ④ Misdiagnosis, such as mistaking one or two symptoms like delayed teething, late walking, dysphoria, profuse sweating, posterior pillow baldness, or general weakness for rickets and administering shock therapy. X-ray examinations often misdiagnose normal variations at the distal end of the ulna as rickets. ⑤ Children sensitive to vitamin D may develop poisoning symptoms after 1 to 3 months of daily intake of 4,000 IU of vitamin D.

The earliest symptoms include loss of appetite, even anorexia, dysphoria, crying, and lethargy, often accompanied by low-grade fever. Other possible symptoms are profuse sweating, nausea, vomiting, diarrhea, or constipation, gradually progressing to polydipsia, frequent urination, and nocturia, with occasional dehydration and acidosis. Older children may complain of headaches, and blood pressure may rise or fall. A systolic murmur may be heard on cardiac auscultation, and the ECG may show an elevated ST segment. Grade I anemia may sometimes occur. Severe cases can present with depression, hypotonia, ataxia, or even unconsciousness, convulsions, and renal failure. Urine tests may reveal low and fixed specific gravity, positive proteinuria, increased cells, and possibly casts. Long-term chronic poisoning can lead to calcification in bones, kidneys, blood vessels, and skin, impairing physical and intellectual development. In severe cases, renal failure may result in death. Vitamin D poisoning during early pregnancy may cause fetal malformations.

bubble_chart Auxiliary Examination

Increased serum 25-hydroxy D, elevated blood calcium (>3.0 mmol/L (12 mg/dl)), normal or slightly low blood phosphorus and alkaline phosphatase. Plasma cholesterol is normal or elevated. In a few cases, blood urea nitrogen is elevated, with abnormal renal function, such as low and fixed urine specific gravity, positive urine protein, increased cells with casts, etc.

X-ray examination

Metaphyseal sclerosis is one of the common X-ray signs of vitamin D poisoning, but it is not a characteristic manifestation. The reliable X-ray signs of vitamin D poisoning are: ① Blurring of the ulnar and radial diaphyseal cortices with periosteal reaction. ② Cortical bone rarefaction or osteoporosis. ③ Metaphyseal "banding" or "dense and sparse" zones in the ulna and radius. ④ Thickening and densification of the diaphyseal cortex. ⑤ Thickening and hardening of the calcification ring of the carpal ossification nuclei. The presence of any three of the above five X-ray signs can diagnose vitamin D poisoning, but of course, it must be combined with clinical history and evidence of excessive vitamin D intake for confirmation. In severe poisoning cases, metastatic calcification may also be observed in the kidneys, blood vessels, heart, and soft tissues of the limbs.

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Vitamin D toxicity often presents with general symptoms and lacks specific manifestations, making mild cases easily overlooked or even mistaken for early signs of rickets, leading to further Vitamin D administration. When symptoms become pronounced, they are often misdiagnosed as other conditions. The main diagnostic criteria include: ① A history of excessive Vitamin D intake, such as daily doses exceeding 4000 IU for several months or repeated high-dose intramuscular injections. ② Elevated blood calcium levels and positive urinary calcium. ③ Abnormal X-ray findings. However, it should be noted that X-ray changes may not be evident in early stages of toxicity, and blood calcium levels may not be elevated during the convalescence or sequelae stages. Symptoms of toxicity do not always correlate with the dosage of Vitamin D. In clinical practice, high doses are not uncommon, yet toxicity is relatively rare, likely due to the metabolic characteristics of Vitamin D. After entering the body, Vitamin D must be converted in the liver to 25(OH)D and then in the kidneys to 1,25(OH)₂D, with only the latter exhibiting strong biological activity. Healthy individuals possess feedback regulation mechanisms that prevent excessive production of 25(OH)D and 1,25(OH)₂D. Toxicity symptoms are thought to arise only when Vitamin D intake is excessively high, overwhelming the body's regulatory capacity, or when regulatory mechanisms malfunction. Chronic, long-term toxicity cases often show X-ray abnormalities, while acute toxicity initially presents with elevated serum 25-OHD and blood calcium levels, followed by changes in the epiphyses. During treatment, blood calcium levels typically normalize first, with epiphyseal X-ray findings gradually improving later. Positive X-ray results can aid diagnosis, but negative findings do not rule out Vitamin D toxicity.

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①Upon diagnosis of VitD toxicity, immediately discontinue D preparations and calcium supplements, avoid sunlight exposure, and provide a low-calcium diet. ②Control infections and correct dehydration and acidosis. Most cases require prolonged treatment before gradual recovery is observed. Blood calcium levels typically take about 2–3 months to normalize, while kidney function may take up to 1.5 years to recover. ③Specific therapy: Adrenal corticosteroids can inhibit intestinal calcium absorption and antagonize VitD. Administer prednisone orally at 1–2 mg/kg/day. Blood calcium levels usually normalize within 1–2 weeks, and treatment can generally be discontinued after 2–3 weeks without rebound hypercalcemia. For severe cases, extend the treatment duration based on blood calcium levels and X-ray findings. Oral sulfate can reduce calcium absorption, with a dose of 1–2 g for older children.

bubble_chart Prevention

① Strictly control the preventive or therapeutic dosage of VitD. The preventive dose should not exceed 400IU per day orally. Parents should be informed about the hazards of VitD overdose, and medication should be taken as prescribed. The vitamin AD-fortified milk used in Beijing can supplement an appropriate amount of VD without causing toxicity. ② Before initiating intensive treatment, thoroughly inquire about the child's past VitD dosage. According to observations from Beijing Children's Hospital, most cases of toxicity occur after long-term, high-dose oral intake of cod liver oil, compounded by subsequent injections of D₂ or D₃, which are more likely to induce toxic symptoms. Therefore, strict adherence to indications is essential before administering high-dose injections. ③ If the therapeutic effect of a standard VitD dose is unsatisfactory, check blood calcium, phosphorus, and alkaline phosphatase levels before deciding whether intensive therapy is necessary. ④ For the prevention and treatment of general nutritional rickets, avoid high-dose VD intensive therapy whenever possible. When high-dose VitD treatment is unavoidable, closely monitor clinical symptoms and measure blood calcium monthly for signs of toxicity, or even biweekly if necessary. Note that VitD is a cumulative drug, stored long-term in body fat and muscles, and the measured calcium levels reflect the cumulative effect of months of treatment. ⑤ Clinical evidence shows that 200,000IU and 400,000IU of VD have equivalent efficacy. When high-dose VitD intensive therapy is necessary, it is best not to exceed 200,000IU, and a second injection is generally unnecessary. For children with normal liver, kidney, and gastrointestinal function, oral administration of VD is as effective as intramuscular injection and is safer. Intramuscular injection should be avoided unless absolutely necessary.

bubble_chart Differentiation

When accompanied by low-grade fever, it is necessary to rule out external contraction infection. Polyuria is easily misdiagnosed as a urinary tract infection, but antibiotic treatment yields unsatisfactory results. When hypercalcemia occurs, it should be differentiated from infantile idiopathic hypercalcemia, hyperparathyroidism, malignant tumor bone metastasis, and hypophosphatasia. Idiopathic hypercalcemia presents similarly to vitamin D toxicity but lacks a history of excessive vitamin D intake. The symptoms of hyperparathyroidism also resemble those of vitamin D toxicity, with elevated blood calcium levels, but X-rays show generalized osteoporosis, and corticosteroid treatment is ineffective. Additionally, based solely on X-ray findings, differentiation is also required from the convalescent stage of rickets, lead or fluoride poisoning, among others. A comprehensive consideration of medical history, signs, bismuth levels, blood calcium, and other factors is necessary.