| disease | Vitamin D Poisoning in Children |
| alias | Vitamin D Intoxication |
Vitamin D intoxication is one of the iatrogenic diseases. Vitamin D toxicity is mainly caused by misdiagnosis and outdated use of vitamin D preparations in the prevention and treatment of rickets, such as cod liver oil, vitamin D2 (calciferol), vitamin D2 (cholecalciferol or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-D3), and calciferol colloidal calcium.
bubble_chart Etiology
disease cause 学
The causes of poisoning in cases observed at Beijing Children's Hospital include the following situations: (1) Failure to thoroughly understand the past vitamin D doses used by the child, simply advising "eat more" or "take frequently" cod liver oil, while neglecting to inform parents of the correct dosage and treatment course of D preparations. Some parents believe that vitamins are nutritional supplements and think "the more, the better," leading to long-term administration to their children. (2) Incomplete analysis of the diagnosis and severity of the child's rickets, or even prescribing high-dose突击 treatment 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, believing that "injections are convenient" or "injections are effective," leading to multiple consecutive administrations 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 physical weakness for rickets and administering突击 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中毒 symptoms after consuming 4,000 IU of vitamin D daily for 1–3 months.
The earliest symptoms include loss of appetite, even anorexia, dysphoria, irritability, and lethargy, often accompanied by low-grade fever. There may also be profuse sweating, nausea, vomiting, diarrhea, or constipation, gradually progressing to polydipsia, frequent urination, and nocturia, occasionally with dehydration and acidosis. Older children may complain of headache, and blood pressure may rise or fall. A systolic murmur may be heard on cardiac auscultation, and ECG may show elevated ST segments. Sometimes, grade I anemia may occur. Severe cases may present with mental depression, hypotonia, ataxia, or even unconsciousness, convulsions, and renal failure. Urine has low and fixed specific gravity, positive protein, increased cells, and possibly casts. Long-term chronic poisoning can lead to corresponding calcifications in bones, kidneys, blood vessels, and skin, affecting physical and intellectual development. In severe cases, death may result from renal failure. Vitamin D poisoning in early pregnancy can cause fetal malformations.[Auxiliary Examination]
Serum 25-hydroxyvitamin D is elevated, blood calcium is increased (>3.0 mmol/l (12 mg/dl)), while blood phosphorus and alkaline phosphatase are normal or slightly low. Plasma cholesterol is normal or elevated. In a few cases, blood urea nitrogen is elevated, and renal function is abnormal, 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 toxicity, but it is not a specific manifestation. The reliable X-ray signs of vitamin D toxicity are: (1) Blurring of the ulnar and radial shafts with periosteal reaction. (2) Cortical bone rarefaction or osteoporosis. (3) Metaphyseal sclerosis or "dense and sparse" bands in the ulna and radius. (4) Thickened and dense cortical bone in the shaft. (5) Thickened and sclerotic calcification rings in the carpal bone nuclei. The presence of any three of these five X-ray signs can diagnose vitamin D toxicity, but it must also be combined with clinical history and evidence of excessive vitamin D intake for confirmation. In severe cases, metastatic calcification may also be observed in the kidneys, blood vessels, heart, and soft tissues of the limbs.
Vitamin D toxicity often presents with general symptoms and lacks specificity, so mild cases are easily overlooked or even mistaken for early signs of rickets, leading to further vitamin D administration. Once 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 4,000 IU for several months or repeated high-dose intramuscular injections. (2) Elevated blood calcium and positive urine calcium. (3) Abnormal X-ray findings. However, it should be noted that X-ray changes may not be obvious in early toxicity, and blood calcium may not be elevated during the convalescent or sequela stages. Symptoms of toxicity do not always correlate with the dose of vitamin D. In clinical practice, high doses are not uncommon, but toxicity is relatively rare, likely due to the metabolic characteristics of vitamin D. Vitamin D must first be converted in the liver to 25(OH)D and then in the kidneys to 1,25(OH) 2 D, with only the latter exhibiting strong biological activity. Normal individuals have feedback regulation mechanisms to prevent excessive production of 25(OH)D and 1,25(OH) 2 D. Toxicity likely occurs only when vitamin D intake is excessive and the body cannot regulate it or when regulatory mechanisms are impaired. Long-term chronic toxicity cases often show X-ray abnormalities, while acute toxicity initially presents with elevated serum 25-(OH)D and blood calcium, followed by changes in the epiphysis. During treatment, blood calcium normalizes first, while X-ray findings in the epiphysis gradually improve later. Positive X-ray findings can aid diagnosis, but negative results do not rule out vitamin D toxicity.
bubble_chart Treatment Measures(1) Upon diagnosis of vitamin D toxicity, immediately discontinue vitamin D preparations and calcium supplements, avoid sunlight exposure, and provide a low-calcium diet. (2) Control infections and correct dehydration and acidosis. Most cases require a prolonged period of recovery with the above treatments. Blood calcium levels typically take about 2–3 months to return to normal, while kidney function may take up to 1.5 years to recover. (3) Specific therapy: Adrenal corticosteroids can inhibit intestinal calcium absorption and antagonize the effects of vitamin D. 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, the duration of therapy may be extended 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.
(1) Strictly control the preventive or therapeutic dosage of vitamin D. The daily oral preventive dose should not exceed 400 IU. Parents should be informed about the hazards of vitamin D overdose, and medication should be taken as prescribed. The vitamin AD-fortified milk used in Beijing can supplement an appropriate amount of vitamin D without causing toxicity. (2) Before initiating intensive therapy, carefully inquire about the child’s past vitamin D dosage. According to observations at Beijing Children’s Hospital, most cases of toxicity occur after long-term high-dose oral cod liver oil, with symptoms worsening after additional injections of D2 or D3. Therefore, strict adherence to indications is necessary before administering high-dose injections. (3) If the response to standard vitamin D doses is unsatisfactory, check blood calcium, phosphorus, and alkaline phosphatase levels before deciding whether intensive therapy is needed. (4) For the prevention and treatment of general nutritional rickets, avoid high-dose vitamin D therapy whenever possible. When high-dose vitamin D treatment is necessary, closely monitor clinical symptoms and measure blood calcium levels monthly for signs of toxicity, or biweekly if needed. Note that vitamin D is a cumulative drug, stored long-term in body fat and muscles, and measured calcium levels reflect the cumulative effect of months of treatment. (5) Studies show that 200,000 IU and 400,000 IU of vitamin D have equivalent effects. If high-dose vitamin D therapy is necessary, the dose should preferably not exceed 200,000 IU, and a second injection is generally unnecessary. For children with normal liver, kidney, and gastrointestinal function, oral vitamin D is as effective as intramuscular injection and safer. Intramuscular injection should be avoided unless absolutely necessary.
When accompanied by low-grade fever, it is necessary to rule out external contraction infection. Polyuria is often misdiagnosed as a urinary tract infection, but antibiotic treatment yields unsatisfactory results. In cases of hypercalcemia, differentiation should be made from infantile idiopathic hypercalcemia, hyperparathyroidism, bone metastases of malignant tumors, and hypophosphatasia. Idiopathic hypercalcemia presents similarly to vitamin D intoxication but lacks a history of excessive vitamin D intake. The symptoms of hyperparathyroidism also resemble those of vitamin D intoxication, 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 required from the convalescent stage of rickets, lead or fluoride poisoning, among others, necessitating comprehensive consideration of disease history, signs, bismuth levels, blood calcium, and other factors.
