A detailed history is very important in making a diagnosis of Vitamin D toxicity. A thorough review of medications list, including the use of over the counter supplements, is pertinent. History should also focus on getting details of chronic medical ailments requiring high doses of vitamin D supplementations osteoporosis, renal osteodystrophy, psoriasis, gastric bypass surgery, celiac, or inflammatory bowel disease. Dietary history, especially the excessive use of vitamin D fortified milk along with the use of supplementary vitamin D, is another important clue. The clinical symptoms for vitamin D toxicity are manifested from the effects of hypercalcemia. These include neurological symptoms like confusion, apathy, agitated, irritability, and in severe cases, stupor and comma. Gastrointestinal symptoms include abdominal pain, nausea, vomiting, constipation, peptic ulcers, and pancreatitis (from malignant calcifications). Renal symptoms manifest polyuria, polydipsia, and nephrolithiasis. Severe hypercalcemia can also lead to cardiac arrhythmias.

In many cases, symptoms can be nonspecific and subtle, like weakness, fatigue, anorexia, and bone pains. Physical exam of patients with signs of toxicity sometimes shows loss of skin turgor and dry mucous membranes (due to dehydration), changes in mental status, abdominal tenderness without rebound, rigidity, or guarding. In many cases, a physical exam can be normal without any overt findings, but high clinical suspicion should be kept in mind based on historical findings.

Vitamin D toxicity is a clinical diagnosis that can be made with a thorough history and clinical symptoms. Laboratory evaluation includes checking serum calcium (often greater than 11 mg/dL), ionized calcium, parathyroid hormone (PTH), which is suppressed due to negative feedback loop. Serum level of 25(OH)D concentration less than 150 ng/ml (375 nmol/l), and normal or increased values of 1,25(OH)2D concentration.[5] A decreased or normal 25(OH)D concentration, and elevated 1,25(OH)2D can be found in patients with coexisting granulomatous diseases. A basic metabolic panel should be done to assess kidney dysfunction due to hypercalcemia or any electrolyte derangements due to excessive vomiting. EKG is to assess the presence of any arrhythmia. The most common EKG findings are a shortened QT interval. It can also reveal a shortened ST segment, flattened T wave, or Osborn waves (J wave), a positive deflection at the J point in precordial leads.Imaging studies are usually not required to make a diagnosis of vitamin D toxicity but can reveal incidental findings of chronic toxicity due to pathological calcifications. Skeletal radiographs usually show periosteal calcifications. CT scan of the abdomen and pelvis can reveal nephrolithiasis. If a patient is significantly altered on admission, a baseline CT scan should be done to reveal alternative intracranial pathologies.

Clinical management of vitamin D toxicity is mainly supportive and focuses on lowering the levels of calcium.

• Discontinue all vitamin D and calcium supplements. Avoid excessive bed rest to prevent hypercalcemia of immobilization.
• Isotonic saline should be used to correct dehydration related kidney injury.
• In cases of severe toxicity causing severe hypercalcemia (serum calcium > 14 gm/dL), calcitonin and bisphosphonates can be used. Intravenous calcitonin at 4 U/kg can be administered, and calcium levels repeated after 6 to 12 hours. IV bisphosphonates can be administered concurrently but are more beneficial to lower hypercalcemia of malignancy.
• It should be kept in mind that calcitonin can lead to tachyphylaxis, while the effect of bisphosphonates can persist for a longer duration. Calcium levels should be carefully monitored during the use of these medications.
• The use of intravenous glucocorticoids is controversial and usually reserved for the treatment of vitamin D toxicity related to the granulomatous disease. It reduced plasma calcium levels by reducing intestinal absorption and increasing urinary excretion of calcium.
• In rare cases, due to significant kidney damage, patients may need hemodialysis to get rid of excessive calcium.
• The patient’s medication list should be reviewed to adjust the future doses of vitamin D supplements.
• Patient education is needed overuse of supplementary vitamin replacements.
• The Endocrine Society suggests monitoring of serum levels of 25-hydroxy vitamin D and calcium for the patients on high dose vitamin D replacement.

Hypervitaminosis due to vitamin D should be differentiated from other causes leading to hypercalcemia or diseases mimicking the symptoms of hypervitaminosis as follow:

• Hypercalcemia of malignancy
• Hypercalcemia of granulomatous diseases
• Primary, secondary and tertiary hyperparathyroidism
• Vitamin A toxicity
• Thyrotoxicosis
• Paget disease
• Hypercalcemia caused by prolonged immobilization
• Milk-alkali syndrome

Most of the cases with vitamin D toxicity recover without any serious complications or sequels. In a few cases, severe hypercalcemia is noted to lead to acute renal failure requiring hemodialysis, but it is rare to have cases of permanent renal damage due to vitamin D toxicity.

The complication of vitamin D toxicity rarely leads to renal failure requiring hemodialysis.[11]

Patient education regarding the harmful effects of overuse of vitamin D supplements is extremely important. Patients should be educated on adhering to the prescription regimen, especially those who are on high doses of vitamin D for the treatment of underlying medical conditions. They should also be made aware of the importance of follow up while being on high dose supplements to avoid the risk of vitamin D toxicity.

Vitamin D is widely prescribed and is also used as over the counter formulation by patients. Health care providers should be aware of close monitoring of these supplements, especially in the population at risk due to high doses requirements. A thorough history and careful review of medication lists, including over the counter supplements should be done in cases of suspected vitamin D toxicity. Patient education and close monitoring of vitamin D levels are needed to prevent toxicities. Physicians should be mindful of various high dose formulation and suggested daily requirements to prevent errors in prescriptions leading to adverse outcomes.