Two cases of vitamin D intoxication

Case 1 A 7 year old girl was admitted with vomiting for 5 days and constipation for 7 days. She was also having migratory arthritis of both knees and ankles for 2 months for which she had been prescribed oral cholecalciferol (Vitamin D), 60,000 IU weekly prophylactically, considering her to be possibly having vitamin D deficiency, although she had not been tested for it. The history revealed that she had been taking the vitamin D sachet (60,000 IU) twice a day for the last 4 weeks, instead of one sachet per week. On admission, her vital signs were stable. Her liver and spleen were palpable 3 cm and 2 cm below the costal margin respectively. The blood urea was 50 mg/dl and the serum creatinine 0.5 mg/dl. The serum calcium was 12.2 mg/dl (normal 8.6-10.2 mg/dl) and the urinary calcium: creatinine (Ca: Cr) ratio was 0.88 (normal <0.25). The vitamin D level was 312 ng/ml. Urine microscopy showed 25-30 red blood cells per high power field. Ultrasound scan of the abdomen did not show any nephrocalcinosis.


Introduction
There is no consensus yet regarding the dose of vitamin D which may lead to intoxication, but maintenance dose of vitamin D has been reported to be safe at 1000 IU/day for ages 0-1 year, 2500 IU/day for ages 1-3 years, 3000 IU/day for ages 3-8 years, and 4000 IU/day for age 9 years and above 1 .
Case 1 A 7 year old girl was admitted with vomiting for 5 days and constipation for 7 days.She was also having migratory arthritis of both knees and ankles for 2 months for which she had been prescribed oral cholecalciferol (Vitamin D), 60,000 IU weekly prophylactically, considering her to be possibly having vitamin D deficiency, although she had not been tested for it.The history revealed that she had been taking the vitamin D sachet (60,000 IU) twice a day for the last 4 weeks, instead of one sachet per week.On admission, her vital signs were stable.Her liver and spleen were palpable 3 cm and 2 cm below the costal margin respectively.The blood urea was 50 mg/dl and the serum creatinine 0.5 mg/dl.The serum calcium was 12.2 mg/dl (normal 8.6-10.2mg/dl) and the urinary calcium: creatinine (Ca: Cr) ratio was 0.88 (normal <0.25).The vitamin D level was 312 ng/ml.Urine microscopy showed 25-30 red blood cells per high power field.Ultrasound scan of the abdomen did not show any nephrocalcinosis.
We initiated rehydration therapy with normal saline (1.5 times maintenance fluid) and intravenous (IV) frusemide in a dose of 4mg/kg/day.However, 5 days after conservative management, the serum calcium level increased to 13.0 mg/dl.A single dose of zoledronic acid injection 5mg/100 ml was administered because of persistent hypercalcaemia.Three days later, the blood urea was 33 mg/dl, the serum creatinine 0.4mg/dl, the serum calcium 8.7mg/dl, the urinary Ca: Cr ratio 0.67 and the vitamin D level had come down to 143 ng/ml._________________________________________ 1  He was treated with IV fluids (rehydration therapy) and frusemide was given at 3mg/kg/day in 3 divided doses.Following treatment repeat investigations showed a blood urea of 37 mg/dl, a serum creatinine of 0.3 mg/dl, a serum calcium of 9.8 mg/dl, a urinary (Ca: Cr) ratio of 0.6 and a vitamin D level of 147 ng/ml.Gradually he started accepting feeds well.Further work up for poor weight gain did not reveal any abnormality.At 2 months follow up he had a weight of 6.5 kg, a serum calcium of 9.8 mg/dl and a vitamin D level of 108 ng/ml.

Discussion
The Indian subcontinent has a prevalence 50-90% of children suffering from Vitamin D deficiency.Dietary deficiency and skin colour are some of the factors which contribute to this deficiency 1 .Recent guidelines have categorized vitamin D levels [25(OH)D] as severe deficiency (<5ng/ml), deficiency (<15ng/ml), sufficiency (>20ng/ml) and risk for toxicity (>50ng/ml) 2 .Hypervitaminosis D (HD) manifests when the levels exceed 150ng/ml [3][4] .There has been a trend to administer over the counter vitamin D to the paediatric population especially to infants and children suffering from bone and joint pain [3][4][5] .Prescription errors are also common.This has contributed to the increasing risk of children being diagnosed to have HD [4][5][6][7] Symptoms of vitamin D intoxication (VDI) arise from the deposition of calcium phosphate crystals within the soft tissues of the body thereby giving rise to poor appetite, nausea, vomiting, constipation, growth retardation, polyuria, dehydration and fever secondary to hypercalcaemia [3][4]7 . Ou patients had vomiting and constipation on admission.Our second case also had failure to gain weight and polyuria which can also happen in prolonged hypercalcaemia 5 .Both our patients had 25(OH)D levels beyond 150ng/ml and hence were diagnosed to have HD.Serum calcium and urine Ca/Cr ratio were also beyond the normal range.
The treatment of VDI focuses on control of hypercalcaemia and immediate removal of the exogenous source.We immediately stopped the oral supplementation of Vitamin D. Rehydration decreases serum calcium level by dilution and corrects prerenal azotaemia.It also increases urine output and thereby calcium excretion.Normal saline, with or without a loop diuretic, is often adequate for treating mild or moderate hypercalcaemia [3][4][5] .Both our patients were given rehydration therapy (1.5 times maintenance fluid) with furosemide.Our second case responded well to fluids and diuretics alone.However, our first case did not show adequate response as her serum calcium went up further.More significant hypercalcaemia requires glucocorticoids, calcitonin and bisphosphonates.Glucocorticoids decrease intestinal absorption of calcium.Usual dosage of prednisone is 1-2 mg/kg/24 hr.Prednisolone for our first patient served as treatment for hypercalcaemia as well as SLE (diagnosed during her hospital stay).Calcitonin also lowers calcium by inhibiting bone resorption.Bisphosphonates inhibit bone resorption through their effects on osteoclasts and have a very rapid response .Zoledronic acid (5mg/100ml) is infused over at least 15 minutes, usually as a single dose.A second dose may be repeated depending on the initial response 6 .A review of literature suggests the role of Pamidronate in treatment of hypercalcemia of adults 5 .Zoledronic acid, although not recommended in children, was given because of unavailability of other bisphosphonates [8][9] .Our first case responded well to a single dose of zoledronic acid.Haemodialysis rapidly lowers serum calcium in patients with refractory severe hypercalcaemia.
Vitamin D should also be eliminated from the diet 2,7 .In both our patients we eliminated vitamin D fortified food (milk, milk products like cheese and egg yolk).Sunscreen lotion was advised to the first child for HD as well as for SLE.All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe HD as we saw in our first patient.Even patients on long term steroids with prophylactic calcium supplements have been documented to have HD 10 . Our second child was receiving vitamin D supplements prophylactically.