Hypercalcemia and acute renal insufficiency following use of a veterinary supplement Hipercalcemia e insuficiência renal aguda após uso de suplemento veterinário

DOI: 10.5935/0101-2800.20170082 A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise. He reported abuse of different substances, including an injectable veterinary vitamin compound, which contains high doses of vitamin A, D and E, and an oily vehicle that induces local edema and enhances muscle volume. Serum creatinine was 3.1 mg/dL, alanine transaminase 160 mg/dL, aspartate transaminase 11 mg/dL, total testosterone 23 ng/dL, 25-OH-vitamin D >150 ng/ mL (toxicity >100), 1,25-OH-vitamin D 80 pg/mL, vitamin A 0.7 mg/ dL, parathormone <3 pg/mL, total calcium 13.6 mg/dL, 24-hour urinary calcium 635 mg/24h (RV 42-353). A urinary tract ultrasound demonstrated signs of parenchymal nephropathy. The diagnosis was hypercalcemia and acute renal failure secondary to vitamin D intoxication. He was initially treated with intravenous hydration, furosemide and prednisone. On the fifth day of hospitalization a dose of pamidronate disodium was added. The patient evolved with serum calcium and renal function normalization. Thirty days later he presented normal clinical and laboratory tests, except 25-OH-vitamin D that was persistently increased (107 ng/mL), as it may take several months to normalize. This case report is a warning of the risks related to the use of veterinary substances for aesthetics purposes. abstRact

A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise.He reported abuse of different substances, including an injectable veterinary vitamin compound, which contains high doses of vitamin A, D and E, and an oily vehicle that induces local edema and enhances muscle volume.Serum creatinine was 3.1 mg/dL, alanine transaminase 160 mg/dL, aspartate transaminase 11 mg/dL, total testosterone 23 ng/dL, 25-OH-vitamin D >150 ng/ mL (toxicity >100), 1,25-OH-vitamin D 80 pg/mL, vitamin A 0.7 mg/ dL, parathormone <3 pg/mL, total calcium 13.6 mg/dL, 24-hour urinary calcium 635 mg/24h (RV 42-353).A urinary tract ultrasound demonstrated signs of parenchymal nephropathy.The diagnosis was hypercalcemia and acute renal failure secondary to vitamin D intoxication.He was initially treated with intravenous hydration, furosemide and prednisone.On the fifth day of hospitalization a dose of pamidronate disodium was added.The patient evolved with serum calcium and renal function normalization.Thirty days later he presented normal clinical and laboratory tests, except 25-OH-vitamin D that was persistently increased (107 ng/mL), as it may take several months to normalize.This case report is a warning of the risks related to the use of veterinary substances for aesthetics purposes.

intRoduction
The society beauty standards change over time, but one characteristic remains: they are generally unreachable for those who did not win the genetic lottery.The widespread idea that a perfect body will bring acceptance and fulfillment lead some individuals to undergo multiple procedures, sometimes harmful, in pursuit of their aesthetic goal.
The consumption of anabolic steroids, supplements and similar products by bodybuilders and athletes grows larger every day.2][3][4][5] Here we report the case of a young man who presented with hypercalcemia and acute kidney injury following ADE injection.

case pResentation
A previously healthy 24-year-old male was admitted with a two-month history of progressively worsening epigastric pain, nausea, vomiting, fatigue and malaise.He denied having taken continuous medication, but he reported abuse of different substances aiming muscle mass increase, among these: growth hormone, nandrolone and other testosterone derivatives.
He also reported parenteral application of 150 mL of a veterinary vitamin formulation (ADE) in the previous four months, containing 20,000,000 IU of vitamin A, 5,000,000 IU of vitamin D3 and 6,800 IU of vitamin E per 100 mL vial.During the investigation, he had no abnormal findings on physical examination and his body mass index was 25.1 kg/m².
The diagnosis was hypercalcemia and acute renal failure secondary to vitamin D (and possibly vitamin A) intoxication.He was treated with vigorous intravenous hydration associated with diuretic (furosemide 80 mg per day) and corticosteroids (prednisone 40 mg per day).On the fifth day of hospitalization a single dose of the osteoclast inhibitor pamidronate disodium 90 mg was added.The patient evolved with serum calcium and renal function normalization, and he was discharged on the 14 th day.Thirty days later he was examined at the outpatient clinic, presenting normal clinical and laboratory tests, except 25-OHvitamin D that was persistently increased (107 ng/ mL).Since vitamin D is stored in fat, it may take several months to normalize.

discussion
Although the vitamin compound ADE is manufactured for strictly veterinary use, it is one of the most commonly used injectable oils by Brazilian bodybuilders, because of its low cost and easy access. 6,7his practice is essentially aesthetic and is not considered anabolic because there is no growth of muscle tissue, but muscle swelling. 1he recommended dietary allowance for vitamin D in healthy adults is 600 IU, 8 and a much higher intake is required for toxicity.According to most reports, the toxicity threshold is around 10,000 to 40,000 UI a day. 9This patient has used about 1,875,000 IU/ month (62,500 IU/day).
Laboratory tests carried out on admission indicated hypervitaminosis D, which leads to hypercalcemia and related complications, such as secondary hypoparathyroidism and acute kidney injury.High levels of vitamin D result in excessive intestinal calcium absorption, causing acute hypercalcemia, which may impair kidney function by direct vasoconstrictive effects on arteriolar smooth muscle.Furthermore, gastrointestinal side effects of hypercalcemia and polyuria due to nephrogenic diabetes insipidus may result in prerenal involvement. 10lthough clearly abnormal, the magnitude of the initial 25-OH-vitamin D elevation could not be precisely determined, as the concentration exceeded the upper limit of detection of the assay.Hypercalcemia has also been described as a complication of vitamin A use; therefore it is possible that hypervitaminosis A have contributed to this clinical scenario.The exact mechanism is not completely understood, but some findings suggest a direct effect of vitamin A on bone. 11he tolerable upper intake levels for preformed vitamin A in adults is 10,000 UI. 12 Despite presenting a serum retinol level in the upper limit of the reference range, most vitamin A is stored in the liver and the patient had ingested about 7,500,000UI per month (250,000 UI per day), with a high probability of causing toxicity. 1he use of anabolic steroids has also been associated with nephrotoxicity, although with a different clinical presentation.Focal segmental glomerulosclerosis with marked proteinuria was reported after a bodybuilding regimen consisting of dietary supplements, testosterone and growth hormone. 13Despite the absence of specific findings, we cannot rule out the use of these substances as a contributing factor to kidney damage.
Additional alterations observed in laboratory tests were high levels of alanine transaminase and low levels of total testosterone.Liver injury has been consistently reported due to anabolic steroids abuse, and may include hepatotoxicity, non-alcoholic fatty liver disease and liver neoplasm. 14Hypervitaminosis A can also produce liver damage, presenting as alterations in liver profile, cholestasis, non-cirrhotic portal hypertension, chronic hepatitis and cirrhosis.Toxicity of vitamin A is apparently a dose-dependent effect of retinoids on hepatic stellate cells. 14egarding testosterone, hypogonadism is a common side effect of anabolic-androgenic steroids, as a result of feedback suppression of the hypothalamicpituitary-gonadal axis.The duration of suppression and the resultant low testosterone levels are highly variable and depend on multiple factors, including type of drug, dose and length of exposure. 15ortunately, the patient had reversal of the situation without serious sequelae.The main objective of this report is to warn the medical community and overall population of the risks related to the use of veterinary substances for aesthetics purposes.2][3][4][5] Reports regarding this practice are scarce on scientific literature, although extensively covered in the lay press and bodybuilding websites.