Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels.

OBJECTIVES: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH. METHODS: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data. RESULTS: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups. CONCLUSIONS: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.

Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report.

Nowadays vitamin D (25-OHD) deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL) who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL) associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

Hypercalcemia and renal function impairment associated with vitamin D toxicity: case report / Hipercalcemia e prejuízo de função renal associados à intoxicação por vitamina D: relato de caso

Abstract Nowadays vitamin D (25-OHD) deficiency is supposed to be a global epidemic condition. Expectedly, vitamin D measurement and intake exponentially increased in Brazil in this decade. Although the benefit of vitamin D to general health is still in debate, its indiscriminate use potentially may lead to enhance the incidence of vitamin D intoxication, which is considered a rare disorder. We report a case of a 70 year old diabetic male with chronic renal disease (blood creatinine of 1.6 mg/dL) who progressed suddenly to acute kidney injury (blood creatinine of 5.7 mg/dL) associated with hypercalcemia and high blood levels of vitamin D. Vitamin D and calcitriol were discontinued and hypercalcemia was managed by hydration followed by furosemide. Thereafter, disodium pamidronate was administered and the patient did not undergo on dialysis. It took approximately 14 months to normalize 25-OHD levels and blood creatinine returned to basal levels only after 24 months. The indicated labeling dosage was 2000 IU, but most likely the vitamin D manipulated preparation was higher as the vitamin D blood levels were very high. Although rare, vitamin D intoxication is becoming more frequent as the patients use frequently manipulated preparations that could be subject to errors in the manufacturing and labeling of the tablets or capsules. The present report alerts to the potential increase in the incidence of severe vitamin D intoxication due to the frequent use of this secosteroid as a nutritional supplement. At the same time, it is necessary to improve regulation on the nutrient supplement market.

Resumo Atualmente, muitos brasileiros têm utilizado vitamina D (25-OHD) como suplemento vitamínico para prevenção de diversas doenças crônicas, apesar da falta de dados científicos consistentes sobre o papel deste secosteroide na prevenção de doenças que não as do metabolismo mineral. A intoxicação por vitamina D é rara, mas devido ao seu uso indiscriminado tem ocorrido com maior frequência. Nesse relato, um homem diabético de 70 anos de idade com doença renal crônica (creatinina sérica de 1,6 mg/dL) passou a fazer uso de colecalciferol e calcitriol para recomposição dos níveis de 25-OHD, que eram de 16 ng/mL. O mesmo desenvolveu quadro de lesão renal aguda (creatinina = 5,7 mg/dL), após 45 dias. Este processo emergiu em paralelo ao surgimento de hipercalcemia e níveis circulantes elevados de vitamina D. Foram suspensas a administração de vitamina D e calcitriol, a hipercalcemia foi tratada com hidratação endovenosa, seguida de diurético de alça e posteriormente pamidronato. O paciente, que havia sido encaminhado para diálise, não necessitou desse tratamento. Os níveis de 25-OHD voltaram ao normal 14 meses após a sua suspensão, e os níveis de creatinina voltaram aos patamares anteriores 24 meses após esse evento. A dose prescrita de vitamina D correspondeu a 2000 UI/dia, a qual não é considerada inadequada segundo recomendações atuais. Existe, no entanto, na literatura controvérsia quanto à sensibilidade individual à vitamina D. Não pode ser descartado o uso inapropriado pelo paciente e nem eventual erro de manipulação. Embora raro, o quadro de intoxicação por vitamina D é grave e potencialmente pode levar a complicações clínicas irreversíveis.

The risk of abuse of vitamin supplements.

The article presents the results of studies on potential risks associated with the abuse of vitamin supplements which until recently had been considered not only highly effica- cious, but also completely safe. Particular consideration is given to vitamins A, E, D and C. The necessity to control the intake of vitamin supplements and even to strictly super- vise the supply to high risk patients is highlighted.

Effect of vitamin D supplementation during pregnancy on the Th1/Th2 cell balance of rat offspring.

Vitamin D has important functions in the immune system, and it may suppress the proliferation of T helper (Th) cells and modulate their cytokine production. In this study, we aimed to investigate the effects of maternal supplementation with different doses of vitamin D on the allergy status of the offspring. We gave pregnant female rats a low dose (48000IU/kg, equal to 800IU/d in human) and a high dose (240000IU/kg,equal to 4000IU/d in human) of vitamin D3 intramuscular injection on gestation day (GD)17, and we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of immune responsive cytokines including IL-4, IgE, and interferon gamma (IFN-gamma) in the offspring. On postnatal day (PND) 21, plasma IL-4 levels were elevated by 10.43% (p < 0.01) in the offspring from the high dose vitamin D3 group compared with the control group. And offspring plasma IL-4 levels in the low dose group decreased by 7.27% (p < 0.05) compared with the control dose group. We found that the offspring of mothers given a low dose of vitamin D3 had a 6.17% (p < 0.01) decrease in their plasma IgE levels compared to control animals, but the high dose of vitamin D3 showed no effect. The serum 25(OH)D3 levels were negatively correlated with the IL-4 (r = -0.561, p < 0.01) and IgE (r = -0.421, p < 0.05) levels of the offspring from the low dose group. In the lung tissues of the offspring of the high dose group, we observed thickening of the alveolar septa and more inflammatory cells compared with the control group and low dose group. Thickened alveolar septa were also found in the lung tissues of the offspring from the control group. We conclude that high dose vitamin D3 maternal supplementation during pregnancy induced an imbalance of Th1 and Th2 cells in their offspring resulting allergic and inflammatory response.

Hypervitaminosis-D, an uncommon reality!

Vitamin D deficiency is highly prevalent in India. This has set off a trend among medical practitioners to prescribe vitamin D supplements empirically. Whilst this approach is generally safe, in predisposed individuals it may lead to hypervitaminosis D. Here we present a case where empirical use of high dose vitamin D supplementation had serious consequences highlighting the need to use vitamin D therapy judiciously and to remain vigilant for side-effects in high-risk individuals.

If vitamins could kill: massive hemolysis following naturopathic vitamin infusion.

INTRODUCTION: Hemolysis from naturopathic remedies remains poorly reported in the medical literature, although it is most commonly noted in the patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive intravascular hemolysis following the infusion of a naturopathic preparation that contains vitamins. CASE REPORT: A 47-year-old African-American man presented to the hospital with 3 days of fever, dyspnea, emesis, dark urine, and progressive confusion. His symptoms began 1 day following an infusion of a vitamin complex. His physical examination was significant for lethargy and scleral icterus. Initial laboratory studies were notable for anemia (hemoglobin, 3.3 g/dL and hematocrit, 11%), brisk reticulocytosis (33%), acute renal insufficiency (creatinine, 2.8 mg/dL), and indirect hyperbilirubinemia (total bilirubin, 4.4 mg/dL). His peripheral smear demonstrated "blister cells," erythrocytes that have been left devoid of precipitated hemoglobin by the spleen, which are commonly seen in patients with G6PD deficiency. His physician revealed that the infusion contained vitamins B and D complex, free amino acids, magnesium, and taurine. The patient clinically improved and was discharged to home. G6PD concentration was significantly reduced to 4.7 U/g Hb upon recovery. DISCUSSION: Life-threatening intravascular hemolysis may occur following a naturopathic vitamin infusion and may identify previously unknown G6PD deficiency. Since most properly formulated naturopathic treatments have few toxic ingredients, the possibilities of improper formulation, toxic diluents, or contaminants should be considered. Inadequate regulatory oversight of naturopathic remedies has the potential to allow serious toxicity especially in genetically predisposed individuals.

Hypercalcemia due to hypervitaminosis D: report of seven patients.

We retrospectively studied seven children (six girls, one boy) aged from 7.5 to 25 months who presented to our institution after taking large doses of vitamin D (900 000-4 000 000 U) prescribed by medical practitioners for wrong indications like failure to thrive, etc. The clinical manifestations were constipation, decreased appetite, lethargy, polyuria, dehydration and failure to thrive. All patients had hypercalcemia (serum calcium ranging from 12 to 16.8 mg/dl), high 25[OH]D levels (ranging from 96 to >150 ng/ml), suppressed intact parathyroid hormone (ranging from <3 to 8.1 pg/ml). Hypercalciuria (urinary calcium/creatinine ranging from 1 to 2.45) was found in all patients, while nephrocalcinosis was present in five patients. All were treated with intravenous fluids, oral prednisolone, restriction of calcium in diet, while four patients received pamidronate infusion for reducing hypercalcemia.

Fatal vitamin C-associated acute renal failure.

Although daily ingestion of high-dose vitamin C is generally regarded as largely innocuous, fatal nephrotoxicity can occur in some rare circumstances. We report a case where the patient, who chose to forgo any advanced conventional medical intervention (dialysis and mechanical ventilation), had failed to disclose his use of high-dose vitamin C and subsequently died. Intra-renal oxalate crystal deposition was demonstrated at autopsy. Directed enquiry with the family then revealed his high-dose vitamin C usage. Even though fully-informed discussion was limited by incomplete prospective disclosure, it remains the prerogative of any competent patient to decline any treatment, including those that may be considered life-saving.

[Severe hypercalcemia due to vitamin D intoxication]. / Hypercalcémie majeure secondaire à une intoxication par la vitamine D.

UNLABELLED: We report on a case of severe hypercalcemia due to vitamin D intoxication in a 4-month-old infant, CASE REPORT: A 4-month-old boy was admitted for anorexia, weakness, hypotonia, constipation and lethargy. Initial physical examination evidenced a severe axial hypotonia, signs of moderate intracellular dehydration, polyuria and leucocyturia. Hemodynamic parameters were normal. The infant's origin was Turkish. Basic blood chemistry showed a high serum calcium concentration of 4.28 and 4.55 mmol/l on a second control. The EKG showed a short QTc interval calculated at 0.34 s. Due to worsening neurological condition, the infant was referred to the pediatric intensive care unit. Because of the association of neurological impairment, EKG abnormality and high serum calcium level, haemodialysis was performed. Treatment included hyperhydration, high doses of intravenous of loop diuretics and sodium pamidronate infusion. Hormonal, radiological, abdominal and cardiac investigations combined with a new parental interview led to the diagnosis of vitamin D intoxication due to excessive daily administration. We were unable to determine the exact total amount because of the language barrier. Clinical outcome was marked by nephrocalcinosis without renal function impairment, iliac venous thrombosis secondary to the dialysis catheter and a full neurological recovery without sequelae after 3 months. DISCUSSION: Fear of rickets, especially in Turkish families residing in France, can lead some parents to administer massive daily quantities of vitamin D. This practice is facilitated by the possibility of purchasing high dosage forms of vitamin D via the Internet. When faced with an infant presenting with digestive disorders such as vomiting and constipation, associated with neurological troubles (lethargy, hypotonia) and hypercalcemia, vitamin D intoxication should be considered after tumoral, hormonal or malformative (Williams-Beuren syndrome) causes have been eliminated. Combined with hyperhydration and loop diuretics, biphosphonate infusion often allows to control hypercalcemia. Nephrocalcinosis seems correlated to chronic administration while cardiovascular disorders are more likely associated with massive acute vitamin D administration, severe dysrhythmia being rare in children in this context.

Universal versus selective iron supplementation for infants and the risk of unintentional poisoning in young children: a comparative study of two populations.

BACKGROUND: Iron continues to be a common cause of poisoning in young children, in part due to its widespread use and easy accessibility. OBJECTIVE: To determine differences in the epidemiology and outcome of unintentional iron ingestion by young children in populations practicing selective (eg, US) versus universal (eg, Israel) iron supplementation to infants. METHODS: All cases of unintentional iron ingestion in children younger than 7 years in a one year period were identified through the poison control center databases of 2 sites (Illinois and Israel). Parameters compared include patient sex and age; type, form, and dose of iron preparation; circumstances and clinical manifestations; management; and outcome. RESULTS: A total of 602 children were identified: 459 in Illinois and 143 in Israel. The majority of Illinois children ingested multivitamin preparations (94%), whereas Israeli children ingested single-ingredient iron preparations (78%) (p < 0.001). Iron doses ingested were higher in Israel (median 14.5 vs 6.6 mg/kg; p < 0.001) but remained within the nontoxic range for most children. No deaths or severe poisonings were reported, and 93% of children in both groups were asymptomatic. The majority of ingestions in both locations were due to unintentional self-ingestion. However, parental miscalculation occurred more frequently in Israel (16%) than in Illinois (1%). CONCLUSIONS: Universal iron supplementation to infants was not associated with a negative impact on the outcome of pediatric unintentional ingestions. Low-dose exposures were safely managed by on-site observation.

Delayed poisoning emergencies.

The American Association of Poison Control Centers (PCCs) has a nationwide toll-free number for contacting regional poison centers. To be automatically connected to a local poison center, call 800/222-1222. EMS providers should follow local protocols to determine how to contact PCCs, either directly or through on-line medical control. Most experts agree that PCCs are a reliable and current source of information on the assessment and treatment of poisoning emergencies.

Pediatric iron poisonings in the United States.

BACKGROUND: Iron overdose is considered a leading cause of poisoning-related injury and death in young children. This report analyzes the nature, trend, and hazard patterns of unintentional pediatric iron overdoses in the United States from 1980 to 1996. METHODS: Analyses include multiple regression and correlation analysis of national data on pediatric iron ingestion-related injuries and deaths and review of in-depth investigation case reports. Data sources include files of the US Consumer Product Safety Commission, National Center for Health Statistics, American Association of Poison Control Centers, and US Census Bureau. RESULTS: Pediatric iron-related injuries increased 150% in 1986, from an annual average of 1,200 from 1980 through 1985 to 3,000 from 1986 through 1996. No such annual trend occurred before or after 1986. About one third of the injuries from 1980 through 1996 involved infants under 2 years old, a third involved 2-year-olds, and a third involved children 3 or 4 years old. Pediatric iron-related fatalities increased in 1986, peaked at 10 in 1991, and declined to 2 by 1995. The children often obtained the iron from a child-resistant container opened by themselves or another child or left open or improperly closed by an adult. CONCLUSIONS: Iron overdose remains a significant public health threat to young children. The frequency of pediatric iron overdose injuries increased in 1986 and has not declined. Unit-dose packaging of potent iron supplements is expected to reduce the frequency of severe pediatric iron overdose incidents.

Toxicological problems resulting from exposure to traditional remedies and food supplements.

The National Poisons Unit, London, carried out a pilot survey to investigate the frequency and severity of adverse effects/toxicity from exposure to traditional medicines and food supplements reported to the Unit. Enquiries related to suspected poisoning events were reviewed retrospectively from January 1983 to March 1989, and prospectively in 1991. Further information about cases identified by the prospective review was obtained, when appropriate, by follow-up questionnaire, clinical consultation by a consultant toxicologist, toxicological analyses of samples from patients and from products, and botanical identification of dried plant material. In total, 5536 enquiries were identified. Symptoms were reported in 657 (12%) of these. There was a large number of reports of accidental ingestion of vitamin preparations by children under 5 years. Appropriate assessment was possible in only relatively few cases, due to insufficient documentation, and poor labelling of certain products. A probable link between exposure and adverse effects was identified in 42 cases, and was highly probable in two. Heavy metal poisoning resulting from use of contaminated traditional remedies was confirmed in 5 cases. There was evidence that some patients took excessive doses of food supplements, without realising that this might result in toxic effects. The results of this pilot study suggest that there is a need for further surveillance to provide an appropriate risk assessment of food supplements and herbal remedies, improved quality control and labelling of these products, and increased awareness of their potential hazard.

Hazards of nonprescription medications.

There are hundreds of nonprescription medications available to the consumer. Among these are a number that have potential for toxicity when taken in overdoses or in combination with other medications. This article addresses the pathophysiology, diagnosis, and treatment of selected over-the-counter medication intoxications including antihistamines, dextromethorphan, sympathomimetics, nutritional supplements, and herbal preparations.