How Much Vitamin D is Too Much? A Case Report and Review of the Literature.

BACKGROUND: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, the determination of doses at which vitamin D becomes toxic remains elusive. CASE PRESENTATION: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting, and muscle weakness. The patient had been assuming a very high dose of cholecalciferol for 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-- conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped, and in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. CONCLUSION: This case confirms that vitamin D intoxication is possible, albeit with a high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary for patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

[Two immigrant children with vitamin D poisoning].

The Danish National Board of Health recommends vitamin D supplement for children under two years, regardless of race or nutrition source. Danish studies have found, that 50-80% of children of Palestinian and Pakistani origin of the ages 0-16 years had vitamin D deficiency. This case report of vitamin D poisoning in two immigrant children shows, that there is a group of people, who are not aware of the correct dosage. Doctors as well as healthcare practitioners should be aware of the problem.

[Severe hypercalcemia of unusual cause, looking for the culprit: Case report and review of the literature]. / Hypercalcémie sévère de cause inhabituelle, à la recherche du coupable : cas clinique et revue de la littérature.

INTRODUCTION: Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found. CASE PRESENTATION: A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia. DISCUSSION: Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D. CONCLUSION: We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

Vitamin D Intoxication In 7-Month-Old Infant With Recommended Daily Intake Of Vitamin D.

Over the past decade there is increased use of vitamin D supplementation because of its benefits on bone health. It is a fat-soluble vitamin and cannot be excreted from the body. There is need for monitoring 25-hydroxyvitamin D levels in infants and children who receive long-term vitamin D supplementation at or above the upper level intake that is currently recommended. Vitamin D intoxication can present from mild ignorable to severe life-threatening symptoms. We present a 7- month-old infant with vitamin D intoxication at recommended daily doses of vitamin D.

[Neonatal intoxication to vitamin D in premature babies: A series of 16 cases]. / Intoxication néonatale à la vitamine D chez des anciens prématurés : une série de 16 cas.

INTRODUCTION: Preterm neonates are particularly at risk of vitamin D (25-D) deficiency. To prevent rickets and osteopenia in this population, international guidelines vary between 800 and 1000IU per day of vitamin D in Europe and recommend 400IU per day in the USA. Target levels of circulating 25-D are not well identified, with the lower target level 50-75nmol/L and the upper target level probably 120nmol/L. METHODS: Between 2013 and 2015, 16 premature infants (born<35WG) were referred to pediatric nephrology clinics because of symptoms secondary to 25-D overdose during the neonatal period. Clinical and biological data were retrospectively reviewed to better define this population. The results are presented as the median (range). RESULTS: Gestational age was 27 (24-35)WG with a birth weight of 810 (560-2120)g. Nephrocalcinosis was the initial symptom in 37% of cases, hypercalcemia in 44%, and hypercalciuria in 19%. Daily vitamin D doses were 333 (35-676)IU. Age and body weight at initial symptom were 36.6 (27.6-47.6)WG and 2300 (640-3760)g, respectively. The 25-D level at the time of the first dosage was 210 (119-350)nmol/L and the 1-25 vitamin D level was 370 (245-718)pmol/L (local normal values for age<240). During follow-up, 12 patients displayed nephrocalcinosis, ten hypercalciuria, and three hypercalcemia. The 25-D level normalized in ten patients within 10 (3-32)months after vitamin D withdrawal. Nephrocalcinosis improved in ten of 12 patients, within 12 (3-30)months. Vitamin D could be readministered in ten patients. When searched (n=3), no CYP24A1 mutation was identified in two patients, but was identified in the heterozygous state in one. CONCLUSION: A 25-D overdose should be systematically ruled out in the presence of nephrocalcinosis, hypercalcemia, and/or hypercalciuria during infancy in children born preterm. Studies are required to assess the exact frequency of 25-D deficiency and overdose in this population, as well as to evaluate the potential deleterious effects of this imbalance on bone, kidney, and brain development.

Acute kidney injury due to excessive and prolonged intramuscular injection of veterinary supplements containing vitamins A, D and E: A series of 16 cases / Daño renal agudo debido a inyección intramuscular excesiva y prolongada de suplementos veterinarios con vitaminas A, D y E: serie de 16 casos

Background: Despite well-documented risks, injectable supplements containing high doses of vitamins are commonly used. Objectives: To describe acute kidney injury (AKI) as a complication of vitamin intoxication. Methods: Our series consisted of 16 patients with kidney complications resulting from the use of veterinary intramuscular injection supplements of vitamin A, D and E. The patients were admitted to two referral hospitals in Fortaleza (Brazil) between January 2010 and January 2015. Results: Patients’ mean age was 28.3±8.9 years (19-53 years), and 11 (68.7%) were male. Main signs and symptoms upon admission were nausea (68.7%), vomiting (62.5%), weight loss (43.7%), epigastric pain (31.2%) and headache (31.2%). At hospital admission the mean laboratory values were: hemoglobin 10±2.0g/dL (6.1-14.2), leukocytes 10,542 ± 4871/mm3 (4100-5,100), creatinine 3.9 ± 5.2mg/dL (0.7-22) and urea 91 ± 88mg/dL (22-306), respectively. Serum calcium was 12 ± 2.2 mg/dL (8.8-15.5), 24-h urine calcium was 575 ± 329 mg (10.7-1058), serum PTH was 55 ± 141pg/mL (2-406), and serum vitamin D concentration was 135 ± 75ng/mL (22-265). Using KDIGO criteria, AKI was diagnosed in 13 patients (81.2%), classified as stage 1 (n = 3), stage 2 (n = 3) or stage 3 (n = 7). No deaths occurred in the study period. Conclusions: Excessive use of veterinary vitamin supplements containing high doses of vitamin A, D and E was associated with AKI. Hypercalcaemia, which was a common finding, appears to be a contributing factor to the development of this type of AKI (AU)

Antecedentes: Suplementos inyectables que contienen altas dosis de vitaminas son utilizados con frecuencia, a pesar de los riesgos bien documentados. Objetivo: Describir la ocurrencia de daño renal agudo (IRA) como complicación de intoxicación por suplementos vitamínicos. Métodos: Esta es una serie de 16 pacientes con complicaciones renales resultantes de la utilización de inyección intramuscular de suplementos veterinarios con vitaminas A, D y E. Los pacientes fueron ingresados en 2 hospitales de referencia en Fortaleza (Brasil), entre enero de 2010 y enero de 2015. Resultados: La edad media de los pacientes fue de 28,3 ± 8,9 años (19-53 años) y 11 (68,7%) eran varones. Signos y síntomas principales al ingreso fueron náuseas (68,7%), vómitos (62,5%), pérdida de peso (43,7%), dolor epigástrico (31,2%) y cefalea (31,2%). Al ingreso en el hospital los valores medios de laboratorio fueron: hemoglobina 10 ± 2,0g/dL (6,1+14,2), leucocitos 10.542 ± 4.871/mm3 (4.100-15.100), creatinina 3,9 ± 5,2mg/dL (0,7-22) y urea 91 ± 88mg/dL (22-306), respectivamente. El nivel de calcio sérico fue de 12 ± 2,2 mg/dL (8,8-15,5), el de calcio en orina de 24 h fue de 575 ± 329 mg (10,7-1.058), el de PTH sérico fue de 55 ± 141 pg/mL (2-406) y el nivel de vitamina D sérica fue de 135 ± 75 ng/mL (22-265). Utilizando criterios KDIGO, se diagnosticó IRA en 13 pacientes (81,2%); fueron clasificadas como clase 1 (n = 3), clase 2 (n = 3) y clase 3 (n = 7). No hubo muertes en el período de estudio. Conclusiones: El uso excesivo de suplementos vitamínicos veterinarios que contienen altas dosis de vitamina A, D y E se asoció con IRA. La hipercalcemia, un hallazgo común, parece ser un factor que contribuye al desarrollo de este tipo de IRA (AU)

High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with Type 1 and Type 2 diabetes.

AIM: To investigate the possible association between vitamin D deficiency and cardiovascular autonomic neuropathy in people with diabetes. METHODS: A total of 113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes duration 22.0 (12-31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic neuropathy using three cardiovascular reflex tests [heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre] and assessment of 5-min resting heart rate and heart rate variability indices. RESULTS: We found an inverse U-shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05). Vitamin D level was non-linearly associated with cardiovascular autonomic neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression models showed that an increase in vitamin D level from 25 to 50 nmol/l was associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95% CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in vitamin D level was associated with a decrease of 2.6% (95% CI -5.8;0.1) and 4.1% (95% CI -5.8;-0.5) in the respective outcome measures. CONCLUSIONS: High and low vitamin D levels were associated with cardiovascular autonomic neuropathy in people with diabetes. Future studies should explore this association and the efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic neuropathy.

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 other side of vitamin D therapy: a case series of acute kidney injury due to malpractice-related vitamin D intoxication
.

BACKGROUND: Vitamin D deficiency is highly prevalent in Indian Kashmir. Many people get injectable vitamin D (600,000 IU/injection). At times, the dose prescribed is far above the permissible limit. We report 62 patients with malpractice-related vitamin D intoxication, presenting with hypercalcemia and acute kidney injury (AKI). METHODS: The diagnosis was made on basis of (1) history of multiple intramuscular vitamin D injections (2) toxic serum levels of 25-OH vitamin D and (3) exclusion of common causes of hypercalcemia (malignancy and hyperparathyroidism). Their presentation was either de novo AKI in 51 (group 1) or acute on top of chronic kidney disease in 11 (group 2). RESULTS: The mean age was 60 ± 14 vs. 62 ± 13 years, approximate number of vitamin D injections received ranged from 4 to 28 (2.4 - 16.8 million units) vs. 3 to 24 (1.8 - 14.4 million units), mean creatinine at presentation was 3.2 ± 0.9 vs. 4.5 ± 1.1 mg/dL, which decreased to 1.2 ± 0.2 vs. 3.3 ± 1.0 mg/dL, mean serum calcium on admission was 13.7 ± 1.4 vs. 13.6 ± 2.0 mg/dL which decreased to 10.7 ± 1.2 vs. 11.0 ± 1.0 mg/dL on follow-up of 7.2 ± 0.6 months, mean vitamin D level was 313.3 ± 54.8 (range 235 - 375) vs. 303.7 ± 48.4 (range 210 - 375) nmol/L and mean PTH was 18.1 ± 9.6 (range 6.2 - 32) vs. 52.3 ± 12.6 (range 28 - 88) pg/mL in group 1 vs. group 2, respectively. The clinical presentation was weakness, constipation, abdominal pain, nausea, vomiting, anorexia, altered sensorium, and oliguria. The treatment received was intravenous fluids (normal saline) in all in group 1 and in 8/11 in group 2, short course of steroids (prednisolone) in 44, and bisphosphonate in 6. CONCLUSION: This is the largest case series of AKI secondary to vitamin D toxicity ever reported.
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Efficacy and safety of pamidronate in children with vitamin D intoxication.

BACKGROUND: Bisphosphonates are used in the treatment of vitamin D intoxication (VDI) after failure of conventional therapy including prednisolone. Safety concerns restrict the use of bisphosphonates from being used as first-line therapy for VDI in children. The aim of this study was to evaluate the efficacy and safety of pamidronate in comparison with prednisolone in children with VDI. METHODS: We reviewed the hospital records of children consecutively diagnosed with VDI at two medical centers in a 15 year period. RESULTS: The subjects consisted of 21 children (age, 0.3-4.2 years) who were treated with prednisolone and/or bisphosphonates. Pamidronate (n = 18) or alendronate (n = 3) was used in six patients after unsuccessful prednisolone treatment, and in 15 patients from baseline. Initial serum calcium and 25-hydroxyvitamin D were 16.1 ± 1.9 mg/dL and 493 ± 219 ng/mL, respectively. The median time to reach normocalcemia in the pamidronate, alendronate and prednisolone groups was 3 days (range, 2-12 days), 4 days (range, 3-6 days) and 17 days (range, 12-26 days), respectively (P = 0.013). The pamidronate group had a fivefold shorter hospital stay than the prednisolone group. Three patients initially treated with prednisolone developed nephrocalcinosis but this did not occur in any patient treated with bisphosphonates from baseline. Apart from transient fever and moderate hypophosphatemia, no side-effect of bisphosphonate treatment was observed. CONCLUSIONS: Pamidronate is efficient and safe for the treatment of VDI in children. Pamidronate use significantly shortens the duration of treatment, and thereby may prevent the development of nephrocalcinosis. Instead of prednisolone, pamidronate should be used together with hydration and furosemide as the first-line therapy for VDI.

[Yellow oat grass intoxication in horses: Pitfalls by producing hay from extensive landscapes? A case report]. / Goldhafer-Intoxikation bei Pferden: Wie sicher ist die Heuqualität von extensiven Standorten? Ein Fallbericht.

Vitamin-D intoxication by yellow oat grass is often reported under the syndrome of enzootic calcinosis in ruminants in the upper regions of the Alps. The intake of Trisetum flavescens in ruminants and horses induces calcification of soft tissue, including vessels, tendons and ligaments, lung, heart and kidneys. Clinical symptoms, including a reluctance to move, inappetence, body-weight loss and impaired organ function, are frequently observed. To date, there are only a very few case reports about yellow-oat-grass intoxication in horses. The present case report describes Vitamin-D intoxication by yellow oat grass in a riding stable in Thuringia, Germany. The horses, which were fed hay with a 50% contamination of Trisetum flavescens, displayed symptoms, including inappetence, body-weight loss, colic, polydipsia and polyuria. The hay, contaminated with Trisetum flavescens, was harvested from an extensively cultivated landscape according to the European Fauna-Flora-Habitat (FFH)-directive. The present case report demonstrates the pitfalls in producing hay from extensively used landscapes and indicates some peculiarities of Vitamin-D metabolism in horses.

Approach to the Child with Hypercalcaemia.

Hypercalcaemia is rare in children. In adulthood, the causes are most frequently malignancy and primary hyperparathyroidism. In children, however, the aetiologies are diverse and age specific, and many have an underlying genetic basis. Hypercalcaemia is a serious condition that frequently leads to end-organ damage. In order to provide the most appropriate treatment, a key part of the management pathway is to establish the correct diagnosis promptly. When considering a practical approach to hypercalcaemia in children, it is helpful to consider the causes of hypercalcaemia according to the accompanying levels of parathyroid hormone (PTH), indicating whether the causes are PTH dependent or PTH independent. This chapter reviews the recent advances in this area and presents a practical approach to the investigation and subsequent management of this condition.

[Vitamin D intoxication caused by drugs bought online. Sky high daily dosage for six months resulted in severe hypercalcemia]. / D-vitamin-förgiftning av preparat köpt på nätet - Skyhög daglig dos under ett halvår gav svår hyperkalcemi.

Intoxication with vitamin D may lead to severe hypercalcemia, renal failure and occasionally to death. An increasing amount of vitamin D supplement is sold over-the-counter (OTC) or over the internet. Here we present a case were a person obtained vitamin D over the internet and administered 50 000 IE daily to his father for a period of six months, in the pursuit to stop or reverse the progression of a vascular dementia. The treatment resulted in a severe hypercalcemia and recurrent hospitalizations. In cases with an unexplained hypercalcemia, being associated with high levels of 25(OH)-vitamin D3 the possibility of intake of D-vitamin sold without a doctor's prescription should be investigated.

[Hypercalcemia and acute renal failure: a case report of vitamin D intoxication]. / Le cas clinique du mois. Hypercalcémie et insuffisance rénale aiguë: un cas clinique d'intoxication à la vitamine D.

Vitamin D (VTD) deficiency has become a topical issue leading to screening with frequent supplementation. The latter can be dangerous and exceptionally causes overdoses. We report the case of a 20 year old patient with abdominal pain in the setting of hypercalcemia due to intoxication by VTD. This case offers the opportunity to describe the differential diagnosis of hypercalcemia and to brownse through the literature in search of clinical practice recommendations for VTD supplementation.