Hypercalcemia and vitamin d intoxication slideshare

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short presentation describing the danger of vitamin D in overdose.

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Hypercalcemia and vitamin d intoxication slideshare

  1. 1. 1<br />Vitamin D intoxication in infant:a growing concern in Switzerlandfrom Case Report to Physiology to Prevention<br />Moullet F, Hassib C, Humbert M, Cachat F<br />Department of Pediatrics, PediatricNephrology Unit<br />UniversityHospital, Lausanne, Switzerland<br />4/20/2011<br />
  2. 2. Case presentation<br />1er enfant d’un couple kosovare<br />NNT, RCIU dysharmonieux<br />Multiples signes dysmorphiques<br />Bilan malformatif:<br /> - US abdominal: Rein G ectopique fusionné<br /> - Caryotype: Trisomie partielle du chromosome 2<br />2<br />4/20/2011<br />vitamin D intoxication<br />
  3. 3. Case presentation<br />Follow up 1 année<br /><ul><li>TA:normale
  4. 4. US: rein G ectopique fusionné, rein D normal, pas de dilatation pyélo-calicielle, bonne croissance
  5. 5. CUM: RVU grade 1 ddc
  6. 6. Scintigraphie rénale: bonne fonction</li></ul>3<br />4/20/2011<br />vitamin D intoxication<br />
  7. 7. Case presentation<br />Bilan fonction rénale:<br />Plasma : Na, K, P, Mg, créatinine, urée, urate dans la norme, Ca tot 2.94 mmol/l (N 2.15-2.70), PTH 42 ng/l (N 10-70)<br />Urine: natriurie, phosphaturie, magnésurie dans la norme, pas de protéinurie, rapport Ca/créatinine: 2.23 mol/mol (N 0,07-1.50)<br />4<br />4/20/2011<br />vitamin D intoxication<br />
  8. 8. Que faites-vous (chez un enfant asymptomatique)?<br />5<br />4/20/2011<br />vitamin D intoxication<br />
  9. 9. Case presentation<br />Recontrôle 2 semaines plus tard<br /><ul><li>Persistance de:
  10. 10. hypercalcémie (Ca tot. 2.82 mmol/l)
  11. 11. hypercalciurie (Ca/créatinine 2.65 mol/mol)</li></ul>6<br />4/20/2011<br />vitamin D intoxication<br />
  12. 12. Suite de la prise en charge?<br />7<br />4/20/2011<br />vitamin D intoxication<br />
  13. 13. Case presentation<br />25-OH Vitamine D : 238 µg/l (N 8.4-52.3)<br />1,25 dihydroxy-vit D3 : 90 pmol/l (N 48-160)<br />PTH 42 ng/l (N 10-70) il y a 2 semaines<br />PO4 1.28 mmol/l (N); PAL 130 UI/l (N), Mg 0.76 mmol/l (N)<br />8<br />4/20/2011<br />vitamin D intoxication<br />
  14. 14. Attitude?<br />Arrêt de la supplémentation en Vitamine D<br />9<br />4/20/2011<br />vitamin D intoxication<br />
  15. 15. Case presentation<br />Contrôle 3 semaines après arrêt de la Vitamine D <br />Plasma: Ca tot. 3.28 mmol/l, Ca ionisé 1.68 mmol/l<br />Urine: Ca /créat: 2.66 mol/mol<br />10<br />4/20/2011<br />vitamin D intoxication<br />
  16. 16. Case presentation<br />Hospitalisation pour prise en charge.<br />Bilan:<br /> 25-OH Vitamine D: 179 µg/l ( N 8,4-52.3)<br /> 1,25-Dihydroxy-Vit D3: 31 pmol/l (N 48-160)<br /> PTH: <3 ng/l<br />11<br />4/20/2011<br />vitamin D intoxication<br />
  17. 17. Case presentation<br />Reprise d’anamnèse<br /><ul><li>Maman donne de l’Oleovit : 1 gtte = 400 U Vit D3 (4x plus concentré que le Vide*), entre 4 gttes et une pipette (= env. 25 gttes)/j
  18. 18. Apport de Vit D3 (Cholécalciférol) : entre 1600 U et 10’000 U/j + apports laitiers: Aptamil 3 450 U Vit D/j</li></ul>12<br />4/20/2011<br />vitamin D intoxication<br />
  19. 19. Case presentation<br />hospitalisation du 31.03 au 02.04 puis du 04 au 06.04<br />Hydratation iv<br />Régime sans Ca<br />Pas apport Vit D po <br />Normalisation lente et progressive de la calcémie<br />Enfant cliniquement asymptomatique<br />13<br />
  20. 20. Definition of hypercalcemia<br />Ionized calcium > 1.35 mmol/l(5.4 mg/dl) or <br />total calcium > 2.7 mmol/l(10.8 mg/dl)<br />Repeatedat least twice<br />Rule out extremelyhighalbumin, total protein, paraproteinlevel(pseudo-hypercalcemia) (increasedprotein-bound calcium, normal ionized calcium!)<br />14<br />
  21. 21. Symptoms of hypercalcemia<br />GI: nausea, vomiting, constipation, anorexia, abdominal pain, pancreatitis<br />Neurologic: pseudo-tumorcerebri, depression, confusion, fatigue, coma, hypotonia<br />Cardiovascular: hypertension, bradycardia, cardiacarrest, vascular calcification<br />Renal: polyuria, dehydration, nephrocalcinosis<br />Kidney stones<br />Symptoms related to the severity of hypercalcemia<br />often asymptomatic if total Ca < 3 mmol/l<br />
  22. 22. Whichactors are<br />Important?<br />Physiological<br />controls of calcium<br />and phosphate<br />metabolism<br />From: Plum L. Vitamin D, diseases, and therapeuticopportunities. Nature Rev Drug Discovery2010;9:948-961 <br />
  23. 23. Physiological control of calcium (and phosphorus)<br />Hormone BloodBone Gut Kidney<br />PTHCa, PO4 osteoclast indirect effect Ca excretion<br />resorbtionthrough PO4 excretion<br />calcitriol<br />CalcitriolCa, PO4 no direct Ca and PO4 no direct effect<br />effect absorption<br />CalcitoninCa, PO4 osteoclast no direct Ca excretion<br />resorbtioneffect PO4 excretion<br />From: Carroll M. A practical approach to hypercalcemia. Am Fam Phys 2003;67:1959-1966<br />
  24. 24. Physiopathological mechanisms leading to (sustained) hypercalcemia<br />Initiation of hypercalcemia<br />Maintenance of hypercalcemia<br />4/20/2011<br />18<br />vitamin D intoxication<br />
  25. 25. 1. Initiation of hypercalcemia<br />Vitamin D intoxication<br />Bone metastasis<br />Bone disease<br />Digestive<br />Calcium intoxication<br />Vitamin D intoxication<br />Granulomatousliver<br /> disease<br />Bone<br />Overdose of calcium<br />Overdose of vitamin D<br />19<br />Iatrogenic<br />Genetic<br />Williams syndrome<br />4/20/2011<br />
  26. 26. 2. Maintenance of hypercalcemia<br />Continuous vitamin D<br />Exposure<br />(variable)<br />Slow release of vitamin<br />D from fat tissue<br />(days to weeks)<br />Renal failure <br />chronic acidosis<br />(variable)<br />20<br />
  27. 27. 21<br />4/20/2011<br />
  28. 28. In summary: the questions (youshouldaskyourself) atthis point (from the history point of view):<br />Doesmy patient takevitamin D?<br />Vitamin D intoxication<br />Doesmy patient producevitamin D?<br />Granulomatousdiseases, sarcoidosis<br />Doesmy patient take calcium?<br />Calcium intoxication<br />Doesmy patient release calcium?<br />Bonediseases<br />22<br />
  29. 29. Laboratoryapproach to hypercalcemiawith a good understanding of the physiologycontrolling calcium metabolism<br />23<br />4/20/2011<br />vitamin D intoxication<br />
  30. 30. Hypercalcemia<br />PTH<br />Increased<br />Normal/decreased<br />Loss of functionCaSR<br /> (SevereneonatalhyperPTH, FHH)<br /> 25(OH)D<br />Heterogenous<br /> 25(OH)D<br /> 1,25(OH)D<br />Janssen<br />PTHrP<br />Malignancy<br />Vitamin A intox.<br />Sarcoidosis<br />Granulomatosis<br />Fat necrosis<br />Hypophophatasia<br />Vitamin D<br />intoxication<br />Williams syndrome<br />
  31. 31. In summary: the questions (youshouldaskyourself) atthis point (from the laboratory point of view):<br />Whatis the PTH level of my patient?<br />Whatis the 25(OH)Vitamin D level of my patient?<br />Expectedlow PTH, high 25(OH)D and normal (/high)1,25(OH)D levels in case of hypervitaminosis D<br />25<br />
  32. 32. Vitamin D intoxication:How does that happen?How can we prevent it?<br />26<br />4/20/2011<br />26<br />vitamin D intoxication<br />
  33. 33. Vitamin D intoxication: how common is it?<br />Number of cases reported to the ToxZentrum Zurich <br />withacute or chronicvitamin D3 intoxication<br />Sharp increase of <br />bothacute and <br />chronic VitD3<br />intoxication over<br />the last decade<br />Related to the differentcurrently<br />availableforms of vitamin D?<br />
  34. 34. Vitamin D intoxication: summary of reported cases in the literature<br />Age cummulative dose duration of intoxication calcium level (mmol/l)<br /> IU<br />7 w 6 millions 200’000 IU/d x 30 d 4.05 <br />3 m 1.2 millions 3000’000 IU/d x 4 d 4.6<br />3 m 2.56 millions 302’000 IU/d x 8 days 4.5<br />6 m 3 millions 300’000 IU/d x 10 d 4.2 <br />2 y 2.4 millions 600’000 IU/d x 4 d 3.6<br />11 m 1.34 millions 300’000 IU/m x 3 m 4.5<br /> 400 IU/d x 11 m<br />4 m 600’000 600’000 IU in 3 w 3.7<br />7 y 4.5 millions 300’000 IU x 15 d<br />7 m 1.8 millions 600’000 IU x 3 8.8 <br />4 m 333’240 unclear 4.28<br />From: Chambellan-Tison C. Hypercalcemie majeure secondaire à une intoxication par la vitamine D. Arch Péd 2007;14:1328-1332 <br />
  35. 35. Vitamin D intoxication: beware of the level, beware of the duration!<br />Acute intoxication: <br />Relativelywelldescribed<br />From 40’000 IU per day for 3 to 4 months (= 3.6 millions to 4.8 millions)<br />Most of the time > 1-2 million IU cummulative dose (see French experience) for symptoms to develop<br />Chronic intoxication: <br />Relativelyunclear<br />From 2’000 to 4’000 IU per day for years<br />29<br />29<br />
  36. 36. Vitamin D intoxication: why does that happen?<br />Multitude of vitamin D<br />availablewithdifferent<br />dispensers and concentration<br />30<br />Double cause for<br />medicationerror<br />
  37. 37. How can we prevent it?<br />What has been done?<br />Medical Information (Forum médical suisse Journal) (2010)<br />Pharmacist Information (pharmajournal) (2008 and 2010)<br />Implementation of recommendations difficult<br />Multitude of different concentrations and dispensersavailable<br />CONFUSION!<br />Over the countervitamins<br />CONFUSION!<br />Effective and presumedbeneficialeffects of vitamin D reported in the literature<br />CONFUSION!<br />BUT errorsstilloccurs !<br />31<br />
  38. 38. Real and presumed beneficial effects of vitamin as of 2010<br />
  39. 39. What have we done so far?How can we improve public safety?<br />4/20/2011<br />33<br />vitamin D intoxication<br />
  40. 40. Improvingimplementation / error<br />prevention<br />1. Leaflet for medicaldoctors<br />and nurses and midwifes for <br />the prevention of vitamin D<br />intoxication<br />In close collaboration with the<br />Central Pharmacy of the<br />Hospital<br />2. Ward round togetherwith a<br />pharmacisttwice a week<br />
  41. 41. Thanks to <br />Marie Humbert, PharmD, PHEL, Central Pharmacy Vevey, for carefulliteraturereview and leaflet conception and writing<br />Christian Schaeli, PharmD, PHEL, for providing excellent service with a pharmacist for weeklyward round in the pediatric department<br />All pediatricians for anouncing all cases of hypervitaminosis in their patients<br />4/20/2011<br />35<br />vitamin D intoxication<br />

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