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Facing the Nuclear Threat: Thyroid Blocking Revisited

Facing the Nuclear Threat: Thyroid Blocking Revisited M. Luster, University Hospital, Marburg, Germany  Chr. Reiners, R. Schneider, H. Hänscheid WHO Radiation Emergency Preparedness Assistance Network, German Collaboration Center, University Hospital, Wuerzburg, Germany .

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Facing the Nuclear Threat: Thyroid Blocking Revisited

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  1. Facing the Nuclear Threat: Thyroid Blocking Revisited M. Luster, University Hospital, Marburg, Germany  Chr. Reiners, R. Schneider, H. Hänscheid WHO Radiation Emergency Preparedness Assistance Network, German Collaboration Center, University Hospital, Wuerzburg, Germany 

  2. Daily Release of I-131, Te-132 and Cs-137 During 10 Days after theChernobylReactorAccident Graphite-Fire I-131: T1/2 8,1d Te-132: T1/2 2,8m Cs-137: T1/2 30a

  3. Distribution of Radioactivity Europe April/May 1986

  4. 25 Years After Chernobyl: ThyroidDoses in Infants 2011

  5. Thyroid Cancer in Young Girls and Females from Belarus after the Chernobyl Accident 2011

  6. 'Funny' Japanese Nuclear Boy Explains Disaster

  7. Dose Limits REAC/TS 2005

  8. Penetrating irradiation Cerebro- vascular 30 Gy Gastrointestinal 10 Gy Mucocutaneous 5 Gy Hematological 1 Gy Subclinical External Exposition

  9. How to react?

  10. Intake of iodine tablets as protective measure in the event of a severe accident in a nuclear power plant – information leaflet

  11. Age dependent Dosage

  12. Suggestions for Intake

  13. Other Options? Bavarian Diet Japanese Diet

  14. Akashi M 2011

  15. Iodine Kinetics of the Thyroid Follicular Epithelium Iodine Blocking

  16. The Sodium(Natrium)-Iodide-Symporter (NIS) I

  17. Radioiodine Uptake I I I

  18. Potassium-Iodide(KI)-Blockade (appr. 100 mg) KI KI I KI I KI KI I KI KI KI

  19. Effectivity of KI-Blockade and Time of Exposure Ilyin 1974, modified by Verger Thyroid 2001

  20. Effectivity of Iodine Blockade and Use of Powdered Milk in Poland after Chernobyl 1986 Naumann und Wolff Am J Med 1993

  21. 1. Do we Have to Consider a Substantial Thyroid Cancer Risk in Adults after Exposure to Radioiodine? • Answers may be derived from: • Modelling of age dependent thyroid doses • Observed thyroid cancer cases after Hiroshima and Nagasaki • Age dependent thyroid cancer risk in Russia after Chernobyl

  22. Modelling: Age and Thyroid Doses after Inhalation or Ingestion Zanzonico PB Health Phys. 2000

  23. Age and Dose Related Risk-Coefficients for Thyroid Cancer Thompson et al. Rad Res 1994

  24. Thyroid Doses (Gy) and Relative Cancer Risk (RR) in Children from Russia after Chernobyl Excess Relative Risk per Gy Girls 0 - 17 years 6.54 P < 0.001 Boys 0 - 17 years 2.24 P < 0.001 Adults > 18 years -1.47 n.s. Ivanov et al. Rad Prot Dosimetry 2012

  25. 2. Does alimentary Iodine Supply influence Blockade with KI? • Answers may be derived from: • Modelling of KI-blockade in relation to iodine supply • Experiences with iodine goiter prophylaxis in Poland • Experiments with KI-blockade in iodine-rich areas

  26. Decrease of I-131 Uptake after Introduction of Goiter Prophylaxis with Iodized Salt in Poland • 24h thyroid I-131 uptake • No Goiter Prophylaxis 45,7 + 6,6% • With KI 30 mg/kg Salt 27,3 + 10,4% Huszno et al. J Endocrinol Invest 2003

  27. Modelling Thyroid Uptake (%), Iodine Supply (250 vs. 50 ug/d) and Protective Effect of KI-Blockade with 100mg Protective Effect 40% Protective Effect 17% Zanzonico & Becker Health Physics 2000

  28. Protective Effect of 38 vs. 76 mg of KI in 8 Patients withGraves´Disease in Japan Protective Effect 79.5% Protective Effect 73.3% Takamura et al. J Radiat Res 2004

  29. 3. Are There Drugs Interacting with KI-Blockade? • Enhancing KI-Blockade: • Other IodineContaing Drugs, eg: • Amiodarone • X-Ray Contrast Media • Antithyroid Drugs: • Carbimazole, Methimazole • Propyl-/Methyl-Thiouracil • Perchlorate • Thyroid Hormones • Tyrosine-Kinase Inhibitors Leung et al. Curr.Opin.Endocrinol.2012 McCruden et al. Acta Endocrol.1985 Reiners et al. Nuklearmedizn 1985 Manavola et al. JCEM 2007

  30. 3. Are There Drugs Interacting with KI-Blockade? • Disturbing KI-Blockade: • IodineContaing Drugs: • ifadministeredtolate(> 24h) • Lithium • Enhancing KI-Blockade: • Other IodineContaing Drugs, eg: • Amiodarone • X-Ray Contrast Media • Antithyroid Drugs: • Carbimazole, Methimazole • Propyl-/Methyl-Thiouracil • Perchlorate • Thyroid Hormones • Tyrosine-Kinase Inhibitors Leung et al. Curr.Opin.Endocrinol.2012 McCruden et al. Acta Endocrol.1985 Reiners et al. Nuklearmedizn 1985 Manavola et al. JCEM 2007 Dietlein et al Nuklearmedizin 2007 Bogazzi et al. JCEM 1999

  31. Effectivity of KI-Blockade and Time of Exposure If KI is administered more than 48h after incorporation of radioiodine, the dose to the thyroid is Increased by appr. 50% Dietlein et al. Nuklearmedizin 2007

  32. 4. How to Proceed in Emergencies with Repeated Releases of Radioiodine? • WHO KI-Guideline (update 1999)

  33. 4. How to Proceed in Emergencies with Repeated Releases of Radioiodine? • Answers may be derived from: • Experimental data by the Wuerzburg group 2011 • Experimental Data of LA Ilyin et al. 1974

  34. 4. How to Proceed in Emergencies with Repeated Releases of Radioiodine? Disappearance of the Protective Effect of a Single Dose of KI > 40 years (n = 15) < 25 years (n = 20) Haenscheid et al. JCEM 2011

  35. 4. How to Proceed in Emergencies with Repeated Releases of Radioiodine? Different daily doses of KI and protective effect Ilyin et al. Atomizdat Moscow 1972

  36. 4. How to Proceed in Emergencies with Repeated Releases of Radioiodine? • Strictly follow general recommendations: • > sheltering, evacuation, ban of contaminated • milk or food • If recommended by the authorities, repeat taking KI-tablets • Strictly follow recommendations for specific check-ups later on: • > especially in newborns, young children and in case of complaints

  37. 5. Which Side Effects of KI-Blocking have to be Taken into Consideration? • Answers may be derived from: • General experiences with iodine containing drugs • Experiences with KI-Blockade after Chernobyl in Poland • Recent literature review by L.Spallek • Animal experiments in chimpanzees

  38. 5. Which Side Effects of KI-Blocking have to be Taken into Consideration? • Systematic Review by Spallek et al. 2011: • 14 articles relevant to the topic (mostly surveys, ecological and intervention studies) • Only one study from Poland about KI-Blockade after Chernobyl directly addressing this question (Nauman & Wolff 1993) • Overall : • No severe adverse reactions to KI in the general public • Evidence however is weak

  39. Possible Side Effects of Potassium Iodide (KI) Iodine Hypersensitivity • True allergy against iodide: exanthema, edema, • sore throat, snuff, swelling of salivary glands, fever • Dermatitis herpetiformis Duhring • Iododerma tuberosum • Hypokomplementemic vasculitis • Myotonia congenita very rare

  40. Possible Side Effects of Potassium Iodide (KI) Iodine Hypersensitivity • True allergy against iodide: exanthema, edema, • sore throat, snuff, swelling of salivary glands, fever • Dermatitis herpetiformisDuhring • Iododermatuberosum • Hypocomplementemicvasculitis • Myotoniacongenita Worsening of Preexisting Thyroid Disease • Elderly: thyrotoxicosis in patients with nodular goiter • Newborns and Infants: hypothyroidism if iodide is administered in large doses very rare relatively frequent Akuelles zur (iod)blockade der Schilddrüse

  41. Detection of Thyroid Nodules 70 Autopsy or ultrasound 60 50 Palpation Prevalence (%) 40 30 20 10 0 age (years) 10 20 30 40 50 60 70 80 90 0 0 Mazzaferri NEJM 1993

  42. Prevalence of Thyroid Nodules in Adults (n = 83.757) 18,8% presence of thyroid enlargement 23,1% presence of thyroid nodlues 10,0% 8,8% Diffuse goiter Nodular goiter Nodules only No pathological findings 14,3% 66,9%

  43. Prevalence of Thyroid Nodules in the Elderly 3,5% 3,5 % 9% Diffuse goiter Nodular goiter Nodules only No pathological findings 39,1 % 57,4 % 48,4% 39,1%

  44. Toxic Nodular Goiter

  45. Thyroidal Side Effects of KI-Blockade in Poland after Chernobyl in Adults ⬆? ⬇ ⬇ ⬇ Naumann and Wolff Am J Med 1993

  46. Thyroidal Side Effects of KI-Blockade in Poland after Chernobyl in Newborns Transient increases of TSH in 0,37% of newborns who received KI on day Naumann and Wolff Am J Med 1993

  47. General Side Effects of Iodine Blockade in Poland after Chernobyl 1986 Naumann and Wolff Am J Med 1993

  48. 5. Which Side Effects of KI-Blocking have to be Taken into Consideration? • Animal experiments in pregnant chimpanzees: • 9 chimpanzees, week 19 – 21 of pregnancy • KI 0.5, 1.95 or 6.5 mg/kg of BW (1.95 equals 130 mg in a pregnant woman) • 1.95 mg/kg daily was effective and without side effects for mother and fetus even if administered up to 10 days Noteboom et al. Rad Res 1997

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