Lithium用於甲状腺肿课件

Lithium用於GravesDisease主講人:郭人瑚指導藥師：張美琪99/7/29Lithium用於GravesDisease主講人:郭人瑚1QuestionQuestion2PatientHistoryObjectiveFamilyhistoryofthyroiddiseaseThyroidGr1-2diffusefirmgoiter,combineGravesdiseasePalpitation,proximalmuscleweakness,menstralcycle:irregular,stoolpassageincreased,softloosestoolPatientHistoryObjective3Drugprofile980728980803980810980817980914981012981109981109981223990208990406990505peptidine

1＃TIDpropanolol1＃TIDbisoprolol0.5＃QD0.5＃BID1#BIDmethimazole2#TID2#TID3#TIDcetirizine1#HS1#HSPTU2#BID2#TID3#QIDalprazolamXR1#HSdiphenidol1#QIDlithium1#QD使用Propanolol耐受性不佳→Bisprolol使用Methimazole會癢→PTUHR一直很快Drugprofile9807289808039808104Lab

DataThyroglbulin:519.2ng/ml[<50ng/ml]TRab:(+)61.79%[(-)<15%]Free-T4正常值0.73-2.01ug/dLTSH正常值0.35-4.94ulU/ml檢驗值LabDataThyroglbulin:519.2ng/5Outline何謂GravesDisease

臨床表徵及診斷治療Outline何謂GravesDisease6WhatisGraves’Disease?Diseaseinwhichtheimmunesystem

attacks

thethyroidgland,causingthethyroidglandtoreactbymakingtoomuchthyroidhormone.

Theover-activityofathyroidglandisreferredtoashyperthyroidism.WhatisGraves’Disease?Diseas7GravesDiseaseGravesDisease8CausesofGraves’Disease GenetictendenciesoftheimmunesystemtoattackitselfStress

CausesofGraves’Disease Gene9SymptomsSymptoms10

Diagnosed

DiagnoseTSH↓＆FT4↑＆RAIU瀰慢性TRAb(+)DiagnosedDiagnoseTSH↓＆FT4↑11TreatmentAnti-thyroiddrugs

Makeitharderforthethyroidglandtocreatehormonesbydecreasingthethyroidgland’sabilitytouseiodineRadioactiveiodine:iodine131

Impairsthyroidcells,therebyreducingtheamountofthyroidhormoneproducedSurgery

RemovalofthemajorityofthethyroidglandTreatmentAnti-thyroiddrugs12Treatment主要藥物治療AntithyroiddrugsmethimazolepropylthiouracilTreatment主要藥物治療13Treatment輔助治療-β-blockerLithiumGlucocorticoidsinhibitperipheralT4toT3conversionand,reducethyroidsecretion.Theyhavebeenusedinpatientswithseverehyperthyroidismandthyroidstorm,althoughtheirefficacyisnotwelldemonstratedTreatment輔助治療-14Lithium用於GravesDisease的治療機轉:作用機轉相似於碘LithiumactsbyinhibitingT4andT3releasefromthethyroidandpossiblyalsobyinhibitingtheirsynthesis.優點不影響甲狀腺碘的攝取停藥後不會加重甲狀腺機能亢進放射碘治療或手術前後的準備和輔助治療。Lithium用於GravesDisease的治療機轉:優15EvidenceMicromedexFDAApproval:Adult,no;Pediatric,noEfficacy:Adult,EvidenceisinconclusiveRecommendation:Adult,ClassIIIStrengthofEvidence:Adult,CategoryBEvidenceMicromedex16ImpactoflithiumonefficacyofradioactiveiodinetherapyforGraves'disease:acohortstudyoncurerate,timetocure,andfrequencyofincreasedserumthyroxineafterantithyroiddrugwithdrawal.Patients:651patientswithnewlydiagnosedGraves'diseaseIntervention:298patientsRAIpluslithium(900mg/dayfor12day)353patientsRAIaloneResults:(1)curerate:RAIpluslithium(91.0%)vsRAIalone85.0%(P=0.030)(2)RAIpluslithiumwerecuredmorerapidly(median60day)thanthosetreatedwithRAIalone(median90day,P=0.000).(3)TreatmentwithlithiumpreventedtheserumfreeT(4)increaseaftermethimazolewithdrawalandRAItherapy.

JClinEndocrinolMetab.2010Jan;95(1):201-8.Impactoflithiumonefficacy17UseoflithiuminthetreatmentofthyrotoxicosisPatients:13名等候以放射性碘或施手術的病人(對Antithyroiddrugs治療有不良反應或對此藥療效不佳)Dosage:500-1500mg/day血清中濃度0.63mmol/LResults:有八名病患對lithium治療反應滿意,且均在1-2星期內FT4減少了40%或以上。4名在治療3-5星期內獲得效果,一名對lithium治療反應緩慢Conclusions:如果病人不能接受thionamides類的治療或對thionamides類的治療沒有療效反應,低劑量的鋰治療是控制甲狀腺機能亢進的另一個安全有效的治療方式

HongKongMedJ2006;12:254-9Useoflithiuminthetreatmen18ComparisonofRadioiodinewithRadioiodineplus

LithiumintheTreatmentofGraves’Hyperthyroidism*Patients:110patientswithnewlydiagnosed,untreatedGraves’disease,agemorethan20yr,recentonsetofhyperthyroidism(≦6months),andnonsevereorabsentGraves’ophthalmopathyDosage:900mg/dayfor6daysstartingonthedayofradioiodineadministrationResults:Goitersshrankinbothgroups(P<0.0001),moreeffectivelyandpromptly(P<0.0005)intheradioiodine-plus-lithiumgroup.JournalofClinicalEndocrinologyandMetabolismJCE&M²1999Vol.84,No.2ComparisonofRadioiodinewith19Successfuloutcomewithmethimazoleandlithiumcombinationtherapyforpropylthiouracil-inducedhepatotoxicity.

49-year-oldmanwithseverethyrotoxicosisand

propylthiouracil-inducedhepatotoxicity,indicesofliverfunctioncontinuedtoincreasedespitediscontinuationofpropylthiouraciltreatment.

Adjunctivetherapywithmethimazoleandlithium

Conclusion：Adjunctivetherapywithmethimazoleandlithiumissynergisticinpromptlyachievingaeuthyroidstate.

EndocrPract.1998Jul-Aug;4(4):197-200.

Successfuloutcomewithmethim20TheUseofLithiumCarbonateinthePreoparationforDefinitiveTherapyinHyperthyroidPatientsPatients:6patientsMethods:

in5patientswithGraves’diseaseandin1patientwithtoxicmultinodulargoiterbecauseofsideeffectsofthionamidein5patientsandineffectivenessofantithyroidmedicationintheremainingpatient.Results:All6patientshadabenigncoursefollowingtreatmentwithoutthyroidstorm.Noadverseeffectsorcomplicationsoflithiumcarbonatewereobserved.Conclusions:Thisreportshowsthatlithiumcarbonatecanbesafelyusedpreoperativelyorpriortoradioiodidetherapyincircumstanceswhereantithyroidmedicationsarecontraindicatedandareineffectiveinobtaininganeuthyroidstatus.MedPrincPract2008;17:167-170

TheUseofLithiumCarbonatei21注意事項Lithium血中濃度Trough:服用藥物8-12小時後,早上給藥前治療範圍：0.60~1.20meq/L警示範圍：1.20-1.50meq/LToxic：Over1.50meq/L血清濃度超過1.5meq/L—產生運動失調、震顫、下瀉、衰弱、鎮定、嘔吐超過2.5meq/L—舞蹈狀、迷惑、痙攣、意識下降、增加肌腱反射、嗜睡、肌肉高張液體、不醒人事，腎臟毒性超過2.5meq/L—昏迷，也有可死亡。注意事項Lithium血中濃度22注意事項其它影響甲狀腺功能Amiodarone-duetoamiodarone’shighiodinecontent注意事項其它影響甲狀腺功能23ConclusionInpatientswhodevelopseriousside-effectsduetothionamidesorwhodonotrespondtothesedrugs,lithiumtherapycanbeusedasaneffectiveinterimmeasurebeforeundertakingdefinitivetherapy.

HongKongMedJ2006;12:254-9ConclusionInpatientswhodeve24ReferenceEndocrinolMetabClinNorthAm-01-JUN-2009;38(2):355-71JClinEndocrinolMetab.2010Jan;95(1):201-8.Micromedex,UptoDate,MDconsult,CMAJHongKongMedJ2006;12:254-9AdaptedfromWeetmanAP:Gravesdisease.NEnglJMed2000;343:1236–1248.AACEThyroidGuidelines,EndocrPract.2002;8(No.6)461EndocrPract.1998Jul-Aug;4(4):197-200.

ReferenceEndocrinolMetabCli25ThankyouforyourattentionThankyouforyourattentio26Propranolol(1)10mg/tab,

(2)40mg/tab,

Bisoprolol25mg/tab非心臟選擇性(β1+β2-Receptor)具心臟選擇性(β1Receptor)短效型20-80mgPOtid;1-2mgIVq4-8h長效型2.5-20mgqd;max:40mg/dayCardiovascular:Bradyarrhythmia,HypotensionDermatologic:Dermatitis,Pruritus,UrticariaGastrointestinal:Nausea,VomitingNeurologic:Fatigue,Insomnia,ParesthesiaPsychiatric:Depression,PsychoticdisorderRespiratory:DyspneaCardiovascular:Bradyarrhythmia(9%),Coldextremities,HypotensionGastrointestinal:Diarrhea(4%),Indigestion,Nausea(2%),Vomiting(2%)Musculoskeletal:Arthralgia(3%)Neurologic:Dizziness(10%),Headache(11%)Psychiatric:Dyssomnia(8%-10%)Respiratory:Cough(3%),Dyspnea(2%),Pharyngitis(2%),Rhinitis(4%),Sinusitis(2%),Upperrespiratoryinfection(5%)Other:Fatigue(8%)

Propranolol(1)10mg/tab,

(2)427Propylthiouracil(PTU)MethimazoleProteinBinding75~80%0T1/2(h)1~26~13InitialDose300~400mg/day,分3~4次服用15mg(mild);30to40mg(moderatelysevere);60mg(severe)ORALLYperdayMaintenanceDose100~150mg/day5~15mg/dayNeonates5~10mg/kg/day0.5~1mg/kg/dayTransplacentalpassageLowHigherLevelsinbreastmilkLowHigherPropylthiouracil(PTU)Methimaz28Lithium用於甲状腺肿课件29Lithium用於甲状腺肿课件30Lithium用於GravesDisease主講人:郭人瑚指導藥師：張美琪99/7/29Lithium用於GravesDisease主講人:郭人瑚31QuestionQuestion32PatientHistoryObjectiveFamilyhistoryofthyroiddiseaseThyroidGr1-2diffusefirmgoiter,combineGravesdiseasePalpitation,proximalmuscleweakness,menstralcycle:irregular,stoolpassageincreased,softloosestoolPatientHistoryObjective33Drugprofile980728980803980810980817980914981012981109981109981223990208990406990505peptidine

1＃TIDpropanolol1＃TIDbisoprolol0.5＃QD0.5＃BID1#BIDmethimazole2#TID2#TID3#TIDcetirizine1#HS1#HSPTU2#BID2#TID3#QIDalprazolamXR1#HSdiphenidol1#QIDlithium1#QD使用Propanolol耐受性不佳→Bisprolol使用Methimazole會癢→PTUHR一直很快Drugprofile98072898080398081034Lab

DataThyroglbulin:519.2ng/ml[<50ng/ml]TRab:(+)61.79%[(-)<15%]Free-T4正常值0.73-2.01ug/dLTSH正常值0.35-4.94ulU/ml檢驗值LabDataThyroglbulin:519.2ng/35Outline何謂GravesDisease

臨床表徵及診斷治療Outline何謂GravesDisease36WhatisGraves’Disease?Diseaseinwhichtheimmunesystem

attacks

thethyroidgland,causingthethyroidglandtoreactbymakingtoomuchthyroidhormone.

Theover-activityofathyroidglandisreferredtoashyperthyroidism.WhatisGraves’Disease?Diseas37GravesDiseaseGravesDisease38CausesofGraves’Disease GenetictendenciesoftheimmunesystemtoattackitselfStress

CausesofGraves’Disease Gene39SymptomsSymptoms40

Diagnosed

DiagnoseTSH↓＆FT4↑＆RAIU瀰慢性TRAb(+)DiagnosedDiagnoseTSH↓＆FT4↑41TreatmentAnti-thyroiddrugs

Makeitharderforthethyroidglandtocreatehormonesbydecreasingthethyroidgland’sabilitytouseiodineRadioactiveiodine:iodine131

Impairsthyroidcells,therebyreducingtheamountofthyroidhormoneproducedSurgery

RemovalofthemajorityofthethyroidglandTreatmentAnti-thyroiddrugs42Treatment主要藥物治療AntithyroiddrugsmethimazolepropylthiouracilTreatment主要藥物治療43Treatment輔助治療-β-blockerLithiumGlucocorticoidsinhibitperipheralT4toT3conversionand,reducethyroidsecretion.Theyhavebeenusedinpatientswithseverehyperthyroidismandthyroidstorm,althoughtheirefficacyisnotwelldemonstratedTreatment輔助治療-44Lithium用於GravesDisease的治療機轉:作用機轉相似於碘LithiumactsbyinhibitingT4andT3releasefromthethyroidandpossiblyalsobyinhibitingtheirsynthesis.優點不影響甲狀腺碘的攝取停藥後不會加重甲狀腺機能亢進放射碘治療或手術前後的準備和輔助治療。Lithium用於GravesDisease的治療機轉:優45EvidenceMicromedexFDAApproval:Adult,no;Pediatric,noEfficacy:Adult,EvidenceisinconclusiveRecommendation:Adult,ClassIIIStrengthofEvidence:Adult,CategoryBEvidenceMicromedex46ImpactoflithiumonefficacyofradioactiveiodinetherapyforGraves'disease:acohortstudyoncurerate,timetocure,andfrequencyofincreasedserumthyroxineafterantithyroiddrugwithdrawal.Patients:651patientswithnewlydiagnosedGraves'diseaseIntervention:298patientsRAIpluslithium(900mg/dayfor12day)353patientsRAIaloneResults:(1)curerate:RAIpluslithium(91.0%)vsRAIalone85.0%(P=0.030)(2)RAIpluslithiumwerecuredmorerapidly(median60day)thanthosetreatedwithRAIalone(median90day,P=0.000).(3)TreatmentwithlithiumpreventedtheserumfreeT(4)increaseaftermethimazolewithdrawalandRAItherapy.

JClinEndocrinolMetab.2010Jan;95(1):201-8.Impactoflithiumonefficacy47UseoflithiuminthetreatmentofthyrotoxicosisPatients:13名等候以放射性碘或施手術的病人(對Antithyroiddrugs治療有不良反應或對此藥療效不佳)Dosage:500-1500mg/day血清中濃度0.63mmol/LResults:有八名病患對lithium治療反應滿意,且均在1-2星期內FT4減少了40%或以上。4名在治療3-5星期內獲得效果,一名對lithium治療反應緩慢Conclusions:如果病人不能接受thionamides類的治療或對thionamides類的治療沒有療效反應,低劑量的鋰治療是控制甲狀腺機能亢進的另一個安全有效的治療方式

HongKongMedJ2006;12:254-9Useoflithiuminthetreatmen48ComparisonofRadioiodinewithRadioiodineplus

LithiumintheTreatmentofGraves’Hyperthyroidism*Patients:110patientswithnewlydiagnosed,untreatedGraves’disease,agemorethan20yr,recentonsetofhyperthyroidism(≦6months),andnonsevereorabsentGraves’ophthalmopathyDosage:900mg/dayfor6daysstartingonthedayofradioiodineadministrationResults:Goitersshrankinbothgroups(P<0.0001),moreeffectivelyandpromptly(P<0.0005)intheradioiodine-plus-lithiumgroup.JournalofClinicalEndocrinologyandMetabolismJCE&M²1999Vol.84,No.2ComparisonofRadioiodinewith49Successfuloutcomewithmethimazoleandlithiumcombinationtherapyforpropylthiouracil-inducedhepatotoxicity.

49-year-oldmanwithseverethyrotoxicosisand

propylthiouracil-inducedhepatotoxicity,indicesofliverfunctioncontinuedtoincreasedespitediscontinuationofpropylthiouraciltreatment.

Adjunctivetherapywithmethimazoleandlithium

Conclusion：Adjunctivetherapywithmethimazoleandlithiumissynergisticinpromptlyachievingaeuthyroidstate.

EndocrPract.1998Jul-Aug;4(4):197-200.

Successfuloutcomewithmethim50TheUseofLithiumCarbonateinthePreoparationforDefinitiveTherapyinHyperthyroidPatientsPatients:6patientsMethods:

in5patientswithGraves’diseaseandin1patientwithtoxicmultinodulargoiterbecauseofsideeffectsofthionamidein5patientsandineffectivenessofantithyroidmedicationintheremainingpatient.Results:All6patientshadabenigncoursefollowingtreatmentwithoutthyroidstorm.Noadverseeffectsorcomplicationsoflithiumcarbonatewereobserved.Conclusions:Thisreportshowsthatlithiumcarbonatecanbesafelyusedpreoperativelyorpriortoradioiodidetherapyincircumstanceswhereantithyroidmedicationsarecontraindicatedandareineffectiveinobtaininganeuthyroidstatus.MedPrincPract2008;17:167-170

TheUseofLithiumCarbonatei51注意事項Lithium血中濃度Trough:服用藥物8-12小時後,早上給藥前治療範圍：0.60~1.20meq/L警示範圍：1.20-1.50meq/LToxic：Over1.50meq/L血清濃度超過1.5meq/L—產生運動失調、震顫、下瀉、衰弱、鎮定、嘔吐超過2.5meq/L—舞蹈狀、迷惑、痙攣、意識下降、增加肌腱反射、嗜睡、肌肉高張液體、不醒人事，腎臟毒性超過2.5meq/L—昏迷，也有可死亡。注意事項Lithium血中濃度52注意事項其它影響甲狀腺功能Amiodarone-duetoamiodarone’shighiodinecontent注意事項其它影響甲狀腺功能53ConclusionInpatientswhodevelopseriousside-effectsduetothionamidesorwhodonotrespondtothesedrugs,lithiumtherapycanbeusedasaneffectiveinterimmeasurebeforeundertakingdefinitivetherapy.

HongKongMedJ2006;12:254-9ConclusionInpatientswhodeve54ReferenceEndocrinolMetab