1、Lithium用於Graves Disease主講人主講人:郭人瑚郭人瑚指導藥師：張美琪指導藥師：張美琪99/7/2999/7/29QuestionPatient HistorylObjectivelFamily history of thyroid diseaselThyroid Gr1-2 diffuse firm goiter,combine Graves diseaselPalpitation,proximal muscle weakness,menstral cycle:irregular,stool passage increased,soft loose stoolDrug pr
2、ofile980728980803980810980817980914981012981109981109981223990208990406990505peptidine 1TIDpropanolol1TIDbisoprolol0.5QD0.5BID1#BIDmethimazole2#TID2#TID 3#TIDcetirizine1#HS1#HSPTU2#BID2#TID3#QIDalprazolamXR1#HSdiphenidol1#QIDlithium1#QD使用使用PropanololPropanolol耐受性耐受性不佳不佳BisprololBisprolol使用使用Methimaz
3、oleMethimazole會癢會癢PTUPTUHR一直很快一直很快Lab DatalThyroglbulin:519.2ng/ml 50ng/mllTRab:(+)61.79%(-)15%lFree-T4 正常值正常值0.73-2.01ug/dL lTSH 正常值正常值0.35-4.94ulU/ml檢驗值檢驗值Outlinel何謂Graves Disease l臨床表徵及診斷l治療What is Graves Disease?lDisease in which the immune system attacks the thyroid gland,causing the thyroid gl
4、and to react by making too much thyroid hormone.lThe over-activity of a thyroid gland is referred to as hyperthyroidism.Graves DiseaseCauses of Graves DiseaselGenetic tendencies of the immune system to attack itselflStress Symptomsl Diagnosed DiagnoselTSH FT4RAIU瀰慢性瀰慢性lTRAb(+)TreatmentlAnti-thyroid
5、drugs Make it harder for the thyroid gland to create hormones by decreasing the thyroid glands ability to use iodinelRadio active iodine:iodine 131 Impairs thyroid cells,thereby reducing the amount of thyroid hormone producedlSurgery Removal of the majority of the thyroid gland Treatment l主要藥物治療主要藥物
6、治療lAntithyroid drugslmethimazole lpropylthiouracil Treatmentl輔助治療輔助治療-l-blockerlLithiumlGlucocorticoidslinhibit peripheral T4 to T3 conversion and,reduce thyroid secretion.They have been used in patients with severe hyperthyroidism and thyroid storm,although their efficacy is not well demonstrated L
7、ithium用於Graves Disease的治療l機轉機轉:l作用機轉相似於碘lLithium acts by inhibiting T4 and T3 release from the thyroid and possibly also by inhibiting their synthesis.l優點優點l不影響甲狀腺碘的攝取l停藥後不會加重甲狀腺機能亢進l放射碘治療或手術前後的準備和輔助治療。EvidencelMicromedexlFDA Approval:Adult,no;Pediatric,nolEfficacy:Adult,Evidence is inconclusivelRec
8、ommendation:Adult,Class IIIlStrength of Evidence:Adult,Category B Impact of lithium on efficacy of radioactive iodine therapy for Graves disease:a cohort study on cure rate,time to cure,and frequency of increased serum thyroxine after antithyroid drug withdrawal.lPatients:651 patients with newly dia
9、gnosed Graves diseaselIntervention:298 patients RAI plus lithium(900 mg/day for 12 day)353 patients RAI alone lResults:(1)cure rate:RAI plus lithium(91.0%)vs RAI alone 85.0%(P=0.030)(2)RAI plus lithium were cured more rapidly(median 60 day)than those treated with RAI alone(median 90 day,P=0.000).(3)
10、Treatment with lithium prevented the serum free T(4)increase after methimazole withdrawal and RAI therapy.J Clin Endocrinol Metab.2010 Jan;95(1):201-8.Use of lithium in the treatment of thyrotoxicosislPatients:l13名等候以放射性碘或施手術的病人名等候以放射性碘或施手術的病人l(對對Antithyroid drugs 治療有不良反應或對此藥療效不佳治療有不良反應或對此藥療效不佳)lDos
11、age:500-1500 mg/day 血清中濃度血清中濃度0.63 mmol/LlResults:l有八名病患對有八名病患對lithium治療反應滿意治療反應滿意,且均在且均在1-2星期內星期內FT4減少了減少了40%或以上或以上。l4名在治療名在治療3-5星期內獲得效果星期內獲得效果,l一名對一名對lithium治療反應緩慢治療反應緩慢lConclusions:l如果病人不能接受如果病人不能接受thionamides類的治療或對類的治療或對 thionamides類的治療類的治療沒有療效反應沒有療效反應,低劑量的鋰治療是控制甲狀腺機能亢進的另一個安全有低劑量的鋰治療是控制甲狀腺機能亢進的另
12、一個安全有效的治療方式效的治療方式 Hong Kong Med J 2006;12:254-9Comparison of Radioiodine with Radioiodine plusLithium in the Treatment of Graves Hyperthyroidism*lPatients:l110 patients with newly diagnosed,untreated Graves disease,age more than 20 yr,recent onset of hyperthyroidism(6 months),and nonsevere or absent
13、 Graves ophthalmopathylDosage:l900 mg/day for 6 days starting on the day of radioiodine administrationlResults:lGoiters shrank in both groups(P0.0001),more effectively and promptly(P 0.0005)in the radioiodine-plus-lithium group.Journal of Clinical Endocrinology and Metabolism JCE&M 1999 Vol.84,No.2S
14、uccessful outcome with methimazole and lithium combination therapy for propylthiouracil-induced hepatotoxicity.l49-year-old man with severe thyrotoxicosis and propylthiouracil-induced hepatotoxicity,indices of liver function continued to increase despite discontinuation of propylthiouracil treatment
15、.l Adjunctive therapy with methimazole and lithium lConclusion：Adjunctive therapy with methimazole and lithium is synergistic in promptly achieving a euthyroid state.Endocr Pract.1998 Jul-Aug;4(4):197-200.The Use of Lithium Carbonate in the Preoparation for Definitive Therapy in Hyperthyroid Patient
16、s lPatients:l6 patients lMethods:lin 5 patients with Graves diseaseand in 1 patient with toxic multinodular goiter because of side effects of thionamide in 5 patients and ineffectiveness of antithyroid medication in the remaining patient.lResults:l All 6 patients had a benign course following treatm
17、ent without thyroid storm.No adverse effects or complications of lithium carbonate were observed.lConclusions:lThis report shows that lithium carbonate can be safely used preoperatively or prior to radioiodide therapy in circumstances where antithyroid medications are contraindicated and are ineffec
18、tive in obtaining an euthyroid status.Med Princ Pract 2008;17:167-170 注意事項lLithium血中濃度血中濃度lTrough:服用藥物8-12小時後,早上給藥前l治療範圍：治療範圍：l0.601.20 meq/Ll警示範圍：1.20-1.50 meq/LlToxic：Over 1.50 meq/Ll血清濃度超過1.5 meq/L 產生運動失調、震顫、下 瀉、衰 弱、鎮定、嘔吐l超過2.5 meq/Ll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l超過2.5 meq/Ll昏迷，也有可死亡。
19、注意事項l其它影響甲狀腺功能lAmiodarone-due to amiodarones high iodine contentConclusionlIn patients who develop serious side-effects due to thionamides or who do not respond to these drugs,lithium therapy can be used as an effective interim measure before undertaking definitive therapy.Hong Kong Med J 2006;12:25
20、4-9Reference lEndocrinol Metab Clin North Am-01-JUN-2009;38(2):355-71lJ Clin Endocrinol Metab.2010 Jan;95(1):201-8.Micromedex,Up toDate,MD consult,CMAJlHong Kong Med J 2006;12:254-9lAdapted from Weetman AP:Graves disease.N Engl J Med 2000;343:12361248.lAACE Thyroid Guidelines,Endocr Pract.2002;8(No.
21、6)461 Endocr Pract.1998 Jul-Aug;4(4):197-200.Propranolol(1)10mg/tab,(2)40mg/tab,Bisoprolol 25mg/tab非心臟選擇性(1+2-Receptor)具心臟選擇性(1 Receptor)短效型20-80 mg PO tid;1-2 mg IV q4-8h 長效型2.5-20mg qd;max:40mg/dayCardiovascular:Bradyarrhythmia,Hypotension Dermatologic:Dermatitis,Pruritus,Urticaria Gastrointestina
22、l:Nausea,Vomiting Neurologic:Fatigue,Insomnia,Paresthesia Psychiatric:Depression,Psychotic disorder Respiratory:DyspneaCardiovascular:Bradyarrhythmia(9%),Cold extremities,Hypotension Gastrointestinal:Diarrhea(4%),Indigestion,Nausea(2%),Vomiting(2%)Musculoskeletal:Arthralgia(3%)Neurologic:Dizziness(1
23、0%),Headache(11%)Psychiatric:Dyssomnia(8%-10%)Respiratory:Cough(3%),Dyspnea(2%),Pharyngitis(2%),Rhinitis(4%),Sinusitis(2%),Upper respiratory infection(5%)Other:Fatigue(8%)Propylthiouracil(PTU)MethimazoleProtein Binding75 80%0T 1/2(h)1 26 13Initial Dose300 400mg/day,分分34次服用次服用15 mg(mild);30 to 40 mg(moderately severe);60 mg(severe)ORALLY per dayMaintenance Dose 100150 mg/day5 15 mg/dayNeonates5 10 mg/kg/day0.5 1 mg/kg/dayTransplacental passageLowHigherLevels in breast milkLowHigher
