内分泌总论、甲亢(英文)分解课件.ppt

1、CLINICAL ENDOCRINOLOGY&METABOLISMINTRODUCTION AND GENERAL CONCEPTS(总论总论)Institute of Metabolism&EndocrinologyEryuan Liao(廖二元廖二元)A.The rapidity and extensiveness of advances in endocrinology have made it increasingly difficult for the students and physicians to take full advantage of information avai

2、lable for the understanding,diagnosis,and treatment of clinical disorders,not only of diseases in endocrinology,but also of that in all clinical specialties.B.What easy to handle is that the general knowledge and the principles of endocrinology and metabolism.C.For interest,be interested in the inte

3、resting medical branch.D.Main subjectsI.Regulation systems of extracellular communicationII.Endocrine gland and hormone-secreting cellsIII.HormonesIV.Hormone secretion rhythmsV.Hormone synthases and its regulationVI.Endocrine regulation axesVII.Mechanisms of hormone actionVIII.Nutrient metabolismIX.

4、Systemic examinationX.Laboratory and special examinationsXI.Therapeutic principlesI.Regulation Systems of Extra-Cellular Communicationnervous systemendocrine systemimmune systemII.Endocrine Gland and Hormone-Secreting Cells（激素分泌细胞）A.Endocrine gland a.hypothalamus&posterior pituitary b.pineal gland(松

5、果体)c.anterior and intermedial pituitary d.thyroid e.parathyroid f.endocrine pancreas(内分泌胰腺)g.adrenal cortex and medulla h.sexual gland(testis or ovary)i.others:thymus(胸腺)，placentaB.Diffuse neuro-endocrine cells APUD(amine precursor uptake and decarboxylation)cells in GI,pancreas,adrenal medulla,etc.

6、)C.Hormone-secreting cells in tissues atrium,endothelium,fibroblast,lipocytes,lymphocytesD.Structure of hormone-secreting cellsE.peptide/protein hormone-secreting cells:F.hormone-containing granules G.(激素颗粒)H.steroid hormone-secreting cells:I.lipid droplet(脂质小滴)A.Classification a.as peptide/protein

7、b.as derivatives of amino acid(catecholamine,5-HT,melatonin,T3/T4)c.as derivates of cholesterol(cortisol,aldosterone,estrogen,androgen,progesterone,1,25-(OH)2D3)B.Storage hormone granules thyroglobulin(甲状腺球蛋白)III.HormonesC.Types of hormone secretionendocrine (内分泌)paracrine (旁分泌)autocrine (自分泌)intrac

8、rine (胞内分泌)neurocrine (神经分泌)juxtacrine (并邻分泌)solinocrine (腔分泌)amphicrine (双重分泌)soluble hormone+binding protein:insulin,GH.IGF.Glucagon-like peptideinsoluble hormone+binding protein:T3,T4,sex steroids,cortisol,vitamin D.D.Hormone transportationhalf-life:peptides and protein:minutes steroids:variable,

9、hrs degradation in liver,kedney,other tissues,or in hormone-secreting cells.E.Hormone degradation and half-lifeA:Biological rhythms（生物节律）milliseconds:nerve impulse,membrane electrolytes.minutes:neurotransmitters hours:LH,TRH,testosterone,cortisol,GH,prolactin,TSH,etc days:FSH peaks weeks:menorrhea m

10、onths:T4,1,25-(OH)2D3,pregnancyIV.Secretion RhythmsB.Circadian rhythms(昼夜节律)biological“clock”in hypothalamus(melatonin),but lost in Cushing disease and psychosisC.24-hr changes of serum and urine hormone(metabolic products)D.Heterogeneity of serum hormones hormone,pro-hormone(激素原),prepro-hormone(前激素

11、原)monomer,dimer,trimer tetramer,etc.fragement of peptides.A.Endocrine regulation active hormone molecule hormone-binding protein hormone receptor on membrane in cytoplasma in nucleolus(nucleoplasm)post-receptor transduction(cascade reaction)tropic-hormone(促激素)feedback cycle target cell reactionV.Hor

12、mone Synthases and Its RegulationB.Paracrine/autocrine regulation exist almost in all tissues.“point-line”(点-线式)regulation networkA.Hormone regulationA:ultra-short feedback(超短反馈)B:short feedback(短反馈)C:positive feedback(正反馈)D:long negative feedback(负反馈):stimulating;:inhibitoryAnerve impulses/cytokine

13、sCNShypothalamuspituitary glandtarget glandDBVI.Endocrine Regulation AxesB.Regulation axes(调节轴)a.hypothalamus-pituitary-thyroid(adrenal cortex,sexual gland)b.GIH/GHRH-GH/GHBP-IGFs/IGFBPS-IGFBP/IGFBPase c.renin-AT-ALD involved in renin,AT,ALD,ANP,AVP,AM(adrenomedullin,肾上腺髓质素)d.axis of endocrine pancr

14、eas-energy metabolism and body weight involved in insulin,glucagon,glucagon-like peptide-1,somatostatin,leptin,etc.e.PTH-CT-1,25-(OH)2D3 involved in PTH,CT,1,25-(OH)2D3,serum Ca2+,Pi3-f.AVP-AVP receptor-AQP(aquaporin,水孔蛋白)V1 receptor:related to regulation of BP V2 receptor:related to H2O reabsorptio

15、nA.Acted as transcription-regulatory factors steroid hormone bindin with receptor (cytoplasm or nucleoplasm)H-R complex+DNA binding domain gene expression proteinVII.Mechanisms of Hormone ActionB.Acted at cell surface a.peptide hormone+membrane R postreceptor cascade reaction b.types of membrane R G

16、-protein coupled receptor(transmenbrane 7 times)involved in PTH,AT,glucagon,LH,FSH,TSH,AVP,CT,HCG,etc.receptor kinases(transmembrane 1 time),with tyrosine kinase(activity),involved in insulin,IGF,EGF,etc.receptor-linked kinases,involved in GH,PRL,leptin receptors of ligand-gated ion channels(transme

17、mbrane 4 or 6 times),involved in 5-HT,GABA,etc.a.metabolism,anabolism and catabolismb.metabolic diseases(related to enzymes,hormones,or ion channels,etc).c.macroelement and microelement(traced element)d.micronutrient(Fe,F,Zn,Cu,Mn,I,Cr,Co,etc)e.vitaminsVIII.Nutrient MetabolismA.General concepts:A.Sy

18、mptom and signs a.body height(genetic factors,GH,TH,sex hormones,IGF-1,nutrition,systemic diseases)b.obesity and weigh loss(genetic constitution,nutrition,systemic disease,GH,TH,insulin,leptin,cortisol,sex hormones)c.polydipsia and polyuria(DM,ALD ,hyperparathyroidism,DI)IX.Systemic Examination d.hy

19、pertension with hypokalemia(primary hyperaldosteronism,reninoma,Cushing syndrome)e.hyperpigmentation(ACTH,MSH,estrogen,progesterone,androgen)f.hair loss or hypertrichosis(hairy,多毛症)genetics,race,androgen.hypertrichosis:PCOS,congenital adrenal hyperplasia,Cushing disease,ovarian tumors,hypothyroidism

20、,drugs.hair loss:cortisol ,androgen ,g.gynecomastia(男性乳腺发育):Klinefelter syndrome,testicular tumors,drugs.)h.exophthalmos(突眼)：Graves disease,chronic lymphocytic thyroiditis,eye diseases.)i.bone pain and fractures(osteoporosis,hyperparathyroidisim,bone or hematologic diseases)A.hormones and biomarkers

21、(生化标志物)in serum and urine:hormones,electrolytes,sugarB.hormone derivatives:VMA,17-OHCS,17-KSX.Laboratory and Special ExaminationsC.Dynemic tests(动态试验)stimulation test(兴奋试验)：hypofunction(hypocortisolism)inhibitory states(TSH in GD)suppression test(抑制试验)：hyperfunction(DXM for Cushing disease)therapeut

22、ic test(治疗试验):(spironolactone treatment in suspected hyperaldosteronism)provocation test(glucagon test for diagnosis of pheochromocytoma)X-ray film(bone diseases,kedney stones)CT&MRI(morphologic changes)radionuclear tomography(thyroid,pancreas,adrenal cortex and medulla,parathyroid,etc)type B US(thy

23、roid,adrenal cortex,ovary,testis)A.Pathogenic therapy:supplement of nutrients,gene treatment.B.Hypofunction:1.hormone replacement therapy(Addison disease,hypothyroidism;hypogonadism)2.drugs to stimulate hormone secretion (sulfonylurea for type 2 DM)3.transplantation(organ,tissue,cells)XI.Therapeutic

24、 PrinciplesC.Hyperfunction 1.drugs to suppress hormone secretion (iodide for GD,spironolactone for hyperaldosteronism.SS for insulinoma)2.radioactive therapy(131I for GD,-knife for pituitary tumors)HYPERTHYROIDISM(THYROTOXICOSIS,甲亢甲亢)Hyperthyroidism is only a diagnosis of excessive thyroid hormone s

25、tatus,not a concrete disease or a syndrome.It is wrong to say“Graves disease(Graves病)”as“hyperthyroidism(甲亢)”in brief.Thyroidal origin Graves disease multiple nodular thyrotoxicosis(多结节性毒性甲状腺肿多结节性毒性甲状腺肿)Plummer disease(toxic thyroid adenoma)automatic hyperfunctional thyroid nodules(自主自主 功能性甲状腺结节功能性甲

26、状腺结节)multiple autoimune endocrine syndrome with hyperthyroidism(多发性自身免疫性内分泌腺多发性自身免疫性内分泌腺 病伴甲亢病伴甲亢)thyroid carcinomasneonatal hyperthyroidismgenetic toxic thyroid hyperplasia/goiteriodine-induced hyperthyroidism(碘甲亢碘甲亢)Pathogenesis of HyperthyroidismPituitary origin pituitary TSHoma thyroid hormone i

27、nsensitivity syndrome(pituitary type,垂体型TH不敏感综合征)paracarcinoma syndrome HCG-related hyperthyroidism carcinomas(lung,GI,pancreas)with hyperthyroidism Ovarian goiter with hyperthyroidism Iatrogenic hyperthyroidism(医源性甲亢)Transient hyperthyroidismSubacute de Quervian thyroiditis(肉芽肿性甲状腺炎)hymphocytic thy

28、roiditis(postpartum,IFN,IL,Li)trumatic thyroiditis radioactive thyroiditisChronic chronic lymphocytic thyroiditisI.PathogenesisII.HistopathologyIII.Clinical presentationIV.Laboratory and special examsV.Diagnosis and differential diagnosisVI.TreatmentGRAVES DISEASE(GD)GD is also called:diffuse toxic

29、goiter Basedow diseaseSubclinical hyperthyroidism is usually referred to a GD state with(ab)normal T3,T4,decreased TSH,and no clinical symptoms of hyperthyroidismGraves Disease(GD)A.Abnormalities of immune system a.TSH-R-Ab+TSH-R mimic the action of TSH hyperfunction and goiter.b.functioning of Ig T

30、h hypersensitivity+IL-1,IL-2 B cells produce TSH-R-Ab(TRAb)I.Pathogenesisstimulating IgG hyperfunction(TSAb)c.TRAbinhibitory IgG hypofunction and antagonistof TSHR andTSAb(TF1Ab,TGBAb)growth-stimulating IgG(TGI)B.Other factors genetic factors infective factors stress(physical or emotional)C.Thyroid-

31、associated ophthalmopathy (TAO)unknown GAG(葡萄聚糖)accumulation,T cell infiltration,edema,fibrosis and sight loss.A.Thyroid goiter:symmetrical,diffuse,soft enlarged after treatment:lobular follicles:hyperplastic column with scant colloid,papillary projections,vascularity increased lymphocytes and plasm

32、a cells infiltrationII.HistopathologyB.Eyes orbital contents increased,containing mucoprotein,GAG(glycosaminoglycan,葡糖聚糖糖),lymphocytes.C.Skin(dermopathy)hyaluronic acid(透明质酸),chondroitin sulfates (硫酸软骨素)increased,collagen fibers separated nodular and plaque formation lymphatic drainage decreasedA.Ge

33、neral considerations male:female 1:46,common in 3040yrs.B.Hypermetabolic states nervousness(99%).irritability(90%),palpatation(88%),tachycardia(82%),insomnia(60%),fatigue(70%),heat intolerance(70%),excessive sweating(40%),weight loss(75%),with voracious appetite(65%),menstrual pattern changed(50%)II

34、I.Clinical PresentationC.Thyroid diffuse goiter:absent in the elderly,consistency:soft,firm,rubbery,symmetrical enlarged,surface:smooth,lobular,thrill with audible bruit eyelid spasm or retractionD.Eyes a.non-infiltrative orbitopathy:fissure widened,sclera exposed,lid retraction,lid tremor,lid lay,g

35、lobe lay.b.infiltrative orbitopathy:excessive tearingexophthalmos(asymmetrical)eyelids unclosedblurred visiondouble visionvisual acuity decreasedcorneas ulcerated,infectedsight lossc.Classification of Graves orbitopathy:NOSPECS (from:American Thyroid Association)ClassDefinition0No physical signs or

36、symptoms1Only signs,no symptoms(signs limited to upper lid retraction,stare,lid lag,and proptosis to 22mm)2Soft tissue involvement(symptom and sign)3Proptosis22mm4Extraocular muscle involvement5Corneal involvement6Sight loss(optic nerve involvement)E.Others tremor of the hands and tongue muscle wast

37、ing rapid reflex response diarrhea liver function wbc ,and anemia,vitiligo(白癜风白癜风),hair loss pretibial myxedema(胫前粘液性水肿胫前粘液性水肿)F.Complications a.cardiopathy and heart failurethyrotoxicosis,arrhythmia,heart enlargement and heart failure,and all disappeared after treatment b.Thyrotoxic crisissymptoms

38、and signs exaggerated abruptlyprecipitating factors:infection,trauma,surgeryradiation thyroiditis,DKA,parturtionAdditional pictures:arrhythmias,pulmonary edema,congestive heart failure,restlessness,delirium,nausea,vomiting,abdominal pain,apathy,stupor,coma,hypotension,shock,etc.c.hypokalemic periodi

39、c paralysismore common in Asiaabruptly paralysis with hypokalemiaprecipitated by dextrose,oral carbohydrateor vigorous exercise.attacks last 7-27 hrs.some companied by myasthenia gravis.A.Serum TH and TSH a.FT3 and FT4 b.TT3 and TT4 c.rT3 d.TSHB.TSH receptor antibodiesIV.Laboratory and Special Exams

40、C.TRH stimulation testeuthyroid Graves ophthalmopathyGD medicationD.131I uptake and T3 suppression testE.pathological examsA.Functional diagnosis GD suspected:(1)weight loss;(2)slight fever;(3)diarrhea;(4)tachycardia;(5)atrial fibrillation;(6)fatigue;(7)dysmenorrhea;(8)with difficult in control of D

41、M,TB,heart failure,CHD,liver diseaseV.Diagnosis and Differential DiagnosisB.TypesFT3 、FT4 ,sTSH(uTSH):hyperthyroidismFT3(orTT3),FT4(TT4)normal,sTSH :T3 hyperthyroidism FT4(orTT4),FT3(TT3)normal,sTSH :T4 hyperthyroidismFT3 and FT4(ab)normal,sTSH :subclinical hyperthyroidismC.Pathogenic diagnosis TRAb

42、,TgAb,TPOAb,HCG,131I uptake,TSHA.General management rest enough,energy and nutrients supplement,sedatives for restlessness and insomnia.B.Management of hyperthyroidism a.medical antithyroid agents:methylthiouracil(MTU)or propylthiouracil(PTU)300600mg/d methimazole(MM)or carbimazole(CMZ)3060mg/dVI.Tr

43、eatmentb.dosage and course1st stage(ca.6 wks):full dosage to control symptoms2nd stage(ca.48wks):dosage decrease gradually 1/6 dosage/wk3rd stage(ca 1yr or more)PTU 50mg(or MM 5mg),Qdc.“block-replace”regimensTH added to prevention of hypothyroidism.T4 50g,Qd.d.drug withdrawalgoiter subsidesminimal d

44、osage to maintain treated effectsTSH return to normalTSAb negativenormal response to TRHe.drug side-effectsprimary and secondary failureagranulocytosis(1%,within 2 mos)WBC count/wk or moC.Radioiodine(131I)a.more active than before,more(USA)VS less (Euro)b.contraindications:pregnant thyrotoxicosis yo

45、ung people(20yrs)severe exophthalmos thyrotoxic crisis failed to I uptake dosage should be calculated by specialistC.Complicationshypothyroidismradiation thyroiditisthyrotoxic crisisexaggarated proptosis(smoking)D.Surgery indications:failed to antithyroidal agent huge thyroid or suspected with tumor

46、s retrosternal goiter contraindications:severe proptosis severe systemic diseases early and late pregnancy thyrotoxicosis not controlledE.Treatment decision-making a.firstly,treated with medications for all patients b.after controlled,decided byagerun course of diseaseseverity&complicationsthyroid s

47、tatesdoctors experiencepatients willings and special entitiesF.Special concerns a.minimal iodide supplement,iodo-NaCl is not suitable for GD b.severe proptosis treated with caution,including TH supplement and prednisone c.thyroid crisis treated with NaI,PTU,DXM,and propranolol d.PTU is the treatment

48、 of choice for hyperthyroidism in pregnancy,never makes TSH 0.5U/L e.heart failure treated with digoxin may be dangerous in some cases高敏TSH检测在甲状腺功能诊断及监测中的意义 甲状腺功能异常是临床上常见的一组疾病。有研究表明，高敏TSH在甲状腺功能诊断方面最为敏感。1999年9月2000年11月在我科实验室所做的5100人次甲状腺功能检查，以了解三项检测指标在甲状腺功能诊断及监测中的意义。1 资料和方法1.1 实验对象我科临床诊断为甲亢的病人及甲亢服药复查的

49、病人共4518份血标本。1.2 实验方法标本收集每次抽肘静脉血3ml，离心后取血清置20保存。检测方法FT3，FT4用放免法，药盒由天津协和试剂公司提供，TSH用免放法，药盒由天津协和试剂公司提供。1.3 统计学处理率的比较采用X2检验。2 结果4518份标本中，FT3、FT4均增高，TSH降低者有1596份，占总数的35.25%；FT3增高，TSH降低，FT4正常者有564份，占总数的12.46%；FT4、FT4正常，仅有TSH降低者有736份，占总数的16.25%；三项结果均正常者有820份，占总数的18.11%；FT3、FT4正常，而TSH升高者有338份，占总数的7.46%；FT3、F

50、T4降低，TSH升高者有46份，占总数的1.02%；FT4降低，TSH升高，FT3正常者有314分，占总数的6.93%；FT4增高，TSH降低，FT3正常者有46份，占总数的1.02%；其他各种组合有29份，占总数的0.64%。2.1 在诊断甲亢方面以TSH降低为诊断指标，其阳性率为65.33%（2952/4518），以FT3升高为诊断指标，阳性率为47.80%（2160/4518）经X2检验，差异有显著性（P0.001），说明以TSH降低为诊断指标，阳性率为36.56%（1652/4518），明显低于TSH和FT3的阳性率（均P0.001），提示在诊断甲亢时，FT4的敏感性最低。2.2 在诊