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1、CLINICAL ENDOCRINOLOGY&METABOLISMINTRODUCTION AND GENERAL CONCEPTS(总论),Institute of Metabolism&Endocrinology,Eryuan Liao(廖二元),CLINICAL ENDOCRINOLOGY&METAB,A.The rapidity and extensiveness of advances in endocrinology have made it increasingly difficult for the students and physicians to take full ad
2、vantage of information available for the understanding,diagnosis,and treatment of clinical disorders,not only of diseases in endocrinology,but also of that in all clinical specialties.,A.The rapidity and extensiven,B.What easy to handle is that the general knowledge and the principles of endocrinolo
3、gy and metabolism.C.For interest,be interested in the interesting medical branch.D.Main subjects,B.What easy to handle is that,Regulation systems of extracellular communicationEndocrine gland and hormone-secreting cellsHormonesHormone secretion rhythmsHormone synthases and its regulationEndocrine re
4、gulation axes,Regulation systems of extracel,Mechanisms of hormone actionNutrient metabolismSystemic examinationLaboratory and special examinationsTherapeutic principles,Mechanisms of hormone action,Regulation Systems of Extra-Cellular Communication,nervous systemendocrine systemimmune system,Regula
5、tion Systems of Extra-Ce,Endocrine Gland and Hormone-Secreting Cells（激素分泌细胞）,A.Endocrine gland a.hypothalamus&posterior pituitary b.pineal gland(松果体)c.anterior and intermedial pituitary,Endocrine Gland and Hormone-Se,d.thyroid e.parathyroid f.endocrine pancreas(内分泌胰腺)g.adrenal cortex and medulla h.s
6、exual gland(testis or ovary)i.others:thymus(胸腺)，placenta,d.thyroid,B.Diffuse neuro-endocrine cells APUD(amine precursor uptake and decarboxylation)cells in GI,pancreas,adrenal medulla,etc.)C.Hormone-secreting cells in tissues atrium,endothelium,fibroblast,lipocytes,lymphocytes,B.Diffuse neuro-endocr
7、ine ce,Structure of hormone-secreting cells peptide/protein hormone-secreting cells:hormone-containing granules(激素颗粒)steroid hormone-secreting cells:lipid droplet(脂质小滴),Structure of hormone-secreti,A.Classification a.as peptide/protein b.as derivatives of amino acid(catecholamine,5-HT,melatonin,T3/T
8、4)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),Hormones,A.Classification Hormones,C.Types of hormone secretion,endocrine(内分泌)paracrine(旁分泌)autocrine(自分泌)intracrine(胞内分泌)neurocrine(神经分泌)juxtacrine(并邻分泌)
9、solinocrine(腔分泌)amphicrine(双重分泌),C.Types of hormone secretione,soluble hormone+binding protein:insulin,GH.IGF.Glucagon-like peptideinsoluble hormone+binding protein:T3,T4,sex steroids,cortisol,vitamin D.,D.Hormone transportation,soluble hormone+binding protei,half-life:peptides and protein:minutes s
10、teroids:variable,hrs degradation in liver,kedney,other tissues,or in hormone-secreting cells.,E.Hormone degradation and half-life,half-life:peptides and protei,A:Biological rhythms（生物节律）milliseconds:nerve impulse,membrane electrolytes.minutes:neurotransmitters hours:LH,TRH,testosterone,cortisol,GH,p
11、rolactin,TSH,etc days:FSH peaks weeks:menorrhea months:T4,1,25-(OH)2D3,pregnancy,Secretion Rhythms,A:Biological rhythms（生物节律）S,B.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),
12、B.Circadian rhythms(昼夜节律),D.Heterogeneity of serum hormones hormone,pro-hormone(激素原),prepro-hormone(前激素原)monomer,dimer,trimer tetramer,etc.fragement of peptides.,D.Heterogeneity of serum horm,A.Endocrine regulation active hormone molecule hormone-binding protein hormone receptor on membrane in cytop
13、lasma in nucleolus(nucleoplasm)post-receptor transduction(cascade reaction)tropic-hormone(促激素)feedback cycle target cell reaction,Hormone Synthases and Its Regulation,A.Endocrine regulationHormon,B.Paracrine/autocrine regulation exist almost in all tissues.“point-line”(点-线式)regulation network,B.Para
14、crine/autocrine regula,A.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;:inhibitory,A,nerve impulses/cytokines,CNS,hypothalamus,pituitary gland,target gland,D,B,Endocrine Regulation Axes,A.Hormone regulationAnerve
15、im,B.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),B.Regulation axes(调节轴),d.axis of endocrine pancreas-energy metabolism and body weight involved
16、 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 reabsorption,d.axis of endocrine pancreas-,A.Acted as tra
17、nscription-regulatory factors steroid hormone bindin with receptor(cytoplasm or nucleoplasm)H-R complex+DNA binding domain gene expression protein,Mechanisms of Hormone Action,A.Acted as transcription-reg,B.Acted at cell surface a.peptide hormone+membrane R postreceptor cascade reaction b.types of m
18、embrane RG-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,leptinreceptors of ligand-gated ion channel
19、s(transmembrane 4 or 6 times),involved in 5-HT,GABA,etc.,B.Acted at cell surface,metabolism,anabolism and catabolismmetabolic diseases(related to enzymes,hormones,or ion channels,etc).macroelement and microelement(traced element)micronutrient(Fe,F,Zn,Cu,Mn,I,Cr,Co,etc)vitamins,Nutrient Metabolism,A.
20、General concepts:,metabolism,anabolism and cata,A.Symptom 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,
21、hyperparathyroidism,DI),Systemic Examination,A.Symptom and signs Systemi,d.hypertension 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
22、,congenital adrenal hyperplasia,Cushing disease,ovarian tumors,hypothyroidism,drugs.,d.hypertension with hypok,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
23、and fractures(osteoporosis,hyperparathyroidisim,bone or hematologic diseases),hair loss:cortisol,androg,A.hormones and biomarkers(生化标志物)in serum and urine:hormones,electrolytes,sugarB.hormone derivatives:VMA,17-OHCS,17-KS,Laboratory and Special Examinations,A.hormones and biomarkers(生化,C.Dynemic tes
24、ts(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)therapeutic test(治疗试验):(spironolactone treatment in suspected hyperaldosteronism),C.Dynemic tests(动态试验),provocation test(glucagon test for diagnosis of
25、 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(thyroid,adrenal cortex,ovary,testis),provocation test(glucagon tes,A.Pathogenic therapy:supplement of nutrients,gene treat
26、ment.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),Therapeutic Principles,A.Pathogenic therapy:supple,C.Hyperfunction 1.drugs to suppress hormone secreti
27、on(iodide for GD,spironolactone for hyperaldosteronism.SS for insulinoma)2.radioactive therapy(131I for GD,-knife for pituitary tumors),C.Hyperfunction,HYPERTHYROIDISM(THYROTOXICOSIS,甲亢),Hyperthyroidism is only a diagnosis of excessive thyroid hormone status,not a concrete disease or a syndrome.It i
28、s wrong to say“Graves disease(Graves病)”as“hyperthyroidism(甲亢)”in brief.,HYPERTHYROIDISM(THYROTOXICOSI,Thyroidal origin Graves disease multiple nodular thyrotoxicosis(多结节性毒性甲状腺肿)Plummer disease(toxic thyroid adenoma)automatic hyperfunctional thyroid nodules(自主 功能性甲状腺结节)multiple autoimune endocrine sy
29、ndrome with hyperthyroidism(多发性自身免疫性内分泌腺 病伴甲亢)thyroid carcinomasneonatal hyperthyroidismgenetic toxic thyroid hyperplasia/goiteriodine-induced hyperthyroidism(碘甲亢),Pathogenesis of Hyperthyroidism,Thyroidal originPathogenesis o,Pituitary origin pituitary TSHoma thyroid hormone insensitivity syndrome(
30、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),Pituitary origin,Transient hyperthyroidismSubacute de Quervian thyroiditis(肉芽肿性甲状腺炎)hymphocytic thyroid
31、itis(postpartum,IFN,IL,Li)trumatic thyroiditis radioactive thyroiditisChronic chronic lymphocytic thyroiditis,Transient hyperthyroidism,PathogenesisHistopathologyClinical presentationLaboratory and special examsDiagnosis and differential diagnosisTreatment,GRAVES DISEASE(GD),PathogenesisGRAVES DISEA
32、SE(GD,GD is also called:diffuse toxic goiter Basedow diseaseSubclinical hyperthyroidism is usually referred to a GD state with(ab)normal T3,T4,decreased TSH,and no clinical symptoms of hyperthyroidism,Graves Disease(GD),GD is also called:diffuse tox,A.Abnormalities of immune system a.TSH-R-Ab+TSH-R
33、mimic the action of TSH hyperfunction and goiter.b.functioning of Ig Th hypersensitivity+IL-1,IL-2 B cells produce TSH-R-Ab(TRAb),Pathogenesis,A.Abnormalities of immune sys,stimulating IgG hyperfunction(TSAb)c.TRAbinhibitory IgG hypofunction and antagonistof TSHR andTSAb(TF1Ab,TGBAb)growth-stimulati
34、ng IgG(TGI),B.Other factors genetic factors infective factors stress(physical or emotional),stimulating IgG hype,C.Thyroid-associated ophthalmopathy(TAO)unknown GAG(葡萄聚糖)accumulation,T cell infiltration,edema,fibrosis and sight loss.,C.Thyroid-associated ophtha,A.Thyroid goiter:symmetrical,diffuse,s
35、oft enlarged after treatment:lobular follicles:hyperplastic column with scant colloid,papillary projections,vascularity increased lymphocytes and plasma cells infiltration,Histopathology,A.Thyroid Histopathology,B.Eyes orbital contents increased,containing mucoprotein,GAG(glycosaminoglycan,葡糖聚糖),lym
36、phocytes.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 decreased,B.Eyes,A.General considerations male:female 1:46,common in 3040yrs.B.Hypermetabolic states nervousness(99%).irritability(90%),palp
37、atation(88%),tachycardia(82%),insomnia(60%),fatigue(70%),heat intolerance(70%),excessive sweating(40%),weight loss(75%),with voracious appetite(65%),menstrual pattern changed(50%),Clinical Presentation,A.General considerationsClini,C.Thyroid diffuse goiter:absent in the elderly,consistency:soft,firm
38、,rubbery,symmetrical enlarged,surface:smooth,lobular,thrill with audible bruit eyelid spasm or retraction,C.Thyroid,D.Eyes a.non-infiltrative orbitopathy:fissure widened,sclera exposed,lid retraction,lid tremor,lid lay,globe lay.,D.Eyes,b.infiltrative orbitopathy:excessive tearingexophthalmos(asymme
39、trical)eyelids unclosedblurred visiondouble visionvisual acuity decreasedcorneas ulcerated,infectedsight loss,b.infiltrative orbitopathy:,c.Classification of Graves orbitopathy:NOSPECS(from:American Thyroid Association)ClassDefinition0No physical signs or symptoms1Only signs,no symptoms(signs limite
40、d 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),c.Classification of Graves or,E.Others tremor of the hands and tongue muscle wasting rapid ref
41、lex response diarrhea liver function wbc,and anemia,vitiligo(白癜风),hair loss pretibial myxedema(胫前粘液性水肿),E.Others,F.Complications a.cardiopathy and heart failurethyrotoxicosis,arrhythmia,heart enlargement and heart failure,and all disappeared after treatment b.Thyrotoxic crisissymptoms and signs exag
42、gerated 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.,F.Complications,c.hypokalemic peri
43、odic paralysismore common in Asiaabruptly paralysis with hypokalemiaprecipitated by dextrose,oral carbohydrateor vigorous exercise.attacks last 7-27 hrs.some companied by myasthenia gravis.,c.hypokalemic periodic paraly,A.Serum TH and TSH a.FT3 and FT4 b.TT3 and TT4 c.rT3 d.TSHB.TSH receptor antibod
44、ies,Laboratory and Special Exams,A.Serum TH and TSHLaboratory,C.TRH stimulation testeuthyroid Graves ophthalmopathyGD medicationD.131I uptake and T3 suppression testE.pathological exams,C.TRH stimulation test,A.Functional diagnosis GD suspected:(1)weight loss;(2)slight fever;(3)diarrhea;(4)tachycard
45、ia;(5)atrial fibrillation;(6)fatigue;(7)dysmenorrhea;(8)with difficult in control of DM,TB,heart failure,CHD,liver disease,Diagnosis and Differential Diagnosis,A.Functional diagnosisDiagnos,B.TypesFT3、FT4,sTSH(uTSH):hyperthyroidismFT3(orTT3),FT4(TT4)normal,sTSH:T3 hyperthyroidism FT4(orTT4),FT3(TT3)
46、normal,sTSH:T4 hyperthyroidismFT3 and FT4(ab)normal,sTSH:subclinical hyperthyroidism,C.Pathogenic diagnosis TRAb,TgAb,TPOAb,HCG,131I uptake,TSH,B.TypesC.Pathogenic diagnosi,A.General management rest enough,energy and nutrients supplement,sedatives for restlessness and insomnia.B.Management of hypert
47、hyroidism a.medical antithyroid agents:methylthiouracil(MTU)or propylthiouracil(PTU)300600mg/d methimazole(MM)or carbimazole(CMZ)3060mg/d,Treatment,A.General management Treatm,b.dosage and course1st stage(ca.6 wks):full dosage to control symptoms2nd stage(ca.48wks):dosage decrease gradually 1/6 dosa
48、ge/wk3rd stage(ca 1yr or more)PTU 50mg(or MM 5mg),Qd,b.dosage and course,c.“block-replace”regimensTH added to prevention of hypothyroidism.T4 50g,Qd.d.drug withdrawalgoiter subsidesminimal dosage to maintain treated effectsTSH return to normalTSAb negativenormal response to TRH,c.“block-replace”regi
49、mens,e.drug side-effectsprimary and secondary failureagranulocytosis(1%,within 2 mos)WBC count/wk or mo,e.drug side-effects,C.Radioiodine(131I)a.more active than before,more(USA)VS less(Euro)b.contraindications:pregnant thyrotoxicosis young people(20yrs)severe exophthalmos thyrotoxic crisis failed t
50、o I uptake dosage should be calculated by specialist,C.Radioiodine(131I),C.Complicationshypothyroidismradiation thyroiditisthyrotoxic crisisexaggarated proptosis(smoking),C.Complications,D.Surgery indications:failed to antithyroidal agent huge thyroid or suspected with tumors retrosternal goiter con
