內分泌總論、甲亢(英文)分解課件

1、CLINICAL ENDOCRINOLOGY & METABOLISMINTRODUCTION AND GENERAL CONCEPTS(總論)Institute of Metabolism & EndocrinologyEryuan Liao (廖二元)CLINICAL ENDOCRINOLOGY & METABA. The rapidity and extensiveness of advances in endocrinology have made it increasingly difficult for the students and physicians to take ful

2、l advantage 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 extensivenB. What easy to handle is that the general knowledge and the principles of end

3、ocrinology and metabolism.C. For interest, be interested in the interesting medical branch.D. Main subjectsB. What easy to handle is thatRegulation systems of extracellular communicationEndocrine gland and hormone-secreting cellsHormonesHormone secretion rhythmsHormone synthases and its regulationEn

4、docrine regulation axesRegulation systems of extracelMechanisms of hormone actionNutrient metabolismSystemic examinationLaboratory and special examinationsTherapeutic principlesMechanisms of hormone actionRegulation Systems of Extra-Cellular Communicationnervous systemendocrine systemimmune systemRe

5、gulation Systems of Extra-CeEndocrine Gland and Hormone-Secreting Cells（激素分泌細胞）A. Endocrine gland a. hypothalamus & posterior pituitary b. pineal gland (松果體) c. anterior and intermedial pituitaryEndocrine Gland and Hormone-Se d. thyroid e. parathyroid f. endocrine pancreas (內分泌胰腺) g. adrenal cortex

6、and medulla h. sexual gland (testis or ovary) i. others: thymus (胸腺)，placenta d. thyroidB. 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, lym

7、phocytesB. Diffuse neuro-endocrine ce Structure of hormone-secreting cells peptide/protein hormone-secreting cells: hormone-containing granules (激素顆粒) steroid hormone-secreting cells: lipid droplet (脂質小滴) Structure of hormone-secretiA. Classification a. as peptide/protein b. as derivatives of amino

8、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 (甲狀腺球蛋白) HormonesA. Classification HormonesC. Types of hormone secretionendocrine (內分泌)paracrine (旁分泌)autocrin

9、e (自分泌)intracrine (胞內分泌)neurocrine (神經分泌)juxtacrine (并鄰分泌)solinocrine (腔分泌)amphicrine (雙重分泌)C. Types of hormone secretionesoluble hormone+binding protein: insulin, GH. IGF. Glucagon-like peptideinsoluble hormone+binding protein: T3, T4, sex steroids, cortisol, vitamin D.D. Hormone transportationsolu

10、ble hormone+binding proteihalf-life: peptides and protein: minutes steroids: variable, hrs degradation in liver, kedney, other tissues, or in hormone-secreting cells.E. Hormone degradation and half-lifehalf-life: peptides and proteiA: Biological rhythms（生物節(jié)律） milliseconds: nerve impulse, membrane el

11、ectrolytes. minutes: neurotransmitters hours: LH, TRH, testosterone, cortisol, GH, prolactin, TSH, etc days: FSH peaks weeks: menorrhea months: T4, 1,25-(OH)2D3, pregnancy Secretion RhythmsA: Biological rhythms（生物節(jié)律） SB. Circadian rhythms (晝夜節(jié)律) biological “clock” in hypothalamus (melatonin), but lo

12、st in Cushing disease and psychosisC. 24-hr changes of serum and urine hormone (metabolic products)B. Circadian rhythms (晝夜節(jié)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 hor

13、mA. 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 reactionHormone Synthases and Its RegulationA. Endocrine regula

14、tionHormonB. Paracrine/autocrine regulation exist almost in all tissues. “point-line” (點-線式) regulation networkB. Paracrine/autocrine regulaA. Hormone regulationA: ultra-short feedback (超短反饋) B: short feedback (短反饋)C: positive feedback (正反饋) D: long negative feedback (負反饋) : stimulating; : inhibitor

15、yAnerve impulses/cytokinesCNShypothalamuspituitary glandtarget glandDBEndocrine Regulation AxesA. Hormone regulationAnerve imB. Regulation axes (調節(jié)軸) 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

16、, ALD, ANP, AVP, AM (adrenomedullin, 腎上腺髓質素)B. Regulation axes (調節(jié)軸)d. axis of endocrine pancreas-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 re

17、ceptor-AQP (aquaporin, 水孔蛋白) V1 receptor: related to regulation of BP V2 receptor: related to H2O reabsorptiond. axis of endocrine pancreas-A. Acted as transcription- regulatory factors steroid hormone bindin with receptor (cytoplasm or nucleoplasm) H-R complex+DNA binding domain gene expression pro

18、tein Mechanisms of Hormone ActionA. Acted as transcription- regB. Acted at cell surface a. peptide hormone + membrane R postreceptor cascade reaction b. types of membrane RG-protein coupled receptor (transmenbrane 7 times) involved in PTH, AT, glucagon, LH, FSH, TSH, AVP, CT, HCG, etc.receptor kinas

19、es (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 channels (transmembrane 4 or 6 times), involved in 5-HT, GABA, etc.B. Acted at cell surfacemetabolism, anabolism and catabo

20、lismmetabolic 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 MetabolismA. General concepts:metabolism, anabolism and cataA. Symptom and signs a. body height (genetic factor

21、s, 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) Systemic ExaminationA. Symptom and signs Systemi

22、 d. hypertension with hypokalemia (primary hyperaldosteronism, reninoma, Cushing syndrome) e. hyperpigmentation (ACTH, MSH, estrogen, progesterone, androgen) f. hair loss or hypertrichosis (hairy, 多毛癥) genetics, race, androgen. hypertrichosis: PCOS, congenital adrenal hyperplasia, Cushing disease, o

23、varian tumors, hypothyroidism, drugs. d. hypertension with hypokhair loss: cortisol , androgen , g. gynecomastia (男性乳腺發(fā)育): Klinefelter syndrome, testicular tumors, drugs.) h. exophthalmos (突眼)：Graves disease, chronic lymphocytic thyroiditis, eye diseases.) i. bone pain and fractures (osteoporosis, h

24、yperparathyroidisim, bone or hematologic diseases)hair loss: cortisol , androgA. hormones and biomarkers (生化標志物) in serum and urine: hormones, electrolytes, sugarB. hormone derivatives: VMA, 17-OHCS, 17-KSLaboratory and Special ExaminationsA. hormones and biomarkers (生化C. Dynemic tests (動態(tài)試驗) stimul

25、ation test (興奮試驗)： hypofunction (hypocortisolism) inhibitory states (TSH in GD) suppression test (抑制試驗)： hyperfunction (DXM for Cushing disease) therapeutic test (治療試驗): (spironolactone treatment in suspected hyperaldosteronism)C. Dynemic tests (動態(tài)試驗)provocation test (glucagon test for diagnosis of

26、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 tesA. Pathogenic therapy: supplement of nutrient

27、s, 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) Therapeutic PrinciplesA. Pathogenic therapy: suppleC. Hyperfunction 1. drug

28、s to suppress hormone secretion (iodide for GD, spironolactone for hyperaldosteronism. SS for insulinoma) 2. radioactive therapy (131I for GD, - knife for pituitary tumors)C. HyperfunctionHYPERTHYROIDISM (THYROTOXICOSIS, 甲亢)Hyperthyroidism is only a diagnosis of excessive thyroid hormone status, not

29、 a concrete disease or a syndrome.It is wrong to say “Graves disease (Graves病)” as “hyperthyroidism (甲亢)” in brief.HYPERTHYROIDISM (THYROTOXICOSIThyroidal origin Graves disease multiple nodular thyrotoxicosis (多結節(jié)性毒性甲狀腺腫)Plummer disease (toxic thyroid adenoma)automatic hyperfunctional thyroid nodule

30、s (自主 功能性甲狀腺結節(jié))multiple autoimune endocrine syndrome with hyperthyroidism (多發(fā)性自身免疫性內分泌腺 病伴甲亢)thyroid carcinomasneonatal hyperthyroidismgenetic toxic thyroid hyperplasia/goiteriodine-induced hyperthyroidism (碘甲亢)Pathogenesis of HyperthyroidismThyroidal originPathogenesis oPituitary origin pituitary T

31、SHoma thyroid hormone insensitivity syndrome (pituitary type, 垂體型TH不敏感綜合征) paracarcinoma syndrome HCG-related hyperthyroidism carcinomas (lung, GI, pancreas) with hyperthyroidism Ovarian goiter with hyperthyroidism Iatrogenic hyperthyroidism (醫(yī)源性甲亢)Pituitary originTransient hyperthyroidismSubacute d

32、e Quervian thyroiditis (肉芽腫性甲狀腺炎) hymphocytic thyroiditis (postpartum, IFN, IL, Li) trumatic thyroiditis radioactive thyroiditisChronic chronic lymphocytic thyroiditisTransient hyperthyroidismPathogenesisHistopathologyClinical presentationLaboratory and special examsDiagnosis and differential diagno

33、sisTreatmentGRAVES DISEASE (GD)PathogenesisGRAVES DISEASE (GDGD 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 hyperthyroidismGraves Disease (GD)GD is also called: dif

34、fuse toxA. Abnormalities of immune system a. TSH-R-Ab + TSH-R 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)PathogenesisA. Abnormalities of immune sysstimulating IgG hyperfunction(TSAb) c. TRAbinhibitory IgG hyp

35、ofunction and antagonistof TSHR andTSAb (TF1Ab, TGBAb)growth-stimulating IgG (TGI)B. Other factors genetic factors infective factors stress (physical or emotional)stimulating IgG hypeC. Thyroid-associated ophthalmopathy (TAO) unknown GAG (葡萄聚糖) accumulation, T cell infiltration, edema, fibrosis and

36、sight loss.C. Thyroid-associated ophthaA. Thyroid goiter: symmetrical, diffuse, soft enlarged after treatment: lobular follicles: hyperplastic column with scant colloid, papillary projections, vascularity increased lymphocytes and plasma cells infiltration HistopathologyA. Thyroid HistopathologyB. E

37、yes orbital contents increased, containing mucoprotein, GAG (glycosaminoglycan, 葡糖聚糖), lymphocytes.C. Skin (dermopathy) hyaluronic acid (透明質酸), chondroitin sulfates (硫酸軟骨素) increased, collagen fibers separated nodular and plaque formation lymphatic drainage decreasedB. EyesA. General considerations

38、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

39、%)Clinical PresentationA. General considerationsCliniC. Thyroid diffuse goiter: absent in the elderly, consistency: soft, firm, rubbery, symmetrical enlarged, surface: smooth, lobular, thrill with audible bruit eyelid spasm or retractionC. ThyroidD. Eyes a. non-infiltrative orbitopathy: fissure wide

40、ned, sclera exposed, lid retraction, lid tremor, lid lay, globe lay.D. Eyesb. infiltrative orbitopathy: excessive tearingexophthalmos (asymmetrical)eyelids unclosedblurred visiondouble visionvisual acuity decreasedcorneas ulcerated, infectedsight lossb. infiltrative orbitopathy: c. Classification of

41、 Graves orbitopathy: NOSPECS (from: American Thyroid Association)ClassDefinition0No physical signs or 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 involvemen

42、t5Corneal involvement6Sight loss (optic nerve involvement)c. Classification of Graves orE. Others tremor of the hands and tongue muscle wasting rapid reflex response diarrhea liver function wbc , and anemia, vitiligo (白癜風), hair loss pretibial myxedema (脛前粘液性水腫)E. OthersF. Complications a. cardiopat

43、hy and heart failurethyrotoxicosis ,arrhythmia, heart enlargement and heart failure, and all disappeared after treatment b. Thyrotoxic crisissymptoms and signs exaggerated abruptlyprecipitating factors: infection, trauma, surgeryradiation thyroiditis, DKA, parturtionAdditional pictures: arrhythmias,

44、 pulmonary edema,congestive heart failure, restlessness, delirium,nausea, vomiting, abdominal pain, apathy, stupor,coma, hypotension, shock, etc.F. Complicationsc. hypokalemic periodic paralysismore common in Asiaabruptly paralysis with hypokalemiaprecipitated by dextrose, oral carbohydrateor vigoro

45、us exercise.attacks last 7-27 hrs.some companied by myasthenia gravis.c. hypokalemic periodic paralyA. Serum TH and TSH a. FT3 and FT4 b. TT3 and TT4 c. rT3 d. TSHB. TSH receptor antibodiesLaboratory and Special ExamsA. Serum TH and TSHLaboratory C. TRH stimulation testeuthyroid Graves ophthalmopath

46、yGD medicationD. 131I uptake and T3 suppression testE. pathological examsC. TRH stimulation testA. 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 DM, TB, heart failu

47、re, CHD, liver diseaseDiagnosis and Differential DiagnosisA. Functional diagnosisDiagnosB. 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 hyperthyr

48、oidismC. Pathogenic diagnosis TRAb, TgAb, TPOAb, HCG, 131I uptake, TSHB. TypesC. Pathogenic diagnosiA. General management rest enough, energy and nutrients supplement, sedatives for restlessness and insomnia.B. Management of hyperthyroidism a. medical antithyroid agents: methylthiouracil (MTU) or pr

49、opylthiouracil (PTU) 300600mg/d methimazole (MM) or carbimazole (CMZ) 3060mg/d TreatmentA. General management Treatmb. 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), Qd

50、b. dosage and coursec. “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 TRHc. “block-replace” regimense. drug side-effectsprimary and secondary f

51、ailureagranulocytosis (1%, within 2 mos)WBC count/ wk or moe. drug side-effectsC. Radioiodine (131I) a. more active than before, more(USA) VS less (Euro) b. contraindications: pregnant thyrotoxicosis young people (20yrs) severe exophthalmos thyrotoxic crisis failed to I uptake dosage should be calcu

52、lated by specialistC. Radioiodine (131I)C. Complicationshypothyroidismradiation thyroiditisthyrotoxic crisisexaggarated proptosis (smoking)C. ComplicationsD. Surgery indications: failed to antithyroidal agent huge thyroid or suspected with tumors retrosternal goiter contraindications: severe proptos

53、is severe systemic diseases early and late pregnancy thyrotoxicosis not controlledD. SurgeryE. Treatment decision-making a. firstly, treated with medications for all patients b. after controlled, decided byagerun course of diseaseseverity & complicationsthyroid statesdoctors experiencepatients willi

54、ngs and special entitiesE. Treatment decision-makingF. 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 propranololF. Special concerns d.

55、PTU is the treatment of choice for hyperthyroidism in pregnancy, never makes TSH 0.5U/L e. heart failure treated with digoxin may be dangerous in some cases d. PTU is the treatment of高敏TSH檢測在甲狀腺功能診斷及監(jiān)測中的意義 甲狀腺功能異常是臨床上常見的一組疾病。有研究表明，高敏TSH在甲狀腺功能診斷方面最為敏感。1999年9月2000年11月在我科實驗室所做的5100人次甲狀腺功能檢查，以了解三項檢測指標在甲

56、狀腺功能診斷及監(jiān)測中的意義。1 資料和方法1.1 實驗對象我科臨床診斷為甲亢的病人及甲亢服藥復查的病人共4518份血標本。1.2 實驗方法標本收集每次抽肘靜脈血3ml，離心后取血清置20保存。檢測方法FT3，F(xiàn)T4用放免法，藥盒由天津協(xié)和試劑公司提供，TSH用免放法，藥盒由天津協(xié)和試劑公司提供。1.3 統(tǒng)計學處理率的比較采用X2檢驗。高敏TSH檢測在甲狀腺功能診斷及監(jiān)測中的意義 2 結果4518份標本中，F(xiàn)T3、FT4均增高，TSH降低者有1596份，占總數(shù)的35.25%；FT3增高，TSH降低，F(xiàn)T4正常者有564份，占總數(shù)的12.46%；FT4、FT4正常，僅有TSH降低者有736份，占總

57、數(shù)的16.25%；三項結果均正常者有820份，占總數(shù)的18.11%；FT3、FT4正常，而TSH升高者有338份，占總數(shù)的7.46%；FT3、FT4降低，TSH升高者有46份，占總數(shù)的1.02%；FT4降低，TSH升高，F(xiàn)T3正常者有314分，占總數(shù)的6.93%；FT4增高，TSH降低，F(xiàn)T3正常者有46份，占總數(shù)的1.02%；其他各種組合有29份，占總數(shù)的0.64%。2.1 在診斷甲亢方面以TSH降低為診斷指標，其陽性率為65.33% （2952/4518），以FT3升高為診斷指標，陽性率為47.80%（2160/4518）經X2檢驗，差異有顯著性（P0.001），說明以TSH降低為診斷指標，陽性率為36.56%（1652/4518），明顯低于TSH和FT3的陽性率（均P0.001），提示在診斷甲亢時，