內(nèi)分泌總論、甲亢英文廖二元分解

1、CLINICAL ENDOCRINOLOGY & METABOLISM—INTRODUCTION AND GENERAL CONCEPTS(總論),Institute of Metabolism & Endocrinology,Eryuan Liao (廖二元),A. The rapidity and extensiveness of advances in endocrinology have made it incr

2、easingly difficult for the students and physicians to take full advantage of information available for the understanding, diagnosis, and treatment of clinical disorders, not only of diseases in endocrinology, but also o

3、f 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 interesting medical branch.D. Ma

4、in subjects,Regulation systems of extracellular communicationEndocrine gland and hormone-secreting cellsHormonesHormone secretion rhythmsHormone synthases and its regulationEndocrine regulation axes,Mechanisms of h

5、ormone actionNutrient metabolismSystemic examinationLaboratory and special examinationsTherapeutic principles,Regulation Systems of Extra-Cellular Communication,nervous systemendocrine systemimmune system,Endocrine

6、 Gland and Hormone-Secreting Cells（激素分泌細(xì)胞）,A. Endocrine gland a. hypothalamus & posterior pituitary b. pineal gland (松果體) c. anterior and intermedial pituitary,d. thyroid e. parathyroid f. endo

7、crine pancreas (內(nèi)分泌胰腺) g. adrenal cortex and medulla h. sexual gland (testis or ovary) i. others: thymus (胸腺)，placenta,B. Diffuse neuro-endocrine cells APUD(amine precursor uptake and decarboxylation) cells

8、 in GI, pancreas, adrenal medulla, etc.)C. Hormone-secreting cells in tissues atrium, endothelium, fibroblast, lipocytes, lymphocytes,Structure of hormone-secreting cells peptide/protein hormone-secreting cells:

9、 hormone-containing granules (激素顆粒) steroid hormone-secreting cells: lipid droplet (脂質(zhì)小滴),A. Classification a. as peptide/protein b. as derivatives of amino acid (ca

10、techolamine, 5-HT, melatonin, T3/T4) c. as derivates of cholesterol (cortisol, aldosterone, estrogen, androgen, progesterone, 1, 25-(OH)2D3)B. Storage hormone granules thyro

11、globulin (甲狀腺球蛋白),Hormones,C. Types of hormone secretion,endocrine (內(nèi)分泌)paracrine (旁分泌)autocrine (自分泌)intracrine (胞內(nèi)分泌)neurocrine (神經(jīng)分泌)juxtacrine (并鄰分泌)solinocrine (腔分泌)amphicrine (雙重分泌),solu

12、ble hormone+binding protein: insulin, GH. IGF. Glucagon-like peptideinsoluble hormone+binding protein: T3, T4, sex steroids, cortisol, vitamin D.,D. Hormone transportation,half-life: peptides and protein: mi

13、nutes steroids: variable, hrs degradation in liver, kedney, other tissues, or in hormone-secreting cells.,E. Hormone degradation and half-life,A: Biological rhythms（生物節(jié)律） milliseconds: nerve impulse, membrane

14、 electrolytes. minutes: neurotransmitters hours: LH, TRH, testosterone, cortisol, GH, prolactin, TSH, etc days: FSH peaks weeks: menorrhea months: T4, 1,25-(OH)2D3, pregnancy,Secr

15、etion Rhythms,B. Circadian rhythms (晝夜節(jié)律) biological “clock” in hypothalamus (melatonin), but lost in Cushing disease and psychosisC. 24-hr changes of serum and urine hormone (metabolic products),D. Heterogene

16、ity of serum hormones hormone, pro-hormone (激素原), prepro-hormone (前激素原) monomer, dimer, trimer tetramer, etc. fragement of peptides.,A. Endocrine regulation active hormone molecule

17、 hormone-binding protein hormone receptor on membrane in cytoplasma in nucleolus (nucleoplasm) post-receptor transduction (cascade reaction) tropic-hormone (促激素) feedback cycle targe

18、t cell reaction,Hormone Synthases and Its Regulation,B. Paracrine/autocrine regulation exist almost in all tissues. “point-line” (點(diǎn)-線式) regulation network,A. Hormone regulationA: ultra-short feed

19、back (超短反饋) B: short feedback (短反饋)C: positive feedback (正反饋) D: long negative feedback (負(fù)反饋) : stimulating; : inhibitory,,,A,nerve impulses/cytokines,CNS,hypothalamus,pituitary gland

20、,target gland,,,,,,D,B,,,,Endocrine Regulation Axes,,,,,,,,,B. Regulation axes (調(diào)節(jié)軸) a. hypothalamus-pituitary-thyroid (adrenal cortex, sexual gland) b. GIH/GHRH-GH/GHBP-IGFs/IGFBPS- IGFBP/IGF

21、BPase c. renin-AT-ALD involved in renin, AT, ALD, ANP, AVP, AM (adrenomedullin, 腎上腺髓質(zhì)素),d. axis of endocrine pancreas-energy metabolism and body weight involved in insulin, glucagon, g

22、lucagon-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

23、 BP V2 receptor: related to H2O reabsorption,A. Acted as transcription- regulatory factors steroid hormone bindin with receptor (cytoplasm or nucleoplasm)

24、 H-R complex+DNA binding domain gene expression protein,,,,,Mechanisms of Hormone Action,B. Acted at cell surface a. peptide hormone + membrane R postreceptor

25、 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 kinases (transmembrane 1 time), with tyrosine

26、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.,,metabolism, a

27、nabolism 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 Metaboli

28、sm,A. General concepts:,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,

29、 nutrition, systemic disease, GH, TH, insulin, leptin, cortisol, sex hormones) c. polydipsia and polyuria (DM, ALD , hyperparathyroidism, DI),,Systemic Examination,d. hypertension with hypokalem

30、ia (primary hyperaldosteronism, reninoma, Cushing syndrome) e. hyperpigmentation (ACTH, MSH, estrogen, progesterone, androgen) f. hair loss or hypertrichosis (hairy, 多毛癥) genetics,

31、 race, androgen. hypertrichosis: PCOS, congenital adrenal hyperplasia, Cushing disease, ovarian tumors, hypothyroidism, drugs.,hair loss: cortisol , androgen , g. gynecomastia

32、 (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 (osteopo

33、rosis, hyperparathyroidisim, bone or hematologic diseases),,,A. hormones and biomarkers (生化標(biāo)志物) in serum and urine: hormones, electrolytes, sugarB. hormone derivatives: VMA, 17-OHCS, 17-KS,Laborat

34、ory and Special Examinations,C. Dynemic tests (動態(tài)試驗(yàn)) stimulation test (興奮試驗(yàn))： hypofunction (hypocortisolism) inhibitory states (TSH in GD) suppression test (抑制試驗(yàn))： hyperfunction (D

35、XM for Cushing disease) therapeutic test (治療試驗(yàn)): (spironolactone treatment in suspected hyperaldosteronism),provocation test (glucagon test for diagnosis of pheochromocytoma)X-ray film (b

36、one 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),A. Pathogenic th

37、erapy: supplement of nutrients, gene treatment.B. Hypofunction: 1. hormone replacement therapy (Addison disease, hypothyroidism; hypogonadism) 2. drugs to stimulate hormone secretion

38、 (sulfonylurea for type 2 DM) 3. transplantation (organ, tissue, cells),Therapeutic Principles,C. Hyperfunction 1. drugs to suppress hormone secretion (iodide for GD, spironolactone for hyperald

39、osteronism. SS for insulinoma) 2. radioactive therapy (131I for GD, γ- knife for pituitary tumors),HYPERTHYROIDISM (THYROTOXICOSIS, 甲亢),Hyperthyroidism is only a diagnosis of excessive thyroid hormone

40、 status, 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 (多結(jié)節(jié)性毒性甲狀腺腫)P

41、lummer disease (toxic thyroid adenoma)automatic hyperfunctional thyroid nodules (自主 功能性甲狀腺結(jié)節(jié))multiple autoimune endocrine syndrome with hyperthyroidism (多發(fā)性自身免疫性內(nèi)分泌腺

42、 病伴甲亢)thyroid carcinomasneonatal hyperthyroidismgenetic toxic thyroid hyperplasia/goiteriodine-induced hyperthyroidism (碘甲亢),Pathogenesis of Hyperthyroidism,Pituitary origin pituitary TSHoma

43、 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 wit

44、h hyperthyroidism Iatrogenic hyperthyroidism (醫(yī)源性甲亢),Transient hyperthyroidismSubacute de Quervian thyroiditis (肉芽腫性甲狀腺炎) hymphocytic thyroiditis (postpartum, IFN, IL, Li) trumatic thyroiditis radi

45、oactive thyroiditisChronic chronic lymphocytic thyroiditis,PathogenesisHistopathologyClinical presentationLaboratory and special examsDiagnosis and differential diagnosisTreatment,GRAVES DISEASE (GD),GD is also

46、 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 (G

47、D),A. 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 ce

48、lls produce TSH-R-Ab (TRAb),Pathogenesis,stimulating IgG hyperfunction(TSAb) c. TRAbinhibitory IgG hypofunction and antagonistof TSHR andTSAb (TF1Ab, TGBAb)growth-stimulating IgG (TGI),,,,,,,

49、B. Other factors genetic factors infective factors stress (physical or emotional),C. Thyroid-associated ophthalmopathy (TAO) unknown GAG (葡萄聚糖) accumulation, T cell infiltrati

50、on, edema, fibrosis and sight loss.,A. Thyroid goiter: symmetrical, diffuse, soft enlarged after treatment: lobular follicles: hyperplastic column with scant colloid, papillary

51、 projections, vascularity increased lymphocytes and plasma cells infiltration,Histopathology,B. Eyes orbital contents increased, containing mucoprotein, GAG (glycosaminoglycan, 葡糖聚糖), lymphocytes.C

52、. Skin (dermopathy) hyaluronic acid (透明質(zhì)酸), chondroitin sulfates (硫酸軟骨素) increased, collagen fibers separated nodular and plaque formation lymphatic drainage decreased,A. General considerations

53、 male: female ≈ 1: 4~6, common in 30~40yrs.B. Hypermetabolic states nervousness (99%). irritability (90%), palpatation (88%), tachycardia (82%), insomnia (60%), fatigue (70%), heat intolerance (70%), ex

54、cessive sweating (40%), weight loss (75%), with voracious appetite (65%), menstrual pattern changed (50%),Clinical Presentation,C. Thyroid diffuse goiter: absent in the elderly, consistency: soft, firm, rub

55、bery, symmetrical enlarged, surface: smooth, lobular, thrill with audible bruit

56、 eyelid spasm or retraction,D. Eyes a. non-infiltrative orbitopathy: fissure widened, sclera exposed, lid retraction, lid tremor, lid lay, globe lay.,b. infiltrative orbitopathy: excessive tearingexop

57、hthalmos (asymmetrical)eyelids unclosedblurred visiondouble visionvisual acuity decreasedcorneas ulcerated, infectedsight loss,,,,c. Classification of Graves orbitopathy: NOSPECS (from: American

58、 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 an

59、d sign)3Proptosis>22mm4Extraocular muscle involvement5Corneal involvement6Sight loss (optic nerve involvement),E. Others tremor of the hands and tongue muscle wasting rapid reflex response

60、diarrhea liver function wbc , and anemia, vitiligo (白癜風(fēng)), hair loss pretibial myxedema (脛前粘液性水腫),,,F. Complications a. cardiopathy and heart failurethyrotoxicosis ,arrhythmia, heart enlargement

61、 and heart failure, and all disappeared after treatment b. Thyrotoxic crisissymptoms and signs exaggerated abruptlyprecipitating factors: infection, trauma, surgeryradiation thyroiditis, DKA, parturtionAddi

62、tional pictures: arrhythmias, pulmonary edema,congestive heart failure, restlessness, delirium,nausea, vomiting, abdominal pain, apathy, stupor,coma, hypotension, shock, etc.,c. hypokalemic periodic paralysismore

63、 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

64、FT4 b. TT3 and TT4 c. rT3 d. TSHB. TSH receptor antibodies,Laboratory and Special Exams,C. TRH stimulation testeuthyroid Graves ophthalmopathyGD medicationD. 131I uptake and T3 suppression testE. pa

65、thological exams,A. 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

66、failure, CHD, liver disease,Diagnosis and Differential Diagnosis,B. TypesFT3 、FT4 , sTSH (uTSH) : hyperthyroidismFT3(orTT3) , FT4(TT4) normal, sTSH : T3 hyperthyroidism FT4(orTT4) , FT3 (TT3) normal, sTSH :

67、 T4 hyperthyroidismFT3 and FT4 (ab)normal, sTSH : subclinical hyperthyroidism,C. Pathogenic diagnosis TRAb, TgAb, TPOAb, HCG, 131I uptake, TSH,A. General management rest enough, energy and nutrients supp

68、lement, sedatives for restlessness and insomnia.B. Management of hyperthyroidism a. medical antithyroid agents: methylthiouracil (MTU) or propylthiouracil (PTU) 300~600mg/d