《内分泌内科学》全册配套教学课件（英文版）.ppt

1、内分泌内科学全册配套教学课件1(英文版）Cushings SyndromeGE QianThe First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology Cushings syndrome is caused by chronic exposure to excess glucocorticoids(cortisol),characterized by truncal obesity,Round face,Plethora,Hirsutism,Violaceous striae,Hy

2、pertension,etc.DefinitionThe hypothalamic-pituitary-adrenal axisfeedbackCause of Cushings syndrome1.ACTH-dependent CortisolPituitary ACTHAdrenal hyperplasia Pituitary microadenomas(10mm)Cushings diseaseTumoursEctopic ACTH Lung small cell carcinoma,bronchial carcinoid tumoursEctopic ACTH syndrome2.AC

3、TH-independent Tumor/HyperplasiaCortisolAutocrinePituitary ACTH Adrenal adenomaAdrenal carcinomaMicronodular adrenal hyperplasia(5mm)Cause of Cushings syndromeEpidemiologyCushings disease:Women:men=4:1Ectopic ACTH syndrome:Women:men=1:1Adrenocortical adenoma/carcinoma:Women:men=4:1Pathophysiology an

4、d Clinical Signs Metabolism(Glucose,Lipid,Protein)Immune system Blood system Reproductive system Central nervous system 1.Typical habitus Truncal obesity“Moon”face“Buffalo”humpViolaceous striaeBruisability OsteoporosisPlethoraPeculiar distributionof adipose tissueProtein catabolismRed blood cellsTru

5、ncal obesity Moon facePlethoraBuffalo humpViolaceous striaeViolaceous striae Osteoporosis：vertebral bodies flatten 2.Hypertension,Electrolyte disturbances Water and sodium retention,potassium depletionHypertension,Hypokalemialeft ventricular hypertrophy,heart failure,cerebrovascular accident,etc.3.I

6、mpaired glucose tolerance,Diabetes mellitus(Steroid diabetes)Stimulation of hepatic gluconeogenesis，resistance of insulin4.InfectiousInfections of Bacteria,Fungi,VirusesImmunosuppression:functions and numbers of neutrophils,lymphocytes,monocytes,macrophages the anatomical barrier function of the ski

7、n5.Sexual dysfunctionwomen -Amenorrhea or Oligomenorrhea -Virilization:Hirsutism,Acne,MastatrophyInhibition of Gonadotropin,Adrenal androgensmen-Decreased libidoNeurologic changes:decreased strength,headaches,decreased memory and cognitionPsychiatric changes:depression,anxiety,irritabilityHyperpigme

8、ntation:Ectopic ACTH syndrome and severe Cushings disease6.OthersMSH(Melanocyte-stimulating hormone)Melanocyte MelaninPigment黑色素细胞黑色素细胞黑色素黑色素Mechanism of hyperpigmentationACTHThe partial action of MSHMelanin pigment depositionHyperpigmentation4.Manifestationp Hyperpigmentation:Tests1.Plasma cortisol

9、 levels 2.24-hour Urine free cortisol(UFC)3.Plasma ACTHDiscrimination of ACTH-dependent and-independent Cushings syndromeCushings diseaseEctopic ACTH-syndromeAdrenal adenoma 4.Plasma cortisol circadian rhythmNormal cortisol circadian rhythmPlasma cortisol circadian rhythm of cushings syndromeNormal

10、Cushings syndrome5.Dynamic tests1 mg overnight dexamethasone suppression test(1mg DST)Method:1 mg by mouth,between 23h and 0h,and the measurement of cortisol between 8h and 9h the following morning.Results:Normal:Cortisol50nmol/L Low-dose dexamethasone suppression test(LDDST)Result Normal:Day 3 plas

11、ma cortisol 50nmol/L Method(2mg/day)0800h1600h0000hDay 1 Dexa0.75mg0.75mg0.5mgDay 2Dexa0.75mg0.75mg0.5mg0700h keep 24-hour urineDay 3 0800h measure plasma cortisol and 24-hour urine cortisol 0800h1400h2000h0200hDay 10700h keep 24h urine,measure plasma cortisolDay 2Dexa3 tablets3 tablets3 tablets2 ta

12、bletsDay 3Dexa3 tablets3 tablets3 tablets2 tablets0700h keep 24h urine Day 40800h measure plasma cortisol and 24h urine cortisol Method(8mg/day)Result Be suppressed:Day 4 plasma cortisol 50%of the basal levelHigh-dose dexamethasone suppression test(HDDST)Discrimination of the causes of Cushings synd

13、rome by HDDST HDDSTACTHCushings diseasesuppressedAdrenal adenoma/carcinomaNo Ectopic ACTH syndromeNo Pituitary MRI：microadenomaPituitary MRI：macroadenoma6.Imaging examinationCT：normal adrenal CT：adrenal adenoma7.Inferior petrosal sinus sampling(BIPSS)Discrimination of Cushings disease and Ectopic AC

14、TH syndromeInvasive TestCushings syndrome(CS)suspected24hUFC,Plasma cortisol circadian rhythm,1mg DSTNormalAbnormalLow-dose DSTCS excludedCS confirmedAbnormalDiagnosis1.Step2.Etiologic diagnosisPlasma ACTHHigh-dose DST3.Location diagnosisPituitary enhanced MRIAdrenal enhanced CTChest enhanced CT/Who

15、le body PET-CTCushings disease ACTH Suppressed by High-dose DST Pituitary lesions by CT,MRI Bilateral adrenal mild hyperplasia4.Differential diagnosisEctopic ACTH syndrome Plasma ACTH Hypokalaemia,Hyperpigmentation Not suppressed by high-dose DST Chest CT/Whole body PET-CTAdrenal adenoma/carcinoma A

16、denoma：progressed gradually Carcinoma：progressed rapidly，evident sign of androgen excess(virilization)Plasma ACTH Not suppressed by high-dose DST Adrenal enhanced CTSurgical treatment Transsphenoidal microsurgery：most widely usedPituitary irradiation post operationHypophysectomy Total adrenalectomyC

17、ushings diseaseTreatmentAdrenal neoplasmaLaparoscopic adrenalectomy Hypopituitarism/hypoadrenocorticism -Glucocorticoid and mineralocorticoid replacement Nelsons syndrome:rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels after total adrenalectomy due to Cushi

18、ngs disease -Periodic pituitary MRI and ACTH measurement -Pituitary irradiation Adverse effects Medical TherapySteroidogenesis inhibitors:Suppression of cortisol productionKetoconazole MetyraponeMitotaneEtomidateCase oneFemale，30-year，Postpartum depression for 6 months，weight gain for 3 months.Physi

19、cal examination：T36.5C,BP164/116mmHg,Round face,Plethora,bearded jaw,hirsute back,wide violaceous strae,distended abdomen.Tests：-24h UFC 1620.9nmmol -Plasma cortisol circadian rhythm:8 am 754.7nmmol/L 16 pm 647.0 nmmol/L 0 am 671.9 nmmol/L -ACTH(8am)1718.76nmmol/L High-dose DST Plasma cortisol 643.3

20、5nmmol/L Urine cortisol 2406.2nmmol/L Not suppressed by both Low-dose and high dose DSTAdrenal CTDiagnosis？Cushings syndromeAdrenal adenoma Treatment AdrenalectomyCase TwoMale，15-year，Growth retardation for 8 years，fatigue and weight gain for 3 months.Physical examination：T36.7C，BP126/96mmHg,“Moon”f

21、ace,“Buffalo”hump,Violaceous striae on bilateral inner thighs.A 2x2cm nodule was touched in thyroid gland,without tenderness,with clear border.Tests：K+3.0mmol/L，Fast plasma glucose(FPG)8.0mmol/L，24h UFC758ug Plasma cortisol circadian rhythm:8 am 1379nmmol/L 16 pm 1379nmmol/L 0 am 1379nmmol/L ACTH(8a

22、m)246pg/mL History Dynamic Tests：-Not suppressed by LDDST and HDDST -Thyroid function：TSH 19.8 IU/ml -Calcitonin 243ng/L -Pituitary MRI：Normal -Adrenal CT：Bilateral adrenal hyperplasia -X-ray：Osteoporosis in spine and pelvis -Cervical CT:Thyroid nodule Diagnosis？Medullary thyroid carcinoma Ectopic A

23、CTH syndromeCushings syndromeTreatmentTotal thyroidectomy Harrisons Internal Medicine 17th Edition Harrisons Endocrinology 3rd EditionReference BookThank you Hypopituitarism(腺垂体功能减退症腺垂体功能减退症)Endocrinology department,the 1st affiliated hospital,chongqing medical universityJian longSella turcica（蝶鞍）（蝶

24、鞍）Bean-shapedWeight:5 g Thyroid gland Adrenal gland Ovary(甲状腺）甲状腺）（肾上腺）（卵巢）（肾上腺）（卵巢）TargetglandAnterior part （前叶）（前叶）(Adenohypophysis)(腺垂体腺垂体)Posterior part (后叶后叶)(Neurohypophysis)(神经垂体）神经垂体）Pituitary stalk (垂体柄垂体柄)Hypothalamus （下丘脑）（下丘脑）1）Positive feedback2）Negative feedbackHypothalamus Pituitary g

25、land Target glands（下丘脑）（下丘脑）（垂体）（垂体）Hypothalamus Pituitary gland Target glands（下丘脑）（下丘脑）（垂体）（垂体）Feedback(反馈反馈)HypothalamusPIF(prolactin inhibiting factor)GHRH(GH releasing hormone)LHRH(LH releasing hormone)TRH(TSH releasing hormone)CRH(Corticotropic releasing hormone)Anterior pituitary glandPRL(Prol

26、actin)（催乳素）GH（growth hormone）(生长激素)LH(luteinizing hormone)(黄体生成素)FSH(follicle stimulating hormone)（卵泡刺激素）TSH（thyroid stimulating hormone)（促甲状腺激素）ACTH(adrenal cortex stimulating hormone)促肾上腺皮质激素)Target glandE2、E3(estrogen)T(testosterone)T3、T4CortisoneHormonesHypopituitarismDefinition:Hypopituitarism

27、is a condition in which the pituitary gland does not produce one or more of its hormones or not enough of them.Etiology(病因学病因学):Primary Secondary1、tumor 2、ischemic necrosis（坏死）（坏死）3、surgery、trauma、radiotherapy（放疗）（放疗）3、infection、infiltration（浸润）（浸润）4、hereditary disease（遗传）（遗传）5、autoimmune disease（自身

28、免疫）自身免疫）1.Secondary:damage to hypothalamus or pituitary stalk2.Primary:damage to pituitarySecondaryPrimary SecondarySimmond disease:is one kind of hypopituitarism,which accures only in adult.Sheehans syndrome:is one kind of hypopituitarism,in which the decreased productions of the anterior pituitary

29、 hormones are due to ischemic postpartum（产后）（产后）pituitary necrosis（坏死）（坏死）or septicemia（败血症）（败血症）after delivery.HypopituitarismSimmond diseaseSheehans syndrome primary disease u the kind of deficient pituitary hormonesu the degree of the deficiency u the rate of disease progression1 kind2 kinds3 kin

30、dsall kindsFunction loss Symptoms and signs50%insidious（隐匿的）75%obvious（显著的）95%serious（严重的）prolactin(PRL)gonadotropin(LH、FSH)growth hormone(GH)thyrotropin(TSH)corticotropin(ACTH)PRL can not lactate(泌乳）after delivery2、Gonadotropin deficiencyAmenorrhoea（闭经）、Infertility（不孕）Regression of secondary sexal

31、characteristics3、Growth hormone(GH)deficiency In adult it is not obvious.Symptoms and signs of hypopituitarismSymptoms and signs of hypopituitarism4、TSH deficiency Intolerance of colddry skinpallor（苍白）（苍白）Periorbital puffiness（浮肿）（浮肿）horseness of voice bradycardia（心动过缓）（心动过缓）weight gainconstipation（

32、便秘）（便秘）loss of hairSymptoms and signs hypopituitarism5、fatigue(乏力）乏力）anorexia（厌食）（厌食）nausea、vomiting loss of hairpostural hypotensionhypoglycemia（低血糖）（低血糖）hypopigmentation（色素减少）（色素减少）Hypopituitarism Primary hypoadrenocorticism(原发性肾上腺皮质功能减退)POMCdecreasedincreasedpigmenthypopigmentation hyperpigmentat

33、ion They possess several kinds of hormone deficiency,or all kinds.Symptoms and signs in hypopituitarism are combined by each kind of symptoms and signs due to hormones deficiency.Investigation1、Measurement of hormones 2、Stimulating test Investigation1、Measurement of hormones level pituitary hormones

34、target glands hormonesPRLGHGnRH(LH、FSH)E2、TTSHT3、T4ACTHCortisonehypopituitarism normal range 2、Stimulating test：1）assess pituitary function 2)assess target gland function1)Assessment of the functions of pituitary GHRH or CRF or LHRH is injecting into humans body,then measure the level of pituitary h

35、ormones and target gland hormones.Hormone from hypothalamus Hormone from pituitary glandGHRHGH CRFACTHLHRHLH、FSHCan not be elevatedHormone from pituitary glandTarget gland hormonesACTHcortisoneTSHT3、T42)Assessment of the function of target glandsInsulin-hypoglycemia stimulating testinsulin injection

36、 to induce hypoglycemiacortisoneAdrenal gland3、others Hypoglycemia Hypotension Hyposalemia(低钠血症低钠血症)Anemia（贫血）（贫血）4、Imageological examination（影像学检（影像学检测）测）CT or MRI X-rayDiagnosis1)history of damage to pituitary gland or hypothalamus2)symptoms and signs related to hormone deficiency3)evidency of ant

37、erior pituitary hormone deficiencyTreatmentHormone replacementAll life replacement1、Adrenal hormone replacement must be first Hydrocortisone 20mg 8AM 10mg 4PM Cortisone 5mg 8AM 2.5mg 4PM Fludrocortisone may be not required if necessary 0.1-0.2mg/d Goal:No symptoms and signs due to adrenal gland horm

38、one deficiency.No symptoms and signs of due to adrenal gland hormone overdose.2、Thyroid hormone replacement L-T4 original dose 12.5-25ug/d maintenance dose 100-200ug/d 3、Sexal hormone Replacement For people in reproductive age or anxiety for fertility Estrgen(雌激素雌激素)the first 25 days in each month P

39、rosteron（孕激素（孕激素）day 15 through 25 Goal:T3 T4 in normal rangePituitary crisisPituitary crisis occurred on the basis of pituitary dysfunction in various stress reactions.Treatment of pituitary crisis 1.Supplement of glucose First 50%glucose,40 to 60 ml,rescue hypoglycemia.10%glucose to maintain input

40、2.Corticosteroids applications Hydrocortisone 200 of 300 mg decreasing the amount gradully to oral.3.Thyroid hormone replacement4.remove incentives(去除诱因去除诱因)5.supportive treatment 原发性醛固酮增多症重庆医科大学附属第一医院内分泌科宋颖 女性，34岁 严重高血压 严重低血钾，碱中毒 通过切除右侧肾上腺的 4cm醛固酮分泌型腺瘤 后而得到治愈引言引言引言 1954年美国的内分泌医生Jerome W.Conn发现第一例原发

41、性醛固酮增多症患者，并把该疾病命名为Conns综合征主要内容1.概述2.病因病理3.临床表现4.实验室检查5.诊断与鉴别诊断6.治疗本课程要求1.了解本病的病因和病理。了解本病的病因和病理。2.熟悉本病的临床表现及鉴别诊断。熟悉本病的临床表现及鉴别诊断。3.掌握本病的实验室检查及治疗原则掌握本病的实验室检查及治疗原则概述 原发性醛固酮增多症(primary aldosteronism,PA)简称原醛症，是由肾上腺皮质病变致醛固酮分泌增多并导致水、钠潴留及体液容量扩增继而血压升高并抑制肾素-血管紧张素系统所致。患病率：在高血压患者中占10%左右，在中国2亿多高血压患者中约2000万左右应属于原醛

42、病人。数量多！诊断率低数量多！诊断率低!危害大危害大!占难治性高血压占难治性高血压(Resistant hypertension)的的20%！概述概述被忽略的常见病被忽略的常见病!概述概述概述概述醛固酮醛固酮细胞内钾降低，钠增加细胞内钾降低，钠增加肾重吸收钠增加肾重吸收钠增加肾脏排钾增加肾脏排钾增加血钠增加血钠增加血浆渗透压增加血浆渗透压增加抗利尿激素增加抗利尿激素增加细胞外液增加细胞外液增加血钾降低血钾降低肾脏泌氢增加肾脏泌氢增加血 中 碱 储 备血 中 碱 储 备（HCO3-）增加）增加概述概述Na+-H+交换交换醛固酮醛固酮肾远曲管、集合管重吸肾远曲管、集合管重吸收钠增加收钠增加肾重吸收

43、钠增加肾重吸收钠增加肾脏排钾增加肾脏排钾增加血钠增加血钠增加血浆渗透压增加血浆渗透压增加抗利尿激素增加抗利尿激素增加细胞外液增加细胞外液增加血钾降低血钾降低肾脏泌氢、排钾增加肾脏泌氢、排钾增加血血HCO3-增加增加（碱中毒）（碱中毒）概述概述Na+-H+交换交换 Na+-K+交换交换按病因分型及相对发病率类型类型相对发病率相对发病率（%）1、醛固酮分泌腺瘤（、醛固酮分泌腺瘤（APA）35352、特发性原醛症（、特发性原醛症（IHA）60603、家族性醛固酮增多症、家族性醛固酮增多症 糖皮质激素可抑制性原醛症（糖皮质激素可抑制性原醛症（GSH或或FH-1）1 1 家族性原醛症家族性原醛症型（型（

44、FH-）未知未知 家族性原醛症家族性原醛症型（型（FH-）未知未知4、分泌醛固酮的肾上腺皮质癌、分泌醛固酮的肾上腺皮质癌1 15、原发性肾上腺增生症（、原发性肾上腺增生症（PAH）1 16、血管紧张素、血管紧张素反应性肾上腺皮质腺瘤反应性肾上腺皮质腺瘤5 57、异位醛固酮分泌性腺瘤和腺癌、异位醛固酮分泌性腺瘤和腺癌罕见罕见病因病理分泌醛固酮的肾上腺皮质腺瘤（aldosterone-producing adenoma,APA）:Conn综合征 较多见，约占35%多为一侧单个腺瘤，直径大多1-2cm 包膜，切面金黄色 光镜：球状带、束状带、致密细胞及杂交细胞右侧肾上腺外侧支小结节影（大右侧肾上腺外

45、侧支小结节影（大10.8cm，HU为为7），），腺瘤可能。腺瘤可能。病因病理病因病理病因病理病因病理特发性醛固酮增多症(idiopathic hyperaldosteronism,IHA）最多见，约占60%双侧肾上腺球状带增生，有时伴结节细胞来源：束状带透明样细胞免疫组化：细胞色素P450，11-羟化酶和醛固酮合成 酶呈阳性生化指标：比APA轻病因病理病因病理病因病理糖皮质激素可抑制性醛固酮增多症（glucocorticoid-suppressible hyperaldosteronism，GSH，家族性醛固酮增多症1型，FH-1）常染色体显性遗传，约占1%青少年起病，可为家族性，也可为散发性

46、血浆醛固酮浓度与ACTH昼夜节律平行糖皮质激素治疗有效发病机制：8号染色体11羟化酶基因与醛固酮合成酶基因形成融合基因，编码的蛋白有醛固酮合成酶活性病因病理分泌醛固酮的肾上腺皮质癌 少见，1%体积较大（3cm），内有出血、坏死、钙化 除醛固酮外，可同时分泌其他皮质类固醇临床表现一.高血压：多为缓慢发展的良性高血压，可最早出现，随病程延长血压逐渐升高二.低血钾：1.1.神经肌肉功能障碍：乏力或周期性瘫痪，呼吸困难、肢端麻木或手足抽搐 2.2.慢性失钾性肾病：高醛固酮致肾大量失钾，肾小管上皮细胞空泡变、浓缩 功能受损，夜尿增多，易发尿路感染或肾盂肾炎。3.3.心脏表现：U U波出现,心脏Q-TQ-

47、T间期延长,心律失常。三.其他：儿童生长发育迟缓，胰岛素分泌减少，糖代谢异 常临床表现实验室检查一、基本生化检查：1.低血钾：大多在2-3mmol/L，且为自发性、持续性 2.高尿钾：血钾25mmol/24h，为肾性失钾 3.碱血症：细胞内钾丢失，钠、氢离子增加，H+向细胞内 转移，细胞外碱血症 4.血钠：可正常或略高 5.尿检:中性或偏碱性，尿比重降低，部分有蛋白尿7.血浆醛固酮(受体位、钠盐摄入及血钾水平影响)：不限钠盐摄入，纠正低钾，晨起后2小时、坐位采血 原醛患者醛固酮水平高于正常8.血浆肾素：放免法测肾素活性：通过血管紧张素I的生成速率间接反映 化学发光法直接测肾素浓度 原醛患者肾素

48、水平低于正常实验室检查实验室检查我科利用我科利用DRCDRC筛查原醛症后，筛查原醛症后，诊断诊断原醛的例数大幅上升原醛的例数大幅上升诊断 筛查：血浆醛固酮/肾素比值（ARR）确诊：4种确诊试验 分型：AVS、影像哪些高血压病人应该筛查原醛？自发或利尿剂诱发的低血钾的高血压；2级、3级高血压；难治性高血压(Resistant hypertension)伴肾上腺意外瘤的高血压；早发（20岁）或年轻（40岁）的脑血管病家族史的高血压 原醛症患者所有患高血压的一级亲属 高血压合并阻塞性呼吸睡眠暂停。难治性高血压：联合使用3种降压药物，其中包括利尿剂，BP140/90mmHg或联合使用4种及以上降压药物

49、，BP140/90mmHg 诊断1筛查：血浆醛固酮/肾素比值（ARR）是筛查原醛的指标 注意：判断结果根据各实验室标准而定影响ARR测定的因素1、停影响ARR的药4-6周：螺内酯、雌二醇（拟盐皮质激素样作用）、排钾利尿剂、氨苯喋啶、甘草等。2、停影响ARR的药2周：受体阻滞剂、ARB、ACEI、NSAIDS等。3、此外、性别、月经周期、妊娠、体位、时间也可影响结果。4、可使用的对ARR影响较少的降压药(非二氢吡啶类、受体阻滞剂、直接血管扩张剂)。假阳性 受体阻滞剂 甲基多巴，可乐定 NSAIDs类 一些口服避孕药 假阴性 利尿药 钙通道阻滞剂（二氢吡啶类）ACEI/ARB SSRI抗抑郁类药物

50、影响影响ARR测定的因素测定的因素因素因素对醛固酮影响对醛固酮影响对肾素影响对肾素影响对对ARR影响影响药物因素药物因素受体阻滞剂（假阳性）非甾体类抗炎药（假阳性）排钾利尿剂（假阴性）潴钾利尿剂（假阴性）ACEI（假阴性）ARBs（假阴性）血钾状态血钾状态低血钾（假阴性）高血钾（假阳性）钠盐摄入钠盐摄入低钠饮食（假阴性）高钠饮食（假阳性）年龄增长年龄增长（假阳性）其他因素其他因素肾功能不全（假阳性）妊娠（假阴性）肾血管性高血压（假阴性）影响影响ARR测定的因素测定的因素二.确诊试验：初筛阳性患者，需进一步选择下述4种之一确诊检查诊断口服钠盐负荷试验静脉盐水负荷试验卡托普利激发试验氟氢可的松抑制