1、1内分泌系统疾病内分泌系统疾病总总 论论Introduction to Endocrinology and Metabolic Diseases 复旦大学附属中山医院内分泌科复旦大学附属中山医院内分泌科 高鑫高鑫2History and development of Endocrinology(1)Roughly a hundred years ago,Starling coined the term hormone to describe secretin,a substance secreted by the small intestine into the blood stream to
2、 stimulate pancreatic secretion.In his Croonian Lectures,Starling considered the endo-crine and nervous systems as two distinct mechanisms for coordination and control of organ function.Thus,endocrinology found its first home in the discipline of mammalian physiology.3Work over the next several deca
3、des by biochemists,physiologists,and clinical investigators led to the characterization of many hormones secreted into the blood stream from discrete glands or other organs.These investigators showed for the first time that diseases such as hypothyroidism and diabetes could be treated successfully b
4、y replacing specific hormones.These initial triumphs formed the foundation of the clinical specialty of endocrinology.History and development of Endocrinology(2)4Advances in cell biology,molecular biology,and genetics over the ensuing years began to help explain the mechanisms of endocrine diseases
5、and of hormone secretion and action.Although these advances have embedded endocrinology into the framework of molecular cell biology,they have not changed the essential subject of endocrinology _the signaling that coordinates and controls the functions of multiple organs and processes.History and de
6、velopment of Endocrinology(2)5Hormone formation may occur either in localized collections of specific cells,in the endocrine glands,or in cells that have additional roles.Many protein hormones:growth hormone?parathyroid hormone?prolactin?insulin?glucagon?Leptin?Formation of small hormone molecules i
7、nitiates with commonly found Precursors:Such as:adrenals,gonads,or thyroid.In the case of the steroid hormones,the precursor is cholesterol,which is modified by various hydroxylations,methylations,and demethylations to form the glucocorticoids,androgens,and estrogens.In contrast,the precursor of vit
8、amin D,7-dehydrocholesterol,is produced in skin keratinocytes,again from cholesterol,by a photochemical reaction.ENDOCRINE GLANDS6 内分泌系统内分泌系统内分泌腺内分泌腺脏器内分泌组织脏器内分泌组织激素激素体液调节系统（包括旁分泌、自分泌）体液调节系统（包括旁分泌、自分泌）代谢过程代谢过程脏器功能脏器功能生长发育生长发育生殖衰老生殖衰老Endocrine System7内分泌学发展三阶段内分泌学发展三阶段n腺体内分泌学腺体内分泌学 Organic Endocrinol
9、ogyn组织内分泌学组织内分泌学 Histological Endocrinologyn分子内分泌学分子内分泌学 Moleculer Endocrinology8激素的种类激素的种类Hormones 肽类肽类/蛋白类激素蛋白类激素（Protein or peptide):ACTH,LH,FSH,PHT,TSH,Insulun,Glucagon,IGFs氨基酸衍生物（氨基酸衍生物（Amino Acid derivatives)：儿茶酚胺类（肾上腺素、去甲肾上腺素）儿茶酚胺类（肾上腺素、去甲肾上腺素）脂肪酸衍生物脂肪酸衍生物(Fatty acid derivatives):前列腺素类、视黄酸前列腺
10、素类、视黄酸 胆固醇衍生物（胆固醇衍生物（Cholesterol derivatives)：考的松，考的松，醛固酮、醛固酮、1,25(OH)2 D3性激素性激素9激素的作用机制（激素的作用机制（1）与膜受体结合与膜受体结合 G蛋白偶联蛋白偶联 发挥生物效应发挥生物效应 （肽类激素、生物胺、前列腺素）与膜受体结合与膜受体结合 受体自身磷酸化受体自身磷酸化 发挥生物学效应发挥生物学效应 （酪氨酸激酶）（生长因子家族、Insulin,IGFs)与核受体结合与核受体结合 与与DNA特异序列结合特异序列结合 功能蛋白转录功能蛋白转录 （甾体类激素）1011G-protein-coupled 7-memb
11、rane spanning receptor12G-protein-coupled 7-membrane spanning receptor13141516激素的作用机制（激素的作用机制（2）激素信息在细胞内的信号传导激素信息在细胞内的信号传导Coris:发现了磷酸化酶的可逆磷酸化发现了磷酸化酶的可逆磷酸化 （无活性的磷酸化酶（无活性的磷酸化酶b/有活性的磷酸化酶有活性的磷酸化酶a之间的互变）之间的互变）获得获得1951年诺贝尔奖。年诺贝尔奖。Sutherland:成功分离和确定的腺苷酸环化酶和磷酸二酯酶成功分离和确定的腺苷酸环化酶和磷酸二酯酶 （cAMP合成与分解的两个关键酶）合成与分解的两
12、个关键酶）提出了激素作用的第二信使学说提出了激素作用的第二信使学说 获得获得1971年诺贝尔生理医学奖。年诺贝尔生理医学奖。Krebs&Fisher:于于60年代末发现蛋白激酶年代末发现蛋白激酶A(PKA)（依赖（依赖cAMP,刺激多种底物蛋白磷酸化刺激多种底物蛋白磷酸化)阐明了阐明了PKA启动的磷酸化和去磷酸化途径。启动的磷酸化和去磷酸化途径。获得获得1992年诺贝尔生理医学奖。年诺贝尔生理医学奖。17内分泌系统的相互调节内分泌系统的相互调节神经神经-内分泌系统的相互调节内分泌系统的相互调节内分泌系统的反馈调节内分泌系统的反馈调节免疫系统与内分泌系统的关系免疫系统与内分泌系统的关系神经神经-
13、内分泌内分泌-免疫网络调节免疫网络调节1819神经神经-内分泌内分泌-免疫网络调节免疫网络调节 （三大系统的共性）（三大系统的共性）该网络在机体全部生命活动中有极其重要的调节作用该网络在机体全部生命活动中有极其重要的调节作用整合作用整合作用 维持机体内环境稳定，抵抗外来有害因素；维持机体内环境稳定，抵抗外来有害因素；储存和记忆信息储存和记忆信息 神经系统和免疫系统均有记忆功能；神经系统和免疫系统均有记忆功能；周期性活动周期性活动 季节性、昼夜节律性；季节性、昼夜节律性；反馈调节机制反馈调节机制年龄影响年龄影响20内分泌疾病的分类内分泌疾病的分类按病变器官分类按病变器官分类按功能分类：亢进、减退
14、、正常；按功能分类：亢进、减退、正常；按病变部位分类：原发性、继发性、三发性按病变部位分类：原发性、继发性、三发性激素分泌缺陷激素分泌缺陷受体基因缺陷受体基因缺陷-激素抵抗激素抵抗21内分泌疾病的诊断原则内分泌疾病的诊断原则三大原则：三大原则：功能诊断功能诊断 定位诊断定位诊断 病因病因/病理诊断病理诊断22内分泌疾病的诊断原则内分泌疾病的诊断原则功能诊断功能诊断症状、体征症状、体征实验室资料：代谢紊乱的证据；实验室资料：代谢紊乱的证据；激素分泌异常的证据；激素分泌异常的证据；内分泌功能试验：兴奋试验内分泌功能试验：兴奋试验 抑制试验抑制试验 激发试验激发试验 同位素检查同位素检查 细胞学检查
15、细胞学检查 骨密度检查骨密度检查23内分泌疾病的诊断原则内分泌疾病的诊断原则 定位诊断定位诊断同位素显象扫描同位素显象扫描磁共振磁共振CT B超声检查超声检查24内分泌疾病的诊断原则内分泌疾病的诊断原则病因诊断病因诊断 免疫学检查免疫学检查 组织病理学检查组织病理学检查 细胞学检查细胞学检查 染色体检查染色体检查 受体测定受体测定 分子生物学检查分子生物学检查25 内分泌疾病的防治原则内分泌疾病的防治原则预防为主：预防为主：地方性甲状腺肿地方性甲状腺肿 甲状腺危象甲状腺危象 肾上腺危象肾上腺危象 低血糖反应低血糖反应 黏液性水肿昏迷黏液性水肿昏迷26治疗原则治疗原则病因治疗：病因治疗：垂体瘤、
16、肾上腺腺瘤、嗜铬细胞瘤、垂体瘤、肾上腺腺瘤、嗜铬细胞瘤、甲状旁腺腺瘤等甲状旁腺腺瘤等纠正代谢紊乱：纠正代谢紊乱：腺体功能亢进的治疗；腺体功能亢进的治疗；腺体功能减退的治疗；腺体功能减退的治疗；27腺体功能亢进的治疗：腺体功能亢进的治疗：手术、放射治疗、抑制激素合成与释放的药物；手术、放射治疗、抑制激素合成与释放的药物；化疗药物；化疗药物；腺体功能减退的治疗：腺体功能减退的治疗：替代治疗替代治疗 补充生理剂量的激素补充生理剂量的激素 甲状腺激素、肾上腺皮质激素、生长激素等甲状腺激素、肾上腺皮质激素、生长激素等治疗原则治疗原则28How to study clinical endocrinolog
17、y29The Endocrine PatientA textbook of medicine is inevitably about disease,but the practice of medicine deals with illness.The topic of “the endocrine patient to be discussed include:initial evaluation,the nature of referral,the fact finding required in clinical evaluation,the use of the laboratory
18、and imaging,the formulation of a differential diagnosis,decision making,and management.30Many features of being an endocrine patient are common to all experiences of illness.A few minutes spent in getting to know the patient can pay enormous dividends in the accuracy of the history obtained and in s
19、etting the stage for further cooperation with testing and treatment.In as much as most endocrine consultation is elective rather than emergent,an experienced physician favors asking a few simple questions,such as Where are you from?What do you do?How did you come to us?Were you referred?and so on.Al
20、most always,some common experience or acquaintance is discovered that provides the basis for a rapport that does not emerge from formal medical questioning.This step also immediately conveys that you are interested in the patient as a person and not just as a disease.General considerations31Numerous
21、 special features of endocrine disease make patient presentation quite different from that seen in general medicine.One is the discovery of abnormality through screening of asymptomatic individuals,for example:a high serum calcium level discovered through multiphasic screening;a high blood glucose l
22、evel discovered in a shopping mall kiosk.The very absence of symptoms lends an unreality to the moment and should become an explicit topic of the patient-doctor interaction.In this circumstance,it is worth emphasizing the value of early discovery and prevention of greater morbidity.SPECIAL FEATURES
23、OF ENDOCRINE ILLNESS32The symptoms of endocrine disorders overlap a great range of normal characteristics,including:body contour,facial configurations,weight distributions,skin and hair coloring,and muscular capacity.They also overlap with other conditions that are far more common,including:depressi
24、on and normal aging.The added adipose tissue of hyperadrenocorticism is more difficult to recognize in a person who is already obese.The nervousness associated with hyperthyroidism is less apparent in a thin,hyperkinetic man than in a person of moderate body weight.The effects of an androgen-produci
25、ng adrenal tumor are less likely to be noticed in a family of swarthy,hirsute individuals.Overlap with Other Diseases(1)33Overlap with Other Diseases(2)Finally,most endocrine disorders evolve gradually over months to years instead of appearing suddenly,.This combination of varied host background and
26、 slow evolution of disease leads to considerable delay in diagnosis:both the patient and primary care physician adapt to the changes as part of the person,and definitive evaluation,now relatively easy for most disorders,is not undertaken.Hypothyroidism and acromegaly are good examples of this phenom
27、enon.All series show a remarkable delay in diagnosis despite sometimes disabling symptoms.34Overlap with Other Diseases(3)Hormones have more distant effects than local effects.This,of course,reflects their messenger status.Unlike an abscess,a myocardial infarction,or an esophageal cancer,endocrine d
28、isorders seldom produce symptoms near the gland of origin.(Subacute thyroiditis and large pituitary tumors,of course,are exceptions.)But because in most endocrinopathies the excess or missing hormone works on several or many systems,the resulting syndrome can be enigmatic.35Overlap with Other Diseas
29、es(4)Several endocrine disorders are important not because of their incidence but because of their curability:Cushings disease,acromegaly,Pheochromocytoma.Although these disorders enter the differential diagnosis of common problems such as diabetes,their occurrence is so rare that the primary care physician does not easily think of them.3637更希望同学们更希望同学们 在这一领域有所追求，在这一领域有所追求，有所探索，有所探索，有所发现！有所发现！
