1
内分泌系统疾病
总 论
Introduction to Endocrinology and
Metabolic Diseases
复旦大学附属中山医院内分泌科 高鑫
2
History 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
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,
3
Work over the next several decades 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 by replacing specific hormones,
These initial triumphs formed the foundation of the clinical
specialty of endocrinology,
History and development of
Endocrinology (2)
4
Advances in cell biology,molecular biology,and
genetics over the ensuing years began to help explain
the mechanisms of endocrine diseases 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 development of
Endocrinology (2)
5
Hormone 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 initiates 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 vitamin D,7-dehydrocholesterol,
is produced in skin keratinocytes,again from cholesterol,
by a photochemical reaction,
ENDOCRINE GLANDS
6
内分泌系统
内分泌腺 脏器内分泌组织
激素
体液调节系统（包括旁分泌、自分泌）
代谢过程 脏器功能 生长发育 生殖衰老
Endocrine System
7
内分泌学发展三阶段
? 腺体内分泌学
Organic Endocrinology
? 组织内分泌学
Histological Endocrinology
? 分子内分泌学
Moleculer Endocrinology
8
激素的种类
Hormones
肽类 /蛋白类激素 （ Protein or peptide),
ACTH,LH,FSH,PHT,TSH,
Insulun,Glucagon,IGFs
氨基酸衍生物（ Amino Acid derivatives),
儿茶酚胺类（肾上腺素、去甲肾上腺素）
脂肪酸衍生物 (Fatty acid derivatives ),
前列腺素类、视黄酸
胆固醇衍生物（ Cholesterol derivatives ),
考的松,醛固酮,1,25(OH)2 D3性激素
9
激素的作用机制（ 1）
与膜受体结合 G蛋白偶联 发挥生物效应
（肽类激素、生物胺、前列腺素）
与膜受体结合 受体自身磷酸化 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 DNA特异序列结合 功能蛋白转录
（甾体类激素）
10
11
G-protein-coupled 7-membrane spanning receptor
12
G-protein-coupled 7-membrane spanning receptor
13
14
15
16
激素的作用机制（ 2）
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
（无活性的磷酸化酶 b/有活性的磷酸化酶 a之间的互变）
获得 1951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
（ cAMP合成与分解的两个关键酶）
提出了激素作用的第二信使学说
获得 1971年诺贝尔生理医学奖。
Krebs & Fisher,于 60年代末发现蛋白激酶 A(PKA)
（依赖 cAMP,刺激多种底物蛋白磷酸化 )
阐明了 PKA启动的磷酸化和去磷酸化途径。
获得 1992年诺贝尔生理医学奖。
17
内分泌系统的相互调节
神经 ---内分泌系统的相互调节
内分泌系统的反馈调节
免疫系统与内分泌系统的关系
神经 -内分泌 -免疫网络调节
18
20
内分泌疾病的分类
按病变器官分类
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
激素分泌缺陷
受体基因缺陷 ---激素抵抗
21
内分泌疾病的诊断原则
三大原则,
功能诊断
定位诊断
病因 /病理诊断
22
内分泌疾病的诊断原则
功能诊断
症状、体征
实验室资料：代谢紊乱的证据；
激素分泌异常的证据；
内分泌功能试验：兴奋试验
抑制试验
激发试验
同位素检查
细胞学检查
骨密度检查
23
内分泌疾病的诊断原则
定位诊断
同位素显象扫描
磁共振
CT
B超声检查
24
内分泌疾病的诊断原则
病因诊断
? 免疫学检查
? 组织病理学检查
? 细胞学检查
? 染色体检查
? 受体测定
? 分子生物学检查
25
内分泌疾病的防治原则
预防为主,地方性甲状腺肿
甲状腺危象
肾上腺危象
低血糖反应
黏液性水肿昏迷
26
治疗原则
病因治疗,垂体瘤、肾上腺腺瘤、嗜铬细胞瘤,
甲状旁腺腺瘤等
纠正代谢紊乱,腺体功能亢进的治疗；
腺体功能减退的治疗；
27
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；
化疗药物；
腺体功能减退的治疗,
替代治疗 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
治疗原则
28
How to study
clinical endocrinology
29
The Endocrine Patient
A 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 and imaging,
the formulation of a differential diagnosis,
decision making,and management,
30
Many 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 setting
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,
Almost 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 considerations
31
Numerous 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 level 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 OF ENDOCRINE ILLNESS
32
The 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,depression 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-producing adrenal tumor are less likely
to be noticed in a family of swarthy,hirsute individuals,
Overlap with Other Diseases (1)
33
Overlap 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 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 phenomenon,
All series show a remarkable delay in diagnosis
despite sometimes disabling symptoms,
34
Overlap 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 disorders 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,
35
Overlap with Other Diseases (4)
Several endocrine disorders are important not because of
their incidence but because of their curability,
Cushing's 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,
36
37
更希望同学们
在这一领域有所追求,
有所探索,
有所发现！
内分泌系统疾病
总 论
Introduction to Endocrinology and
Metabolic Diseases
复旦大学附属中山医院内分泌科 高鑫
2
History 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
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,
3
Work over the next several decades 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 by replacing specific hormones,
These initial triumphs formed the foundation of the clinical
specialty of endocrinology,
History and development of
Endocrinology (2)
4
Advances in cell biology,molecular biology,and
genetics over the ensuing years began to help explain
the mechanisms of endocrine diseases 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 development of
Endocrinology (2)
5
Hormone 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 initiates 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 vitamin D,7-dehydrocholesterol,
is produced in skin keratinocytes,again from cholesterol,
by a photochemical reaction,
ENDOCRINE GLANDS
6
内分泌系统
内分泌腺 脏器内分泌组织
激素
体液调节系统（包括旁分泌、自分泌）
代谢过程 脏器功能 生长发育 生殖衰老
Endocrine System
7
内分泌学发展三阶段
? 腺体内分泌学
Organic Endocrinology
? 组织内分泌学
Histological Endocrinology
? 分子内分泌学
Moleculer Endocrinology
8
激素的种类
Hormones
肽类 /蛋白类激素 （ Protein or peptide),
ACTH,LH,FSH,PHT,TSH,
Insulun,Glucagon,IGFs
氨基酸衍生物（ Amino Acid derivatives),
儿茶酚胺类（肾上腺素、去甲肾上腺素）
脂肪酸衍生物 (Fatty acid derivatives ),
前列腺素类、视黄酸
胆固醇衍生物（ Cholesterol derivatives ),
考的松,醛固酮,1,25(OH)2 D3性激素
9
激素的作用机制（ 1）
与膜受体结合 G蛋白偶联 发挥生物效应
（肽类激素、生物胺、前列腺素）
与膜受体结合 受体自身磷酸化 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 DNA特异序列结合 功能蛋白转录
（甾体类激素）
10
11
G-protein-coupled 7-membrane spanning receptor
12
G-protein-coupled 7-membrane spanning receptor
13
14
15
16
激素的作用机制（ 2）
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
（无活性的磷酸化酶 b/有活性的磷酸化酶 a之间的互变）
获得 1951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
（ cAMP合成与分解的两个关键酶）
提出了激素作用的第二信使学说
获得 1971年诺贝尔生理医学奖。
Krebs & Fisher,于 60年代末发现蛋白激酶 A(PKA)
（依赖 cAMP,刺激多种底物蛋白磷酸化 )
阐明了 PKA启动的磷酸化和去磷酸化途径。
获得 1992年诺贝尔生理医学奖。
17
内分泌系统的相互调节
神经 ---内分泌系统的相互调节
内分泌系统的反馈调节
免疫系统与内分泌系统的关系
神经 -内分泌 -免疫网络调节
18
20
内分泌疾病的分类
按病变器官分类
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
激素分泌缺陷
受体基因缺陷 ---激素抵抗
21
内分泌疾病的诊断原则
三大原则,
功能诊断
定位诊断
病因 /病理诊断
22
内分泌疾病的诊断原则
功能诊断
症状、体征
实验室资料：代谢紊乱的证据；
激素分泌异常的证据；
内分泌功能试验：兴奋试验
抑制试验
激发试验
同位素检查
细胞学检查
骨密度检查
23
内分泌疾病的诊断原则
定位诊断
同位素显象扫描
磁共振
CT
B超声检查
24
内分泌疾病的诊断原则
病因诊断
? 免疫学检查
? 组织病理学检查
? 细胞学检查
? 染色体检查
? 受体测定
? 分子生物学检查
25
内分泌疾病的防治原则
预防为主,地方性甲状腺肿
甲状腺危象
肾上腺危象
低血糖反应
黏液性水肿昏迷
26
治疗原则
病因治疗,垂体瘤、肾上腺腺瘤、嗜铬细胞瘤,
甲状旁腺腺瘤等
纠正代谢紊乱,腺体功能亢进的治疗；
腺体功能减退的治疗；
27
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；
化疗药物；
腺体功能减退的治疗,
替代治疗 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
治疗原则
28
How to study
clinical endocrinology
29
The Endocrine Patient
A 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 and imaging,
the formulation of a differential diagnosis,
decision making,and management,
30
Many 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 setting
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,
Almost 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 considerations
31
Numerous 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 level 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 OF ENDOCRINE ILLNESS
32
The 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,depression 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-producing adrenal tumor are less likely
to be noticed in a family of swarthy,hirsute individuals,
Overlap with Other Diseases (1)
33
Overlap 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 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 phenomenon,
All series show a remarkable delay in diagnosis
despite sometimes disabling symptoms,
34
Overlap 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 disorders 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,
35
Overlap with Other Diseases (4)
Several endocrine disorders are important not because of
their incidence but because of their curability,
Cushing's 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,
36
37
更希望同学们
在这一领域有所追求,
有所探索,
有所发现！
