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1、Definitions and scope of endocrinology,Classical endocrinology（经典内分泌学） is the study of endocrine glands which are a group of glands in the body secreting hormones to evoke a specific response in other cells of the body.,Classical endocrine glands,Pineal（松果体） Pituitary （垂体） Thyroid （甲状腺） Parathyroid
2、（甲状旁腺） Adrenal （肾上腺） Islets （胰岛） gonads （性腺）,Endocrine endo-crine endo-a combining form meaning “within,” used in the formation of compound words: endocardial; endocrinology crine: paracrine autocrine exocrine,Endocrinology,With development, the definition and scope of investigative and clinical end
3、ocrinology continues to expand. For example: heart, kidney, adipose tissue,Components of the endocrine and metabolic systems,Architectural and functional properties of endocrine and metabolic system,Endocrine system,Endocrine system consists of two main parts: Endocrine glands Sporadic endocrine tis
4、sues and cells in non-endocrine organ,Hypothalamus-pituitary-target gland,Hypothalamus-pituitary,anterior pituitary releases six hormones: ACTH、TSH、FSH、LH、PRL、GH posterior pituitary releases two hormones that are actually produced in the hypothalamus: antidiuretic hormone (ADH) acts on the kidneys t
5、o conserve water and also promotes constriction of blood vessels. oxytocin stimulates uterine contractions and promotes milk “letdown” in the breasts during lactation.,An excess of growth hormone in children causes giantism. In adults it causes acromegaly. dwarfism (lack of growth hormone). Excess A
6、CTH overstimulates the adrenal cortex, resulting in Cushing disease.,Increased prolactin causes milk secretion, or galactorrhea, in both males and females. A specific lack of ADH from the posterior pituitary results in diabetes insipidus(polyuria and polydipsia).,Hormones,Pituitary TSH，ACTH， GH，PRL，
7、LH，FSH Peripheral gland Thyroid：T3，T4 Parathyroid：PTH Adrenal：cortisol、aldosterone Gonads：T，DHT，E ， P Liver：IGF kidney：1，25(OH)2D3 islets：insulin, glucagon（胰高血糖素）,Apart from these glands, there are many tissues and cells sparsely distributed in non-endocrine organs, such as the atrium of the heart,
8、the liver, the kidney, the gastrointestinal tract and the adipose tissues.,Classification of hormone,Hormones are customarily divided into three groups: Proteins and peptides: insulin （蛋白质和肽类激素） Steroids: cortisol （类固醇激素） Amino acid analogues: T3, T4 （氨基酸类激素）,Steroids,Tissues which produce steroid h
9、ormones include ovary/testis, adrenal cortex, placenta and skin(vitamin D). All steroid hormones are based on the precursor molecule cholesterol.,Regulation of hormone levels,Spontaneous, or basal, hormone release Feedback inhibition by hormones of their synthesis and/or release Stimulation or inhib
10、ition of hormone release by substances that may or may not be regulated by the same hormones,Establishment of circadian rhythms for hormone release by systems such as the brain Brain mediated stimulation or inhibition of hormone release in response to anxiety anticipation of a specific activity, or
11、other sensory inputs.,Hypothalamus-pituitary-adrenal axis,The hypothalamus produces CRH, which travels down the portal vessels through the hypothalamic stalk to the anterior pituitary, where it stimulates ACTH release. ACTH then travels to the adrenal gland, where it stimulates the release of cortis
12、ol.,Cortisol in turn inhibits both CRH and ACTH release（feedback inhibition）. The brain establishes circadian rhythms and can trigger increased CRH release in response to stress.,CRH,ACTH,cortisol,Mechanisms of hormone action,Peptide and catecholamine hormones and prostaglandins bind to receptors on
13、 the cell surface. Steroid and thyroid hormones act for the most part by binding to intracellular receptors.,binding to receptors on the cell surface,binding to intracellular receptors,hormones bind to receptors on the cell surface,Peptide and catecholamine hormones and prostaglandins bind to recept
14、ors on the cell surface, where the hormone-receptor interactions affect intracellular mediators, or second messengers.,Second messengers,cAMP: Glucagon, ACTH, PTH Protein kinase activity Insulin Calcium Alpha-adrenergic agonists, AT II phospholipids ADH, GnRH, TRH.,hormones bind to receptors on the
15、cell surface,binding to intracellular receptors,intracellular receptors,Disorders of the endocrine and metabolic system,Most recognizable disorders of the endocrine system are due to an excess or a deficiency of particular hormones, whether caused by abnormalities of endocrine glands, ectopic produc
16、tion of hormones, abnormal conversion of prohormones to their active forms, or iatrogenic factors.,Hypofunction of endocrine glands,Endocrine glands may be injured or destroyed by neoplasia, infections, hemorrhage, autoimmune disorders, and other causes.,Hormone deficiency secondary to extraglandula
17、r disorders,Impaired conversion of a prohormone to a hormone occurs in chronic renal failure, in which there is defective conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.,Hyporesponsiveness to hormones,Hormone levels may be normal or even elevated in the presence of manifest
18、ations of endocrine deficiency.,Hormone exess syndrome,Hyperfunction of endocrine glands Ectopic hormone production Hormone administration Tissue hypersensitivity,Hyperfuction of endocrine glands,The most common cause of hormone excess syndromes is hyperfunction of endocrine glands secondary to tumo
19、rs of the glands or hyperplasia of several causes.,Metabolic disorders,Diabetes mellitus Hypoglycemia Hyperuricemia and gout Disorders of lipid metabolism Nutritional/vitamin deficiencies,Symptoms and signs of endocrine and metabolic diseases,Hormones affect the function of all tissues and organ sys
20、tems. Consequently, the symptoms and signs of endocrine disease are extremely diverse. They may vary from generalized, such as fatigue, to localized, such as weakness of the extraocular muscles.,Generalized symptomes,Weakness and fatigue Mental changes Unintended weight loss Weight gain Abnormal bod
21、y temperature,Hypersecretion of Adrenal Cortex,Symptomes,Ophthalmic abnormalities Abnormal skin pigmentation Hirsutism Gynecomastia Galactorrhea Abnormal appetite Diarrhea,Symptomes,Anemia Tachycardia and bradycardia Polyuria Amenorrhea or oligomenorrhea Infertility Bone pain and pathologic fracture
22、,Hyposecretion of TH,GH = pituitary dwarfism,Physical and laboratory examination and diagnosis,History and physical examination,Many syndromes of hormonal excess or deficiency display manifestations that are readily apparent at the time of initial presentation, e.g., severe thyrotoxicosis and cushin
23、gs syndrome. In other instances, the clinial presentation is more subtle and the physician must rely on laboratory testing to establish a diagnosis.,Laboratory testing,The level of free rather than total hormone is usually the best index of the effective hormone concentration in plasma. A measuremen
24、t of the 24-h urine free cortisol usually provides a reasonable estimate of the integrated levels of free plasma hormone.,正常人,2400 0800 1600,库欣病患者,2400 0800 1600,正常人和库欣患者的血F昼夜节律,Clinical interpretation,The clinicians must remember that in both mormal subjects and patients with endocrine and other di
25、seases, hormone levels are extensively regulated. For instance, plasma insulin levels should be evaluated in relation to the plasma glucose concentration, and PTH levels should be considered in relation to serum calcium levels.,Clinical interpretation,Since cortisol production integrated over a 24-h
26、 period is increased in cushings syndrome, the 24-h urinary free cortisol provides a more accurate index of cortisol hypersecretion.,Clinical interpretation,Sometimes the significance of hormone levels can be evaluated only by the simultaneous measurement of more than one hormone. For instance, with
27、 progressive damage to the thyroid hormones, secretion of TSH increases in a compensatory fashion so that normal plasma levels of the thyroid hormones may be maintained.,GD的自身免疫发病机制,Clinical interpretation,Plasma estrogens are low in ovarian failure. If ovarial failure is due to disease of the ovary
28、, plasma gonadotropins will be elevated. If ovarian failure is secondary to pituitary or hypothalamic disease, plasma gonadotropin levels will be normal or decreased.,Dynamic testing,Provocative testing assesses the ability of a gland to respond to stimuli as an index of its reserve capacity. Insuli
29、n induced hypoglycemia is used to assess the secretory ability of cells that produce growth hormone.,Tests that provide indirect information,Diagnosis of diabetes mellitus and assessment of therapy depend on measurement of plasma glucose rather than insulin levels. It is helpful to follow the serum
30、calcium levels in hyperparathyroidism and the serum potassium levels in primary aldosteronism.,Tests that provide indirect information,For instance, serum sodium is almost always greater than 139mEq/liter in patients with an aldosterone producing adenoma, plasma cholesterol tends to be high in hypot
31、hyroidism and low in hyperthyroidism.,Treatment of endocrine and metabolic disease,For endocrine deficiency syndromes, hormones are generally administered to counter the deficiency.,Vitamin D is given instead of PTH to treat hypoparathyroidism, since it can increase the extracellular Ca+.,In cases i
32、n which hormone resistance is present, steps are taken when possible to alleviate this, such as through diet restriction in type 2 diabetes.,In hormone-excess syndromes, a variety of approaches are used. Hyperfuctioning tumors are removed or destroyed with radiotherapy when possible, and sometimes h
33、yperplastic glands are removed.,In other cases drugs are given to block hormone production and release, such as methimazole/propylthiouracil for thyrotoxicosis and cabergoline/bromocriptine for prolactin-producing adenomas.,Antagonists such as spironolactone can some times be useful in primary aldosteronism due to hyperplasia.,