1、Classical endocrine glands Pineal(松果体)(松果体)Pituitary(垂体)(垂体)Thyroid(甲状腺)(甲状腺)Parathyroid(甲状旁腺)(甲状旁腺)Adrenal(肾上腺)(肾上腺)Islets(胰岛)(胰岛)gonads(性腺)(性腺)Endocrineendo-crineendo-a combining form meaning“within,”used in the formation of compound words:endocardial;endocrinologycrine:paracrine autocrine exocrin
2、e Endocrinology With development,the definition and scope of investigative and clinical endocrinology continues to expand.For example:heart,kidney,adipose tissue Components of the endocrine and metabolic systemsArchitectural and functional properties of endocrine and metabolic systemEndocrine system
3、Endocrine system consists of two main parts:Endocrine glands Sporadic endocrine tissues and cells in non-endocrine organHypothalamus-pituitary-target glandHypothalamus-pituitaryanterior pituitary releases six hormones:ACTH、TSH、FSH、LH、PRL、GHposterior pituitary releases two hormones that are actually
4、produced in the hypothalamus:antidiuretic hormone(ADH)acts on the kidneys to conserve water and also promotes constriction of blood vessels.1.oxytocin stimulates uterine contractions and promotes milk“letdown”in the breasts during lactation.HORMONETARGET FUNCTIONThyroid(TSH)Stimulating Thyroid gland
5、TH synthesis&releaseGrowth(GH)Many tissuesgrowthAdrenocortico-Tropin(ACTH)Adrenal cortexCortisol release(androgens)Prolactin(Prl)BreastMilk productionFollicle(FSH)GonadsEgg/sperm prod.Luteinizing(LH)GonadsSex hormones An excess of growth hormone in children causes giantism.In adults it causes acrome
6、galy.dwarfism(lack of growth hormone).Excess ACTH 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 polydips
7、ia).Hormones PituitaryPituitary TSH,ACTH,GH,PRL,LH,FSH Peripheral glandPeripheral gland ThyroidThyroid:T3,T4 ParathyroidParathyroid:PTH AdrenalAdrenal:cortisolcortisol、aldosteronealdosterone GonadsGonads:T,DHT,E,P LiverLiver:IGF kidneykidney:1,25(OH)2D3 isletsislets:insulin,glucagoninsulin,glucagon(
8、胰高血糖素)(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,the liver,the kidney,the gastrointestinal tract and the adipose tissues.Classification of hormoneHormones are customarily divided into three groups:Prote
9、ins and peptides:insulin (蛋白质和肽类激素)(蛋白质和肽类激素)Steroids:cortisol (类固醇激素)(类固醇激素)Amino acid analogues:T3,T4 (氨基酸类激素)(氨基酸类激素)Steroids Tissues which produce steroid hormones include ovary/testis,adrenal cortex,placenta and skin(vitamin D).All steroid hormones are based on the precursor molecule cholestero
10、l.Regulation of hormone levels Spontaneous,or basal,hormone release Feedback inhibition by hormones of their synthesis and/or release Stimulation or inhibition of hormone release by substances that may or may not be regulated by the same hormones Establishment of circadian rhythms for hormone releas
11、e by systems such as the brain Brain mediated stimulation or inhibition of hormone release in response to anxiety anticipation of a specific activity,or other sensory inputs.Hypothalamus-pituitary-adrenal axis The hypothalamus produces CRH,which travels down the portal vessels through the hypothalam
12、ic stalk to the anterior pituitary,where it stimulates ACTH release.ACTH then travels to the adrenal gland,where it stimulates the release of cortisol.Cortisol in turn inhibits both CRH and ACTH release(feedback inhibition).The brain establishes circadian rhythms and can trigger increased CRH releas
13、e in response to stress.Mechanisms of hormone action Peptide and catecholamine hormones and prostaglandins bind to receptors on 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
14、receptorshormones bind to receptors on the cell surface Peptide and catecholamine hormones and prostaglandins bind to receptors on the cell surface,where the hormone-receptor interactions affect intracellular mediators,or second messengers.Second messengershormones bind to receptors on the cell surf
15、acebinding to intracellular receptorsintracellular receptorsDisorders of the endocrine Disorders of the endocrine and metabolic systemand metabolic system Most recognizable disorders of the endocrine system are due to an excess or a deficiency of particular hormones,whether caused by abnormalities o
16、f endocrine glands,ectopic production 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 s
17、econdary to extraglandular 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 t
18、he presence of manifestations of endocrine deficiency.Hormone exess syndromeHyperfuction of endocrine glands The most common cause of hormone excess syndromes is hyperfunction of endocrine glands secondary to tumors of the glands or hyperplasia of several causes.Metabolic disorders Diabetes mellitus
19、 Hypoglycemia Hyperuricemia and gout Disorders of lipid metabolism Nutritional/vitamin deficienciesSymptoms and signs of endocrine and metabolic diseases Hormones affect the function of all tissues and organ systems.Consequently,the symptoms and signs of endocrine disease are extremely diverse.They
20、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 body temperatureHypersecretion of Adrenal CortexSymptomes Ophthalmic abnormalities Abnormal skin pi
21、gmentation Hirsutism Gynecomastia Galactorrhea Abnormal appetite DiarrheaSymptomes Anemia Tachycardia and bradycardia Polyuria Amenorrhea or oligomenorrhea Infertility Bone pain and pathologic fractureHyposecretion of THGH=pituitary dwarfismPhysical and laboratory examination and diagnosisHistory an
22、d 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 cushings syndrome.In other instances,the clinial presentation is more subtle and the physician must rely on labor
23、atory 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 measurement of the 24-h urine free cortisol usually provides a reasonable estimate of the integrated levels of free plasm
24、a hormone.-75-75-50-50-25-250 025 2550 5075 75100100151520202525303035354040Clinical interpretation The clinicians must remember that in both mormal subjects and patients with endocrine and other diseases,hormone levels are extensively regulated.For instance,plasma insulin levels should be evaluated
25、 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 period is increased in cushings syndrome,the 24-h urinary free cortisol provides a more accurate index of
26、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 progressive damage to the thyroid hormones,secretion of TSH increases in a compensatory fashion so that normal
27、 plasma levels of the thyroid hormones may be maintained.Clinical interpretation Plasma estrogens are low in ovarian failure.If ovarial failure is due to disease of the ovary,plasma gonadotropins will be elevated.If ovarian failure is secondary to pituitary or hypothalamic disease,plasma gonadotropi
28、n 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.Insulin induced hypoglycemia is used to assess the secretory ability of cells that produce growth hormone.Tests that provide indirect inf
29、ormation 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 calcium levels in hyperparathyroidism and the serum potassium levels in primary aldosteronism.Tests that provide indirect information
30、 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 hypothyroidism and low in hyperthyroidism.Treatment of endocrine and metabolic disease For endocrine deficiency syndromes,hormones are genera
31、lly administered to counter the deficiency.Vitamin D is given instead of PTH to treat hypoparathyroidism,since it can increase the extracellular Ca+.In cases in which hormone resistance is present,steps are taken when possible to alleviate this,such as through diet restriction in type 2 diabetes.In
32、hormone-excess syndromes,a variety of approaches are used.Hyperfuctioning tumors are removed or destroyed with radiotherapy when possible,and sometimes hyperplastic 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.