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1、Disorders of endocrine and metabolic systemWang xinjun（王新军）（王新军）Department of endocrinology Hainan medical collegeMP:Definitions and scope of endocrinologyClassical endocrinology（经典内分泌学）（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 spe
2、cific response in other cells of the body.Classical endocrine glandsPineal（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）EndocrinologyWith development,the definition and scope of investigative and clinical endocrinology continues to ex
3、pand.For example:heart,kidney,adipose tissueEndocrine systemEndocrine system consists of two main parts:Endocrine glandsSporadic endocrine tissues and cells in non-endocrine organHypothalamus-pituitaryanterior pituitary releases six hormones:ACTH、TSH、FSH、LH、PRL、GHposterior pituitary releases two hor
4、mones that are actually produced in the hypothalamus:1.antidiuretic hormone(ADH)acts on the kidneys to conserve water and also promotes constriction of blood vessels.2.oxytocin stimulates uterine contractions and promotes milk“letdown”in the breasts during lactation.HORMONETARGET FUNCTIONThyroid(TSH
5、)Stimulating Thyroid glandTH synthesis&releaseGrowth(GH)Many tissuesgrowthAdrenocortico-Tropin(ACTH)Adrenal cortexCortisol release(androgens)Prolactin(Prl)BreastMilk productionFollicle(FSH)GonadsEgg/sperm prod.Luteinizing(LH)GonadsSex hormonesIncreased prolactin causes milk secretion,or galactorrhea
6、,in both males and females.A specific lack of ADH from the posterior pituitary results in diabetes insipidus(polyuria and polydipsia).HormonesPituitaryPituitaryTSH，ACTH，GH，PRL，LH，FSHPeripheral glandPeripheral glandThyroidThyroid：T3，T4ParathyroidParathyroid：PTHAdrenalAdrenal：cortisolcortisol、aldoster
7、onealdosteroneGonadsGonads：T，DHT，E，PLiverLiver：IGFkidneykidney：1，25(OH)2D3isletsislets：insulin,glucagoninsulin,glucagon（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 gastroin
8、testinal tract and the adipose tissues.SteroidsTissues which produce steroid hormones include ovary/testis,adrenal cortex,placenta and skin(vitamin D).All steroid hormones are based on the precursor molecule cholesterol.Regulation of hormone levelsSpontaneous,or basal,hormone releaseFeedback inhibit
9、ion by hormones of their synthesis and/or releaseStimulation or inhibition of hormone release by substances that may or may not be regulated by the same hormonesEstablishment of circadian rhythms for hormone release by systems such as the brainBrain mediated stimulation or inhibition of hormone rele
10、ase in response to anxiety anticipation of a specific activity,or other sensory inputs.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.CRHCRHACTHACTHcortisolMechanisms of horm
11、one actionPeptide 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 surfacebinding to intracellular receptorshormones bind to receptors on the c
12、ell surfacePeptide and catecholamine hormones and prostaglandins bind to receptors on the cell surface,where the hormone-receptor interactions affect intracellular mediators,or second messengers.Second messengers cAMP:Glucagon,ACTH,PTHProtein kinase activityInsulinCalcium Alpha-adrenergic agonists,A
13、T II phospholipidsADH,GnRH,TRH.hormones bind to receptors on the cell surface binding to intracellular receptorsintracellular receptorsDisorders of the endocrine Disorders of the endocrine and metabolic systemand metabolic systemMost recognizable disorders of the endocrine system are due to an exces
14、s or a deficiency of particular hormones,whether caused by abnormalities of endocrine glands,ectopic production of hormones,abnormal conversion of prohormones to their active forms,or iatrogenic factors.Hypofunction of endocrine glandsEndocrine glands may be injured or destroyed by neoplasia,infecti
15、ons,hemorrhage,autoimmune disorders,and other causes.Hormone deficiency secondary to extraglandular disordersImpaired 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.Hyporespo
16、nsiveness to hormonesHormone levels may be normal or even elevated in the presence of manifestations of endocrine deficiency.Hormone exess syndromeHyperfunction of endocrine glandsEctopic hormone productionHormone administrationTissue hypersensitivityHyperfuction of endocrine glandsThe most common c
17、ause of hormone excess syndromes is hyperfunction of endocrine glands secondary to tumors of the glands or hyperplasia of several causes.Metabolic disordersDiabetes mellitusHypoglycemiaHyperuricemia and goutDisorders of lipid metabolismNutritional/vitamin deficienciesSymptoms and signs of endocrine
18、and metabolic diseasesHormones affect the function of all tissues and organ systems.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 symptomesWeakness and
19、 fatigueMental changesUnintended weight lossWeight gainAbnormal body temperatureHypersecretion of Adrenal CortexSymptomesOphthalmic abnormalitiesAbnormal skin pigmentationHirsutismGynecomastiaGalactorrheaAbnormal appetiteDiarrheaSymptomesAnemiaTachycardia and bradycardiaPolyuriaAmenorrhea or oligome
20、norrheaInfertilityBone pain and pathologic fractureHyposecretion of THGH=pituitary dwarfismPhysical and laboratory examination and diagnosisHistory and physical examinationMany syndromes of hormonal excess or deficiency display manifestations that are readily apparent at the time of initial presenta
21、tion,e.g.,severe thyrotoxicosis and cushings syndrome.In other instances,the clinial presentation is more subtle and the physician must rely on laboratory testing to establish a diagnosis.Laboratory testingThe level of free rather than total hormone is usually the best index of the effective hormone
22、 concentration in plasma.A measurement of the 24-h urine free cortisol usually provides a reasonable estimate of the integrated levels of free plasma hormone.正常人正常人2400 0800 16002400 0800 1600库欣病患者库欣病患者2400 0800 16002400 0800 1600正常人和库欣患者的血正常人和库欣患者的血F昼夜节律昼夜节律Clinical interpretationThe clinicians mus
23、t 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 in relation to the plasma glucose concentration,and PTH levels should be considered in relation to serum calcium leve
24、ls.Clinical interpretationSince 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 cortisol hypersecretion.Clinical interpretationSometimes the significance of hormone levels can be evaluated only by th
25、e 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 plasma levels of the thyroid hormones may be maintained.GD的自身免疫发病机制的自身免疫发病机制Clinical interpretationPlasma estrogens are
26、 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 gonadotropin levels will be normal or decreased.Dynamic testingProvocative testing assesses the ability of a gla
27、nd 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 informationDiagnosis of diabetes mellitus and assessment of therapy depend on measurement of plasma gluco
28、se 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 informationFor instance,serum sodium is almost always greater than 139mEq/liter in patients with an aldosterone pr
29、oducing adenoma,plasma cholesterol tends to be high in hypothyroidism and low in hyperthyroidism.Treatment of endocrine and metabolic diseaseFor endocrine deficiency syndromes,hormones are generally administered to counter the deficiency.Vitamin D is given instead of PTH to treat hypoparathyroidism,
30、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 hormone-excess syndromes,a variety of approaches are used.Hyperfuctioning tumors are removed or destroyed
31、 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.