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1、Disorders of endocrine and metabolic systemWang xinjun（王新军）（王新军）Department of endocrinology Hainan medical collegeMP: 18789826999Definitions 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 t
2、o evoke a specific 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） Endocrineendo-crineendo-a combining form meaning “within,” used in the formation of compound
3、words: endocardial; endocrinologycrine: paracrine autocrine exocrine EndocrinologyWith development, the definition and scope of investigative and clinical endocrinology continues to expand.For example: heart, kidney, adipose tissueComponents of the endocrine and metabolic systemsArchitectural and fu
4、nctional properties of endocrine and metabolic systemEndocrine systemEndocrine system consists of two main parts:Endocrine glandsSporadic endocrine tissues and cells in non-endocrine organHypothalamus-pituitary-target glandHypothalamus-pituitaryanterior pituitary releases six hormones: ACTH、TSH、FSH、
5、LH、PRL、GHposterior pituitary releases two hormones 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 d
6、uring lactation. HORMONETARGET FUNCTIONThyroid (TSH) 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 hormone
7、sAn excess of growth hormone in children causes giantism. In adults it causes acromegaly.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
8、 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、aldosteronealdosteroneGonadsGonads：T，DHT，E ， PLiv
9、erLiver：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 gastrointestinal tract and the adipose t
10、issues.Classification of hormoneHormones are customarily divided into three groups:Proteins 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）SteroidsTissues which produce steroid hormones include ovary/testis, adrenal cortex, pla
11、centa and skin(vitamin D).All steroid hormones are based on the precursor molecule cholesterol.Regulation of hormone levelsSpontaneous, or basal, hormone releaseFeedback inhibition by hormones of their synthesis and/or releaseStimulation or inhibition of hormone release by substances that may or may
12、 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 release in response to anxiety anticipation of a specific activity, or other sensory inputs.Hypothalamus-pituitary-adrenal axis
13、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 cortisol. Cortisol in turn inhibits both CRH and ACTH release（fe
14、edback inhibition）. The brain establishes circadian rhythms and can trigger increased CRH release in response to stress.CRHCRHACTHACTHcortisolMechanisms of hormone actionPeptide and catecholamine hormones and prostaglandins bind to receptors on the cell surface.Steroid and thyroid hormones act for t
15、he most part by binding to intracellular receptors.binding to receptors on the cell surfacebinding to intracellular receptorshormones bind to receptors on the cell surfacePeptide and catecholamine hormones and prostaglandins bind to receptors on the cell surface, where the hormone-receptor interacti
16、ons affect intracellular mediators, or second messengers.Second messengers cAMP:Glucagon, ACTH, PTHProtein kinase activityInsulinCalcium Alpha-adrenergic agonists, AT II phospholipidsADH, GnRH, TRH.hormones bind to receptors on the cell surface binding to intracellular receptorsintracellular recepto
17、rsDisorders of the endocrine Disorders of the endocrine and metabolic systemand metabolic systemMost 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 production of hormones, abnorm
18、al conversion of prohormones to their active forms, or iatrogenic factors.Hypofunction of endocrine glandsEndocrine glands may be injured or destroyed by neoplasia, infections, hemorrhage, autoimmune disorders, and other causes.Hormone deficiency secondary to extraglandular disordersImpaired convers
19、ion 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 hormonesHormone levels may be normal or even elevated in the presence of manifestations of endocrine deficiency
20、.Hormone exess syndromeHyperfunction of endocrine glandsEctopic hormone productionHormone administrationTissue hypersensitivityHyperfuction of endocrine glandsThe most common cause of hormone excess syndromes is hyperfunction of endocrine glands secondary to tumors of the glands or hyperplasia of se
21、veral causes.Metabolic disordersDiabetes mellitusHypoglycemiaHyperuricemia and goutDisorders of lipid metabolismNutritional/vitamin deficienciesSymptoms and signs of endocrine and metabolic diseasesHormones affect the function of all tissues and organ systems.Consequently, the symptoms and signs of
22、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 fatigueMental changesUnintended weight lossWeight gainAbnormal body temperatureHypersecretion of Adrenal CortexSymptome
23、sOphthalmic abnormalitiesAbnormal skin pigmentationHirsutismGynecomastiaGalactorrheaAbnormal appetiteDiarrheaSymptomesAnemiaTachycardia and bradycardiaPolyuriaAmenorrhea or oligomenorrheaInfertilityBone pain and pathologic fractureHyposecretion of THGH = pituitary dwarfismPhysical and laboratory exa
24、mination and diagnosisHistory and physical examinationMany 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 an
25、d 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 concentration in plasma.A measurement of the 24-h urine free cortisol usually provides a reasonable estimate of th
26、e 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 must remember that in both mormal subjects and patients with endocrine and other diseases, hormone levels are extensiv
27、ely 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 interpretationSince cortisol production integrated over a 24-h period is increased in cushings syndr
28、ome, 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 the simultaneous measurement of more than one hormone.For instance, with progressive damage to the thyroid hormon
29、es, 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 low in ovarian failure.If ovarial failure is due to disease of the ovary, plasma gonadotropins will be eleva
30、ted.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 gland to respond to stimuli as an index of its reserve capacity.Insulin induced hypoglycemia is used to assess
31、 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 glucose rather than insulin levels.It is helpful to follow the serum calcium levels in hyperparathyroidism and t
32、he 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 producing adenoma, plasma cholesterol tends to be high in hypothyroidism and low in hyperthyroidism.Treatmen
33、t 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, since it can increase the extracellular Ca+.In cases in which hormone resistance is present, steps are
34、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 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.
