11 内分泌疾病的代谢紊乱 总论

nullEndocrinology Endocrinology Content 1. Endocrine Control 2. Pituitary function 3. Growth disordersContent 1. Endocrine Control 2. Pituitary function 3. Growth disordersNew words and expressions（1）New words and expressions（1）Endocrine　内分泌 Paracrine　旁分泌 Autocrine　自分泌 Hypothalamic　下丘脑 Pituitary　垂体 Thyrotrophin 　促甲状腺激素 Gonadotrophin　促性腺激素 Adrenaline　肾上腺素 Thyroid hormone　甲状腺素 Steroid hormone　类固醇激素 Acronyms　首字母缩略词1. Endocrine ControlNew words and expressions （2）New words and expressions （2）Adrenocorticotrophic hormone (ACTH)　 促肾上腺皮质激素 Arginine vasopressin (AVP) 精氨酸加压素（ADH） Corticotrophin releasing hormone (CRH) ACTH释放激素 Follicle stimulating hormone (FSH) 卵泡刺激素 Gonadotrophin releasing hormone (GnRH)　 促性腺激素释放激素New words and expressions （3）New words and expressions （3）Luteinizing hormone (LH)　黄体生成素 Parathyroid hormone (PTH)　甲状旁腺激素 Thyroid stimulating hormone (TSH)　促甲状腺素 Thyrotrophin releasing hormone (TRH) 促甲状腺素释放激素 Thyroxine (T4)　甲状腺素 Triiodothyronine (T3) 三碘甲状腺原氨酸 Prolactin　催乳素 New words and expressions （4）New words and expressions （4）Glycoprotein　糖蛋白 Neurotransmitter　神经递质 Pulsatile　搏动的 Hypocalcemia 低钙血症 Diabetes mellitus　糖尿病 Insulin　胰岛素 Acromegaly 肢端肥大症 Thyrotoxicosis　甲亢 Prolactinoma　催乳素瘤 Synacthen　合成ACTH Hypoglycaemia 　低血糖 Dexamethasone　地塞米松nullEndocrinology(内分泌学)is the study of hormones, chemical agents which are secreted from specialized glands into the blood to influence the activity of cells at distant sites in the body. Hormones are one type of biochemical regulator.nullBiochemical regulation of cell functionInfluence the activity of cells at distant sitesAct on the adjacent cellsStimulate the very cell responsible for their synthesisclassical hormones neurotransmittersendocrine hormoneTypes of hormoneTypes of hormoneAccording to their structure Peptides or proteins Amino acid derivatives Steroid hormones Peptides or proteinsPeptides or proteins Most hormones fall into this class, such as thyrotrophin(促甲状腺激素) releasing hormone, gonadotrophin(促性腺激素) releasing hormone, growth hormone releasing hormone, growth hormone release-inhibiting hormone.Amino acid derivativesAmino acid derivatives A few hormones fall into this class, e.g. adrenaline（肾上腺激素） and thyroid hormones（甲状腺激素）.Steroid hormonesSteroid hormones　 These are all derivatives of cholesterol (胆固醇). Such as glucocorticoid hormone (糖皮质激素) and aldosterone(醛固酮).nullTable 1 Acronyms for some hormonesHormone binding in plasmaHormone binding in plasma In the plasma, there are two types of existence patterns for some hormones (such as steroid and thyroid hormones). Bound fraction: be bound to specific hormones binding glycoprotein. Unbound or free fraction: biologically active Factors controlling hormone secretion Factors controlling hormone secretion Hormone secretion is under a variety of influences: Stimulatory and inhibitory agents, such as hypothalamic(下丘脑) peptides or neurotransmitters, may influence hormone synthesis or release.Many hormones, such as GnRH, are released in a pulsatile fashion.Many hormones, such as GnRH, are released in a pulsatile fashion.circadian rhythm(日周期) lunar rhythm(月周期) Cir-annual rhythm(年周期) GnRH: gonadotrophin releasing hormone Factors controlling hormone secretionnullChanges of hormone concentrations in the blood during a 28-day menstrual cycle, and the associated changes in follicular development and ovulation (follicular phase), formation and degeneration of the corpus luteum (黄体) (luteal phase), cyclical growth and degeneration of the endometrium （子宫内膜）, and changes in basal body temperature. Factors controlling hormone secretion Factors controlling hormone secretion Some hormones exhibit a circadian rhythm (昼夜节律). ACTH, and consequently cortisol, is a well known example, but prolactin(催乳素), TSH, GH and even parathyroid hormone have peak secretion at different times during the day or night. ACTH: adrenocorticotrophin hormone TSH: thyroid stimulating hormone GH: growth hormone Factors controlling hormone secretion Factors controlling hormone secretionStress can increase hormone synthesis and release. Examples are ACTH, GH and prolactin (stress hormone). Hormones synthesized by target organ cells may feed back to the endocrine glands.null Feedback interactions in a hypothalamic(下丘脑 )-pituitary(脑垂体) -endocrine gland system Factors controlling hormone secretion Factors controlling hormone secretionChanges in metabolic products as a result of hormone action may likewise exert feedback control. Other hormones or drugs may modulate(调节 ) normal endocrine responses. nullPlasma hormone concentrations are variableEndocrine diseaseEndocrine diseaseEndocrine disease : over- or under- secretion of hormone. e.g. Parathyroid glands are unable to make sufficient hormone Malfunctioning receptor mechanism in the target cells In practice, many endocrine diseases are managed without direct knowledge of the hormone concentration itself. Diabetes mellitus Hypocalcaemia(低钙血症)Commonly used dynamic tests in the investigation of endocrine disease(1)Commonly used dynamic tests in the investigation of endocrine disease(1) Oral glucose tolerance test (OGTT) commonly used in the diagnosis of diabetes mellitus FPG (0min) 75g glucose+300mlH2O, 5min 30, 60, 120, 180min Plasma glucose and urinary glucose Diagnostic criteria of OGTT Diagnostic criteria of OGTT Oral Glucose Tolerance Test (OGTT): 2 hours after the drink, if your glucose is higher than normal (140 mg/dl), you have what's called "Impaired Glucose Tolerance" (IGT), which suggests pre-diabetes. A diagnosis of Diabetes is made when an OGTT level is greater than 200 mg/dl Diagnostic criteria of OGTTClinical employment of OGTTClinical employment of OGTTdiabetes mellitus gestational diabetes(妊娠糖尿病） IGT （糖耐量下降） Unaccountable renal disease , neural disease and retina(视网膜）disease，but RBS (random blood sugar) ＜7.8mmol/L(140mg／dl） Commonly used dynamic tests in the investigation of endocrine disease(2)Commonly used dynamic tests in the investigation of endocrine disease(2)TRH test TRH pituitary gland release of TSH and prolactin before TSH1 TRH 200~400μg i. v. after TSH 2(1/2h) Diagnostic criteria of TRH testDiagnostic criteria of TRH testMale: TSH 2(1/2h)-TSH1> 3~9mIU/L Female: TSH 2(1/2h)-TSH1> 4~12mIU/L normal ( positive reaction ) TSH 2(1/2h)-TSH1< 2mIU/L negative reaction TSH 2(1/2h)-TSH1>25 mIU/L strong positive reaction Clinical employment of TRH testClinical employment of TRH testnegative reaction (subnormal TSH responses ) thyrotoxicosis（甲亢） in cases of damage to the pituitary thyrotroph cells strong positive reaction hypothyroidism (甲减) Commonly used dynamic tests in the investigation of endocrine disease(3)Commonly used dynamic tests in the investigation of endocrine disease(3)GnRH test elicits release of LH and FSH investigate possible damage to pituitary gonadotrophin secreting cellsGnRH testGnRH test before LH1+FSH1 GnRH 100μg i. v. (0min) after LH2+FSH2 (20,60min) Serum concentration Diagnostic criteria of GnRH testDiagnostic criteria of GnRH testGnRH testGnRH testsubnormal responses Pituritary disease gonadal hormone disorder normal responses/delayed peak value (20 60min) hypothalamic(下丘脑) disease gonadal hormone disorder Commonly used dynamic tests in the investigation of endocrine disease(4)Commonly used dynamic tests in the investigation of endocrine disease(4)Synacthen test elicits release of cortison the damage of adrenal cortex subnormal responses diagnosis of Addison’s disease Commonly used dynamic tests in the investigation of endocrine disease(5)Commonly used dynamic tests in the investigation of endocrine disease(5) Insulin-induced hypoglycaemia test Insulin(0.1~0.15U/kg) i.v. blood glucose < 2.2 mmol/L plasma cortisol >550nmol/L hypoglycaemia (20μg/dl) GH >460pmol/L(10ng/ml) normalInsulin-induced hypoglycaemia testInsulin-induced hypoglycaemia testInvestigation of hypothalamic-pituitary-adrenocortical axis diagnosis of Cushing’s syndrome Investigation of growth hormone deficiency Commonly used dynamic tests in the investigation of endocrine disease(6)Commonly used dynamic tests in the investigation of endocrine disease(6)Dexamethasone suppression tests synthetic cortisol analogue reverse feedback to CRH suppress pituitary producing of ACTH suppress cortisol diagnosis of Cushing’s syndrome Dexamethasone suppression testsDexamethasone suppression testsinhibitory reaction pituitary adenoma (垂体腺瘤) hyperadrenocorticism(肾上腺皮质功能亢进) did not respond Adrenal cortical adenocarcinoma(肾上腺皮质腺癌) independent secretion hyperadrenocorticism Commonly used dynamic tests in the investigation of endocrine disease(7)Commonly used dynamic tests in the investigation of endocrine disease(7)Combined anterior pituitary function test (CAPFT) Insulin stimulates ACTH,GH and prolactin TRH stimulates TSH and prolactin GnRH stimulates FSH and LH investigation of pituitary disorder Summary -Endocrine controlSummary -Endocrine controlEndocrinology is the study of hormones, a class of biochemical regulators which are secreted into blood to act at distant sites in the body. Hormone concentrations in plasma are very variable. For the clear demonstration of abnormalities of hormone secretion or regulation, dynamic tests are often necessary.Content 1. Endocrine Control 2. Pituitary function 3. Growth disorders and acromegaly Content 1. Endocrine Control 2. Pituitary function 3. Growth disorders and acromegaly New words and expressions（1）New words and expressions（1）Bony cavity　蝶鞍 Adenohypophysis　腺垂体 Neurohypophysis　神经垂体 Hyperprolactinaemia　高催乳素血症 Infertility　不育 Amenorrhoea　闭经2. Pituitary functionNew words and expressions（2）New words and expressions（2）Galactorrhoea　乳溢 Hypothyroidism　甲低 Idiopathic　自发的，特发的 Dopamine　多巴胺 Osmolality　渗透压 Baroreceptor　压力感受器The pituitary glandThe pituitary gland The pituitary gland is a complex structure of secretory cells, blood vessels and nervous tissue lying in a bony cavity at the base of the skull. tiny, but important anterior pituitary (adenohypophysis)75% posterior pituitary (neurohypophysis) Pituitary function is regulated by the hypothalamus.Two partsThe pituitary glandThe pituitary glandAnterior pituitary hormonesAnterior pituitary hormones TSH (thyroid stimulating hormone): acts specifically on the thyroid gland elicits secretion of thyroid hormones ACTH (adrenocorticotrophic hormone): acts specifically on the adrenal cortex elicits secretion of cortisol LH ( luteinizing hormone ) FSH ( follicle stimulating hormone ) act on the ovaries in women and the testes in men to stimulate sex hormone secretion and reproductive processesGonadotrophinsAnterior pituitary hormonesAnterior pituitary hormonesGH (growth hormone): acts directly on many tissues to modulate metabolism Prolactin: acts directly on the mammary glands to control lactation high prolactin concentration impair gonadal function null Hypothalamic factors which regulate anterior pituitary function Hyperprolactinaemia (高催乳素血症)Hyperprolactinaemia (高催乳素血症) Hyperprolactinaemia is common and can cause infertility(不育) in both sexes. 　in women: early indication: amenorrhoea ( 闭经) and galactorrhoea（溢乳） in men: usually no early signs，the first indication may be a large growing tumour that begins to interfere with the optic nervesHyperprolactinaemiaHyperprolactinaemia stress Causes of hyperprolactinaemia drugs primary hypothyroidism other pituitary disease If these causes are excluded, the differential diagnosis is between: Prolactinoma and idiopathic hypersecretion Dopamine (the hypothalamic factor, inhibits prolactin release) secretion is impairedPosterior pituitary hormonesPosterior pituitary hormonesArginine vasopressin (AVP): also known as Antidiuretic hormone (ADH) main functions: regulate fluid and electrolyte stimulating factors include: increased plasma osmolality via hypothalamic osmoreceptors (渗透压感受器) severe blood volume depletion via cardiac baroreceptors (压力感受器) stress and nausea Oxytocin (催产素)Pituitary tumourPituitary tumourPituitary tumors may be either functional or non-functional. Functional: tumors can secrete hormones Non-functional: can’t secrete hormonesPituitary tumourPituitary tumourDiagnosis methods: Radiological investigations (x-ray, CT, MRI) Clinical lab is commonly called upon to establish if there is excessive hormone secretion. If a pituitary tumour is suspected, it’s important to establish the extent of damage to other pituitary function. the combined anterior pituitary function testnull Normal responses in a combined anterior pituitary function test.Summary -PituitarySummary -PituitaryAdenomas secreting each of the anterior pituitary hormones have been identified. Around 20% of pituitary tumours appear not to secrete hormone. It is important to establish if a pituitary tumour, whether hormone secreting or not, has interfered with the other hypothalamic-pituitary connections. Hyperprolactinaemia (高催乳素血症) is common. Once stress, drugs or other disease have been eliminated as possible causes, dynamic tests and detailed radiology are used to differentiate between prolactinoma and idiopathic hypersecretion.Content 1. Endocrine Control 2. Pituitary function 3. Growth disorders and acromegaly Content 1. Endocrine Control 2. Pituitary function 3. Growth disorders and acromegaly New words and expressions(1)New words and expressions(1)Acromegaly　肢端肥大症 Puberty　青春期 Utero　子宫 Achondroplasia 软骨发育不全 Dwarfism　侏儒症 Gastrointestinal　胃肠道 Nocturnal　夜间的3. Growth disorders and acromegalyNew words and expressions(2)New words and expressions(2)Gigantism　巨人症 Congenital　先天性的 Adrenal　肾上腺 Hyperplasia　增生 Karyotype 　染色体组型 Prognathism　下颌前突Normal growthNormal growthGrowth in children can be divided into three stages: The first 2 years of life: rapid growth period the rate is influenced by conditions in utero and the adequacy of nutrition in the postnatal period. The next 9 years: relatively steady growth period the rate is controlled mainly by GH Puberty: rapid growth period the growth is caused by the effect of the sex hormones and GHThe normal regulation of GH secretionThe normal regulation of GH secretionShort statureShort stature normal feature abnormal (diseases) It is important to differentiate between normal slow growth and growth failure caused by diseases. Children with short statureShort statureShort stature Causes of short stature are: Having parents who are both short Inherited diseases such as achondroplasia(软骨发育不全), the commonest cause of severe dwarfism(侏儒症) Poor nutrition Systemic chronic illness, such as renal disease, gastrointestinal disorders or respiratory disease Psychological(心理的，精神的) factors such as emotional deprivation(剥夺，丧失) Hormonal disordersGrowth hormone insufficiencyGrowth hormone insufficiencyThe syndromes of GH deficiency: Short stature Slow growth rate Delayed bone age Normal intelligence Lower serum GH concentrationLeft : A 6-year-old child with a growth hormone deficiency Right :his normal fraternal twin Tests of growth hormone insufficiencyTests of growth hormone insufficiency GH deficiency may be inherent(遗传) or due to later pituitary failure. GH deficiency testing methods: Plasma (serum) GH concentration test: higher during sleep than in the morning Exercise stimulating test (运动刺激试验): GH concentration is higher after exercise Medicine stimulating test: insulin-hypoglycemia test (hazard, abandoned) clonidine (可乐定): stimulate the GH secretionTests of growth hormone insufficiencyTests of growth hormone insufficiency Other notes: The GH response to stimulation may be blunted before puberty, and priming with the appropriate sex steroid is necessary before investigating GH reserve. Increasingly, urinary growth hormone measure-ments are being used to assess possible GH lack in children.TreatmentTreatment Genetically engineered GH is available and is used in the treatment of that small group of children with proven GH deficiency.Excessive growthExcessive growth　　　　Excessive growth hormone 　　　 Children gigantism(巨人症) 　　　 Adult acromegaly(肢端肥大症) Causes of tall stature in children include: Pituitary tumour (main cause) Congenital adrenal hyperplasia(先天性肾上腺增生) Hyperthyroidism(甲亢) Inherited disorders such as Klinefelter’s syndrome(a 47 XXY karyotype)AcromegalyAcromegaly Clinical features include: Coarse facial features(粗糙面容) Soft tissue thickening, e.g. the lips Characteristic ‘spade-like’ hands Protruding jaw (prognathism 突颚) Sweating Inpaired glucose tolerance or diabetes mellitusDiagnosis of Acromegaly (1)Diagnosis of Acromegaly (1)Basal serum GH concentrations (morning and nocturnal) Oral glucose tolerance test (高血糖抑制GH释放试验） normal GH<2μg/L Acromegaly can not be inhibited nullDiagnosis of Acromegaly (2)Diagnosis of Acromegaly (2)Elevated concentrations of IGF 1 in serum confirm the diagnosis of acromegaly Piturary tumour investigation Combined anterior pituitary function test (CAPFT) Summary -Growth disordersSummary -Growth disordersGH deficiency is a rare cause of short stature in children, and is investigated only after other causes of short stature have been eliminated. Diagnosis of GH deficiency is made on the failure of serum GH to rise in response to clonidine. Gigantism in children is caused by increased GH secretion, usually from a pituitary tumour. Acromegaly is the consequence of increased GH secretion in adults.Summary - Growth disordersSummary - Growth disordersLack of suppression of serum GH levels in response to a glucose tolerance test is the diagnostic test for acromegaly. Serum IGF 1 concentrations are of value in the diagnosis of acromegaly and the monitoring of treatment