內分泌系統教學課件：Hypoglycemia

《內分泌系統教學課件：Hypoglycemia》由會員分享，可在線閱讀，更多相關《內分泌系統教學課件：Hypoglycemia（46頁珍藏版）》請在裝配圖網上搜索。

1、HypoglycemiaHypoglycemiaDefinitionHypoglycemia can be arbitrarily define as a plasma glucose level 2.8 mmol/LTo establish the diagnosis,the following three criteria are necessary:1.Symptoms and signs of hypoglycemia2.Low plasma glucose level in symptomatic patient3.Relief of symptoms or signs on rai

2、sing the glucose levels after ingestion of carbohydratesWhipples triadPresence of symptoms:When plasma glucose3.3 mmol/L,autonomic transmtters releasedWhen plasma glucose2.8 mmol/L,neuroglycopenia ensuesAdrenergic:sweating,anxiety,tremors,tachycardia,palpitationsNeuroglycopenia:seizure,fatigue,synco

3、pe,headache,behavior changes,visual disturbances,hemiplegiaHypoglycemia unawareness(1)This is referes to a loss of the warning symptoms that alter individuals to the presence of hypoglycemia and prompt them to eat and abort the episode.In this case,the first manifestation of hypoglycemia is neuro-gl

4、ycopenia,when it is too late for patients to treat themselves.This is usually associated with autonomic failure in T1DM and blunting counterregulateory hormone secretion,therefore,adrenergic responses(sweating,anxiety,tremors,tachycardia,palpitations)are absent.Hypoglycemia unawareness(2)Prolonged h

5、ypoglycemia may cause permanent brain damage and death,prompt recognition and treatment are mandatory.In most unconscious patients,possibility of hypoglycemic coma must be considered.Hypoglycemia unawareness(3)The symptoms and signs of hypoglycemia depend on:Degree of hypoglycemiaThe age of the pati

6、entThe rapidity of the declineIn poor controlled DM patients treated with insulin,a precipitous fall in plasma glucose from hyperglycemia toward euglycemia may produce neuroglycopenic symptoms.This is also known as“hypoglycemia reaction”.1.Reactive hypoglycemia(nonfasting hypoglycemia)2.Fasting hypo

7、glycemia3.Iatrogenic or drug-induced:Classification of HypoglycemiaFerri FF.Practical Guide to the care of the medical treatment(6th Edt),2006Classification of Hypoglycemia1.Reactive hypoglycemia(nonfasting hypoglycemia)a.Usually occurs 2-5 hours after a meal rich in carbohydrate,b.The patients neve

8、r have symptoms in the fast state and rarely experience loss of consciousness secondary to their hypoglycemiac.Patients who have had subtotal gastrectomy rapidly absorb carbohydrate(“dumping syndrome”),causing an early and very high plasma glucose level followed by a insulin surge that reached its p

9、eak when most of the glucose has been absorbed and that results in hypoglycemia.This usually occurs within 2-3 hours after a meal.Ferri FF.Practical Guide to the care of the medical treatment(6th Edt),2006Classification of Hypoglycemia1.Reactive hypoglycemia(nonfasting hypoglycemia)d.Patients with T

10、2DM can experience hypoglycemia 4-5 hours postprandiallye.Congenital deficiencies of enzymes necessary for carbohydrate metabolism and functional idiopathic hypoglycemia also manifested as reactive hypoglycemiaFerri FF.Practical Guide to the care of the medical treatment(6th Edt),2006Classification

11、of Hypoglycemia2.Fasting hypoglycemiaa.Sympotoms usually appear in the absence of food intake(at night or during early morning)b.Etiology:insulinoma,mesenchymal tumors that produce IGF-II,adrenal failure,glycogen storage disorders,severe liver disease or renal disease3.Iatrogenic or drug-induced:hyp

12、oglycemic drugs,excessive insulin replacement,factitious hypoglycemia ethanol-inducedFerri FF.Practical Guide to the care of the medical treatment(6th Edt),2006Common causes of symptomatic hypoglycemia in adultsFastingWith hyperinsulinemia Insulin reaction SU overdose Surreptitious insulin or SU sel

13、f-administration Autoimmune hypoglycemia (idiopathic insulin antibodies,insulin receptor autoantibodies)Pentamidine-induced hypoglycemia Pancreatic cell tumorsWithout hyperinsulinemia Severe hepatic dysfunction Chronic renal function Inanition Hypocortisolism Alcohol use Nonpancreatic tumorsNonfasti

14、ng Alimentary Functional Noninsulinoma pancreatogenous hypoglycemic syndrome(NIPHS)Occult diabetes Ethanol ingestion with sugar mixersDiagnosis1.Whipples triad:2.Lab tests(1)Plasma insulin and proinsulin(2)C-peptide(3)Plasma and urine SU levels3.72 fast test:fasting hypoglycemia4.Mixed meal challeng

15、e:of postprandial hypoglycemia Plasma insulinIf plasma glucose 3 U/mL(ICMA)or 6 U/mL(RIA):Hypoglycemia with hyperinsulinemiaRatio of insulin(U/mL)/plasma glucose(mg/dL):Normal subjects0.4If plasma glucose is normal,this ratio0.3 has no clinical meaning.Most center no longer calculate this ratio and

16、rely only on the absolute concentrations of insulinPlasma proinsulin and C peptidePlasma glucose300 pmol/L,Proinsulin 20 pmol/L3.72 fast testA test performed in a hospital to ID causes of hypoglycemia,especially in patients suspected having insulinomas.It should be carried out under supervision.Meth

17、ods:Collect blood samples at the start for measurement of blood glucose,insulin,C peptide.Blood sample can collected every 6 hours until blood glucose 3.3 mmol/L.After that,blood samples are collected every 1-2 hourTest should be terminated immediately as soon as symptoms and lab confirmation (blood

18、 glucose5 pmol/L(ICMA),C peptide 200 pmol/L:If insulin level is high and C peptide level is low:insulinomaexogenous insulin-induced hypoglycemia.4.5 hour OGTTUse to ID occult diabetes Methods:75 g glucose,measure the blood glucose,insulin and C peptide at 0,30,60,120,180,240,300 min.To test endogeno

19、us insulin secretionThe patient is more phlegmatic and often obese,frequently having a family history of diabetes.Test meals for evaluation of postprandial hypoglycemia after Roux-en-Y gastric bypass surgeryHigh Carbohydrate Meal:79%Carbo11%Fat10%Protein405 KcalLow Carbohydrate Meal:2%Carbo74%Fat24%

20、Protein415 Kcal8 oz of orange juice1 slice of toast with 1 tspof margrine and 2 tsp of jamDecaffeinated black coffee or tea(without sugar)1 egg,a 1-oz sausange pattyand 0.5-oz slice of cheeseDay1:High Carbohydrate MealDay 2:High Carbohydrate Meal Blood sample:0,30,60,90,120,150,180 after meal for gl

21、ucose and insulinDiagnostic evalution of pateints with hypoglycemiaClinical clueslDrugs pentamidine,salicylates,etc.ethanollEnd-stage liver,renal diseaselSepsislEndocrine deficienciesl Non-cell tumorslPrior gastric surgerylInherited metabolic disordersSuspected hypoglycemiaNo diabetesdiabetesTreated

22、 with Insulin sulfonylureasAdjust regimenDocument Improvement and monitorTreat underlying disease,provide adequate glucosehistoryApparently healthyFasting glucose2.8 mmol/L2.8mmol/LMixed mealstrongweakExtended fast2.8mmol/L2.8mmol/LInsulin,+symptomsWhipples triadReactive hypoglycemiaHypoglycemia exc

23、ludedC-peptideC-peptideInsulinomaAutoimmune hypoglycemiaSulfonylurea+Likely factitiousExogenous insulin Ab+TreatmentUrgent Treatment1.Oral treatment with glucose solution,sweet drinks,candy,or food if patient is able to and willing to take these2.If patient has neuroglycopenia,parenteral therapy is

24、necessary.Intravenous glucose(25 g should be given using 50%solution)followed by a constant infusion of 5 or 10%dextrose3.If the effect of intravenous glucose infusion do not works,hydrocortisol 100 mg is necessary.4.Etiological treatmentInsulinomaInsulinoma is also known as pancreatic cell tumors.I

25、t is mainly manifestate as spontaneous fasting hypoglycemia.80%:Single and benign10%:Malignant(if metastasis are ID)10%:Multiple,with scattered micro-or macroadenomas interspersed with normal islet tissue.Insulinoma(pancreatic cell tumors can occurs with tumors of parathyroid glands and the pituitar

26、y(MEN I)99%of them are located within the pancreas and 1%in ectopic pancreatic tissueClinical findingsSymptoms and signs are mainly subacute neuroglycopenia rather than adrenergic discharge.The symptoms and signs usually occur at times of exercise or fastingThe neuroglycopenic symptoms often lead to

27、 delayed diagnosis following prolonged psychiatric care or treatment for seizure disordersor TIA(transient ischemic attack)Diagnosis1.Most important is to consider it:fasting hypoglycemia+symptoms of central nervous system dysfunction such as confusion or abnormal behavior2.Lab test:Plasma glucose3

28、U/mL(ICMA)3.Exclude other causes of hyperinsulinemic hypoglycemia,such as surreptitious administration of insulin or sulfonylurea.Suggested hospital protocol for supervised rapid diagnosis of insulinoma(1).Obtain baseline serum glucose,insulin,proinsulin,and C-peptide measurement at onset of fast an

29、d place intravenous cannula.(2).Permit only calorie-free and caffeine-free fluids and encourage supervised activity(such as walking).Suggested hospital protocol for supervised rapid diagnosis of insulinomaSuggested hospital protocol for supervised rapid diagnosis of insulinoma(3).Measure urine for k

30、etones at the beginning and every 12 hours and at the end of fast.Suggested hospital protocol for supervised rapid diagnosis of insulinoma(4).Obtain capillary glucose measurements with a reflectance meter every 4 hours until values 3.3 mmol/L are obtained.Then increase the frequency of fingersticks

31、to each hour,and when capillary glucose value is 2.7 mmol/L,send a venous blood sample to the laboratory for serum glucose,insulin,proinsulin,and C-peptide measurements.Check frequently for manifestations of neuroglycopenia.(5).If symptoms of hypoglycemia occur or if a laboratory value of serum gluc

32、ose is 2.5mmol/L or if 72 hours have elapsed,then conclude the fast with a final blood sample for serum glucose,insulin,proinsulin,C-peptide,betahydroxybutyrate or acetone,and sulfonylurea measurements.Then give oral fast acting carbohydrate followed by a meal.If the patient is confused or unable to

33、 take oral agents,administer 50 ml of 50%dextrose intravenously over 3-5 minutes.Do not conclude a fast based simply on basis of a capillary blood glucose measurement-wait for the laboratory glucose value.Suggested hospital protocol for supervised rapid diagnosis of insulinomaDiagnostic criteria for

34、 insulinoma after a 72 hour fastserum glucose 10 years)diazoxide therapy with no apparent ill effect(3).Dose of 300-400 mg/day(divided),may up to 800 mg/day.(4).Side effect:edema due to sodium retention(with hydrochlorothiazide 25-50 mg daily),gastric irritation and mild hirsutism.(1).It can maintai

35、n euglycemia in most patients with insulin-secreting tumor.It is the treatment of choice in patients with inoperable functioning islet cell carcinoma and in those who are poor candidates for operationTreatment of Insulinoma2.A calcium channel blockerIndication:when patients are unable to tolerate di

36、azoxide because of side effectVerapamil:80 mg Q8h3.Octreotide:50 g IH,QD may be used for patients with islet cell carcinoma,selective arterial administration can avoid undue renal toxicity.Medical treatmentTreatment of Insulinoma4.STZSpecific hypoglycemic disordersSymptomatic fasting hypoglycemia wi

37、th hyperinsulinemiaInsulin reaction1.Indequate food intake2.Exercise:loss the regulation of glucose in insulin-treated diabetic patients3.Impaired glucose counter-regulation in diabetesSpecific hypoglycemic disorders4.Miscellaneous causes of hypoglycemia in insulin-treated diabetics(1).Stress(2).Hyp

38、ocortisolism:Addison disease(3).Diabetic gastroparesis:diagnosed by radiologic studies of gastric motility(4).Pregnancy(5).Renal insufficiency:impairement of insulin degradation and renal gluconeogenesis(6).Drugs:ethanol,salicylates,adrenergic blockers,Symptomatic fasting hypoglycemia with hyperinsu

39、linemiaInsulin reactionSpecific hypoglycemic disordersSymptomatic fasting hypoglycemia with hyperinsulinemiaSulfonylurea overdose1.Overdose most likely occurs in older patients,esp.those with impaired heptic or renal function 2.Drugs prolong the SU effect:warfarin,phenylbutazone,certain sulfonamideS

40、pecific hypoglycemic disordersSymptomatic fasting hypoglycemia with hyperinsulinemiaSurreptitious insulin or SU administration(Factitious hypoglycemia)1.Many patients have severe psychiatric disturbance or a need for attention 2.When insulin is used to induce hypoglycemia,high immunoreactive insulin

41、 and suppressed C peptide are found.Antibodies to insulin(usually see only in insulin-treated individuals)occur.3.When SU is used to induce hypoglycemia,there is elevated levels of C peptide and insulin with detectable SU by HPLC4.Treatment:Psychiatric therapy and social counselingSpecific hypoglyce

42、mic disordersSymptomatic fasting hypoglycemia with hyperinsulinemiaAutoimmune hypoglycemiaMost in Japan,HLA class II allels are associated with this syndrome.Hypoglycemia generally occurs 3-4 h after a meal and follows an early postprandial hyperglycemia.It attributed to a dissociation of insulin-an

43、tibody immune complex,releasing free insulin.Most commonly reported in methimazole-treated patients with Graves disease.1.Insulin antibodiesIn the most cases the hypoglycemia is transient and usually resolves spontaneously within 3-6 months,particularly when offending medications are stoppedTreatmen

44、t:frequent low-carbohydrate small meals;prednisone 30-60 mg/daySpecific hypoglycemic disordersSymptomatic fasting hypoglycemia with hyperinsulinemiaAutoimmune hypoglycemia2.Insulin receptor autoantibodiesAn extremely rare syndromeMost cases have occurred in women often with a history of autoimmune d

45、isease.Almost all of these patients have also had episodes of insulin-resistance diabetes and acanthosis nigricansTheir hypoglycemia may be either fasting or postprandial and severe.Hypoglycemia was found to respond to glucocorticoids therapySpecific hypoglycemic disordersSymptomatic fasting hypogly

46、cemia w/o hyperinsulinemiaDisorders associated with low heptic glucose outputReduced heptic gluconeogenesis:acute yellow atrophy from fulminant viral heptitis or toxic damageDisorders reducing AA supply to heptic parenchyma:severe muscle wasting,inanition from anorexia nervosa,chronic starvation,ure

47、mia,and glucocorticoids defect from adreno-cortical deficiency.Specific hypoglycemic disordersSymptomatic fasting hypoglycemia w/o hyperinsulinemiaEthanol hypoglycemia:Most patients present with neuroglycopenic symptoms,difficult to differentiate from neurotoxic effect of the ethanolIntravenous dext

48、rose should be administered promptly in all such stuporous or comatose patientsPrevention:adequate food intake during alcohol ingestionEthanol inhibits gluconeogenesis but no effect on heptic glycogenolysisSpecific hypoglycemic disordersSymptomatic fasting hypoglycemia w/o hyperinsulinemiaNonpancrea

49、tic TumorsMost are large and mesenchymal in origin,retroperitoneal fibrosarcomaDiagnosis:fasting hypoglycemia(2.5 mmol/L)associated with serum insulin levesl 5 U/mL Due excess expression and release of incompletely process IGF-II Treatment:target primary tumor+frequent feedingSpecific hypoglycemic d

50、isordersNonfasting hypoglycemia(reactive hypoglycemia)Postgastrectomy alimentary hypoglycemiaIn a patient with a history of partial gastrectomy or intestinal resection,symptoms occur 1-2 h after eatingFrequent small meals with reduced carbohydrate content may ameliorate symptomsFunctional Alimentary

51、 hypoglycemiaSymptoms suggest hypoglycemia,which may or may not be confirmed by plasma glucose measurement,occur in some patients who have not undergone GI surgery.The symptoms tend to develop 3-5 h after mealsCurrent evaluation and management of the disease are imprecise Noninsulinoma pencreatogeno

52、us hypoglycemic syndrome(NIPHS)Specific hypoglycemic disordersNonfasting hypoglycemia(reactive hypoglycemia)Noninsulinoma pencreatogenous hypoglycemic syndrome(NIPHS)1.Patients with hyperinsulinemic hypoglycemia who were diagnosed as having generalized islet hyperplasia and nesidioblastosis2.Hypogly

53、cemia occurred only 2-4 h after meals and not at all with fasting up to 72 hours3.Patients have severe neuroglycopenic symptoms(diplopia,dysarthria,confusion,disorientation,and even convulsion and coma)4.Differentiation from reactive hypoglycemia:neuroglycopenic symptoms predominant,and adrenergic symptoms predominant in the latter.5.Patients had positive response to selective arterial calcium stimulation6.No mutation was detected in the KIR6.2 and SUR1 gene(children with a syndrome of familial hyperinsulinemic hypoglycemia)Differentiation from insulinoma:no fasting hypoglycemia