内分泌英文病历讨论学生版

CaseDiscussionA35-year-oldpregnantwoman(gravida2胎次,para1)wasadmittedtothishospitalat19weeksand6daysofgestation怀孕期becauseoftherecentonsetofhypertensionanddiabetes.Threeweeksbeforeadmission,ataroutineprenatalvisit,herbloodpressurewas150/100(150over100)mmHg(millimetershydragyrim).Onthesamedayshesawherprimarycarephysician,whorecordedabloodpressureof172/102mmHg.Theresultsofaphysicalexaminationwerenormal.Urinalysisshowedglucose(4+).TheresultsofotherlaboratorytestsareshowninTable1.Thenextday,thebloodpressurewas180/100mmHg.Thebloodglucoselevel1houraftertheoraladministrationofglucose(50g)was346mgperdeciliter['desili:t]分升(19.2mmolperliter).Treatmentwithlabetalol拉贝洛尔，glyburide格列本月尿(优降糖)，andpotassium[p't田sim]车甲supplementswasinitiated.Theresultsoffetalultrasoundexaminationwerenormalforthegestationalageofthefetus['fits].Threeweekslater,despiteincreasingdosesoflabetalol,thepatient'sbloodpressureremainedintherangeof180/110mmHgandherfastingbloodglucoselevelrangedbetween140and180mgperdeciliter(7.8and10.0mmolperliter);thepatientwasadmittedtothehospital.Thepatienthadgained6.8kginweightduringthepregnancy.Shehadrecentlyhadpolyuriaandpolydipsiaandincreasedfacialpuffiness虚胖;hercomplexion面色waschronicallyruddy红润.Shedidnothaveheadaches,proximalmuscleweakness,bruising挤压伤，flushing激动脸红,abdominalpain,edema,palpitations心悸,diaphoresis[,daif'日囱5]发汗(sweat),edema,orchangesinvision.Hermenseshadbeenregularbeforepregnancy,andshehadhadnodifficultyconceiving怀胎witheitherthispregnancyorapregnancy3yearsearlier,duringwhichshehadmild,diet-controlledgestationaldiabetes.Shehadbeenmildlyoverweight,withabody-massindex(BMI)(theweightinkilogramsdividedbythesquareoftheheightinmeters)ofapproximately25forseveralyears.Shedidnotsmoke,drinkalcohol,oruseillicit[i'lisit]非法的drugs.Shewasmarried,witha2-year-olddaughter.Hermotherandmaternal[m't:nl]母亲方面的grandmotherhadtype2diabetesmellitus,andmanyfamilymembershadhypertension.Q1:What’sthepossiblecauseofthepatient?Give3ormorediseasesforhypertensionduringpregnancy..preeclampsiaoreclampsia.chronichypertensionprobablediagnosis.preeclampsiaoreclampsiasuperimposedonchronichypertension4.gestationalhypertensionWhenIsawthispatientduringherfirstadmission,shehadmarkedhypertension,poorlycontrolleddiabetesmellitus,andhypokalemia.Thefourhypertensivedisordersthatarerecognizedduringpregnancyarepreeclampsia[prii'kl比mpsi]先兆子痫oreclampsia[ek'l笈mpsi]子痫惊厥，chronichypertension(including"essential"hypertensionandsecondaryhypertension),preeclampsiaoreclampsiasuperimposed[,sju:prim'puzd]onchronichypertension,andgestationalhypertension.Althoughthispatienthadproteinuria,itwasnotsevereenoughtowarrant正当理由adiagnosisofpreeclampsia;inaddition,theonsetofpreeclampsiawouldbeunlikelythisearlyinthepregnancy.Gestationalhypertensionwouldalsobeunlikelythisearlyinpregnancy.Thus,Iwasleftwithaprobablediagnosisofchronichypertension.Inapatientwithnewlydiagnosedchronichypertension,themajorquestioniswhetheritisessentialhypertensionorassociatedwithanothercondition.Apregnantpatientwithchronichypertensionisatincreasedriskforsuperimposedpreeclampsia,intrauterine子宫内的growthrestriction(growslowly),abruption分裂placentae[pl1sent]胎盘(胎盘早剥正常20weektobirth),prematurebirth,andperinatal[peri'neitl]围产期death.Effortstocontrolbloodpressurewithlabetalolormethyldopa甲基多巴toreducetheincidenceofpreeclampsiaanditsassociatedperinatalmorbidity发病率havebeendisappointing;thus,asearchforasecondarycauseinacasesuchasthisismandatory必要的强制的.Inthispatient,thepresenceofhypokalemiaincreasedmysuspicionthattheproblemwassecondaryhypertension.Q2:Didthepatienthavepreexisting,undiagnoseddiabetes?Why?YesTheglycatedhemoglobinvalueof8.2%at16weeksand6days'gestationledmetosuspectthatshehadhadhyperglycemiaforsometimebeforeherpregnancybegan.Thebroaddefinitionofgestationaldiabetesincludesthecoincidentaldevelopmentoftype1duringpregnancyaswellasthepresenceofpreexisting,undiagnosedtype2.DiabetesinPregnancyThispatientalsohadcarbohydrateintolerance,withglycosuriaat16weeksand6days'gestation,aswellasgestationaldiabetes(definedascarbohydrateintoleranceofanydegreeofseverity,withanonsetorfirstrecognitionduringpregnancy).Theglycatedhemoglobinvalueof8.2%at16weeksand6days'gestationledmetosuspectthatshehadhadhyperglycemiaforsometimebeforeherpregnancybegan.Thebroaddefinitionofgestationaldiabetesincludesthecoincidental巧合的developmentoftype1duringpregnancyaswellasthepresenceofpreexisting,undiagnosedtype2.Thevastmajorityofpatientswhoreceiveadiagnosisofgestationaldiabeteshavearelativelymilddegreeofcarbohydrateintolerancethatdevelopslateinpregnancyandisassociatedwiththeinsulinresistanceofpregnancy.Itseemedfairlycleartomethatthiswomanhadpreexisting,undiagnosedtype2diabetes.Theresultsofadditionallaboratorytests(Table2)ledmetosuspectthatshehadCushing'ssyndromeandtorequestaconsultationwithanendocrinologist.Q3:Whatiskeypointinthenextphysicalexamination?BMIandweightgainbloodpressureandpulseedema(faceorbitalperipheral)extraocularmovementsandvisualfieldsthyroidsupraclavicularordorsaladiposetissue,hirsutism,bruising座疮abdomenstriaeProximalmusclestrengthandreflexesCushing'sSyndromeinPregnancyInacasethatissuggestiveofCushing'ssyndrome,thegoalsaretoconfirmthepresenceofapathologicexcessofendogenouscortisol,todetermineitssource,andtoremovethesourcetopreventillnessanddeath.Boththediagnosisandmanagementinthiscasewerefurthercomplicatedbythepatient'spregnanc.ThediagnosisofCushing'ssyndromeinpregnancyisconfoundedbythenormalhormonalandbiochemicalchangesofpregnancy;themanagementisconfoundedbytheprofoundly极度的leteriouseffectofhypercortisolemiaonbothmotherandfetus,thesideeffectsofmedications,andthetechnicalproblemsinvolvedinundertakingsurgicalresection.ThecomplicationsofpregnancyforwomenwithCushing'ssyndromeincludehypertension,diabetes,preeclampsia,andinfection.Fetalcomplicationsincludeprematurityandintrauterinegrowthretardation延迟.ThispatienthadnosignsorsymptomsofCushing'ssyndromebeforepregnancy.ConsiderationofthediagnosisofCushing'ssyndromeistypicallybasedonclinicalfeatures.However,manyfeaturesofthisdiseasearesimilartothoseofnormalpregnancy,includingweightgain,amenorrhea[ei.men1ri:]无月经,striae条纹，fatigue[ftig]劳累，backpain,moodchanges,andplethora['pleOr]过量过剩.Inthispatient,clinicallysignificanthypertensionandabnormalglucosetolerancewerepresent;althoughthesefindingsarecommoninCushing'ssyndrome,theyarenonspecific.ObjectivesignsfavoringadiagnosisofCushing'ssyndrome-suchasweakness,particularlyproximalweakness,spontaneous[span'tenis]自然发生的ecchymoses[eki'musis]瘀斑，andwidestriae-werenotseeninthiscase,probablybecausethedevelopmentofhypercortisolemiahadbeenrapid.ThesinglefindingthatappropriatelypromptedanevaluationofthispatientforCushing'ssyndromewasunexplainedhypokalemia.Onphysicalexamination,thepatient'sweightwas80kgandheight170cm,withabody-massindexof28.Thebloodpressurewas180/100mmHg,andthepulsewas88beatsperminute;othervitalsignswerenormal.Herfacewasslightlyrounded,therewasmildperorbital眼窝的edema,andherfacialcomplexionwasruddy.Extraocular[,ekstr'okjul]眼夕卜的movementsandvisualfieldswereintact未受损伤.Thethyroidwasnormalinsize,withnopalpablenodules.Therewasnoincreaseinsupraclavicular锁骨上的ordorsaladipose脂肪tissue,hirsutism多毛症，orevidenceofbruising擦伤.Theabdomenwasgravid怀孕的，nontender,andwithoutstriae.Proximalmusclestrengthandreflexeswerenormal.Therewasnoperipheraledema.Tmbk】ResultsofS&rumandUrmeChemicalTestsbetween16Weeks6Tmbk】ResultsofS&rumandUrmeChemicalTestsbetween16Weeks6and19Weeks6Chi”户VariablfiNbeMR»ngeValuesinPatientSodium(ee叫liter)135-145139Pg第ium(mmol/liber)3.JE2.6Chloride1(mmgl/iiter)100-10E99Carbondioxide(mmol/IIter)23.0-31.9312Ureanitrogen(mg/dl)aCrritimncimg/dl)06-1.50年Glucose(rtig/dl)170-no240CalciumJmg/dl)8.5-1059.2Protein(g/dl)6.0-80GAlbumin(g/dl)3.1-4.33.4Globulin(g/dl)2$-4.131Alkalim?photphatiK(U/liter)30^]004QAspartateaminotrart'sfora'st5-2512(U/liter)Xlanine?mino-transfErase(U/litcr)加3Q22Lactatedehydrogenase(U/Iiter)110-210Bilirubing©出))Total0-1.00.4Conjugated0-040.1Urmarytotalprotein hr)D-135Glycatedhemoglobin工80-64。*To»convertthevaluesforureanitrogentomillimakrsperliter,multiplyby0,357,ToconvertThefdrereatinlneIsmicromolesperliter,multiplybyBS4,ToconvertIhevalues^irglucosetomiHimolesperliter,multipl>by0.051551-Tqconcertthevaluesforcalciumtomilhmole-5perIiKejmultiplyby0.250.TooomvertthevaluesfortotalandconjugatedbilirubintomicromoIe5perliter,multiplyby17PLQ4:Thenwhatisyourdiagnosis?Why?chronichypertensiongestationaldiabetes(type2diabetes)hypokalemiaCushing,ssyndrome?Q5:Arethereanyotherexaminationsweshouldtake?Why?Confirmationofapathologicexcessofcortisolisbasedononeormoreofthreemethods:assessmentoftotalcortisolproductionovera24-hourperiodwithadeterminationof24-hoururinaryfreecortisoldocumentationofthelossofnormaldiurnalvariationincortisolsecretiononthebasisofalate-nightsalivarycortisolmeasurementdocumentationofthelossoffeedbackinhibitionofcortisolonthehypothalamic-pituitary-adrenalaxiswithdexamethasonesuppressiontestingToruleoutanaldosterone-secretingtumorasacauseofhypokalemiaaldosteronelevelandelevatedplasmareninactivitytofindthelocationofthelesion(adrenal,pituitaryorectopic)magneticresonanceimaging(MRI)todetermineiftheCushing'ssyndromecausedbyexcesscorticotropinornotanundetectablecorticotropinlevelora9a.m.levelbelow10pgpermilliliterwithatwo-siteimmunoradiometricassayQ6:Whatisyourprescriptionforthispatient?Labetalol(untilthebloodpressurebecamenormal)硝苯地平insulinandpotassiumsupplementationInthispatient,rapidlyescalatinghypertensionandinsulin-requiringdiabetesmadesurgicalcureanimmediategoal.Ifsurgerycannotbeperformedinacasesuchasthis,theuseofinterimmedicaltherapytoblockcortisolproductionshouldbeconsidered.Inthiscase,metyrapone美替拉酮,adrugthatblockstheconversionof11-deoxycortisol脱氧可的松tocortisol,wasusedbrieflywhilesurgerywasbeingscheduled.Theuseofmetyraponeduringpregnancyhasbeenreportedinafewcases15,16,17,18;however,definitivesurgeryusuallyshouldnotbedelayeduntilthecortisollevelisnormalized.Otherdrugsmorecommonlyusedtotreathypercortisolemia,suchasketoconazole酮康唑,crosstheplacenta,inhibitprogesteroneproduction,andmaybebothteratogenic[,tertu'd§enik]产生畸形andassociatedwithfetalloss.Oneweeklater,thepatientwasseenintheneuroendocrineclinic.TheresultsofadditionallaboratorytestswereshowedinTable2.Arepeated24-hoururinarycortisolmeasurementshowedthatthelevelwas1805咯TableLResultsofEndocrineTests*VariableNormalRangeOnAdmissioncorticatropin(pg/ml)6763Serumaldosterone(ng/dl)471287Plasmareninactivity(ng/ml/hr)0.65-5.01L6DeliydroepianclrosterciiiesulfateS2TQ。13Teytostcrone(ng/df)48643Thyrotropin0A-5.00.21Freethyroxine(ng/dl)0.824-hrurinarycortisol()Jg/24hr)20-70BQ2*Toconvertthevaluesforcorticotropintopicomoksperliterhmultiplyby02202Toconvertthevaluesforaldosteronetopicomolesperliter,multiplyby27.74.Taconvertthevaluesfordehydroep^ndrostercnesulfatetonanomolesperliter,multiplyby27.21..T□convertthevaluerfbrlestosterorttonanomolesperliter,multiplyby003467.Toconvertthevaluesforfreethyroxinetopicomolesper【iter,multiplyby12.87.Q7:Howtoconfirmthepresenceofapathologicexcessofcortisol?Confirmationofapathologicexcessofcortisolisbasedononeormoreofthreemethods:assessmentoftotalcortisolproductionovera24-hourperiodwithadeterminationof24-hoururinaryfreecortisol,documentationofthelossofnormaldiurnalvariationincortisolsecretiononthebasisofalate-nightsalivarycortisolmeasurement,anddocumentationofthelossoffeedbackinhibitionofcortisolonthehypothalamic-pituitary-adrenalaxiswithdexamethasonesuppressiontesting.Thebiochemicaldiagnosisofhypercortisolemiainpregnancyiscomplicatedbytwofactors.DetectingPathologicallyExcessiveCortisolProductionConfirmationofapathologicexcessofcortisolisbasedononeormoreofthreemethods:assessmentoftotalcortisolproductionovera24-hourperiodwithadeterminationof24-hoururinaryfreecortisol,documentationofthelossofnormaldiurnalvariationincortisolsecretiononthebasisofalate-nightsalivarycortisolmeasurement,anddocumentationofthelossoffeedbackinhibitionofcortisolonthehypothalamic-pituitary-adrenalaxiswithdexamethasonesuppressiontesting.Thebiochemicaldiagnosisofhypercortisolemiainpregnancyiscomplicatedbytwofactors.First,cortisolproductionratesmarkedlyincreaseduringpregnancy,sothaturinaryfreecortisollevelsinthesecondandthirdtrimestersmayoverlapwithlevelsseeninCushing'ssyndrome.Second,levelsofcorticotropin促肾上腺皮质激素risedespiteincreasingcortisollevels,whichisconsistentwiththeoccurrenceofdecreasedfeedbackoncorticotropinsecretion.Therefore,unlesscortisollevelsaremarkedlyelevated,theresultsofthesetestsmaybedifficulttointerpret.Inhealthypeople,cortisolsecretionpeaksinearlymorningandreachesanadirasmidnightapproaches;thedifferenceincortisolsecretionbetweensuchpeopleandthosewithCushing'ssyndromeismaximalatapproximately11p.m.4However,althoughthisdifferenceprovidesanexcellentscreeningtestforCushing'ssyndrome,normallate-nightsalivarycortisollevelsarenotwellestablishedduringpregnancy.Low-dosedexamethasonesuppressiontestingcanbeusedtodiagnoseCushing'ssyndromedespitetheoccurrenceoffalsenegativeresults.Duringpregnancy,however,falsepositiveresultscanoccur.Possiblereasonsforfalsepositiveresultsincludeanestrogen-inducedelevationinthecortisol-bindingglobulin;theimpairedsuppressibilityofthehypothalamic-pituitary-adrenalaxis;placentalproductionofcorticotropinandcorticotropin-releasinghormone,whichisnotregulatedbynegativefeedbackcontrol;tissuerefractorinesstoglucocorticoids;andpossibleantiglucocorticoideffectsofprogesterone.4g2天每天4次Inthiscase,urinaryfreecortisollevelsthatweremorethan1000|igabovetheupperlimitofthenormalrangeduringtwo24-hourperiodsintheabsenceofglucocorticoidtherapyclearlyestablishedthediagnosisofCushing'ssyndrome.Thehypokalemiareflectedthemagnitudeofthisexcesscortisol.Thenormalaldosteronelevelandelevatedplasmareninactivitywereconsistentwithpregnancy,rulingoutanaldosterone-secretingtumorasacauseofhypokalemia.Q8:Howtodeterminethesourceofapathologicexcessofcortisol?Corticotropin-independentCushing'ssyndromeisduetoanadrenallesion,whereasthecorticotropin-dependentformofthediseasecanbetracedtoeitherapituitary垂体的oranectopicsource.InCushing'ssyndromecausedbyexcesscorticotropinfromanysource,corticotropinlevelsaretypicallyinthenormalrange—whichisinappropriategiventhelevelofcortisol—ortheyareelevated.Incorticotropin-independentCushing'ssyndrome,corticotropinlevelsshouldbesuppressed.Inthesettingofhypercortisolemia,anundetectablecorticotropinlevelora9a.m.levelbelow10pgpermilliliter(2pmolperliter)withatwo-siteimmunoradiometric免疫放射测定assayisconsideredtobesuggestiveofcorticotropin-independentCushing'ssyndrome.DeterminingtheCauseofExcessCortisolProductionOncepathologichypercortisolemiahasbeenidentified,thenextstepistodeterminewhetherthehormoneexcessiscorticotropin-dependent.Corticotropin-independentCushing'ssyndromeisduetoanadrenallesion,whereasthecorticotropin-dependentformofthediseasecanbetracedtoeitherapituitary垂体的oranectopicsource.ThemostcommoncauseofendogenousCushing'ssyndromeisoverproductionofcorticotropinbyabenignpituitarycorticotropictumor.Thevastmajorityofsuchtumorsaremicroadenomas(<1cmindiameter);approximatelyonethirdaretoosmalltobevisualizedonsensitivehigh-resolutionmagneticresonanceimaging(MRI).Ectopic易位的Cushing'ssyndromeiscausedbyaneoplasmoutsideofthepituitaryglandthatproducescorticotropinor,inrarecases,corticotropin-releasinghormone.ManytumorshavebeenreportedtocauseectopicCushing'ssyndrome,butthemostcommonarepulmonaryinorigin,rangingfromcarcinoidtumorstobronchogeniccarcinomas.InCushing'ssyndromecausedbyexcesscorticotropinfromanysource,corticotropinlevelsaretypicallyinthenormalrange——whichisinappropriategiventhelevelofcortisol——ortheyareelevated.Incorticotropin-independentCushing'ssyndrome,corticotropinlevelsshouldbesuppressed.Inthesettingofhypercortisolemia,anundetectablecorticotropinlevelora9a.m.levelbelow10pgpermilliliter(2pmolperliter)withatwo-siteimmunoradiometric免疫放射测定assayisconsideredtobesuggestiveofcorticotropin-independentCushing'ssyndrome.However,becausecorticotropinlevelsmaybehigherinpregnantwomenthaninnonpregnantwomen,thismeasuremaybemisleading.Therefore,unlesscorticotropinlevelsarelowerthannormal,acorticotropin-dependenttumormaybeerroneouslydiagnosed.Inthiscase,thecorticotropinlevelof3pgpermilliliter(0.6nmolperliter)inthesettingofprofoundhypercortisolemiawasstronglysuggestiveofanadrenalsourceofCushing'ssyndrome,anditledustoorderanadrenalMRIwithouttheadministrationofcontrastmaterial.Q9:WhatisthemostcommoncauseofendogenousCushing,ssyndrome?ThemostcommoncauseofendogenousCushing'ssyndromeisoverproductionofcorticotropinbyabenignpituitarycorticotropictumor.Ectopic易位的Cushing'ssyndromeiscausedbyaneoplasmoutsideofthepituitaryglandthatproducescorticotropinor,inrarecases,corticotropin-releasinghormone.ManytumorshavebeenreportedtocauseectopicCushing'ssyndrome,butthemostcommonarepulmonaryinorigin,rangingfromcarcinoidtumorstobronchogeniccarcinomas.

TheabdominalMRIscanrevealsaleftadrenalmass,5.4by4.3by3.8cm,withwell-definedborders,thatisrelativelyhomogeneous同性质insignalintensity.Figure1.AxialMRIoftheLeftAdrenalGland.PanelAshowsaverywell-circumscribedmass(arrow)intheleftadrenalglandwithalow,relativelyhomogeneoussignalintensityonthisin-phaseTAsub1A-weightedimage(echotime,4.2msec)andnoevidenceoflocalinvasion.InPanelB,theout-of-phaseTAsub1A-weightedimage(echotime,2.1msec)反相位showsnomarkeddecreaseinthesignalintensityofthemass(arrow),unlikeatypicaladenoma.InPanelC,aTAsub2A-weightedimageshowsthatthemass(arrow)hasonlyintermediate中等signalintensity,unlikeatypicalpheochromocytoma[,fi:kru