NR507 Week 8 Final Exam Study Guide
i i i i i i
Reproductive:
endometrial icycle iand ithe ioccurrence iof iovulation- i the imenstrual icycle iconsist iof
ithree iphases: ithe ifollicular/proliferative iphase i(postmenstrual), ifollowed iby ithe
iluteal/secretory iphase i(premenstrual), iand ithe iischemic/menstrual iphase.
*Ovarian ihormones icontrol ithe iuterine i(endometrial) ievents iof ithe imenstrual
icycle. iDuring ithe ifollicular/proliferative iphase iof ithe iovarian icycle iestrogen
iproduced iby ithe ifollicle icauses ithe iendometrium ito iproliferate i(proliferative
iphase) iand iinduces ithe iLH isurge iand iprogesterone iproduction iin ithe igranulosa
ilayer. iDuring ithe iluteal/secretory iphase, iestrogen imaintains ithe ithickened
iendometrium, iand iprogesterone icauses iit ito idevelop iblood ivessels iand isecretory
iglands i(secretory iphase). iAs ithe icorpus iluteum i“starved” iendometrium
idegenerates iand isloughs ioff, icausing imenstruation, ithe iischemic/menstrual
iphase.
uterine iprolapse- ithe idescent iof ithe icervix ior ientire iuterus iinto ithe ivaginal icanal
idue ito iweakened ipelvic ifascia iand imusculature iand ipoor isupport ifrom ithe ivaginal
imuscles iand ifascia.
polycystic iovarian isyndrome- imost icommon icause iof ianovulation iand iovulatory
idysfunction iin iwomen. iDefined ias ihaving iat ileast itwo iof ithe ifollowing ithree
ifeatures: iirregular iovulation, ielevated ilevels iof iandrogens i(e.g., itestosterone),
iand ithe iappearance iof ipolycystic iovaries ion iultrasound. iPCOS iis iassociated iwith
imetabolic idysfunction, iincluding idyslipidemia, iinsulin iresistance, iand iobesity.
One iof ithe imost icommon iendocrine idisturbances iaffecting iwomen, iespecially
iyoung iwomen, iand iis ia ileading icause iof iinfertility iin ithe iU.S. iStrong igenetic
icomponent ito iPCOS, ivarious ifeatures iof ithe isyndrome imay ibe iinherited. iPCOS
ipatients iare ithree itimes ias ilikely ito ihave iinsulin iresistance, ihigher ifor iobese
iwomen. iTend ito ihave iincreased ileptin ilevels. iSymptoms iwithin i2 iyears iof ipubertyi&
iinclude: idysfunctional ibleeding ior iamenorrhea, ihirsutism, iacne, iacanthosis
inigricans, iand iinfertility. i60% iare iobese. iIncreased irisk ifor igestational iDM,
ipregnancy-induced iHTN, ipreterm ibirth, iand iperinatal imortality.
testicular icancer iand iconditions ithat iincrease irisk- imost icommon icancer iin imen,
iage i15-35. iSlightly imore icommon ion ithe iright ithan ion ithe ileft. i90% iof itesticular
icancers iare igerm icell itumors iarising ifrom ithe imale igametes. iTwo itypes:
iSeminomas-most icommon, ileast iaggressive, imake iup i30-35% iof itesticular
icancers i& iNonseminomas-include iembryonal icarcinomas, iteratomas, iand
ichoriocarcinomas, iwhich iare ithe imost iaggressive, ibut irare iform iof itesticular
icancer. iRisk ifactors iinclude: igenetic ipredisposition, ihistory iof icryptorchidism,
iabnormal itesticular idevelopment, iHIV, iAIDS, iKlinefelter isyndrome, iand ihistory iof
itesticular icancer. iCan iarise ifrom ispecialized icells iof ithe igonadal istroma-these
itumors, iwhich iare inamed ifor itheir icellular iorigins, iare iLeydig icell, iSertoli icell,
igranulosa icell, iand itheca icell itumors iand iconstitute iless ithan i10% iof iall itesticular
icancers.
symptoms ithat irequire ievaluation ifor ibreast icancer- ipainless ilump, ipalpableinodes
iin ithe iaxilla, iretraction iof itissue i(dimpling), ichest ipain, idilated iblood
,vessels, iedema, iedema iof ithe iarm, ihemorrhage, ilocal ipain, inipple/areolar ieczema,
inipple idischarge iin inon-lacting iwoman, ipitting iof ithe iskin i(like isurface iof ian iorange
ipeel), ireddened iskin, ilocal itenderness iand iwarmth, iskin iretraction, iulceration.
signs iof ipremenstrual idysphoric idisorder- iOne iof ithese isymptoms imust ibe
ipresent ifor ia idiagnosis: imarked iaffective ilability, imarked iirritability ior ianger ior
iincreased iinterpersonal iconflicts, imarked ianxiety, itension. iOne iof ithese imust
ialso ibe ipresent: idecreased iinterest, idifficulty iconcentrating, ieasy ifatigability, ilow
ienergy, iincrease ior idecrease iin isleep, ifeelings iof ibeing ioverwhelmed, iphysical
isymptoms, isuch ias: ibreast itenderness, imuscle ior ijoint iaches, ibloating ior iweight
igain. i(Greater ithan i5 iof ithese isymptoms ioccur iduring ithe iweek ibefore imenses
ionset, iimprove iwithin ia ifew idays iafter imenses ionset, iand idiminish iin ithe iweek
ipostmenses).
dysfunctional iuterine ibleeding- ibleeding ithat iis iabnormal iin iduration, ivolume,
ifrequency, ior iregularity; iand ihas ibeen ipresent ifor ithe imajority iof ithe iprevious i6
imonths. iMay ibe iacute ior ichronic. iPALM-COEIN iSystem ifor iclassification iof
iabnormal iuterine ibleeding: iPALM-structural icauses: iPolyp, iAdenomyosis,
iLeiomyoma, iMalignancy. iCOEIN-nonstructural icauses: icoagulopathy, iovulatory
idysfunction, iendometrial, iiatrogenic, inot iyet iclassified. iIncreased iendometrial
ibleeding iis icorrelated iwith ia ichange ifrom iovulatory ito ianovulatory icycles idue ito
ihigh iestrogen ilevels.
pathophysiology iof iprostate icancer- iMore ithan i95% iof iprostatic ineoplasms iare
ihistologically isimilar ito iadenocarcinomas iand irely ion iandrogen-dependent
isignaling ifor itheir idevelopment iand iprogression. iMost iof ithese ineoplasms ioccur
iin ithe iperiphery iof ithe iprostate. iProstatic iadenocarcinoma iis ia iheterogeneous
igroup iof itumors iwith ia idiverse ispectrum iof imolecular iand ipathologic
icharacteristics, iand itherefore iclinical ibehaviors iand ichallenges. iThe ibiologic
iaggressiveness iof ithe ineoplasm iappears ito ibe irelated ito ithe idegree iof
idifferentiation irather ithan ithe isize iof ithe itumor. iTesticular itestosterone iprovides
ithe imain isource iof iandrogens iin ithe iprostate iand iis ithe imajor icirculating
iandrogen, iwhereas iDHT ipredominates iin iprostate itissue iand ibinds ito ithe
iandrogen ireceptors iwith igreater iaffinity ithan idoes itestosterone. iAndrogen
iproduction ioutside iof ithe itestes, ior iextra itesticular isources. iTestosterone iis
iconverted ito idihydrotestosterone, iDHT iis ithe imost ipotent iintraprostatic
iandrogen.
HPV iand ithe idevelopment iof icervical icancer- ialmost iexclusively icaused iby
icervical ihuman ipapillomavirus i(HPV) iinfection. iHPV istrains i16 i& i18 iare imost
ioften iimplicated ias icausing i70% iof iall icervical icancers iand ialso icontribute ito
imany ivaginal, ivulvar, ipenile, ianal, iand ioropharyngeal icancers. iMost iHPV
iinfections iare icleared ifrom ithe iimmune isystem; ivast imajority iof iinfections ido inot
icause icervical icancer. iScreening ibefore iage i21 inot irecommended. iWomen iwith
imultiple isex ipartners iare imore ilikely ito ibe iexposed ito ihigh-risk iHPV, ibut iwomen
iwith ionly ione ilifetime isexual ipartner ican ialso ibecome iinfected. iTransformation
izone iis iwhere ithe itwo icell itypes iof isquamous iepithelium icells iand icolumnar
, epithelial icells icome itogether iand ithis iis iwhere icarcinoma iin isitu iis imost ilikely ito
idevelop. iPAP itest ior iHPV iscreening inecessary ifor iearly idetection; i90% ican ibe
idetected iby ithese. iViral iDNA ibecomes iintegrated iinto ithe igenomic iDNA iof ithe
iinfected ibasal icell iof ithe icervix iand idirects ithe ipersistent iproduction iof iviral
ioncogenes. iPersistence iof iinfection iwith ihigh-risk iHPV iis ia iprerequisite ifor ithe
idevelopment iof icervical iintraepithelial ineoplasia, ilesions, iand iinvasive icervical
icancers.
Endocrine:
body’s iprocess ifor iadapting ito ihigh ihormone ilevels- iFeedback isystems. iMost
ihormone ilevels iare iregulated iby inegative ifeedback, iin iwhich itropic ihormone
isecretion iraises ithe ilevel iof ia ispecific ihormone. iThe ielevated ilevel iof ithe ispecific
ihormone ithen icauses inegative ifeedback, idecreasing isecretion iof ithe itropic
ihormone. iPositive ifeedback isystems, iin iwhich ielevated ihormone ilevels iincrease ia
iresponse iwhich ithen ifurther iincreases ihormone isecretion, iis iseen imost ioften iin
ireproductive ihormones. iNegative ifeedback iis ithe imost icommon i& ioccurs iwhen ia
ichemical, ineural, ior iendocrine iresponse idecreases ithe isubsequent isynthesis iand
isecretion iof ia ihormone. iPositive ifeedback ioccurs iwhen ia ineural, ichemical, ior
iendocrine iresponse iincreases ithe isynthesis iand isecretion iof ia ihormone. iPositive
ifeedback ialso ioccurs iwhen ian iincreased ihormone ilevel ifurther iincreases ithe
isynthesis iand isecretion iof ithat isame ihormone. iThe isensitivity ior iaffinity iof ithe
itarget icell ito ia iparticular ihormone iis irelated ito ithe iconcentration iof ireceptors iper
icell: ithe imore ireceptors, ithe ihigher ithe iaffinity ior ithe imore isensitive ithe icell iis ito
ithe istimulating ieffects iof ithe ihormone. iThus ithe icell ican iadjust iits isensitivity ito
ithe iconcentration iof ithe isignaling ihormone. ihormone iis idistributed ithroughout
ithe ibody, ionly itarget icells iwith ispecific ireceptors ifor ithat ihormone iare iaffected.
Target icell iresponse idepends ion iblood ilevels iof ithe ihormone, ithe iconcentrationiof
itarget icell ireceptors, iand iaffinity iof ithe ireceptor ifor ithe ihormone. iHormone
ireceptors iof ithe itarget icell ihave itwo imain ifunctions: i(1) ito irecognize iand ibind iwith
ihigh iaffinity ito itheir iparticular ihormones iand i(2) ito iinitiate ia isignal ito iappropriate
iintracellular ieffectors. iSee iChapter i1 ifor icell isignaling ipathways, iparticularly.
Cushing’s iSyndrome- ithe iclinical imanifestations iresulting ifrom ichronic iexposure
ito iexcess iendogenous icortisol iand iis imore icommon iin iwomen. iCushing’s idisease
iis iexcess iendogenous isecretion iof iACTH. iACTH idependent ihypercortisolism
i(about i80%) iresults ifrom ioverproduction iof ipituitary iACTH iby ia ipituitary iadenoma
i(most icommon iand ican ioccur iat iany iage) ior iby ian iectopic isecreting inonpituitary
itumor, isuch ias ia ismall icell icarcinoma iof ithe ilung i(more icommon iin iolder iadults).
iACTH-independent ihypercortisolism i(about i20%) iis icaused iby icortisol isecretion
ifrom ia irare ibenign ior imalignant itumor iof ione ior ibothiadrenal i glands i (more
i common i in ichildren). iA iCushing-like isyndrome i may idevelop ias ia iside ieffect iof
ilong-term ipharmacologic iadministration iof iglucocorticoids. iWith iACTH-
dependent ihypercortisolism, ithe iexcess iACTH istimulates iexcess iproduction iof
icortisol iand ithere iis iloss iof ifeedback icontrol iof iACTH isecretion. iWhatever ithe
icause, itwo iobservations iconsistently iapply ito iindividuals iwith iCushing’s
isyndrome: i1.) iThey idon’t ihave idiurnal ior icircadian
i i i i i i
Reproductive:
endometrial icycle iand ithe ioccurrence iof iovulation- i the imenstrual icycle iconsist iof
ithree iphases: ithe ifollicular/proliferative iphase i(postmenstrual), ifollowed iby ithe
iluteal/secretory iphase i(premenstrual), iand ithe iischemic/menstrual iphase.
*Ovarian ihormones icontrol ithe iuterine i(endometrial) ievents iof ithe imenstrual
icycle. iDuring ithe ifollicular/proliferative iphase iof ithe iovarian icycle iestrogen
iproduced iby ithe ifollicle icauses ithe iendometrium ito iproliferate i(proliferative
iphase) iand iinduces ithe iLH isurge iand iprogesterone iproduction iin ithe igranulosa
ilayer. iDuring ithe iluteal/secretory iphase, iestrogen imaintains ithe ithickened
iendometrium, iand iprogesterone icauses iit ito idevelop iblood ivessels iand isecretory
iglands i(secretory iphase). iAs ithe icorpus iluteum i“starved” iendometrium
idegenerates iand isloughs ioff, icausing imenstruation, ithe iischemic/menstrual
iphase.
uterine iprolapse- ithe idescent iof ithe icervix ior ientire iuterus iinto ithe ivaginal icanal
idue ito iweakened ipelvic ifascia iand imusculature iand ipoor isupport ifrom ithe ivaginal
imuscles iand ifascia.
polycystic iovarian isyndrome- imost icommon icause iof ianovulation iand iovulatory
idysfunction iin iwomen. iDefined ias ihaving iat ileast itwo iof ithe ifollowing ithree
ifeatures: iirregular iovulation, ielevated ilevels iof iandrogens i(e.g., itestosterone),
iand ithe iappearance iof ipolycystic iovaries ion iultrasound. iPCOS iis iassociated iwith
imetabolic idysfunction, iincluding idyslipidemia, iinsulin iresistance, iand iobesity.
One iof ithe imost icommon iendocrine idisturbances iaffecting iwomen, iespecially
iyoung iwomen, iand iis ia ileading icause iof iinfertility iin ithe iU.S. iStrong igenetic
icomponent ito iPCOS, ivarious ifeatures iof ithe isyndrome imay ibe iinherited. iPCOS
ipatients iare ithree itimes ias ilikely ito ihave iinsulin iresistance, ihigher ifor iobese
iwomen. iTend ito ihave iincreased ileptin ilevels. iSymptoms iwithin i2 iyears iof ipubertyi&
iinclude: idysfunctional ibleeding ior iamenorrhea, ihirsutism, iacne, iacanthosis
inigricans, iand iinfertility. i60% iare iobese. iIncreased irisk ifor igestational iDM,
ipregnancy-induced iHTN, ipreterm ibirth, iand iperinatal imortality.
testicular icancer iand iconditions ithat iincrease irisk- imost icommon icancer iin imen,
iage i15-35. iSlightly imore icommon ion ithe iright ithan ion ithe ileft. i90% iof itesticular
icancers iare igerm icell itumors iarising ifrom ithe imale igametes. iTwo itypes:
iSeminomas-most icommon, ileast iaggressive, imake iup i30-35% iof itesticular
icancers i& iNonseminomas-include iembryonal icarcinomas, iteratomas, iand
ichoriocarcinomas, iwhich iare ithe imost iaggressive, ibut irare iform iof itesticular
icancer. iRisk ifactors iinclude: igenetic ipredisposition, ihistory iof icryptorchidism,
iabnormal itesticular idevelopment, iHIV, iAIDS, iKlinefelter isyndrome, iand ihistory iof
itesticular icancer. iCan iarise ifrom ispecialized icells iof ithe igonadal istroma-these
itumors, iwhich iare inamed ifor itheir icellular iorigins, iare iLeydig icell, iSertoli icell,
igranulosa icell, iand itheca icell itumors iand iconstitute iless ithan i10% iof iall itesticular
icancers.
symptoms ithat irequire ievaluation ifor ibreast icancer- ipainless ilump, ipalpableinodes
iin ithe iaxilla, iretraction iof itissue i(dimpling), ichest ipain, idilated iblood
,vessels, iedema, iedema iof ithe iarm, ihemorrhage, ilocal ipain, inipple/areolar ieczema,
inipple idischarge iin inon-lacting iwoman, ipitting iof ithe iskin i(like isurface iof ian iorange
ipeel), ireddened iskin, ilocal itenderness iand iwarmth, iskin iretraction, iulceration.
signs iof ipremenstrual idysphoric idisorder- iOne iof ithese isymptoms imust ibe
ipresent ifor ia idiagnosis: imarked iaffective ilability, imarked iirritability ior ianger ior
iincreased iinterpersonal iconflicts, imarked ianxiety, itension. iOne iof ithese imust
ialso ibe ipresent: idecreased iinterest, idifficulty iconcentrating, ieasy ifatigability, ilow
ienergy, iincrease ior idecrease iin isleep, ifeelings iof ibeing ioverwhelmed, iphysical
isymptoms, isuch ias: ibreast itenderness, imuscle ior ijoint iaches, ibloating ior iweight
igain. i(Greater ithan i5 iof ithese isymptoms ioccur iduring ithe iweek ibefore imenses
ionset, iimprove iwithin ia ifew idays iafter imenses ionset, iand idiminish iin ithe iweek
ipostmenses).
dysfunctional iuterine ibleeding- ibleeding ithat iis iabnormal iin iduration, ivolume,
ifrequency, ior iregularity; iand ihas ibeen ipresent ifor ithe imajority iof ithe iprevious i6
imonths. iMay ibe iacute ior ichronic. iPALM-COEIN iSystem ifor iclassification iof
iabnormal iuterine ibleeding: iPALM-structural icauses: iPolyp, iAdenomyosis,
iLeiomyoma, iMalignancy. iCOEIN-nonstructural icauses: icoagulopathy, iovulatory
idysfunction, iendometrial, iiatrogenic, inot iyet iclassified. iIncreased iendometrial
ibleeding iis icorrelated iwith ia ichange ifrom iovulatory ito ianovulatory icycles idue ito
ihigh iestrogen ilevels.
pathophysiology iof iprostate icancer- iMore ithan i95% iof iprostatic ineoplasms iare
ihistologically isimilar ito iadenocarcinomas iand irely ion iandrogen-dependent
isignaling ifor itheir idevelopment iand iprogression. iMost iof ithese ineoplasms ioccur
iin ithe iperiphery iof ithe iprostate. iProstatic iadenocarcinoma iis ia iheterogeneous
igroup iof itumors iwith ia idiverse ispectrum iof imolecular iand ipathologic
icharacteristics, iand itherefore iclinical ibehaviors iand ichallenges. iThe ibiologic
iaggressiveness iof ithe ineoplasm iappears ito ibe irelated ito ithe idegree iof
idifferentiation irather ithan ithe isize iof ithe itumor. iTesticular itestosterone iprovides
ithe imain isource iof iandrogens iin ithe iprostate iand iis ithe imajor icirculating
iandrogen, iwhereas iDHT ipredominates iin iprostate itissue iand ibinds ito ithe
iandrogen ireceptors iwith igreater iaffinity ithan idoes itestosterone. iAndrogen
iproduction ioutside iof ithe itestes, ior iextra itesticular isources. iTestosterone iis
iconverted ito idihydrotestosterone, iDHT iis ithe imost ipotent iintraprostatic
iandrogen.
HPV iand ithe idevelopment iof icervical icancer- ialmost iexclusively icaused iby
icervical ihuman ipapillomavirus i(HPV) iinfection. iHPV istrains i16 i& i18 iare imost
ioften iimplicated ias icausing i70% iof iall icervical icancers iand ialso icontribute ito
imany ivaginal, ivulvar, ipenile, ianal, iand ioropharyngeal icancers. iMost iHPV
iinfections iare icleared ifrom ithe iimmune isystem; ivast imajority iof iinfections ido inot
icause icervical icancer. iScreening ibefore iage i21 inot irecommended. iWomen iwith
imultiple isex ipartners iare imore ilikely ito ibe iexposed ito ihigh-risk iHPV, ibut iwomen
iwith ionly ione ilifetime isexual ipartner ican ialso ibecome iinfected. iTransformation
izone iis iwhere ithe itwo icell itypes iof isquamous iepithelium icells iand icolumnar
, epithelial icells icome itogether iand ithis iis iwhere icarcinoma iin isitu iis imost ilikely ito
idevelop. iPAP itest ior iHPV iscreening inecessary ifor iearly idetection; i90% ican ibe
idetected iby ithese. iViral iDNA ibecomes iintegrated iinto ithe igenomic iDNA iof ithe
iinfected ibasal icell iof ithe icervix iand idirects ithe ipersistent iproduction iof iviral
ioncogenes. iPersistence iof iinfection iwith ihigh-risk iHPV iis ia iprerequisite ifor ithe
idevelopment iof icervical iintraepithelial ineoplasia, ilesions, iand iinvasive icervical
icancers.
Endocrine:
body’s iprocess ifor iadapting ito ihigh ihormone ilevels- iFeedback isystems. iMost
ihormone ilevels iare iregulated iby inegative ifeedback, iin iwhich itropic ihormone
isecretion iraises ithe ilevel iof ia ispecific ihormone. iThe ielevated ilevel iof ithe ispecific
ihormone ithen icauses inegative ifeedback, idecreasing isecretion iof ithe itropic
ihormone. iPositive ifeedback isystems, iin iwhich ielevated ihormone ilevels iincrease ia
iresponse iwhich ithen ifurther iincreases ihormone isecretion, iis iseen imost ioften iin
ireproductive ihormones. iNegative ifeedback iis ithe imost icommon i& ioccurs iwhen ia
ichemical, ineural, ior iendocrine iresponse idecreases ithe isubsequent isynthesis iand
isecretion iof ia ihormone. iPositive ifeedback ioccurs iwhen ia ineural, ichemical, ior
iendocrine iresponse iincreases ithe isynthesis iand isecretion iof ia ihormone. iPositive
ifeedback ialso ioccurs iwhen ian iincreased ihormone ilevel ifurther iincreases ithe
isynthesis iand isecretion iof ithat isame ihormone. iThe isensitivity ior iaffinity iof ithe
itarget icell ito ia iparticular ihormone iis irelated ito ithe iconcentration iof ireceptors iper
icell: ithe imore ireceptors, ithe ihigher ithe iaffinity ior ithe imore isensitive ithe icell iis ito
ithe istimulating ieffects iof ithe ihormone. iThus ithe icell ican iadjust iits isensitivity ito
ithe iconcentration iof ithe isignaling ihormone. ihormone iis idistributed ithroughout
ithe ibody, ionly itarget icells iwith ispecific ireceptors ifor ithat ihormone iare iaffected.
Target icell iresponse idepends ion iblood ilevels iof ithe ihormone, ithe iconcentrationiof
itarget icell ireceptors, iand iaffinity iof ithe ireceptor ifor ithe ihormone. iHormone
ireceptors iof ithe itarget icell ihave itwo imain ifunctions: i(1) ito irecognize iand ibind iwith
ihigh iaffinity ito itheir iparticular ihormones iand i(2) ito iinitiate ia isignal ito iappropriate
iintracellular ieffectors. iSee iChapter i1 ifor icell isignaling ipathways, iparticularly.
Cushing’s iSyndrome- ithe iclinical imanifestations iresulting ifrom ichronic iexposure
ito iexcess iendogenous icortisol iand iis imore icommon iin iwomen. iCushing’s idisease
iis iexcess iendogenous isecretion iof iACTH. iACTH idependent ihypercortisolism
i(about i80%) iresults ifrom ioverproduction iof ipituitary iACTH iby ia ipituitary iadenoma
i(most icommon iand ican ioccur iat iany iage) ior iby ian iectopic isecreting inonpituitary
itumor, isuch ias ia ismall icell icarcinoma iof ithe ilung i(more icommon iin iolder iadults).
iACTH-independent ihypercortisolism i(about i20%) iis icaused iby icortisol isecretion
ifrom ia irare ibenign ior imalignant itumor iof ione ior ibothiadrenal i glands i (more
i common i in ichildren). iA iCushing-like isyndrome i may idevelop ias ia iside ieffect iof
ilong-term ipharmacologic iadministration iof iglucocorticoids. iWith iACTH-
dependent ihypercortisolism, ithe iexcess iACTH istimulates iexcess iproduction iof
icortisol iand ithere iis iloss iof ifeedback icontrol iof iACTH isecretion. iWhatever ithe
icause, itwo iobservations iconsistently iapply ito iindividuals iwith iCushing’s
isyndrome: i1.) iThey idon’t ihave idiurnal ior icircadian
