PituitaryPathophysiology

FrankVuitch,MD

ObjectivesPituitary
Describepituitaryanatomyandphysiology:
Secretoryproductsofadenohypophysis
Secretoryproductsofneurohypophysis
Discussgross&microscopicmorphology,and
clinicalfeaturesofpituitaryadenomas:
Manifestationsrelatedtomasseffect
Endocrinemanifestations,especiallythose
relatedtotheproductionof:
Prolactin,Growthhormone,ACTH

Discusscausesofhypopituitarism:
Adenoma,Sheehansyndrome,emptysella
Discussposteriorpituitarysyndromes:
SIADH,DiabetesInsipidus

PituitaryGlandAnatomy
Locatedatbaseofskullinsella
turcica,underopticchiasm
Beanshaped:0.5grams,1cm
Attachedtohypothalamusbyastalk,
portalvenoussystemcarries
releasingfactors,exceptprolactin
suppression,GHboth+and
Twodistinctcomponentlobes:
Anterior:Adenohypophysis
Posterior:Neurohypophysis

Adenohypophysis
AnatomyandPhysiology
80%ofgland,derived
embryologicallyfrom
Rathkepouch(oral)
Enlargesinpregnancy
Onroutinehistology,
threecelltypesby
cytoplasmicstaining:
Acidophils,eosinophilic
Basophils,basophilic
Chromophobes,clear

Adenohypophysis
AnatomyandPhysiology
Antibodiesagainstpituitarypolypeptidehormones
show5celltypeswithneurosecretorygranules:
Somatrophs(acidophils):Halfofallhormone
producingcellsGrowthhormone
Lactotrophs(acidophils)Prolactin
Corticotrophs(basophils)ACTH,MSH,
endorphinsandlipotropin
Thyrotrophs(basophils)TSH
Gonadotrophs(basophils)FSHandLH

Neurohypophysis
AnatomyandPhysiology
Embryologicaloutpouchingfromthirdventricle
Functionalneurohypophysisconsistsofaxonal
processesextendingfromnervecellbodies
withinthehypothalamus
Neurohypophysisdoesnotmakeanyhormones,
butratherstoresandreleasesoxytocinand
vasopressin(ADH)producedinhypothalamus

Adenohypophysis
ManifestationsofDisease
Increasedordecreasedsecretionofhormone(s).
Mostcasesofincreaseareduetoadenomas
withintheanteriorlobe
Localmasseffectsofadenoma:
Radiographicenlargementofsellaturcica
Visualfieldabnormalities
Increasedintracranialpressure
Localinvasion,suchasbone(diagnosisof
carcinomarequiresmetastasis,veryrare)

PituitaryAdenomas
10%ofallintracranialmassescomingtoclinicalattention,
incidentalinupto14%ofroutineautopsies
Usuallyinadults:Peak4thto6thdecades.
Microadenoma(<1cm)versusMacroadenoma(>1cm)
Mostaresporadic;5%areMEN1orotherpredisposition
40%GHmutatedGsproteinalphasubunit,blocksGTPase,
mimicscontinuouslyactivatingextracellulargrowthfactor
Functionalornonfunctional;expandingnonfunctional
adenomamaydestroynormaladjacentsecretingtissue
Monoclonal,functionaladenomasusuallyofonecelltype
singlehormone,someplurihormonal:GH/Prolactin

MorphologyofPituitary
Adenomas
Incidentalnoduleingland
Small,circumscribedmass,
confinedwithinthesella
Largermassesextendsuperiorly
diaphragmsellaopticchiasm
30%ofcases:Nonencapsulated,
erodeandinfiltratebone,dura,
cavernous/sphenoidsinus,brain
Acutehemorrhageinadenoma
rapidenlargement(pituitary
apoplexyemergency!)

HistologyofPituitary
Adenomas
Architecture:relatively
uniformpolygonalcells
arrangedinsheetsorcords,
sparseconnectivetissue
(lackreticulinnetwork)
Nuclei:uniformor
pleomorphic
Mitoticrate:modest
Cytoplasm:acidophilic,
basophilicorchromophobic

ClinicalCourseof
PituitaryAdenomas
SymptomsEndocrine
abnormality,masseffect
Masseffects:
Radiographicabnormalities
ofsellaturcica
Visualfieldabnormalities
(bitemporalhemianopsia)
IncreasedICP:headache,
nausea&vomiting
Therapyusuallysurgical:
Transsphenoidalifsmall,
craniotomyiflarge

Prolactinoma
Mostfrequent:30%ofpituitaryadenomas
Acidophilicorchromophobic(granuledensity)
Frommicroadenomatolargeexpansilemasses
Efficientandproportionalhormoneproduction
Increasedserumprolactinamenorrhea,galactorrhea,
lossoflibido,infertility(25%ofamenorrheacases)
Men/oldwomen,symptomsmaybesubtle:masseffects
Othercausesofhyperprolactinemia(usuallymild):
pregnancy,lactotrophhyperplasia(stalkeffecton
dopamineinhibition,suchasheadtrauma),drugs
(phenothiazines,haloperidol)
Treatwithsurgeryorbromocriptine(dopamineagonist)

GrowthHormoneAdenoma
Secondmostcommonfxnltype,oftensomeprolactin
Acidophilicorchromophobic(granuledensity)
Usuallyquitelargebythetimethetumorcomesto
attentionbecauseincreaseinGHissubtle
Clinically:
Children(beforeclosureofepiphyses)gigantism
Adultsacromegaly(thickenedbones,viscera)
OtherSx:gonadaldysfunction,diabetesmellitus
(hepaticsecretionofinsulinlikegrowthfactor1),
hypertension,arthritis,congestiveheartfailure,
andincreasedriskofGIcancer

CorticotrophCellAdenoma
Usuallymicroadenomas
Basophilicorchromophobic
ExcessiveproductionofACTH
adrenalcorticalhyperplasia
excessiveproductionofcortisol
Cushingdisease(Cushingsyndrome),
mayhavehyperpigmentation(stimulation
ofmelanocytesbyMSH)
Nelsonsyndrome,postadrenalectomy

Hypopituitarism
Pituitaryadenoma
Lackshormonalsyndrome,glandatrophy
Othermasses,craniopharyngioma,
meningioma,metastasis,cyst
Sheehansyndrome
Ischemicnecrosis,postpartuminfarction
Emptysellasyndrome
PrimaryherniatedarachnoidandCSF
Secondarypostsurgical

PosteriorPituitary
Syndromes
DiabetesInsipidus
InsufficientADH,effectatrenaltubules
Excesswaterlossbydiluteurination
SyndromeofInappropriateADH(SIADH)
ExcessiveADH,effectatrenaltubules
Waterretention,hyponatremia,CNSedema
Usuallycausedbyectopicproduction
Nosyndromeforoxytocin