Pituitary adenomas can be functional (hormone producing) or nonfunctioning (not producing hormone), or silent (i.e., demonstration of hormone production at the tissue level only, without clinical manifestations of hormone excess). Both functional and nonfunctioning pituitary adenomas usually are composed of a single cell type and produce at most a single predominant hormone, but there are exceptions. Some pituitary adenomas secrete two different hormones (growth hormone and prolactin being the most common combination); rarely, pituitary adenomas are plurihormonal.
Pituitary adenomas are designated as microadenomas if they are less than 1 cm in diameter and macroadenomas if they exceed 1 cm in diameter.
Table20.1ClassificationofPituitaryAdenomas • Nonfunctioning adenomas are likely to come to clinical attention at a later stage and are, therefore, more likely to be macroadenomas. Because of their larger size, nonfunctioning adenomas may encroach upon and destroy adjacent anterior pituitary parenchyma, leading to hypopituitarism.
Several genetic abnormalities associated with pituitary adenomas have been identified: • G-protein mutations are one of the most common genomic alterations in pituitary adenomas. G-proteins play a critical role in signal transduction, transmitting signals from cell surface receptors e.g. growth
MammosomatotrophProlactin,GHMammosomatotrophadenomasCombinedfeaturesofGHandprolactinexcess
GonadotrophFSH,LHGonadotrophadenomasHypogonadism,masseffects,Silentgonadotrophadenomas(“nullcell,”oncocyticadenomas)andhypopituitarism
ACTH,Adrenocorticotrophichormone;FSH,follicle-stimulatinghormone;GH,growthhormone;LH,luteinizinghormone;POMC,pro-opiomelanocortin;TSH,thyroid-stimulatinghormone.*Notethatnonfunctional(silent)adenomasineachcategoryexpressthecorrespondinghormone(s)withintheneoplasticcells,asdeterminedbyspecialimmunohistochemicalstainingontissues.However,theseadenomasdonotproducetheassociatedclinicalsyndrome,andtypicallypresentwithmass effects accompaniedbyhypopituitarism duetodestructionofnormalpituitaryparenchyma.Thesefeaturesareparticularlycommonwithgonadotrophadenomas.PartiallyadaptedfromAsaSL,EssatS:Thepathogenesisofpituitarytumors.AnnuRevPathol4:97,2009.
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P P GDP ˜°˛P P P GTP P P GDP Receptor Ligand (GHRH, TSH, PTH) ˜°˛P P P GTP Adenyl cyclase cAMP Proliferation Hormone synthesis and secretion Mutation ˜°˛
Fig.20.3G-proteinsignalinginendocrineneoplasia.MutationsthatleadtoG-proteinhyperactivityareseeninavarietyofendocrineneoplasms,includingpituitary,thyroid,andparathyroidadenomas.Gproteinsplayacriticalroleinsignaltransduction,transmittingsignalsfromcellsurfacereceptors(GHRH,TSH,orPTHreceptor)tointracellulareffectors(e.g.,adenylcyclase),whichthengeneratesecondmessengers(cAMP,cyclicadenosinemonophosphate).GDP, Guanosinediphosphate;GTP, guanosinetriphosphate;P, inorganicphosphate.