Frontalskullbossing (resultinginanunusuallyprominentforeheadandheavybrow ridge),mandibularprognathism(protrudinglowerjaw),jawmalocclusionandoverbite,skinthickening,andincreasedshoeand ringsize(Figure1).ChronicexposuretoGHandIGF1hypersecretionleadstosofttissueswellingoftongue,heart,kidney,colon, andvocalcordsandperiarticularandcartilaginousthickening, resultingultimatelyinpainfullarge-jointosteoarthritis.Upto60 ofpatientsexhibitspinalkyphoscoliosis(outwardcurvatureofthe spine)anddiffuseskeletalhyperostosis(overgrowthofbone).Diseaseduration,IGF1levels,andconcurrenthypogonadismdeterminetheprevalenceofvertebralfractures(S2).Elevatedlevelsof thehormoneprolactin(PRL),observedinapproximately30 of individuals,canbeascribedtomixedtumorGHandPRLcosecretionortopituitarystalkimpingementbythetumormass.Rarely, plurihormonaltumorscosecretethethyroid-stimulatinghormone thyrotropin(TSH),leadingtohyperthyroxinemia(elevatedcirculatingthyroxinelevels),oradrenocorticotropin(ACTH),leadingto hypercortisolemia(elevatedcirculatingcortisollevels).Conflictofinterest:Theauthorreceivespreclinicalresearchgrantsupportfrom...