Rst-lineprimarytherapy;(b)forindividualstoofrailfor anesthesia;(c)forthosewhodeclinesurgery;(d)preoperativelyto assuremaximalsurgicaloutcomes(109);(e)postoperativelyfor persistentandinevitabledisease;(85)or(f)whileawaitingradiotherapyimpacttomanifest.BiochemicalcontrolbyprimarySRLTheJournalofClinicalInvestigation http://www.jci.org Volume119 Number11 Novemberscience in medicineUsingconventionalassays,GHlevelsappeartoincreaseafterdrug administration,likelyduetoattenuationofnegativeIGF1feedbackonsomatotrophsecretion. Efficacy.In177patientsreceivingdailypegvisomantdosesof 100mg,76 achievednormalIGF1levelsafter24months(123), withimprovementofsymptoms,includingsoft-tissueswelling, perspiration,cardiomyopathy,andheartfailure(S38).In75 of patientsresistanttomaximalSRLdoses,pegvisomantnormalizedIGF1levelsandimprovedcardiovascularriskmarkersand insulinsensitivity.PegvisomantisadditivewithSRIFanalogsin controllingIGF1levelsinpatientsresistanttoSRIFalone.In26 patientsreceivingmonthlySRLs,additionofweeklypegvisomant injectionsnormalizedIGF1levelsin95 ofpatients(S39).Therefore, longerdosingintervalsandcombinationtherapyoffereffective pharmacologiccontrolforanoverwhelmingmajorityofpatients. Side effects.About5 ofpatientsreceivingpegvisomantdevelop upto3-foldormoreincreasedhepatictransaminaselevels(123), andthisisinvariablyreversible.Othersideeffectsincludeinjection-sitereactionsandlipohypertrophy,likelyreflectinglocal adipocyteGHinsensitivity.AslossofIGF1negativefeedbackon thesomatotrophcouldconceivablyleadtopersistentcellproliferation,possiblecontinuedpituitarytumorgrowthshouldbe monitoredbyMRI,especiallyinthosepatientsinwhomSRLs have already been discontinued. While GH antibodies could type, pegvisomanttachyphylaxisisnotobserved.Pegvisomant-mediatedloweringofIGF1levelstobelownormallimitsmayresultin featuresofadultGHdeficiency. NovelGHRantagonistsindevelopmentincludesmallorally activemolecules,recombinantGHantagonists,GHRantibodies, andantisensemoleculesdirectedagainsttheGHR.1.Melmed,S.2006.Medicalprogress:acromegaly. N. Engl. J. Med.355:2558573. two.Ayuk,J.,andSheppard,M.C.2008.DoesacromegalyenhancemortalityRev. Endocr. Metab. Disord. 9:339. three.Nachtigall,L.,etal.2008.Changingpatternsin diagnosis and therapy of acromegaly over two decades.J. Clin. Endocrinol. Metab. 93:2035041. four.Molitch, M.E. 1992. Clinical manifestations of acromegaly. Endocrinol. Metab. Clin. North Am. 21:59714. five.Colao,A.,Ferone,D.,Marzullo,P.,andLombardi, G.Miconazole nitrate 2004.Cromolyn sodium Systemiccomplicationsofacromegaly: epidemiology, pathogenesis, and management. Endocr. Rev.25:10252. six.Sata, A., and Ho, K.K. 2007.PMID:24275718 Development hormone measurementsinthediagnosisandmonitoringof acromegaly.Pituitary.10:16572. 7.Pokrajac,A.,etal.2007.VariationinGHandIGF-I assayslimitstheapplicabilityofinternationalconsensuscriteriatolocalpractice.Clin. Endocrinol. (Oxf). 67:650. 8.Melmed,S.,etal.2009.Guidelinesforacromegaly management:anupdate.J. Clin. Endocrinol. Metab. 94:1509517. 9.Freda,P.U.,Post,K.D.,Powell,J.S.,andWardlaw, S.L.1998.Evaluationofdiseasestatuswithsensitivemeasuresofgrowthhormonesecretionin60 postoperative individuals with acromegaly. J. Clin. Endocrinol. Metab. 83:3808816. ten.Clemmons,D.R.,etal.1979.Evaluationofacromegalybyradioimmunoassayofsomatomedin-C. N. Engl. J. Med.301:1138142. 11.Brabant,G.,etal.2003.Seruminsulin-likegrowth factorIreferencevaluesforanautomatedchemiluminescenceimmunoassaysystem:resultsfroma multicenterstudy.Horm. Res. 60:530. 12.Massart,C.,andPoirier,J.Y.2006.SeruminsulinAssessmen.