C3. Curs Adenoame Hipofizare Si Hipopituitarism Studenti

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  • TUMORILE HIPOFIZARE SI HIPOPITUITARISMULDr. Galoiu Simona

  • CUPRINS Tumori hipofizareAcromegaliaProlactinomulBoala CushingTireotropinoameGonadotropinomulIncidentalomul hipofizarHipopituitarismul

  • Lechan RM., Endocrinology and Metabolism Clinics 16:475-501, 1987 ANATOMIA HIPOFIZEI

  • TUMORI HIPOFIZARE -DEFINITIEtumori in majoritatea cazurilor benigne (adenoame) (
  • EPIDEMIOLOGIE15% din tumorile intracranienePrevalenta: 80/100000Autopsii - - microadenoameImagistic: 10% din pac. fara simptomatologie clinica

  • ETIOLOGIETumori benigne: adenoame hipofizare craniofaringioame meningioameHiperplazie hipofizara lactotrofe (sarcina) tireotrofe, gonadotrofe somatotrofe (GHRH ectopicH)Tumori maligne primitive germinoame (pineloame ectopice), sarcoame, cordoame, carcinoame hipofizare) -secundare carcinom pulmoar, de sanChisturi: punga lui Rathke, arahnoide, dermoideAbceseHipofizita limfocitaraFistule arteriovenoase ale carotidei

  • CLASIFICAREmicroadenoame (< 1 cm)macroadenoame (> 1 cm)

    Clasificarea Hardy modificata

    0 - microadenom; sa turca normala I - microadenom intrahipofizar; invazia focala a peretelui sellar II - macroadenom intrasellar; sa turca difuz largita, fara invazie III - macroadenom; invazie sellara i/sau destructie localizata IV - macroadenom; invazie i/sau destructie sellara difuza

  • CLASIFICARESecretante GH (15 %)acromegalie / gigantismPRL (30 %)amenoree - galactoreeACTH (10 %)boala CushingTSH (0,9 %)tireotoxicozaClinic nefunctionalebFSH, bLH, a / GH, PRL, TSH (mute clinic)(30%)null cell adenoma

    monohormonaleplurihormonale ex.GH-PRL (mammosomatotrofe)GH, PRL, TSH, a

  • PROPORTIA DIFERITELOR TIPURI SECRETORII

  • Hipofiza hipopituitarismChiasma optica pierderea perceptiei culorii rosii, hemianopsie bitemporala, cvadranopsie temporosuperioara, scotoame, cecitateHipotalamus - tulb. de termoreglare, de apetit, obezitate, ale setei, diabet insipid, ritm somn-veghe, tulb. de comport. , tulb. vegetativeSinus cavernos diplopie, oftalmoplegie, tulb de sensib. facialaLob frontal - tulb. de personalitate, anosmieCerebral cefalee, hidrocefalee, psihoza, dementa, crize gelasticeCLINICA TUMORILOR HIPOFIZARE EFECTUL DE COMPRESIE

  • SINDROMUL DE CHIASMA OPTICA

  • PARACLINICHipersecretia tumoralaGH in OGTT PRLCortizol dupa inhibitie cu DXMfT4, TSHestradiol /testosteron, FSH, LH

    HipopituitarismTeste bazale: cortizol, fT4, estradiol /testosteron, FSH, LHTeste in dinamica stimulare GH ITT, Arg -cortizol - ITT

  • IMAGISTIC - RMN

  • IMAGISTIC - CTCG 24 years

    Macro PRMSSEPRL=3,100 ng/ml

  • NFABors Ion, M, 37 ani, SCHO, NFA IV SSE

  • LH - ICC FSH ICC ANATOMIE PATOLOGICA - IMUNOHISTOCHIMIE

  • DIAGNOSTIC POZITIVClinicaImagisticHormonii hipofizari nesupresibili (teste de inhibiie)Hormonii hipofizari deficitari (teste de stimulare)Complicaii: (oftalmologice, metabolice)

  • DIAGNOSTIC DIFERENTIALRx- sindromul de sa turca goala-malformatii arteriovenoase (anevrism carotidian), - chisturi arahnoidiene sau dermoide- tumori (craniofaringiom/ meningiom / gliom nerv optic/ germinom / metastaze)- incidentaloame hipofizare- infiltrat hipofizar hipofizite, sarcoidozaAl sindroamelor clinice specifice hipersecreiilor hormonale adenohipofizare (ex: galactoreea, acromegaloidia, melanodermia, hipercortizolismul, tireotoxicoza) Al insuficienei secreiei hipofizare se face cu insuficienele glandulare primare

  • Sindromul de sa turceasca gola

  • ETIOPATOGENIEHeaney & Melmed, Endocrine related cancer, 7, 2000

  • ETIOLOGIEtumori monoclonalemutatii genetice -activarea unor oncogene -inactivarea unor supresori tumorali

    Sd. MEN1 mutatia menineiHPTHTumora enteropancreatica - insulinom, gastrinomCarcinoid bronsic, intestinalAngiofibroame cutanate

  • TRATAMENTObiective: distrugerea celulelor tumorale cu blocarea secreiei tumorale si prezervarea hipofizei normale.Metode:chirurgia hipofizeiradioterapiachimioterapiacombinat

  • TRATAMENTUL CHIRURGICALTipuri transfenoidala /transfrontalaIndicatiiContraindicatiiEficientaEfecte adverse

  • TRATAMENTUL CHIRURGICALIndicatii:Acuitatii vizualeCresterea tumoriiAdenoame functionale, cu exceptia PRMTranscranial tumori mari, asimetriceTransfenoidal -endoscopic -RMN intraoperator -microchirurgie -neuronavigatieM. Buchfelder, S. Schlaffer / Best Practice & Research Clinical Endocrinology & Metabolism 23 (2009) 677692

  • RADIOTERAPIAnormovoltat (raze X cu energii de keV) convenional supravoltat (accelerator liniar, betatron, cobaltron cu energii de ordinul MeV)radiochirurgia (Gamma Knife) in care 200 surse independente de cobalt incluse intr-o casc sunt focalizate selectiv in funcie de volumul tumorii. interstiial: Au198, Ytriu90 risc de nevrit optic;

  • RADIOTERAPIA HIPOFIZARARadioterapia fractionata conventionala 50 GyRadioterapia fractionata stereotactica 20 GyRadiochirurgia Gamma knife 10-15 Gy

  • ACROMEGALIA -DEFINITIEBoal determinat de hipersecreia de GH, ce duce la creterea accentuat a scheletului i viscerelor. determinata in peste 95% din cazuri de un adenom hipofizar, rareori fiind o secreie paraneoplazica de GHRH (tumori pancreatice).

  • ACROMEGALIA DATE EPIDEMIOLOGICEIncidena: 3-4 cazuri/ 1 000 000 /anPrevalena: 69 / 1 000 000Rata mortalitii: 2-3 X populaia general 1.16Kauppinen-Makelin et al. J Clin Endocrinol Metab, July 2005, 90(7):40814086

    Cauza de decesn=56 (66+12 ani)Frecvena % (n) n acromegalieFrecvena % n populaia generalBoala coronariana23.2 (15)25.6Boli cerebrovasculare14.3 (8)10Alte boli cardiovasculare16.1 (9)7.2Neoplasme21.4 (12)21.3Tumori hipofizare5.4 (3)Accidente8.9 (5)8.4Altele10.7 (6)27.5

  • CLINICSemne determinate de excesul de GH:

    mrirea minilor i picioarelor modificarea fizionomiei tegumente groase, mate, umede, cu miros particular; visceromegalie: cardiomegalie, cu agravarea prognosticului;respirator: modificri ale vocii, obstrucie nalt de tract respirator i apnee de somn;cardiovascular: cardiomegalie, HTA secundara macrogenitosomie.

  • Semne comune cu alte tumori hipofizare, determinate de compresie (sindrom neurologic): sindrom neurooftalmic cefaleesemne clinice de insuficien hipofizaraCLINIC

  • CLINIC

  • PARACLINICProbe uzualeGH minim in OGTT > 1 ng/mlIGF-1 crescut pentru varsta si sexPRLCortizol, fT4, estradiol/testosteron, FSH, LH

    Ex. oftalmologic: CV, AV, FO

  • ACROMEGALIA CRITERII DE DIAGNOSTIC SI EFICIENTA A TRATAMENTULUIIncidenta: 5/1000000, prevalenta: 60/1000000.

  • IMAGISTIC

  • DIAGNOSTIC DIFERENTIAL1. creterea nontumoral a GH seric: insuficien hepatic / renal, malnutriia, diabet zaharat dezechilibrat, efortul fizic.2. alte cauze de mrire a minilor: munca manual, obezitatea, amiloidoz primar, hipotiroidismul, osteoartropatia pneumic Pierre Marie 3. acromegaloidie4. Sarcina -HPL.

  • ETIOPATOGENIE1. hipofizar i. tumori hipofizare secretante de GH (90% din cazuri); ii. carcinom de celule somatotrofe (foarte rar).iii. hiperplazie de celule somatotrofe prin hipersecreie de GHRH 2. extrahipofizar: i. adenom hipofizar ectopic (
  • FIZIOPATOLOGIEEfecte dependente de IGF-IEfecte independente de IGF-I

  • TRATAMENTChirurgical de prima intentieMedicamentosAnalogi de somatostatin octreotid sc, 3X50 ug/zi -sandostatin LAR -lanreotid PR, autogelAgonisti dopaminergici bromocriptina, cabergolinaAntagonisti de receptori de GH -pegvisomantRadioterapia supravoltata/ gamma knife

  • ACROMEGALIA -TRATAMENT Chanson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 23 (2009)

  • CHIMIOTERAPIAAgonisti dopaminergici bromocriptina - cabergolinaAnalogi de somatostatin octreotid-lanreotidAntagonisti de receptori de GH -pegvisomant

  • EVOLUTIE, COMPLICATIICardiovasculare cardiomiopatia, HTA secundara, aritmii, valvulopatii, insuficienta cardiacaRespiratorii sindrom de apnee in somnMetabolice DZ secundarDigestive polipi coloniciArticulare artropatia acromegalicaHipopituitarismSindrom de chiasma opticaComplicatiile tratamentului

  • SUPRAVIETUIREA PACIENTILOR ROMANI CU ACROMEGALIE IN FUNCTIE DE GHp=0.005 (log rank test)SMR=0.34 (0.09-0.88)SMR=1.3 (0.7-2.1)

  • PROLACTINOMULTumora hipofizara secretanta de PRLcea mai frecventa tumora hipofizaraClinic: oligomenoree amenoreegalactoreeinfertilitateTDSinfertilitatesemne date de tumora SCHO, cefalee, hipopituitarism

  • PARACLINICPRL >100 ng/ml >200 ng/mlTeste de insuficienta hipofizaraEx. oftalmologicImagistic

  • DIAGNOSTIC DIFERENTIAL ALTE CAUZE DE HIPERPROLACTINEMIEfiziologice - sarcina, alaptatul - stimularea peretelui toracic, stress, somnmedicamentoase: i. blocani ai receptorilor dopaminergici: haloperidol, fenotiazine (clorpromazin), domperidone, metoclopramid; antidepresive triciclice.ii. rezerpin, metildopa (fac depleie central de dopamin);iii. estrogeniiiv.TRH, cimetidin, verapamil, opioide.leziuni hipotalamice sau ale tijei hipofizare-tumori, infiltrate- seciunea sau compresia tijei, traumatism, chirurgicalalte tumori hipofizare, cu secreie mixt, de PRL i GH / ACTH;hipotiroidism primar (secreie reactiva de TRH);insuficiena renal cronic, insuficien hepatic

  • PROLACTINOMUL (PRM) -DIAGNOSTICPRL > 500 ng/mlmacroprolactinomPRL > 250ng/mlPRMPRL > 200 ng/mlPRM / medicamente / sarcina PRM < 200 ng/ml PRM/alte cauze

  • ETIOLOGIA HIPERPROLACTINEMIEIMacroprolactinemia: Big-big + big > 50% Frequency: 19% (16/84)1628178638

    c PRL elecsys-irma

    29.8437584.1187520.779572300768.8421694288

    45.70883.05243.945642861765.9870124513

    11.261111111122.32777777782.31011557878.2359188605

    IRMA

    Elecsys

    PRL (ng/ml)

    c HPRL causes

    Sheet1

    NNomPrenomN dossierSexeDate de naissanceAgeGPPRAdnomeIHCOPpriode de OPcause de hyperprolactinemiecause de simptomsATCD pers.ATCD familieux thyroideATCD familieux autresLatence diagnostiqueCirconstance du diagnostiquecdcyclecdgalcdinfertcdautrescyclesgalactorrheinfertilitbaisse libidoautres signes cliniquesIRM hypTDM hypPRL initialedatePRL TimonedatePRL Martindaterponse au TRHrponse au MCPbigbigbigmonomerFSHrponse au LHRHLHrponse au LHRHTSHATPOAc anti TGautres Acevolutiontraitementpriode de traitementgrosseses sous traitementPRL TimonePRL directePRL traitex2,3% macroprolactine

    7Verdier/GuillaumeMarie Jose2021047020.06.19564611ndnd0macroprolactinemiephase luteale courtegoitre multinodulaire0nd0.750,1,3=mastodynies110100strilet au progestndmastodynies41351.09.200181.06.200222.506.20021066.2924.85.6116.111.600nd2Dostinex11/2001-05/2002087.12.35.325.5

    10MuselliDominique202187705.09.196042221100macroprolactinemiendmnometrorrhagies sous strilet, papillom mamaire oper-19980HTA, D1, D2, mre avec mnopause precoce38 ans16.000.1110002ndndcephales, obesit androide0101.08.2002101.08.2002203.708.20021146.111.642.33.814.902.1ndndnd0Parlodel1997-200201067.233.273.0-8.7

    3Faure/IsouardMichle2012645031.10.1962405214nd0macroprolactinemiemnopausens0tante=mnopause 42 ans0.670, 3=bouffes de chaleur10002MP0ndndbouffes de chaleur4331.02.200110.51.12.200119.712.20011132.119.848.1120nd58nd1ndndndndsans10.58.23.58.11.8

    16Gratereau/CorneauAnnie Claude2020572024.02.195250441300macroprolactinemiesndHTA, Luthenyl il y a 2 ans0PR0100030ndndcephales3511.10.2000151.03.200231.71159.77.133.24.3nd5.75.71.6ndndnd2sans1512.73.58.136.6

    15Bataille/MyardFrancoise2020702016.04.1951512213011982-2001macroprolactinemiemnopausensndnd0.170, 3=cephales10012MP0ndndcephales614.51.06.2001161.05.200255.904.20021159.314.526.2105nd68nd0.8ndndndndsans1618.15.813.326.3

    6BleicherAude2020415011.01.197527001301en 1988 Diane 35 pour acnmacroprolactinemiehyperandrogenieamnorrhe rsposive aux progestatifs en 19970D2, HTA, IR0.25010002 MP0ndndhirsutisme, acn peribucale0421997191.02.20024402.20021166.118.115.85.7nd8.2nd1.2ndndnd0sans1914.34.710.824.4

    12ContatSylvie202213308.07.19614122nd01Androcur, Diane 35; arret 3 mois avant 09.2002macroprolactinemiendfibrom uterin0nd15.001010000ndnd0adnome hypophysaire en 1987211.09.2002211.09.200260.609.20020174.51312.5ndndndnd0.7ndndndndParlodel1987-199211 grossesse aprs Parlodel2118.23.88.752.0

    2JudiconeAnnie202057503.10.19544822170124 ansmacroprolactinemiendhisterectomie totale pour endometriose avec preservation des ovaires, depression traite avec Floxybral, Tranxne, Seropram, anomalie genetique du FV1D20.173=asthenie, cephales000140ndndcephales frontales et occipitales3631.02.20022304.200233.803.20021155.318.825.98.9nd58.1nd3.2ndndTRAB26 en 2001

    sous Dostinex

    primaire

    regle sousLuthenyl?

    sous Parlodel

    TSH=37 en ce moment

    fT3=8,3, fT4=13,1

    sous Duphaston

    Sheet2

    NNomSexeAgeGPPRAdnomeIHCOPpriode de OPcause de hyperprolactinemiecause de simptomsATCD pers.ATCD familieux thyroideATCD familieux autresLatence diagnostiqueCirconstance du diagnostiquecdcyclecdgalcdinfertcdautrescyclesgalactorrheinfertilitbaisse libidoautres signes cliniquesIRM hypTDM hypPRL initialedatePRL TimonedatePRL Martindaterponse au TRHrponse au MCPbigbigbigmonomerFSHrponse au LHRHLHrponse au LHRHTSHATPOAc anti TGautres Acevolutiontraitementpriode de traitementgrosseses sous traitementPRL TimonePRL directePRL traitex2,3% macroprolactine

    7Verdier/Guillaume04611ndnd0macroprolactinemiephase luteale courtegoitre multinodulaire0nd0.750,1,3=mastodynies110100strilet au progestndmastodynies41351.09.200181.06.200222.506.20021066.2924.85.6116.111.600nd2Dostinex11/2001-05/2002087.12.35.325.5

    10Muselli042221100macroprolactinemiendmnometrorrhagies sous strilet, papillom mamaire oper-19980HTA, D1, D2, mre avec mnopause precoce38 ans16.000.1110002ndndcephales, obesit androide0101.08.2002101.08.2002203.708.20021146.111.642.33.814.902.1ndndnd0Parlodel1997-200201067.233.273.0-8.7

    3Faure/Isouard0405214nd0macroprolactinemiemnopausens0tante=mnopause 42 ans0.670, 3=bouffes de chaleur10002MP0ndndbouffes de chaleur4331.02.200110.51.12.200119.712.20011132.119.848.1120nd58nd1ndndndndsans10.58.23.58.11.8

    16Gratereau/Corneau050441300macroprolactinemiesndHTA, Luthenyl il y a 2 ans0PR0100030ndndcephales3511.10.2000151.03.200231.71159.77.133.24.3nd5.75.71.6ndndnd2sans1512.73.58.136.6

    15Bataille/Myard0512213011982-2001macroprolactinemiemnopausensndnd0.170, 3=cephales10012MP0ndndcephales614.51.06.2001161.05.200255.904.20021159.314.526.2105nd68nd0.8ndndndndsans1618.15.813.326.3

    6Bleicher027001301en 1988 Diane 35 pour acnmacroprolactinemiehyperandrogenieamnorrhe rsposive aux progestatifs en 19970D2, HTA, IR0.25010002 MP0ndndhirsutisme, acn peribucale0421997191.02.20024402.20021166.118.115.85.7nd8.2nd1.2ndndnd0sans1914.34.710.824.4

    12Contat04122nd01Androcur, Diane 35; arret 3 mois avant 09.2002macroprolactinemiendfibrom uterin0nd15.001010000ndnd0adnome hypophysaire en 1987211.09.2002211.09.200260.609.20020174.51312.5ndndndnd0.7ndndndndParlodel1987-199211 grossesse aprs Parlodel2118.23.88.752.0

    2Judicone04822170124 ansmacroprolactinemiendhisterectomie totale pour endometriose avec preservation des ovaires, depression traite avec Floxybral, Tranxne, Seropram, anomalie genetique du FV1D20.173=asthenie, cephales000140ndndcephales frontales et occipitales3631.02.20022304.200233.803.20021155.318.825.98.9nd58.1nd3.2ndndTRAB

  • FIZIOPATOLOGIE

  • TRATAMENTMedicamentos!Agonisti dopaminergici bromocriptina 5-30 mg/zi -...