C3. Curs Adenoame Hipofizare Si Hipopituitarism Studenti

TUMORILE HIPOFIZARE SI HIPOPITUITARISMULDr. Galoiu Simona

CUPRINS Tumori hipofizareAcromegaliaProlactinomulBoala CushingTireotropinoameGonadotropinomulIncidentalomul hipofizarHipopituitarismul

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

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.

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 - cabergolina 0,5-2 mg/saptEfect antisecretor si citonecroticChirurgicalRadioterapia

Sarcina

PRLDiam. tumoral 1 cm, cu SCHO> 1 cm, fara SCHO2 anitemozolomidTRATAMENTUL HIPERPROLACTINEMIEIGhidul Endocrine Society, 2011COCPRM maligne

BOALA CUSHINGDefiniie: hipersecreie relativ autonoma de ACTH de ctre un adenom hipofizar. De regul un microadenom, care secret ACTH i uneori peptide derivate din POMC, determinnd hiperplazie corticosuprarenal bilateral cu hipersecreie de cortizol.

CLINICVergeturi rosii-violaceePiele subtire, fragilitate capilaraScaderea fortei musculaturii proximale

Obezitate centralaHipertensiune arteriala secundaraIntoleranta la glucoza/diabet zaharat sceundarOsteoporozaAlterare afect (depresie), cognitie, somn

PARACLINIC Cortizol pl. ora 8, ora 24, CLU, 17 OHCS crescutiDXM 1mg overnightDXM 2mg x 2DXM 8 mg x 2ACTH crescutTeste uzualeTest la CRHCateterizare sinus pietros inferior

GHIDUL ENDOCRINE SOCIETY (2008) DE DIAGNOSTIC AL SINDROMULUI CUSHING80%Boala Cushing

X. Bertagna et al. / Best Practice & Research Clinical Endocrinology & Metabolism 23 (2009)

TRATAMENTHipofizectomie selectivaSuprarenalectomie bilateralaComplicatii: sindrom NelsonIradiere hipofizara supravoltataMedicatie adjuvanta ketoconazol, aminoglutetimid, mitotan

TRATAMENTUL BOLII CUSHINGX. Bertagna et al. J Clin Endocrinol Metab, April 2013, 98(4)

COMPLICATIISindromul NelsonInsuficienta corticosuprarenalarecidiva

Feelders, J Clin Endocrinol Metab, February 2013

Barber T M et al. Eur J Endocrinol 2010;163:495-507 2010 European Society of EndocrinologySindrom Nelson

CONCLUZIITumorile hipofizare sunt tumori intracraniene cu frecventa crescuta, evolutie in general benignamortalitate crescutasecretie tumorala, efect compresiv tratament uneori excesiv

COMPLICATIIHipogonadism pe termen scurt -pe termen lung - osteoporozaInfertilitateDate de tumoraDate de tratament

GONADOTROPINOMULAdenom hipofizar secretant de gonadotropi FSH, LH, a30-40% din tumorile hipofizareSecreia nepulsatil de gonadotropi tumorali blocheaz de regul funcia gonadic. Uneori se poate manifesta cu hiperstimulare ovariana/testicularaTratament chirurgical, radioterapie

TRATAMENTchirurgical -hipofizectomieMedical- Octreotid sau Lanreotidradioterapie hipofizar

Tiroidectomia sau antitiroidienele de sintez agraveaz evoluia sindromului tumoral

INCIDENTALOAMELE HIPOFIZAREGhidul Endocrine Society, 2011

HIPOPITUITARISMULDeficitul de GH: nanism la copil; afectare metabolic la adult

Deficitul de gonadotropi: hipogonadism hipogonadotropla copil: pubertate intrziatla femeie: anovulaie cronic, amenoree, infertilitatela brbat: TDS, infertilitate

Deficit de TSH: hipotiroidism central

Deficit de ACTH: insuficiena adrenal secundara

Deficitul de PRL: agalactia postpartum

HIPOPITUITARISMULS.C. Erridge et al. / Radiotherapy and Oncology 93 (2009)N= 385AVC n=78, RR=1.45 M, 2.2 F 4 tumori maligne intracraniene

CAUZE DE DECES LA PACIENTII CU HIPOPITUITARISMN=1286 pac. cu hipopituitarism

Zueger, J Clin Endocrinol Metab, October 2012, 97(10)SUPRAVIETUIREA PACIENTILOR CU INSUFICIENTA CORTICOTROPA SUBSTITUITA

EtiologieGENETIC:

Insuf. hipof. multipl: mutaii HEX1: displazia septo-optica+deficit de GH Pit-1, Prop1: deficit de GH, PRL,TSH, gonadotropi

Insuf. hipof. izolat: mutaii:KAL: sdr. KALLMANN = hipogonadism hipogonadotrop+ anosmieDAX1: hipogonadism hipogonadotrop+hipoplazie adrenal congenitalGH1: nanism hipofizar familialAVP-NEUROFIZINAII: diabet insipid centralTSH-: hipotiroidism centralLH- : hipogonadism hipogonadotropFSH- : hipogonadism hipogonadotropGHRH: nanism hipofizar familialGnRH: hipogonadism hipogonadotropTSH receptor: hipotiroidism central

Etiologie2. TUMORAL:T.disembrioplazice: craniofaringiom, chisturi arahnoide sau chisturi deriv. din punga Rathke;T. pituitare: funcionale sau nefuncionaleT. extrasellare: germinoame, teratoame, meningioame, astrocitoame, ependimoame, chist dermoid sau epidermoidT. metastatice: de origine renal, mamar

3. INFILTRATIVBoli granulomatoase: sarcoidoza, granulomul eozinofil, TBC, sifilis, granulomatoza WegenerHistiocitoxa X (Langerhans)Meningita bazal

4. SDR. DE A TURCIC GOAL (empty sella)

Etiologie5. VASCULAR: Apoplexia pituitar (Sdr. Sheehan) Malformaii vasculare: anevrisme

6. AUTOIMUN: hipofizita limfocitar deficitul izolat de ACTH

7. IRADIERE

8. TRAUMATIC: seciune de tij pituitar: sdr. de hipofiz izolat (insuf. adenohipofizar+ diabet insipid central + hiperprolactinemie)

9. IATROGEN: chirurgia hipofizei radioterapie hipofizar9 I: invasive, infarction, infiltrative, injury, immunologic, iatrogenic,infectious, idiopathic, isolated

FIZIOPATOLOGIEDeficitul de GH: nanism la copil; afectare metabolic la adult

Deficitul de gonadotropi: hipogonadism hipogonadotropla copil: pubertate intrziatla femeie: anovulaie cronic, amenoree, infertilitatela brbat: TDS, infertilitate

Deficit de TSH: hipotiroidism central

Deficit de ACTH: insuficiena adrenal

Deficitul de PRL: agalactia postpartum

INSUFICIENA ADENOHIPOFIZAR GLOBAL

Deficitul de GH

Nanismul hipofizar greutate i talie normale la natere scderea velocitii de cretere postnatal

deficitul izolat de GH: nanism armonic, supraponderalitate troncularfacies infantil, hipoplazie maxilarOGE miciPubertate usor ntarziatVrsta taliei=vrsta osoas < vrsta cronologic

test de stimulare a GH prin:hipoglicemie indus de insulin>10aniGlucagon

Cauze de nanismMalnutriia si deprivarea emoionalStatura mic familialntrzierea constituional a creterii si pubertiiDeficitul de GH (8%)Retardul de cretere intrauterin (7,5%)Displazii scheletice (acondroplazia, hipocondroplazia)Sdr. genetice dismorfice (Turner, Down)Boli cronice:IRC, boala celiac, malformaii cardiace, Boli endocrine: hipotiroidismhipoparatiroidismSdr. CushingRahitismul carenial comun sau vit. D rezistentSdr. de rezisten la GH nanism Laron: GH crescut, IGF-I sczut40%

Deficitul de GH al adultului Scderea energiei vitale i a strii de bine

Izolare social Dispozitie depresiv Anxietate crescut

Creterea adipozitaii centrale i scderea masei musculare Scderea sensibilitii la insulin cu alterarea toleranei la glucoz Creterea LDL colesterolului si a apoB; scderea HDL

Scderea densitaii minerale osoase cu risc crescut de fractura patologic

Scderea masei miocadice Creterea fibrinogenului plasmatic i a inhibitorului tisular de plasminogen Ateroscleroza accelerat

Deficitul de GH al adultuluinainte de tratamentDup tratament

INSUFICIENA ADENOHIPOFIZAR DG. PARACLINICTeste bazale: msurarea h. hipofizari i ai glandelor int

ACTH, Cortizol 9a.m. Testosteron 9a.m. sau estradiol ; FSH, LHPRLGH, IGF-ITSH, fT4, fT3

Teste dinamice :Test de stimulare la insulin (ITT)pentru aprecierea rezervei de GH(n>7ng/ml) si cortizol (n>21g/dl)Test de stimulare cu glucagon, cand ITT este contraindicatTest de stimulare cu ACTH pentru aprecierea rezervei adrenale (dg. dif. cu b.Addison)

TRATAMENTUL INSUFICIENTEI HIPOFIZARETratarea cauzeiInsuficienta CSR: Hidrocortizon 15-30 mg/zi in 2-3 prize sau prednison 5-10 mg/ziInsuficienta tiroidiana: levothyroxina, 1,6 ug/Kg/zi (100 ug/zi)Insuficienta gonadica: estrogeni+progesteron ciclic testosteron FSH+LH pentru restabilirea fertilitatiiDeficitul de GH