CAP.I. HIPOFIZA. AXA SOMATOTROP I.1. ANATOMIE. EMBRIOLOGIE I.2. FIZIOLOGIE I.3. HORMONUL DE CRETERE I.3.1. STRUCTUR I.3.2. SINTEZ I.3.3. TRANSPORT I METABOLISM I.3.4. RECEPTORII I.3.5. ACIUNI CAP.II. ACROMEGALIA II.1.DEFINITIE, EPIDEMIOLOGIE II.2.ETIOLOGIE, PATOGENIE II.3.DIAGNOSTIC CLINIC, PARACLINIC, DIFERENTIAL II.4.COMPLICAII II.4.1. COMPLICAII TUMORALE II.4.2. COMPLICAII METABOLICE II.4.3. COMPLICAII GENERALE II.4.4. COMPLICAII ENDOCRINE II.4.5. ACROMEGALIA I CANCERELE II.5.EVOLUTIE I PROGNOSTIC II.6.TRATAMENT CAP.III. STUDIUL RETROSPECTIV AL CAZURILOR DE ACROMEGALIE ( 235 cazuri) I INCIDENA NEOPLAZIILOR.

INTRODUCERE

Descris n 1986 de ctre Pierre-Marie, acromegalia afeciune rar n populaia general cauzat n 99% din cazuri de dezvoltarea unui adenom hipofizar secretant de GH este o boal cronic progresiv ce creaz importante disabiliti fizice, costuri sociale medicale ridicate i scurtarea net a speranei de via. Dei reprezint o maladie de competena endocrinologului, prin complicaiile sale acromegalia este n realitate o maladie de grani ce suscit interesul i necesit intervenia mai multor specialiti medicale: oftalmologia, neurologia, neurochirurgia, oto-rinolaringologia, cardiologia, oncologia, neuroimagistica. Pornind de la primul mare studiu al lui H. Cushing The Pituitary Body and Disorders din 1912, cercetrile ulterioare au ncercat s aprofundeze etiopatogenia bolii i a complicaiilor sale. Progresul tiiific medical i achiziiile tehnice ale ultimilor 25 ani, cum ar fi dozrile hormonale radioimunologice, CT, RMN, studii de genetic molecular, inducerea terapiei cu Somatostatin i recent cu Octreotid au ameliorat progresiv calitatea i durata vieii pacientului acromegalic i au permis diagnosticarea precoce a bolii.

Cap. I: Hipofiza. Axa SomatotropI.1. Anatomie. Embriologie : Hipofiza este o gland endocrin cu localizare endocranian exocerebral, situat n fosa pituitar (aua turceasc) a osului sfenoid i legat de hipotalamus prin tija hipofizar. Organ impar i median, are o form oval comparat clasic cu un bob de nut bilateral simetric i dimensiuni de 13 mm n sens transversal, 9 mm antero-posterior i 6 mm vertical. Greutatea variaz ntre 0,4 0,9 g, este mai mare la femei i prezint variai fiziologice n cursul vieii. Hipofiza este derivat embriologic din dou surse: poriunea epitelial, ce include pars distalis, lomul intermediar i pars tuberalis, provine din exodermul stomodeumului primitiv care se invagineaz formnd punga lui Ratke; poriunea neural ce include infundibulul, tija neural i lobul posterior, se formeaz n sacul infundibular ce provine din diencefal. La sfritul lunii a treia de gestaie pot fi recunoscute compartimentele mari ale hipofize care se gsete afundat n aua turceasc a osului sfenoid. Aproximativ n sptmna a opta, esutul conjunctiv i vasele de snge prolifereaz n lobul anterior, stabilind o legtur neuronal direct cu hipotalamusul. Celulele productoare de GH i ACTH pot fi identificate din a noua sptmn de sarcin, dup care ncepe producerea subunitilor i ale hormonilor glicoproteici. Irigaia sangvin a hipofizei provine din cele dou artere hipofizare inferioare, ramuri din carotidele interne i / sau din arterele comunicante posterioare. Arterele hipofizare anterioare se distribuie lobului neural i dau doar cteva ramuri adenohipofizei, iar arterele hipofizare superioare se anastomozeaz liber la nivelul eminenei medane a hipotalamusului i n tija pituitar, se adun n venele prin care neurohormonii hipotalamici ajung n adenohipofiz sistemul port hipofizar formeaz o nou reea capilar la nivelul lobului anterior hipofizar i se colecteaz apoi n vene care dreneaz n sinusul cavernos i de aici n venele jugulare. Hipofiza este esutul cel mai puternic vascularizat: 0,8 ml snge / g / minut. Lobul anterior hipofizar nu are inervaie simpatic i parasimpatic, controlul sintezei i eliberrii hormonilor fiind realizat de ctre neurohormonii hipotalamici transportai prin sistemul vascular portal. Lobul posterior primete inervaii prin fibre nervoase nemielinizate provenite din tractul supraoptico-hipofizar, nucleii paraventriculari i alte arii hipotalamice.

Hipotalamusul

PARTEA PERSONAL1. SCOPUL LUCRRII Acromegalia este o afeciune rar n populaia general, dar frecvena n cazuisticile serviciilor de endocrinologie, care, n pofida numeroaselor achiziii n domeniul tehnicilor de detectare, urmrire i terapie, continu s determine o reducere semnificativ a speranei de via a bolnavilor, att prin propria evoluie, ct i prin numeroasele i variatele ei complicaii. Pacienii cu acromegalie au o speran de via redus, aproximativ 80% murind naintea vrstei de 60 de ani, rata tumorilor maligne fiind de 2 ori mai mare la bolnavii cu acromegalie fa de pacienii cu prolactinoame sau tumori pituitare non-funcionale. Lucrarea de fa i propune s fac unele aprecieri privind asocierea tumorilor maligne la subiecii cu acromegalie, studiind un lot de 235 cazuri internate cu aceast afeciune n Clinica Endocrinologic Iai ntre anii 1975-2002. Cu mijloace tehnice i de observaie de care am dispus am urmrit n acest studiu retrospectiv urmtoarele obiective: inventarierea metodelor de explorare endocrinologic utilizate n lotul celor 235 de acromegali studiai aprecierea frecvenei complicaiilor la subiecii acromegali stabilirea unor corelaii ntre manifestrile fiziopatologice, clinice i explorrile paraclinice la pacienii cu tumori maligne i pacienii fr tumori maligne stabilirea unor corelaii ntre acromegalie i diferii factori de risc n apariia cancerelor prezentarea unor cazuri particulare prin evoluia complicaiilor 2. MATERIAL I METOD Lotul de acromegali studiai cuprinde 235 de bolnavi din care 148 de femei i 87 de brbai. Condiiile includerii n acest studiu au fost existena unei explorri metabolice i endocrine ct mai complete att la debut ct i pe parcursul perioadei urmrite. Diagnosticul de acromegalie s-a bazat n toate cazurile pe prezena sindroamelor caracteristice: somato-visceral, tumoral i endocrino-metabolic. n acest sens explorarea subiecilor acromegali a parcurs mai multe etape, complexitatea investigaiilor variind n funcie de momentul internrii bolnavilor, avnd n vedere c unele metode de investigaie erau imposibile n trecut. Astfel, s-au practicat urmtoarele explorri:

examen clinic general: evidenierea modificrilor dismorfice status acromegalic calculul indicelui de mas corporal BMI (body mass index) investigaia sindromului endocrin: determinarea valorilor hormonului de cretere GH, att bazal ct i prin teste de stimulare determinarea evoluiei valorilor GH n cursul probei de supresie prin hiperglicemie provocat oral (HGPO) investigarea sindromului metabolic rezultat direct din excesul de GH - glicemia a jeun i hiperglicemia provocat - determinarea valorii fosforului plasmatic i fosfatazei alcaline - determinarea excreiei urinare a OH-prolinei investigarea sindromului tumoral hipofizar - evidenierea modificrilor osoase la nivelul craniului i aprecierea volumului selar pe radiografia standard - determinarea extinderii tumorii hipofizare prin tomografie computerizat (CT) sau rezonan magnetic nuclear (RMN) - msurarea cmpului vizual i a acuitii vizuale precum i determinarea modificrilor la nivelul fundului de ochi pentru stabilirea eventualei hipertensiuni intracraniene sau angiopatii hipertensive Diagnosticul tumoral a folosit ca metode de explorare urmtoarele: radiografie cranian radiografie toracic echografie - tiroidian - mamar - abdominal colonoscopia avnd n vedere c numeroase cazuri sunt din anul 1975, la aceti pacieni nu s-a putut efectua colonoscopia 3. REZULTATE I DISCUII Structura lotului

Au fost inclui 235 acromegali care au beneficiat de explorri ct mai complete, n limitele impuse de condiiile tehnice de care a dispus serviciul. Repartiia pe sexe Au dominat subiecii de sex feminin 148 (63%) fa de brbai (37%). Totui compoziia lotului nu poate fi considerat semnificativ deoarece luarea n studiu nu a fost randomizat ci s-a impus de la nceput o selecie determinat de calitatea explorrilor. Din acest motiv nu se poate afirma c raportul femei/barbai din grupul studiat este semnificativ i nici nu se poate afirma c datele noastre le contrazic pe cele din literatur, care afirm c boala afecteaz n proporii similare cele dou sexe.

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