Acromegalia

Acromegalia

Acromegalia este o maladie endocrin ca rezultat a producerii excesiv a adenohipofizei de hormon somatotrop (STH). Dup pubertate. Denumirea de acromegalie provine de la cuvintele Greceti acro -"extremiti" i megalos -mari. Afecteaz adulii cu vrst medie (frecvena 6 bolnavi la 100,000 aduli).

Care sunt cauzele Acromegaliei?

Producie n exces de durat a STH.

1. Tumoare hipofizar 2. Tumoare extrahipofizar

Etiologie

98%

Tumorile hipofizare

n 90 % acromegalia este cauzat de producie excesiv de STH, determinat de o tumoare benign a hipofizei adenom hipofizar. Aceste tumori produc n exces STH, i cnd ele se extind pot comprima esuturile adiacente, dintre care i nervul optic. De asemenea compresia esutului normal hipofizar poate duce la dereglarea producerii altor hormoni hipofizari. Unele adenome au o cretere rapid, altele progreseaz lent.

Macroadenom hipofizar

Tumori extrahipofizare

La un procentaj mic de pacieni, acromegalia este cauzat de o tumoare a pancreasului, pulmonar, sau a suprarenalelor. Aceste tumori pot secreta n exces STH, sau frecvent produc somatoliberin, care stimuleaz sinteza adenohipofizar de STH. La aceti pacieni se poate detecta o cantitate majorat a somatoliberinei n plasma sanguin.

Generaliti despre STH

Este secretat de celulel eozinofile ale adenohipofizei Aciunea principal este creterea longitudinal Alte efecte importante: aciune asupra metabolismului lipidic, glucidic i lipidic Secreie pulsatil, stimulat de somn, exerciiu fizic i post alimentar (foame). Nivel crescut al STH este prezent la tineri, cu vrsta se observ scderea concentraiei lui. Nivel redus de STH este determinat la persoanele obeze.

Patogenie
Metabolism
Glucidic

Fiziopatologie
Antagonism insulinic: micoreaz insulinosecreia, crete gluconeogeneza, scade utilizarea periferic
Lipoliza Mobilizarea

Anomalii biologice
Hiperglicemie Insulinorezisten Scade tolerana la glucoz AGL majorai

Lipidic Proteic Hidroelectrolitic Fosfor-Ca

AG din estul adipos Bilan azotic pozitiv hipervolemie Ca ser normal Ca urin P n ser

Anabolism Crete reabsorbia de Na

absorbia intestinal de Ca; reabsorbia tubular de P; reabsorbia tubular de Ca; renoirea Ca osos

Clasificarea (Pronin V.1996)

Preacromegalia semne Stadiul hipertrofic Stadiul tumoral Stadiul caectic

Acuze
amenoree/galactoree impoten sexual cefalee tulburri vizuale dureri osteoarticulare diabet zaharat dismorfism

Tabloul clinic

Sindrom tumoral
Sindrom dismorfic Sindromul endocrino-metabolic
Sindromul dereglrilor reproductive Sindromul afectrii nervilor cranieni Sindrom radiologic Sindrom biologic

Sindrom tumoral
Cefalee - frontal, retroorbitar, permanente, pronunate, (cauzate de creterea tensiunii intracraniene i compresia diafragmei eii turceti ). Hemianopsie bitemporal

Sindrom somato-visceral

Tegumente groase, cutis girata, transpiraie excesiv (creterea numrului i hipersecreia glandelor sudoripare i sebacee), hipertrichoz, acantozis nigricans. Mucii n debut hipertrofie cu creterea forei musculare apoi degenereaz (are loc proliferarea esutului conjunctiv i rmnerea n urm a creterii vaselor sanguine n comparaie cu masa muscular).

Masivul facial

Frunte ngust, arcade sprncenare i zigomatice proeminente Nasul, buzele ngroate Limba - macroglosie, aspect geografic al limbii, amprente dentare Mandibula prognatism, Dinii diasteme, cad uor, carii frecvente, cu apariia tulburrilor masticatorii

Extremitile

Minele late degete cilindrice, palme capitonate Picioarele- late, calcaneu mrit, numrul la pantofi crete

Acromegalie

Torace i abdomen

Cifoz dorsal, lordoz Stern proeminent torace globulos abdomen proeminent

Visceromegalie

Infiltraia laringelui voce rguit Glanda tiroid hipertrofic, noduli tiroidieni Cord global mrit, hipertrofie concentric cardiomiopatie hipertrofic cardiomiopatie dilatativ ICC; bradicardie, HTA TD constipaie, hepatosplenomegalie, gastrit hipertrofic, megacolon, dolicocolon, cancere i polipi. Rinichii mari, litiaz urinar

Manifestri asociate

Amenoree, galactoree femei, impoten, hipogonadism brbai (hipersecreie de prolactin sau de efectele similare cu lae prolactinei care inhib secreia de gonadoliberine) Diabet zaharat insulinorezistena, HTA CPI Artralgii, parestezii sindrom de tunel carpal (hipertrofia esutului cartilaginos) Apnee n somn (mrirea n volum a esuturilor moi a cilor respiratorii superioare i afectarea centrelor respiratorii) Osteoporoz

Progresarea Acromegaliei

Acromegaly

Overgrowth of bone and soft tissues due to hypersecretion of growth hormone Increase in enchondral bone formation at the physes (in the immature skeleton) and at cartilage-bone junctions in adults Radiologic findings in the skull include enlargement of the paranasal sinuses, sella turcica, thickening of the cranial vault, enlargement of the mandible and hypercementosis of the teeth.

Acromegaly

In the hands and wrists, patients with acromegaly often have

thickening of the soft tissues thickening and squaring of the phalanges and metacarpals overtubulation of the phalanges, and widened articular spaces osseous proliferations at tendon and ligament attachments prominence of the ungual tufts

Acromegaly

Articular abnormalities in the appendicular skeleton typically affect the knees, hips and shoulders Thickening of the articular cartilage can lead to early radiographic findings of relative widening of the joint space Later in the disease process, the alteration in cartilage morphology leads to degenerative changes, similar to those of primary osteoarthritis

Tratamentul Acromegaliei

Chirurgical Medicamentos

Radio Terapie

Chirurgical

Removal of pituitary tumor is often preferred treatment; tends to give best results in shortest time Results depend on size of tumor & skill of surgeon Sometimes, GH levels are reduced by the operation, but acromegaly is not cured. Therefore, additional treatment such as drug therapy and/or radiotherapy necessary

Acces transfenoidal

Terapie medicamentoas

n prezent se utilizeaz 3 grupe de remedii medicamentoase:

Agonitii Dopaminei Analogi ai Somatostatinei Antagoniti ai receptorilor STH

Agonitii Dopaminei

Inhib direct secreia de STH

Simpli n administrare pe cale oral

Bromocriptine (denumire comercial Parlodel) Cabergoline (denumire comercial Dostinex)

Aproximativ la 50% din pacieni se observ diminuarea nivelului STH i reducerea dimensiunilor tumorii

Analogi ai Somatostatinei

Inhib secreia STH

Reduce indirect nivelul IGF-I precum i dimensiunile tumorii

Octreotide (denumire comercial Sandostatin)

injecii s.c. (3 ori/zi) sau Intramuscular (o dat n lun)

Lanreotide (denumire comercial Somatuline LA)

I.m. fiecare 7-14 zile sau Deep s.c. injection once a month

Antagonitii receptorilor STH

Blocheaz receptorii pentru STH Pegvisomant: denumire comercial Somavert Does not stop the production of GH by tumor but does block IGF-I secretion Does not reduce tumor size

Radiation Therapy
X-rays carefully targeted to the tumor are given in small doses 5 x/week over about a month Gradual reduction in tumor size & GH release Slow improvement Drug treatment to lower GH levels while patient wait for results of radiotherapy