Aldosterone, Iper-ipo-aldosteronismo

L’aldosterone, identificato nel 1953, è il principale ormone mineralcorticoide presente in circolo, esso è reposto alla regolarizzazione del volume dei liquidi extracellulari e dei livelli sierici di sodio e di potassio. E’ prodotto nella zona juxta-glomerulare della corteccia surrenale con l’ausilio dell’enzima aldosterone-sintetasi (CYP11B2) (1-5).

L’aldosterone rappresenta l’effettore finale del sistema renina-angiotensina-aldosterone (RAA).  Il sistema RAA e il potassio sono i maggiori regolatori, mentre l’ormone adrenocorticotropo (ACTH), il sodio, vasopressina, dopamina, peptide natriuretico atriale, sostanze adrenergiche, serotonina e somatostatina sono modulatori minori (6-8).

La renina, un enzima prodotto dalle cellule juxtaglomerulari renali, interviene nel clivaggio della macroglobulina epatica angiotensinogeno che si trasforma in angiotensina I. L’angiotensina I a sua volta viene rapidamente trasformata dall’enzima di conversione dell’angiotensina (ACE) , prodotto dai polmoni, nell’octapeptide angiotensina II. Il clivaggio del residuo NH-terminale dell’angiotensina II produce angiotensina III. Mentre angiotensina I non ha attività biologica nota, l’angiotensina II e l’angiotensina III stimolano la secrezione di aldosterone in modo simile, sebbene l’angiotensina II sia un agente vasocostrittore più potente. Le angiotensine vengono poi inattivate nell’arco di alcuni minuti ad opera di peptidasi plasmatiche e tissutali. Le angiotensine  provocano anche la secrezione di cortisolo e deossicorticosterone, anche se in misura molto minore (9-22).

La secrezione della renina è stimolata dalla riduzione del volume ematico e del flusso nelle arteriole afferenti renali, dalla riduzione della concentrazione del sodio nel fluido tubulare, percepito dalla macula densa, e dall’iperattività del sistema nervoso simpatico renale. Fattori che riducono il flusso renale sono: disidratazione, emorragie, restrizione sodica, posizione ortostatica o stenosi delle arterie renali e questi fattori aumentano la secrezione di renina (23-34).

Al contrario, fattori che aumentano il flusso renale, come aumentato introito di sodio, vasocostrizione periferica, o posizione clinostatica, riducono la secrezione di renina. Anche l’angiotensina II inibisce la secrezione di renina tramite un meccanismo diretto di feedback negativo.  L’ipokaliemia aumenta e l’iperkaliemia riduce il rilascio di renina (35-46).

L’aldosterone riduce i livelli di renina tramite un’azione indiretta attraverso meccanismi di ritenzione idrosalina ed espansione di volume.

Tra i fattori ipofisari va ricordato l’ACTH, che stimola la secrezione di aldosterone in modo acuto ma
non cronico.

FUNZIONI DELL’ALDOSTERONE: regola il bilancio elettrolitico e idrico aumentando la ritenzione renale di sodio e l’escrezione di potassio a livello dei tubuli distali e collettori del rene. Su tutte le cellule dell’organismo agisce facilitando l’ingresso dell’acqua e del sodio e la fuoriuscita del potassio (contribuendo così a riequilibrare riportandoli alla norma, valori pressori bassi) (47-55). 

Inizialmente  si ritenne che l’azione esclusiva dell’aldosterone fosse quella sodio-ritentiva a livello renale,  in seguito l’attenzione sull’aldosterone fu ampliata per il suo ruolo nello sviluppo di processi infiammatori e fibrotici nell’ambito di svariate patologie cardiovascolari.

IPERALDOSTERONISMO –  patologia di non comune riscontro; interessa prevalentemente i soggetti di sesso femminile di età compresa fra i 30 e i 50 anni. Esistono varie forme di iperaldosteronismo che, essenzialmente, possiamo distinguere in due categorie: primario e secondario (44-60).

Iperaldosteronismo primario: sindrome  caratterizzata da ipersecrezione di aldosterone provocata da patologia interna al surrene:  iperplasia surrenalica, adenoma o carcinoma.  Esistono varie forme di iperaldosteronismo primario; la più comune (60% dei casi circa), tanto da esserne considerata un sinonimo è la sindrome di Conn  in cui è presente un adenoma surrenalico.  

L’iperaldosteronismo primario idiopatico è presente nel 40% circa dei casi ed è dovuto a iperplasia surrenalica bilaterale.  L’iperplasia delle surrenali può presentarsi in due tipi: tipo I (sopprimibile con desametasone) e tipo II. 

Piuttosto rari sono i casi di iperaldosteronismo primario dovuti a carcinoma secernente aldosterone e a iperplasia monolaterale.

Iperaldosteronismo secondario:  dovuto ad una iperattività del sistema renina-angiotensina, da iperplasia fibromuscolare, stenosi dell’arteria renale, tumore delle cellule iuxta-glomerulari e altre cause summenzionate che inducono iperattivazione del sistema RAA.

Altri fattori che influenzano i valori dell’aldosteronemia sono la postura, lo stress e la gravidanza. Anche le variazioni del sodio nella dieta possono influire sui livelli plasmatici di aldosterone.

Ipoaldosteronismo: La secrezione di aldosterone diminuisce nell’iperplasia surrenalica congenita,  nell’insufficienza corticosurrenalica primitiva (morbo di Addison),  deficit di aldosterone-sintetasi, (CYP11B2), utilizzo di farmaci (alcuni diuretici, antinfiammatori non steroidei o FANS, ACE inibitori, ciclosporina). nella sindrome di Turner, nell’etilismo acuto e nel diabete mellito.  “Ipoaldosteronismo isolato” viene utilizzato per descrivere bassi livelli di aldosterone senza cambiamenti corrispondenti nei livelli di cortisolo e si differenzia dall’Ipoaldosteronismo iporeninemico in cui coesistono diminuzione della produzione di angiotensina 2 e disfunzioni intrasurrenaliche (120-129).

Terapia: 

• Il deficit di Aldosterone dovrebbe essere trattato con un mineralocorticoide (come ad esempio il fludrocortisone, Florinef® cpr 0.1 mg), e possibilmente con un glucocorticoide per il deficit di cortisolo, se presente.
• L’ipoaldosteronismo iporeninemico è suscettibile di trattamento con fludrocortisone (Florinef® cpr 0.1 mg), ma la coesistenza di ipertensione ed edema in questi pazienti richiede associazione di terapia con la bendroflumetiazide (Aprinox® cpr),  La bendroflumetiazide è un diuretico tiazidico che agisce a livello del tubulo contorto prossimale dove avviene il 65% della filtrazione dell’acqua. I tiazidici inibiscono l’anidrasi carbonica inibendo in tal modo la metabolizzazione del bicarbonato HCO3^– e manacata formazione di CO2 e H⁺. In tal modo Na⁺, HCO3^– e H₂O non vengono riassorbiti a livello del tubulo contorto prossimale. Ma verranno comunque in gran parte riassorbiti a livello dell’ansa di Henle, a livello del tubulo contorto distale e del tubulo collettore. La bendroflumetiazide inibisce anche la secrezione di latte di latte materno nelle donne ed è talvolta usato per questo scopo.

Effetti collaterali dei diuretici: astenia, ipotensione, stanchezza cronica, lipotimie, vertigini, poliuria, aumento della sete, acidosi metabolica, calcolosi renale. 

Oltre ai diuretici tiazidici si possono utilizzare i diuretici dell’ansa, come la furosemide (Lasix® cpr 25 mg).

References:

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