Non Functioning Pituitary Adenomas Francesco Minuto Cattedra di Endocrinologia DiSEM Università di...

Non Functioning Pituitary Adenomas

Francesco MinutoCattedra di Endocrinologia

DiSEMUniversità di Genova

08/07/2010 Università di Genova


Adenohypophysial tumors are still classified according to the staining characteristics of the secretory granules into chromophobe, acidophil or basophil types …….

……. From a clinical point of view, it would be preferable to classify these tumors by their secretory products.

1974

THE PREVALENCE OF PITUITARY ADENOMAS. A SYSTEMATIC REVIEWS. Ezzat, S. L. Asa, W. T. Couldwell, C. E. Barr, W. E. Dodge, M. Lee Vance, I. E. McCutcheonCancer 2004;101:613–9.


All studies: 16.7%

Post mortem: 14.4%

Radiologic: 22.5%

Classificazione NFPA

Colorimetrica •Adenomi cromofobi

Immunoistochimica •Null cell, oncocitomi•Gn (αSu) adenomi•Silenti (ACTH, TSH, GH)


DIFFERENZIAZIONE CELLULARE DELL’IPOFISIFattori di trascrizione



MRI, due to its superior contrast resolution and multiplanar capability, has virtually replaced other imaging methods as the technique of choice for investigation of suprasellar lesions in defining the origin of a mass, its morphology, and signal characteristics.


304 51.6 29.8% 10.4%

NFPAscelte terapeutiche

1. Chirurgia2. Radioterapia


NFPATerapia medica?

Dopamino agonisti Analoghi della

somatostatina


D2 long

D2 short

D2 long

D2 short

D2 long > D2 short

D2 short > D2

long

08/07/2010Università di Genova

http://jcem.endojournals.org/cgi/content/full/83/4/1368/F1

http://jcem.endojournals.org/cgi/content/full/83/4/1368/F2

After 1 yr of cabergoline treatment (3 mg/week), tumor shrinkage was evident in 56% of patients and was associated with D2 expression (χ2=5.6;P<0.05)

18 operated NFA, 9 pts 1 yr of therapy

D2 67%D2l 50%D2s 17%both 33%


Effect of dopamine agonists on NFA growth

no effect on the size of the tumor

Bevan et al. 1986 Clin Endocrinol (Oxf) 25:561–572

Grossman et al. 1985 Clin Endocrinol (Oxf) 22:679–686

tumor shrinkage in up to 20% of the patients

Liuzzi et al 1991 In: Faglia et al eds. Pituitary adenomas: new trends in basic and clinical research. New York: Elsevier Science; 383–390

Conflicting results


Weckbecker G et al Nature Rev 2003, 2: 999-1017

SSTR signal transduction


mRNA expression of the 5 somatostatin receptor mRNA expression of the 5 somatostatin receptor subtypes in different pituitary adenoma histotypessubtypes in different pituitary adenoma histotypes

% of positive tumors% of positive tumors

sstsst11 sst sst22 sst sst3 3 sst sst44 sst sst55ADENOMASADENOMAS

GH-secretingGH-secreting

ProlactinomasProlactinomas

ACTH-secretingACTH-secreting

NonfunctioningNonfunctioning

4444

9696

5656

3838

9696

6363

6767

7575

4444

3535

2525

4343

55

66

00

1313

8686

7171

8686

4848

Modified from Hofland LJ & Lamberts SWJ


SSTR5SSTR1

SSTR5SSTR5

Rocheville et al. 2000 J Biol Chem

SSTR5DR2

Rocheville et al. 2000 Nature

SSTR2SSTR3

Pfeiffer et al. 2001 J Biol Chem

SSTR5SSTR2

Shimon et al. 1997 J Clin InvestSaveanu et al. 2001 J Clin Endocrinol Metab

DR2SSTR2

Saveanu et al. 2002 J Clin Endocrinol Metab

SSTRs dimerization


Somatostatin-Dopamine Chimera

5sst1-5 Ki (nM)

BIM-23A760

D2R Ki (nM)43212

nM>1000160 420.0384316

Potent on sst2 e D2, moderate on sst5 Potent on sst2 e D2, moderate on sst5


BIM-23A760= sst2, sst5, D2


Inhibition of angiogenesisbFGF

VEGF

PDGF

IL-8

HGFTGF

reduced neoplastic

growth

Barrie et al 1993; Danesi et al 1996 & 1997; Dasgupta et al 1999

INDIRECT EFFECTS


Terapia medica degli NFPA La riduzione di volume degli adenomi è un fenomeno

complesso in cui rivestono un ruolo importante gli SSA e DA.

I diversi sottotipi recettoriali possono esercitare effetti differenti.

La scoperta di nuove proprietà degli SSTR e DR può offrire nuove prospettive di trattamento dei tumori NFPA.

L’interazione tra SSTR e DR sulla membrana cellulare potrebbe indurre vie di trasduzione alternative che potenziano il controllo sulla crescita cellulare.

I nuovi analoghi e le molecole ibride con ampio spettro d’azione potrebbe allargare l’impiego della terapia medica degli adenomi ipofisari.


Non Functioning Pituitary Adenomas Francesco Minuto Cattedra di Endocrinologia DiSEM Università di...

Documents

Transcript of Non Functioning Pituitary Adenomas Francesco Minuto Cattedra di Endocrinologia DiSEM Università di...