master patologie ipotalamo ipofisarie. acido retinoico e malattia di cushing
TRANSCRIPT
MEDICAL TREATMENT OF CUSHING’S DISEASE:
FOCUS ON RETINOIC ACID
Massimiliano Andrioli
Master Universitario II livello
DIAGNOSI E TERAPIA DELLE PATOLOGIE IPOTALAMO IPOFISARIE
• Inoperabile patients;• Waiting for surgery, when quick symptoms control is needed;• Waiting for radiosurgery results;• Occult ACTH-dependent hypercortisolism
INDICATIONS
ADRENAL STEROIDOGENESIS
INHIBITORS
PITUITARY TARGET
MEDICAL TREATMENT
KETOCONAZOLE
ADRENAL STEROIDOGENESIS INHIBITORS
MITOTANE
ADRENAL STEROIDOGENESIS INHIBITORS
METOPIRONE
ADRENAL STEROIDOGENESIS INHIBITORS
ETOMIDATE
ADRENAL STEROIDOGENESIS INHIBITORS
MIFEPRISTONE (RU486)
ADRENAL STEROIDOGENESIS INHIBITORS
PPRγ AGONISTS
DOPAMINE AGONISTS
SOM230
RETINOIC ACID
PITUITARY TARGET
RETINOIC ACID
• ↓ ACTH/POMC (restricted tumoral corticotrops)
• antiproliferative action on tumoral corticotropes
• ↓ corticosterone secretion
• ↓ adrenal cells proliferation
Pa´ez-Pereda J Clin Invest 2001Giacomini Endocrinology 2006Castillo Endocrinology 2006
BACKGROUND
• ↓ cortisol/symptoms
• ↓ tumor growth
in vitro, murine cells
in vivo, murine
in vivo, dogs
Retinoid acid currently used in: severe acne
psoriasisacute promyelocitica leukemia
AIMS
• Efficacy (↓ excess cortisol secretion)
• Safety profile
PATIENTS & METHODS
• Clinical chemistry
• Comorbididities: osteoporosis, hypertension, diabetes
PATIENTS & METHODS
RESULTS
• ↓ UFC 60% (22-77%), stable in 2/5
RESULTS
RESULTS
• ↓ UFC 60% (22-77%), stable in 2/5
• ↓ HBA1c (0.4-1.2%),
• ↓ fasting (14%) and postprandial (30%) glucose
• ↓ blood pressure
• ↓ body weight (5%)
• amelioration (facial acne, pletora, hirsutism, depression)
• negligible side effects
CONCLUSIONS
• retinoic acid can restrain excess cortisol secretion
• retinoic acid can contain symptoms