1. Master Universitario II livello
DIAGNOSI E TERAPIA DELLE PATOLOGIE IPOTALAMO IPOFISARIE
MEDICAL TREATMENT OF
CUSHING’S DISEASE:
FOCUS ON RETINOIC ACID
Massimiliano Andrioli

2. INDICATIONS
• Inoperabile patients;
• Waiting for surgery, when quick symptoms control is needed;
• Waiting for radiosurgery results;
• Occult ACTH-dependent hypercortisolism

3. MEDICAL TREATMENT
ADRENAL PITUITARY TARGET
STEROIDOGENESIS
INHIBITORS

4. ADRENAL STEROIDOGENESIS INHIBITORS
KETOCONAZOLE

5. ADRENAL STEROIDOGENESIS INHIBITORS
MITOTANE

6. ADRENAL STEROIDOGENESIS INHIBITORS
METOPIRONE

7. ADRENAL STEROIDOGENESIS INHIBITORS
ETOMIDATE

8. ADRENAL STEROIDOGENESIS INHIBITORS
MIFEPRISTONE
(RU486)

9. PITUITARY TARGET
PPRγ AGONISTS
DOPAMINE AGONISTS
SOM230
RETINOIC ACID

10. RETINOIC ACID

11. BACKGROUND
Retinoid acid currently used in:
severe acne
psoriasis
acute promyelocitica leukemia
• ↓ ACTH/POMC (restricted tumoral corticotrops)
• antiproliferative action on tumoral corticotropes
in vitro, murine
• ↓ corticosterone secretion cells
• ↓ adrenal cells proliferation
• ↓ tumor growth in vivo, murine
• ↓ cortisol/symptoms in vivo, dogs
Pa´ez-Pereda J Clin Invest 2001
Giacomini Endocrinology 2006
Castillo Endocrinology 2006

12. AIMS
• Efficacy (↓ excess cortisol secretion)
• Safety profile

13. PATIENTS & METHODS
• Clinical chemistry
• Comorbididities: osteoporosis, hypertension, diabetes

14. PATIENTS & METHODS

15. RESULTS
• ↓ UFC 60% (22-77%), stable in 2/5

16. RESULTS

17. 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

18. CONCLUSIONS
• retinoic acid can restrain excess cortisol
secretion
• retinoic acid can contain symptoms