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