master patologie ipotalamo ipofisarie. acido retinoico e malattia di cushing

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

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Page 1: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

MEDICAL TREATMENT OF CUSHING’S DISEASE:

FOCUS ON RETINOIC ACID

Massimiliano Andrioli

Master Universitario II livello

DIAGNOSI E TERAPIA DELLE PATOLOGIE IPOTALAMO IPOFISARIE

Page 2: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

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

INDICATIONS

Page 3: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

ADRENAL STEROIDOGENESIS

INHIBITORS

PITUITARY TARGET

MEDICAL TREATMENT

Page 4: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

KETOCONAZOLE

ADRENAL STEROIDOGENESIS INHIBITORS

Page 5: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

MITOTANE

ADRENAL STEROIDOGENESIS INHIBITORS

Page 6: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

METOPIRONE

ADRENAL STEROIDOGENESIS INHIBITORS

Page 7: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

ETOMIDATE

ADRENAL STEROIDOGENESIS INHIBITORS

Page 8: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

MIFEPRISTONE (RU486)

ADRENAL STEROIDOGENESIS INHIBITORS

Page 9: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

PPRγ AGONISTS

DOPAMINE AGONISTS

SOM230

RETINOIC ACID

PITUITARY TARGET

Page 10: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

RETINOIC ACID

Page 11: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

• ↓ 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

Page 12: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

AIMS

• Efficacy (↓ excess cortisol secretion)

• Safety profile

Page 13: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

PATIENTS & METHODS

• Clinical chemistry

• Comorbididities: osteoporosis, hypertension, diabetes

Page 14: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

PATIENTS & METHODS

Page 15: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

RESULTS

• ↓ UFC 60% (22-77%), stable in 2/5

Page 16: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

RESULTS

Page 17: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

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

Page 18: Master Patologie Ipotalamo Ipofisarie. Acido Retinoico e Malattia di Cushing

CONCLUSIONS

• retinoic acid can restrain excess cortisol secretion

• retinoic acid can contain symptoms