Endocrine Abstracts

Introduction: Pituitary surgery is the first line treatment for most patients with Cushing’s disease (CD) but after failure or recurrence after surgery 3 main strategies can be proposed: medical treatment (MT), a 2 nd pituitary surgery, bilateral adrenalectomy (BA). Pituitary radiotherapy is a 4^th strategy, generally combined with one of the 3 others. Medical treatment (MT) emerges as an attractive strategy but there are little data on long-term control after failure of pituitary surgery or recurrence.

Objective: To evaluate long term control of CD with MT after failure of pituitary surgery or recurrence.

Methods: Monocentric retrospective study of all 119 patients who had pituitary surgery for CD between 2001 and 2020 in our institution, with 36 patients candidates for a second line therapy, including 19 with pituitary failures (19/119 =16%, surgical remission rate 84%) and 17 with recurrences (17/100=17%)

Results: The second line treatment was medical treatment (MT) in 28/36 patients (78%) 2^nd pituitary surgery in 5/36 patients (14%) and BA in 3/36 patients (8%). The long-term control was achieved by MT in 11/36 patients (30%), 2^nd pituitary surgery in 8/36 patients (22%) and BA in 14 patients (39%), while 3/36 patients (8%) remained uncontrolled. During the whole follow-up 29 patients received at least one drug and 67 introductions of drug treatment were performed (average 29/67=1.7/patient), using inhibitors of steroidogenesis: ketoconazole (27), metyrapone (15), osilodrostat (8), mitotane (3) or inhibitors of ACTH secretion: cabergoline(11), pasireotide (3). On long term 11/29 (38%) patients were maintained on MT (group A, duration of treatment 49.6 months) while 18/29 (62%) patients abandoned MT (group B duration of treatment 20.8 months,) for lack of long-term efficiency (66%), intolerance and/or lack of compliance (34%). A normal Urinary Free Cortisol (UFC) was obtained at least one time during 38/67 introductions of treatment (57%), including 36/53 (68%) with steroidogenesis inhibitors and 2/14 (14%) with inhibitors of ACTH secretion. The last treatment used in group A was osilodrostat (6); ketoconazole (3) ketoconazole+metyrapone (1) metyrapone (1). Group A patients had a higher age (55.9 vs 47.9P=0.04), and a tendency toward more different treatments (2.5 vs 1.7P=0.06) but were no different regarding sex and initial UFC. All female patients under 35 years ended in-group B. In conclusion, in this study MT was a long-term solution for 38% of the patients who experienced failure or recurrence after pituitary surgery for CD. Steroidogenesis inhibitors appeared more efficient.