A. Ghalawinjia (Dr), J. Cristanteb (Dr), M. Mullerb (Dr), V. Lefournierc (Dr), P. Chaffanjond (Prof), N. Sturme (Prof), L. Drezetf (Mr), C. Pasterisg (Dr), E. Gayh (Prof), O. Chabre*a (Prof)

a CHU Grenoble Alpes, Grenoble, FRANCE ; b Endocrinologie CHU Grenoble Alpes, Grenoble, FRANCE ; c Neuroradiologie Clinique du Mail, Grenoble, FRANCE ; d Chirurgie Endocrine CHU Grenoble Alpes, Grenoble, FRANCE ; e Pathologie Cellulaire CHU Grenoble Alpes, Grenoble, FRANCE ; f Ã‰cole Polytechnique Universitaire de l'Institut polytechnique de Grenoble, Grenoble, FRANCE ; g Radiothérapie CHU Grenoble Alpes, Grenoble, FRANCE ; h Neurochirurgie CHU Grenoble Alpes, Grenoble, FRANCE

* OlivierChabre@chu-grenoble.fr


In case of failure of transsphenoidal surgery (TSS) or recurrence, the different second-line therapies used for treatment of Cushing’s disease (CD) include drug treatment (DT), 2nd transsphenoidal surgery (2ndTSS), bilateral adrenalectomy (BA), pituitary radiotherapy (PR). We aimed to evaluate the long-term control by DT.

Design and Methods

Monocentric retrospective study of 119 patients treated by PS for CD in 2001-2020, with 36 candidates for a second-line therapy, including 19 PS failures (surgical remission rate 84%) and 17 recurrences (recurrence rate 17%).


The 36 patients were treated either/or by DT: 29/36(80%); 2ndTSS: 16/36(50%); BA: 14/36(39%) and PR: 3/36(8%). In the 29 DT patients the drugs used were ketoconazole (27/29), metyrapone (15/29), cabergoline (11/29), osilodrostat (8/29), mitotane (3/29), pasireotide (3/29).

At the end of the study, control of CD was achieved by DT in 11 patients (30% of 36 patients, 34% of DT treated patients) 2nd TSS in 8 patients (22% of 36 patients, 50% of reoperated patients) and BA in 14 patients (39% of 36 patients, 100% of operated patients). The 11 patients controlled by DT were using either ketoconazole (6/27 exposed), metyrapone (1/15 exposed) or osilodrostat (6/8).


In patients with Cushing’s disease and either primary failure of transsphenoidal surgery or recurrence after a first transsphenoidal surgery, drug treatment allowed long-term control of 11/36 (30%) patients, who were all treated by adrenal cortisol synthesis inhibitors. Drug treatment also allowed to delay surgery in 13/16 patients treated by a 2nd transsphenoidal surgery and in 11/14 patients treated by bilateral adrenalectomy

The author has declared no conflict of interest.