OR02-4 Presurgical Medical Treatment in Patients with Cushing's Syndrome. Results from the European Registry on Cushing's Syndrome (ERCUSYN)

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: OR02-Diagnosing and Treating Cortisol Excess and Deficiency
Clinical
Saturday, June 21, 2014: 11:30 AM-1:00 PM
Presentation Start Time: 12:15 PM
W190 (McCormick Place West Building)
Elena Valassi, MD, PhD1, Alicia Santos2, Romana T. Netea-Maier, MD, PhD3, Richard A. Feelders, MD PhD4, Thierry Brue, MD, PhD5, John A. Wass, MA, MD, FRCP6, Philippe Chanson, MD7, Maria Yaneva8, Stylianos Tsagarakis, MD, PHD, FRCP9, Kathrin Zopf10, Olivier Chabre, MD, PhD11, Irina V Komerdus12, Miklos Toth, MD, PhD, DSci13, Holger Franz14, C J Strasburger15, Steven W.J. Lamberts, MD PhD4, P J Trainer, MD FRCP16 and Susan M Webb17
1IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autònoma de Barcelona (UAB), ISCIII; Barcelona, Spain, 2IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Cerdanyola del Vallès, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain, 3Radboud University Nijmegen Medical Center, Nijmegen, Netherlands, 4Erasmus Medical Center, Rotterdam, Netherlands, 5Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille (CRN2M) - CNRS UMR7286, Marseille, France, 6University of Oxford, Churchill Hospital, Oxford, United Kingdom, 7Univ Paris-Sud, UMR-S693, Le Kremlin Bicêtre, France, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, Paris, France, Le Kremlin-Bicêtre, France, 8Medical University of Sofia, 9Evangelisnos Hospital, Athens, Greece, 10Division of Clinical Endocrinology, Department of Medicine CCM, Charité- Universitätsmedizin, Berlin, Germany, 11Service d’Endocrinologie-Diabétologie-Nutrition, Grenoble Cedex, France, Grenoble, France, 12Moscow Regional Research Clinical Institute, Moscow, Russia, 13Semmelweis University, Budapest, Hungary, 14Lohmann and Birkner Health Care Consulting GmbH, Berlin, Germany, 15Division of Clinical Endocrinology, Department of Medicine CCM, Charité- Universitätsmedizin, Berlin, Germany, Berlin, Germany, 16Department of Endocrinology, Christie Hospital, Manchester, UK, 17IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autònoma de Barcelona (UAB) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII; 08025 Barcelona, Spain
Background: Surgery is the treatment of choice for Cushing’s syndrome (CS) but preoperative medical therapy (PMT) may be used to lower circulating cortisol and improve patient’s condition. The most commonly used medications for CS include ketoconazole (KTZ), metyrapone (MTP) and cabergoline (CAB); mifepristone, mitotane, etoposide and aminogluthetimide may also be employed depending on etiology of CS and availability of drugs.

Objective: 1) To study the prevalence of PMT in CS patients throughout Europe; and 2) To evaluate any differences in surgical outcome between patients who received PMT vs. those who did not.

Methods/Design: In October 2013 ERCUSYN included 1023 patients (821 F, 202 M; mean age (+SD) 44.7±13.5 years) from 57 centers in 28 countries. It comprises 669 (65%) pituitary-dependent CS (PIT-CS), 249 (24%) adrenal-dependent CS (ADR-CS), and 105 (11%) from other etiologies, including ectopic (ECT-CS).

Results: Two hundred and twenty-eight CS patients of 930 (25%) with therapy data available took PMT vs. 634 who did not (68%). A subset of 65/930 (7%) was excluded from analysis because only medical treatment was given, but no subsequent surgery. More than half of CS patients who were medically treated before surgery were from the Netherlands, France and Spain. Patients with PIT-CS received PMT more frequently than the other etiologic groups (82% PIT-CS vs. 7% ADR-CS and 10% ECT-CS; p<0.01 for both comparisons). KTZ was the most commonly used medication, given to 171 of 228 patients (75%; alone or in combination) vs. MTP administered to 53 (23%), CAB to 18 (8%), and mifepristone to 10 (4%) patients. Mitotane and aminogluthetimide were taken by 2 and 1 patients, with PIT-CS. Median duration of PMT was 103 days (range:1-1155 days). Median cumulative dose of KTZ and MTP was 66 gr (range:1,6-1314gr) and 120gr, (range: 6-1838.5gr), respectively. Median cumulative dose of CAB was 0.06 gr (range: 0.015-8.6 gr). Of 471 PIT-CS patients in remission in the immediate postoperative period (within 2 weeks since surgery), 326 (69%) had not received any PMT vs. 144 (31%) who had been medically treated (p<0.01). Early hypoadrenalism was reported in significantly more patients without PMT (70%), as compared with those who had taken PMT (30%) (p<0.01). After a median follow-up of 975 days (range:181-8153 days), 319 PIT-CS were in remission, of whom 196 (61%) had not taken PMT vs. 123 (38%) who had been medically treated before surgery (p<0.01).        

Conclusions:

- PMT may be associated with lower prevalence of postoperative hypoadrenalism in PT-CS patients; this may be due to decreased negative feedback, leading to recovery of pituitary-adrenal axis function.

- PMT appears to be associated with lower prevalence of long-term remission in PIT-CS patients, although this may be determined by a more severe initial clinical presentation.

 


 

Disclosure: TB: Clinical Researcher, Pfizer, Inc., Clinical Researcher, Novo Nordisk, Clinical Researcher, Novartis Pharmaceuticals, Clinical Researcher, Ipsen, Clinical Researcher, Serono, Clinical Researcher, Sandoz. CJS: Advisory Group Member, Chiasma. PJT: Principal Investigator, HRA Pharma. Nothing to Disclose: EV, AS, RTN, RAF, JAW, PC, MY, ST, KZ, OC, IVK, MT, HF, SWJL, SMW

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: ERCUSYN has been supported by the EU PHP 800/200 and the European Society of Endocrinology