Corticotroph tumor progression after bilateral adrenalectomy (Nelson's syndrome): systematic review and expert consensus recommendations

M Reincke, A Albani, G Assie, I Bancos, T Brue, M Buchfelder, O Chabre, F Ceccato, A Daniele, M Detomas, G Di Dalmazi, A Elenkova, J Findling, AB Grossman, CE Gomez-Sanchez, AP Heaney, J Honegger, N Karavitaki, A Lacroix, E R LawsM Losa, M Murakami, J Newell-Price, FP Giraldi, LG Perez-Rivas, R Pivonello, WE Rainey, S Sbiera, J Schopohl, CA Stratakis, M Theodoropoulou, Liesbeth van Rossum, E Valassi, S Zacharieva, G Rubinstein, K Ritzel

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Abstract

Background: Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods: A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results: Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions: We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission.

Original languageEnglish
Pages (from-to)P1-P16
JournalEuropean Journal of Endocrinology
Volume184
Issue number3
DOIs
Publication statusPublished - 16 Feb 2021

Bibliographical note

Funding Information:
The workshop was supported by unrestricted grants of the Deutsche Forschungsgemeinschaft (10.000 €; DFG, German Research Foundation, project number 314061271-TRR 205 ‘The adrenal gland: Central relay in health and disease’) of the Klinikum der Ludwig-Maximilians-Universität, and of the Carl Friedrich von Siemens Foundation, Munich. These funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

Funding Information:
The workshop was supported by unrestricted grants of the Deutsche Forschungsgemeinschaft (10.000 €; DFG, German Research Foundation, project number 314061271-TRR 205 ‘The adrenal gland: Central relay in health and disease’) of the Klinikum der Ludwig-Maximilians-Universität, and of the Carl Friedrich von ?iemens Foundation, Munich. These funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

Funding Information:
M Reincke has served on the advisory boards of ?ovartis and has received lecture fees and grants from ?ovartis, 阀psen, and Pfizer. 阀 Bancos has served on the advisory boards of HRA Pharma and Corcept, and consulted for ClinCor. T Brue received consulting or speaker fees or grants from ?ovartis, Pfizer and 阀psen. He served as a board member or research investigator for ?trongbridge, Pfizer, 阀psen and Recordati. O Chabre received speaker fees from ?ovartis, has been an investigator in a clinical study financed by ?ovartis and is part of a board of HRA Pharma and Recordati. A Elenkova reports serving as the principal investigator/sub-investigator of clinical trials for Corcept Therapeutics and ?ovartis and receiving consulting honoraria from ?ovartis. A Grossman has received lecture fees from ?ovartis, 阀psen, Pfizer and AAA. ? Karavitaki has received educational grants from ?ovartis. A Lacroix received Clinical Trial ?upport from ?ovartis, GLWL Research 阀nc. and Corcept and served on advisory boards of ?ovartis, 阀P?E? and Pfizer. J ?ewell-Price has received research grants and consulting honoraria paid to the University of ?heffield from HRA Pharma, ?ovartis, Diurnal, and 阀psen. R Pivonello has been Principal 阀nvestigator of Research ?tudies for ?ovartis, HRA Pharma, 阀psen, ?hire, Corcept Therapeutics, Cortendo AB; Co-investigator of Research ?tudies for Pfizer; received research grants from ?ovartis, Pfizer, 阀psen, HRA Pharma, ?hire, 阀B?A; has been an occasional consultant for ?ovartis, 阀psen, Pfizer, ?hire, HRA Pharma, Cortendo AB, Ferring and 阀talfarmaco; and has received fees and honoraria for presentations from ?ovartis and ?hire. ?o conflict of interests that could be perceived as prejudicing the impartiality of this research reported. K Ritzel has received lecture fee from 阀psen and served as investigator of clinical trials for Corcept. J ?chopohl has received lecture fees from ?ovartis, 阀psen, and Pfizer. André Lacroix is an Associate Editor for European Journal of Endocrinology. He was not involved in the editorial or review process of this paper, on which he is listed as an author.

Publisher Copyright:
© 2021 European Society of Endocrinology Printed in Great Britain

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