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

Author:

Reincke Martin1,Albani Adriana1,Assie Guillaume2,Bancos Irina3,Brue Thierry4,Buchfelder Michael5,Chabre Olivier6,Ceccato Filippo7ORCID,Daniele Andrea7,Detomas Mario8,Di Dalmazi Guido9,Elenkova Atanaska10,Findling James11,Grossman Ashley B12,Gomez-Sanchez Celso E13,Heaney Anthony P14,Honegger Juergen15,Karavitaki Niki161718ORCID,Lacroix Andre19ORCID,Laws Edward R20,Losa Marco21,Murakami Masanori122,Newell-Price John23,Pecori Giraldi Francesca24ORCID,Pérez‐Rivas Luis G1,Pivonello Rosario25,Rainey William E26,Sbiera Silviu8,Schopohl Jochen1,Stratakis Constantine A27,Theodoropoulou Marily1,van Rossum Elisabeth F C28,Valassi Elena29,Zacharieva Sabina10,Rubinstein German1,Ritzel Katrin1

Affiliation:

1. 1Klinikum der Ludwig-Maximilians-Universität München, Medizinische Klinik und Poliklinik IV, Munich, Germany

2. 2Department of Endocrinology, Université de Paris, Institut Cochin, INSERM, CNRS, Center for Rare Adrenal Diseases, Hôpital Cochin, Paris, France

3. 3Division of Endocrinology, Mayo Clinic Minnesota, Diabetes, Metabolism, Nutrition, Rochester, Minnesota, USA

4. 4Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut MarMaRa and Endocrinology Department, Conception Hospital, Assistance Publique-Hôpitaux de Marseille (APHM), Marseille, France

5. 5Universitätsklinikum Erlangen, Neurochirurgische Klinik, Erlangen, Germany

6. 6CHU Grenoble-Alpes, Unit of Endocrinology, Pavillon des Ecrins, Grenoble, France

7. 7Department of Medicine, University of Padova, Padova, Veneto, Italy

8. 8Division of Endocrinology and Diabetology, Department of Internal Medicine, University of Würzburg, Wurzburg, Bayern, Germany

9. 9Department of Medical and Surgical Sciences, Endocrinology and Diabetes Prevention and Care Unit, University of Bologna, S. Orsola Policlinic, Bologna, Italy

10. 10Department of Endocrinology, Medical University Sofia, Sofia, Bulgaria

11. 11Division of Endocrinology and Molecular Medicine, Medical College of Wisconsin, Menomonee Falls, Wisconsin, USA

12. 12Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Centre for Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, UK

13. 13Department of Pharmacology and Toxicology and Medicine, Endocrine Service, G.V. Montgomery VA Medical Center, University of Mississippi Medical Center, Jackson, Mississippi, USA

14. 14Division of Endocrinology, Medical Director, Pituitary & Neuroendocrine Tumor Program, UCLA School of Medicine, Los Angeles, California, USA

15. 15Department of Neurosurgery, University of Tübingen, Tübingen, Germany

16. 16Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham

17. 17Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners

18. 18Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

19. 19Division of Endocrinology, Department of Medicine, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada

20. 20Pituitary/Neuroendocrine Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

21. 21Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy

22. 22Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

23. 23Dept of Oncology and Metabolism, The Medical School University of Sheffield, Sheffield, UK

24. 24Department of Clinical Sciences & Community Health, University of Milan Neuroendocrinology Research Laboratory, Instituto Auxologico Italiano IRCCS, Milan, Italy

25. 25Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy

26. 26Departments of Molecular & Integrative Physiology and Medicine, University of Michigan, Ann Arbor, Michigan, USA

27. 27Section on Genetics & Endocrinology Eunice Kennedy Shriver National Insitute of Child Health & Human Development (NICHD) National Institute of Health (NIH), NIH Clinical Research Center, Bethesda, Maryland, USA

28. 28Department of Internal Medicine, division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

29. 29IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, UAB, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain

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. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension

Publisher

Bioscientifica

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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