Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN

Elena Valassi; Frédéric Castinetti; Amandine Ferriere; Stylianos Tsagarakis; Richard A. Feelders; Romana T. Netea-Maier; Michael Droste; Christian J. Strasburger; Dominique Maiter; Darko Kastelan; Philippe Chanson; Susan M. Webb; Frank Demtröder; Valdis Pirags; Olivier Chabre; Holger Franz; Alicia Santos; Martin Reincke

doi:10.1530/ERC-22-0074

Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN

Elena Valassi^*, Frédéric Castinetti, Amandine Ferriere, Stylianos Tsagarakis, Richard A. Feelders, Romana T. Netea-Maier, Michael Droste, Christian J. Strasburger, Dominique Maiter, Darko Kastelan, Philippe Chanson, Susan M. Webb, Frank Demtröder, Valdis Pirags, Olivier Chabre, Holger Franz, Alicia Santos, Martin Reincke

^*Corresponding author for this work

Internal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

Abstract

Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.

Original language	English
Pages (from-to)	681-691
Number of pages	11
Journal	Endocrine-Related Cancer
Volume	29
Issue number	12
DOIs	https://doi.org/10.1530/ERC-22-0074
Publication status	Published - 1 Dec 2022

Bibliographical note

Funding Information:
ERCUSYN was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from Novartis, Ipsen, HRA and the European Society of Endocrinology. We are indebted to Ignasi Gich MD, PhD, Department of Epidemiology and Cochrane Iberoamérica, Hospital Sant Pau, for his statistical assistance. ERCUSYN Study Group: A Ambrogio, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; V Amodru, Hospital Sant Pau, Barcelona, Spain; G Aranda, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; M Arosio, Unit of Endocrine Diseases & Diabetology, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; M Balomenaki, Athens Polyclinic General Hospital, Evangelismos Hospital, Athens, Greece; P Beck-Peccoz, Endocrinology and Diabetology Unit, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; C Berr-Kirmair, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; M. Bolanowski, Wroclaw Medical University, Wroclaw, Poland; J Bollerslev, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, University in Oslo, Oslo, Norway; Brue Thierry, Association pour le Devéloppement des Recherches Biologiques et Médicales; D Carvalho, Hospital de San Joao, Porto, Portugal; F Cavagnini, Istituto Auxologico Italiano IRCCS, Milan, Italy; E Christ, University Hospital of Bern, Inelspital, Division of Endocrinology, Diabetology and Clinical Nutrition, Bern, Switzerland; F Demtröder Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtröder & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund, Germany; J Denes, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; C Dimopoulou, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Dreval, Moscow Regional Research Clinical Institute n.a. Vladimirsky, Moscow, Russia; T Dusek, Department of Endocrinology, University Hospital Zagreb, School of Medicine University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; E Erdinc, Uludag University School of Medicine, Bursa, Turkey; J A Evang, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, Oslo University in Oslo, Oslo, Norway; J Fazel, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; S Fica, Elias Hospital, Bucharest, Romania; E Ghigo, Molinette Hospital, Department of Internal Medicine, Turin, Italy; M Goth, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; Y Greenman, Institute of Endocrinology, Metabolism and hypertension, Tel Aviv, Israel; V Greisa, Medizinische Universitat Wien, Wien, Austria; I Halperin, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; F A Hanzu, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; A Hermus, Radboud University Medical Center, Nijmegen The Netherlands; G Johannsson, Goteborg University, Goteborg, Sweden; P Kamenicky, Univ Paris-Sud, Université Paris-Saclay UMR-S1185, Le Kremlin Bicêtre, Paris F-94276, France, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, Paris, F-94275, Institut National de la Santé et de la Recherche Médicale U1185, Le Kremlin Bicêtre, Paris F-94276, France; A Kasperlik-Zaluska, Centre for Postgraduate Medical Education, Warsaw, Poland; J Kirchner, Division of Clinical Endocrinology, Department of Medicine CCM, Charité-Universitätsmedizin, Berlin, Germany; Kastelan Darko, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; I Kraljevic, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; A Kruszynska, Centre for Postgraduate Medical Education, Warsaw, Poland; I Lambrescu, Elias Hospital, Bucharest, Romania; S Lang, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Luger, Medizinische Universitat Wien, Wien, Austria; N Marpole, Christie Hospital, NHS Trust, Manchester, UK; S Martin, Elias Hospital, Bucharest, Romania; M Martinie, Service d’Endocrinologie-Diabétologie-Nutrition, Grenoble Cedex, France; O Moros, Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtröder & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund; J Newell-Price, The University of Sheffield, Sheffield, UK; M Orbetzova, Clinic of Endocrinology and Metabolic Diseases, ‘Sv.Georgy’ University Hospital, Medical University, Plovdiv, Bulgaria; I Paiva, Hospitais da Universidade de Coimbra; F Pecori Giraldi, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; AM Pereira, Leiden University Medical Center, Leiden, The Netherlands; J Pickel, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; V Pirags, Pauls Stradiņš Clinical University Hospital, University of Latvia, Riga, Latvia; O Ragnarsson, Goteborg University, Goteborg, Sweden; AD Reghina, Elias Hospital, Bucharest, Romania; P Riesgo, Neurosurgery Department, Hospital Universitario de la Ribera, Alzira, Spain; M Roberts, Christie Hospital, NHS Trust, Manchester, UK; S Roerink, Radboud University Medical Center, Nijmegen The Netherlands; O Roig, IIB-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; C Rowan, Christie Hospital, NHS Trust, Manchester, UK; P Rudenko, Estonian Endocrine Society, Tallinn, Estonia; MA Sahnoun, Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344 Cedex 15, Marseille, and APHM, Hôpital Conception, Marseille, France; J Salvador, University of Navarra, Pamplona, Spain; HA Sigurjonsdottir, Landspitali University Hospital, Reykjavik, Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland; T Skoric Polovina, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; R Smith, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK; B Stachowska, Department of Endocrinology, Diabetology and Isotope Therapy Wroclaw Medical University, Wroclaw, Poland; G Stalla, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; J Tőke, 2nd Departement of Medicine, Semmelweis University, Budapest, Hungary; E Hubina, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; S Vinay, Christie Hospital, NHS Trust, Manchester, UK; M Wagenmakers, Radboud University Medical Center, Nijmegen The Netherlands; S Werner, Praxis für Endokrinologie Droste, Oldenburg, Germany; J Young, Univ Paris-Sud, Université Paris-Saclay UMR-S1185, Le Kremlin Bicêtre, Paris F-94276, France, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, Paris, F-94275, Institut National de la Santé et de la Recherche Médicale U1185, Le Kremlin Bicêtre, Paris F-94276, France; P Zdunowski, Centre for Postgraduate Medical Education, Warsaw, Poland; K Zopf, Division of Clinical Endocrinology, Department of Medicine CCM, Charité- Universitätsmedizin, Berlin, Germany; S Zopp, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; I Zosin, Romanian Society for Endocrinology, Timisoara, Romania.

Funding Information:
ERCU?Y? was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from ?ovartis, 阀psen, HRA and the European ?ociety of Endocrinology.

Publisher Copyright:
© 2022 Society for Endocrinology Published by Bioscientifica Ltd.

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10.1530/ERC-22-0074

Cite this

Valassi, E., Castinetti, F., Ferriere, A., Tsagarakis, S., Feelders, R. A., Netea-Maier, R. T., Droste, M., Strasburger, C. J., Maiter, D., Kastelan, D., Chanson, P., Webb, S. M., Demtröder, F., Pirags, V., Chabre, O., Franz, H., Santos, A., & Reincke, M. (2022). Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN. Endocrine-Related Cancer, 29(12), 681-691. https://doi.org/10.1530/ERC-22-0074

@article{fdd92ca3fb224d24b1de0ba3baa68a0f,

title = "Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN",

abstract = "Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.",

author = "Elena Valassi and Fr{\'e}d{\'e}ric Castinetti and Amandine Ferriere and Stylianos Tsagarakis and Feelders, {Richard A.} and Netea-Maier, {Romana T.} and Michael Droste and Strasburger, {Christian J.} and Dominique Maiter and Darko Kastelan and Philippe Chanson and Webb, {Susan M.} and Frank Demtr{\"o}der and Valdis Pirags and Olivier Chabre and Holger Franz and Alicia Santos and Martin Reincke",

note = "Funding Information: ERCUSYN was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from Novartis, Ipsen, HRA and the European Society of Endocrinology. We are indebted to Ignasi Gich MD, PhD, Department of Epidemiology and Cochrane Iberoam{\'e}rica, Hospital Sant Pau, for his statistical assistance. ERCUSYN Study Group: A Ambrogio, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; V Amodru, Hospital Sant Pau, Barcelona, Spain; G Aranda, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; M Arosio, Unit of Endocrine Diseases & Diabetology, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; M Balomenaki, Athens Polyclinic General Hospital, Evangelismos Hospital, Athens, Greece; P Beck-Peccoz, Endocrinology and Diabetology Unit, Fondazione IRCCS Ca{\textquoteright} Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; C Berr-Kirmair, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universit{\"a}t M{\"u}nchen, M{\"u}nchen, Germany; M. Bolanowski, Wroclaw Medical University, Wroclaw, Poland; J Bollerslev, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, University in Oslo, Oslo, Norway; Brue Thierry, Association pour le Dev{\'e}loppement des Recherches Biologiques et M{\'e}dicales; D Carvalho, Hospital de San Joao, Porto, Portugal; F Cavagnini, Istituto Auxologico Italiano IRCCS, Milan, Italy; E Christ, University Hospital of Bern, Inelspital, Division of Endocrinology, Diabetology and Clinical Nutrition, Bern, Switzerland; F Demtr{\"o}der Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtr{\"o}der & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund, Germany; J Denes, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; C Dimopoulou, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Dreval, Moscow Regional Research Clinical Institute n.a. Vladimirsky, Moscow, Russia; T Dusek, Department of Endocrinology, University Hospital Zagreb, School of Medicine University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; E Erdinc, Uludag University School of Medicine, Bursa, Turkey; J A Evang, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, Oslo University in Oslo, Oslo, Norway; J Fazel, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universit{\"a}t M{\"u}nchen, M{\"u}nchen, Germany; S Fica, Elias Hospital, Bucharest, Romania; E Ghigo, Molinette Hospital, Department of Internal Medicine, Turin, Italy; M Goth, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; Y Greenman, Institute of Endocrinology, Metabolism and hypertension, Tel Aviv, Israel; V Greisa, Medizinische Universitat Wien, Wien, Austria; I Halperin, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; F A Hanzu, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; A Hermus, Radboud University Medical Center, Nijmegen The Netherlands; G Johannsson, Goteborg University, Goteborg, Sweden; P Kamenicky, Univ Paris-Sud, Universit{\'e} Paris-Saclay UMR-S1185, Le Kremlin Bic{\^e}tre, Paris F-94276, France, Assistance Publique-H{\^o}pitaux de Paris, H{\^o}pital de Bic{\^e}tre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bic{\^e}tre, Paris, F-94275, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U1185, Le Kremlin Bic{\^e}tre, Paris F-94276, France; A Kasperlik-Zaluska, Centre for Postgraduate Medical Education, Warsaw, Poland; J Kirchner, Division of Clinical Endocrinology, Department of Medicine CCM, Charit{\'e}-Universit{\"a}tsmedizin, Berlin, Germany; Kastelan Darko, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; I Kraljevic, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; A Kruszynska, Centre for Postgraduate Medical Education, Warsaw, Poland; I Lambrescu, Elias Hospital, Bucharest, Romania; S Lang, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Luger, Medizinische Universitat Wien, Wien, Austria; N Marpole, Christie Hospital, NHS Trust, Manchester, UK; S Martin, Elias Hospital, Bucharest, Romania; M Martinie, Service d{\textquoteright}Endocrinologie-Diab{\'e}tologie-Nutrition, Grenoble Cedex, France; O Moros, Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtr{\"o}der & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund; J Newell-Price, The University of Sheffield, Sheffield, UK; M Orbetzova, Clinic of Endocrinology and Metabolic Diseases, {\textquoteleft}Sv.Georgy{\textquoteright} University Hospital, Medical University, Plovdiv, Bulgaria; I Paiva, Hospitais da Universidade de Coimbra; F Pecori Giraldi, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; AM Pereira, Leiden University Medical Center, Leiden, The Netherlands; J Pickel, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; V Pirags, Pauls Stradiņ{\v s} Clinical University Hospital, University of Latvia, Riga, Latvia; O Ragnarsson, Goteborg University, Goteborg, Sweden; AD Reghina, Elias Hospital, Bucharest, Romania; P Riesgo, Neurosurgery Department, Hospital Universitario de la Ribera, Alzira, Spain; M Roberts, Christie Hospital, NHS Trust, Manchester, UK; S Roerink, Radboud University Medical Center, Nijmegen The Netherlands; O Roig, IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, UAB, and Centro de Investigaci{\'o}n Biom{\'e}dica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII; C Rowan, Christie Hospital, NHS Trust, Manchester, UK; P Rudenko, Estonian Endocrine Society, Tallinn, Estonia; MA Sahnoun, Aix-Marseille Universit{\'e}, CNRS, CRN2M UMR 7286, 13344 Cedex 15, Marseille, and APHM, H{\^o}pital Conception, Marseille, France; J Salvador, University of Navarra, Pamplona, Spain; HA Sigurjonsdottir, Landspitali University Hospital, Reykjavik, Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland; T Skoric Polovina, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; R Smith, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK; B Stachowska, Department of Endocrinology, Diabetology and Isotope Therapy Wroclaw Medical University, Wroclaw, Poland; G Stalla, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; J T{\H o}ke, 2nd Departement of Medicine, Semmelweis University, Budapest, Hungary; E Hubina, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; S Vinay, Christie Hospital, NHS Trust, Manchester, UK; M Wagenmakers, Radboud University Medical Center, Nijmegen The Netherlands; S Werner, Praxis f{\"u}r Endokrinologie Droste, Oldenburg, Germany; J Young, Univ Paris-Sud, Universit{\'e} Paris-Saclay UMR-S1185, Le Kremlin Bic{\^e}tre, Paris F-94276, France, Assistance Publique-H{\^o}pitaux de Paris, H{\^o}pital de Bic{\^e}tre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bic{\^e}tre, Paris, F-94275, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U1185, Le Kremlin Bic{\^e}tre, Paris F-94276, France; P Zdunowski, Centre for Postgraduate Medical Education, Warsaw, Poland; K Zopf, Division of Clinical Endocrinology, Department of Medicine CCM, Charit{\'e}- Universit{\"a}tsmedizin, Berlin, Germany; S Zopp, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universit{\"a}t M{\"u}nchen, M{\"u}nchen, Germany; I Zosin, Romanian Society for Endocrinology, Timisoara, Romania. Funding Information: ERCU?Y? was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from ?ovartis, 阀psen, HRA and the European ?ociety of Endocrinology. Publisher Copyright: {\textcopyright} 2022 Society for Endocrinology Published by Bioscientifica Ltd.",

year = "2022",

month = dec,

day = "1",

doi = "10.1530/ERC-22-0074",

language = "English",

volume = "29",

pages = "681--691",

journal = "Endocrine-Related Cancer",

issn = "1351-0088",

publisher = "Bioscientifica Ltd",

number = "12",

}

Valassi, E, Castinetti, F, Ferriere, A, Tsagarakis, S, Feelders, RA, Netea-Maier, RT, Droste, M, Strasburger, CJ, Maiter, D, Kastelan, D, Chanson, P, Webb, SM, Demtröder, F, Pirags, V, Chabre, O, Franz, H, Santos, A & Reincke, M 2022, 'Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN', Endocrine-Related Cancer, vol. 29, no. 12, pp. 681-691. https://doi.org/10.1530/ERC-22-0074

TY - JOUR

T1 - Corticotroph tumor progression after bilateral adrenalectomy

T2 - data from ERCUSYN

AU - Valassi, Elena

AU - Castinetti, Frédéric

AU - Ferriere, Amandine

AU - Tsagarakis, Stylianos

AU - Feelders, Richard A.

AU - Netea-Maier, Romana T.

AU - Droste, Michael

AU - Strasburger, Christian J.

AU - Maiter, Dominique

AU - Kastelan, Darko

AU - Chanson, Philippe

AU - Webb, Susan M.

AU - Demtröder, Frank

AU - Pirags, Valdis

AU - Chabre, Olivier

AU - Franz, Holger

AU - Santos, Alicia

AU - Reincke, Martin

N1 - Funding Information: ERCUSYN was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from Novartis, Ipsen, HRA and the European Society of Endocrinology. We are indebted to Ignasi Gich MD, PhD, Department of Epidemiology and Cochrane Iberoamérica, Hospital Sant Pau, for his statistical assistance. ERCUSYN Study Group: A Ambrogio, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; V Amodru, Hospital Sant Pau, Barcelona, Spain; G Aranda, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; M Arosio, Unit of Endocrine Diseases & Diabetology, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; M Balomenaki, Athens Polyclinic General Hospital, Evangelismos Hospital, Athens, Greece; P Beck-Peccoz, Endocrinology and Diabetology Unit, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; C Berr-Kirmair, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; M. Bolanowski, Wroclaw Medical University, Wroclaw, Poland; J Bollerslev, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, University in Oslo, Oslo, Norway; Brue Thierry, Association pour le Devéloppement des Recherches Biologiques et Médicales; D Carvalho, Hospital de San Joao, Porto, Portugal; F Cavagnini, Istituto Auxologico Italiano IRCCS, Milan, Italy; E Christ, University Hospital of Bern, Inelspital, Division of Endocrinology, Diabetology and Clinical Nutrition, Bern, Switzerland; F Demtröder Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtröder & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund, Germany; J Denes, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; C Dimopoulou, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Dreval, Moscow Regional Research Clinical Institute n.a. Vladimirsky, Moscow, Russia; T Dusek, Department of Endocrinology, University Hospital Zagreb, School of Medicine University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; E Erdinc, Uludag University School of Medicine, Bursa, Turkey; J A Evang, Section of Specialized Endocrinology, Oslo University Hospital, and Faculty of Medicine, Oslo University in Oslo, Oslo, Norway; J Fazel, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; S Fica, Elias Hospital, Bucharest, Romania; E Ghigo, Molinette Hospital, Department of Internal Medicine, Turin, Italy; M Goth, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; Y Greenman, Institute of Endocrinology, Metabolism and hypertension, Tel Aviv, Israel; V Greisa, Medizinische Universitat Wien, Wien, Austria; I Halperin, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; F A Hanzu, Department of Endocrinology, Hospital Clinic Barcelona, IDIBAPS, UB, Barcelona, Spain; A Hermus, Radboud University Medical Center, Nijmegen The Netherlands; G Johannsson, Goteborg University, Goteborg, Sweden; P Kamenicky, Univ Paris-Sud, Université Paris-Saclay UMR-S1185, Le Kremlin Bicêtre, Paris F-94276, France, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, Paris, F-94275, Institut National de la Santé et de la Recherche Médicale U1185, Le Kremlin Bicêtre, Paris F-94276, France; A Kasperlik-Zaluska, Centre for Postgraduate Medical Education, Warsaw, Poland; J Kirchner, Division of Clinical Endocrinology, Department of Medicine CCM, Charité-Universitätsmedizin, Berlin, Germany; Kastelan Darko, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; I Kraljevic, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; A Kruszynska, Centre for Postgraduate Medical Education, Warsaw, Poland; I Lambrescu, Elias Hospital, Bucharest, Romania; S Lang, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; A Luger, Medizinische Universitat Wien, Wien, Austria; N Marpole, Christie Hospital, NHS Trust, Manchester, UK; S Martin, Elias Hospital, Bucharest, Romania; M Martinie, Service d’Endocrinologie-Diabétologie-Nutrition, Grenoble Cedex, France; O Moros, Zentrum fur Endokrinologie, Diabetologie, Rheumatologie Dr Demtröder & Kollegen im MVZ Dr. Eberhard & Partner und Klinikum Dortmund; J Newell-Price, The University of Sheffield, Sheffield, UK; M Orbetzova, Clinic of Endocrinology and Metabolic Diseases, ‘Sv.Georgy’ University Hospital, Medical University, Plovdiv, Bulgaria; I Paiva, Hospitais da Universidade de Coimbra; F Pecori Giraldi, Istituto Auxologico Italiano IRCCS, University of Milan, Italy; AM Pereira, Leiden University Medical Center, Leiden, The Netherlands; J Pickel, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; V Pirags, Pauls Stradiņš Clinical University Hospital, University of Latvia, Riga, Latvia; O Ragnarsson, Goteborg University, Goteborg, Sweden; AD Reghina, Elias Hospital, Bucharest, Romania; P Riesgo, Neurosurgery Department, Hospital Universitario de la Ribera, Alzira, Spain; M Roberts, Christie Hospital, NHS Trust, Manchester, UK; S Roerink, Radboud University Medical Center, Nijmegen The Netherlands; O Roig, IIB-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; C Rowan, Christie Hospital, NHS Trust, Manchester, UK; P Rudenko, Estonian Endocrine Society, Tallinn, Estonia; MA Sahnoun, Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344 Cedex 15, Marseille, and APHM, Hôpital Conception, Marseille, France; J Salvador, University of Navarra, Pamplona, Spain; HA Sigurjonsdottir, Landspitali University Hospital, Reykjavik, Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland; T Skoric Polovina, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; R Smith, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK; B Stachowska, Department of Endocrinology, Diabetology and Isotope Therapy Wroclaw Medical University, Wroclaw, Poland; G Stalla, Max-Planck-Gessellschaft zur Forderung der Wissenschaften e.V., Munich, Germany; J Tőke, 2nd Departement of Medicine, Semmelweis University, Budapest, Hungary; E Hubina, Division of Endocrinology, 2nd Department of Medicine, State Health Center, Budapest, Hungary; S Vinay, Christie Hospital, NHS Trust, Manchester, UK; M Wagenmakers, Radboud University Medical Center, Nijmegen The Netherlands; S Werner, Praxis für Endokrinologie Droste, Oldenburg, Germany; J Young, Univ Paris-Sud, Université Paris-Saclay UMR-S1185, Le Kremlin Bicêtre, Paris F-94276, France, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, Paris, F-94275, Institut National de la Santé et de la Recherche Médicale U1185, Le Kremlin Bicêtre, Paris F-94276, France; P Zdunowski, Centre for Postgraduate Medical Education, Warsaw, Poland; K Zopf, Division of Clinical Endocrinology, Department of Medicine CCM, Charité- Universitätsmedizin, Berlin, Germany; S Zopp, Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universität München, München, Germany; I Zosin, Romanian Society for Endocrinology, Timisoara, Romania. Funding Information: ERCU?Y? was set up with funding from the EU (PHP 800200) and been supported by unrestricted grants from ?ovartis, 阀psen, HRA and the European ?ociety of Endocrinology. Publisher Copyright: © 2022 Society for Endocrinology Published by Bioscientifica Ltd.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.

AB - Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.

UR - http://www.scopus.com/inward/record.url?scp=85141888729&partnerID=8YFLogxK

U2 - 10.1530/ERC-22-0074

DO - 10.1530/ERC-22-0074

M3 - Article

C2 - 36197784

AN - SCOPUS:85141888729

SN - 1351-0088

VL - 29

SP - 681

EP - 691

JO - Endocrine-Related Cancer

JF - Endocrine-Related Cancer

IS - 12

ER -

Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN

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