lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Prevention Medicine in Bilateral Phaeochromocytoma

35 Pages Posted: 3 Dec 2018

See all articles by Uliana Tsoy

Uliana Tsoy

Almazov National Medical Research Centre

Vincent Amodru

Hôpital de la Conception

Martin K. Walz

Huyssens Foundation Clinics

Irina Bancos

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

Ravinder Kaur Jeet

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

Xiaoping Qi

Wenzhou Medical University

Tushar Bandgar

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Sanjeet Kumar Jaiswal

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Roman Petrov

Bakhrushin Brothers Moscow City Hospital

Anna Roslyakova

Endocrinology Research Center

Marina Y. Yukina

Endocrinology Research Center

Anouk N. A. van der Horst-Schrivers

University of Groningen - University Medical Center Groningen (UMCG)

Annika M.A. Berends

University of Groningen - University Medical Center Groningen (UMCG)

Ana O. Hoff

University of São Paulo (USP)

Luciana Audi Castroneves

University of São Paulo (USP)

Alfonso Massimiliano Ferrara

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Silvia Rizzati

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Caterina Mian

University of Padua

Sarka Dvorakova

National Academy of Sciences of Ukraine - Institute of Endocrinology (Prague)

Kornelia Hasse-Lazar

Maria Curie Sklodowska University

Andrey Kvachenyuk

National Academy of Sciences of Ukraine - Institute of Endocrinology (Prague)

Mariola Peczkowska

Cardinal Wyszynski National Institute of Cardiology

Paola Loli

Ospedale Niguarda Cà Granda

Feyza Erenler

Tufts New England Medical Center (NEMC)

Stefan Zschiedrich

University of Freiburg

Tobias Krauss

University of Freiburg

Madson Q. Almeida

University of São Paulo (USP)

Maria C. B. V. Fragoso

University of São Paulo (USP)

Maria A. A. Pereira

University of São Paulo (USP)

Longfei Liu

Central South University

Minghao Li

Central South University

Feizhou Zhu

Central South University

Mònica Recasens

University of Girona

Josefina Biarnes Costa

University of Girona

Nelson Wohllk

University of Chile

Eleonora Corssmit

Leiden University - Medical Center (LUMC)

Zulfiya Shafigullina

North-western State Medical University

Jan Callissendorff

Karolinska Institutet

Carl Christofer Juhlin

Karolinska Institutet - Karolinska University Hospital

Simona Grozinsky-Glasberg

Hebrew University of Jerusalem - Hadassah Medical Center

David Gross

Hebrew University of Jerusalem - Hadassah Medical Center

Tada Kunavisarut

Mahidol University

Alice H. D. Violante

Universidade Federal do Rio de Janeiro (UFRJ)

Tomaz Kocjan

University Medical Centre Ljubljana

Joanne Ngeow

Nanyang Technological University (NTU)

Uri Yoel

Soroka University Medical Center

Merav Fraenkel

Soroka University Medical Center

Ilgin Yildirim Simsir

Ege University

Umit Ugurlu

Marmara University

Athanasia Ziagaki

Charité - Universitätsmedizin Berlin

Camilla Schalin-Jäntti

University of Helsinki

Luis Robles Díaz

Hospital Universitario 12 de Octubre

Inna Stepanovna Kudlai

Endocrinology Center of Regional Hospital №2

Oliver Gimm

Linkoping University

Christina Rebecca Scherbaum

University of Duesseldorf

Giovanni Barbon

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Elisa Taschin

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Angelica Malinoc

University of Freiburg

Natalia Valeryevna Khudiakova

North-western State Medical University

Nikita V. Ivanov

North-western State Medical University

Frederic Castinetti

Hôpital de la Conception

Petr Vlček

Charles University in Prague

Marija Pfeifer

University Medical Centre Ljubljana

Dmitry Beltsevich

Endocrinology Research Center

Viacheslav I. Egorov

Bakhrushin Brothers Moscow City Hospital

Stefania Zovato

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Ursula Ploeckinger

University of Helsinki

Özer Makay

Ege University

Elena Grineva

Almazov National Medical Research Centre

Francesca Schiavi

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Barbara Jarzab

Maria Sklodowska-Curie Institute - Oncology Center

Andrzej Januszewicz

Institute of Cardiology (Poland)

Giuseppe Opocher

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Nalini Shah

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Jochen Seufert

University of Freiburg

Thera P. Links

University of Groningen - University Medical Center Groningen (UMCG)

Catharina Larsson

Karolinska Institutet - Karolinska University Hospital

Ronald M. Lechan

Tufts University

Birke Bausch

University of Freiburg

William F. Young

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

Charis Eng

Cleveland Clinic, Lerner Research Institute, Genomic Medicine Institute; Cleveland Clinic, Lerner College of Medicine, Department of Molecular Medicine; Case Western Reserve University, School of Medicine, Case Comprehensive Cancer Center; Case Western Reserve University, School of Medicine, Department of Genetics and Genome Sciences; Cleveland Clinic - Taussig Cancer Institute

Hartmut P. H. Neumann

University of Freiburg - Section for Preventive Medicine

More...

Multiple version iconThere are 2 versions of this paper

Abstract

Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking.  

Methods: A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas.  

Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival.  

Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities.    

Funding Statement: Supported in part by the grant AZV 16-32665A to Sarka Dvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng.

Declaration of Interests: None of the authors have relevant conflicts of interest.

Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.     

Suggested Citation

Tsoy, Uliana and Amodru, Vincent and Walz, Martin K. and Bancos, Irina and Jeet, Ravinder Kaur and Qi, Xiaoping and Bandgar, Tushar and Jaiswal, Sanjeet Kumar and Petrov, Roman and Roslyakova, Anna and Yukina, Marina Y. and Horst-Schrivers, Anouk N. A. van der and Berends, Annika M.A. and Hoff, Ana O. and Castroneves, Luciana Audi and Ferrara, Alfonso Massimiliano and Rizzati, Silvia and Mian, Caterina and Dvorakova, Sarka and Hasse-Lazar, Kornelia and Kvachenyuk, Andrey and Peczkowska, Mariola and Loli, Paola and Erenler, Feyza and Zschiedrich, Stefan and Krauss, Tobias and Almeida, Madson Q. and Fragoso, Maria C. B. V. and Pereira, Maria A. A. and Liu, Longfei and Li, Minghao and Zhu, Feizhou and Recasens, Mònica and Costa, Josefina Biarnes and Wohllk, Nelson and Corssmit, Eleonora and Shafigullina, Zulfiya and Callissendorff, Jan and Juhlin, Carl Christofer and Grozinsky-Glasberg, Simona and Gross, David and Kunavisarut, Tada and Violante, Alice H. D. and Kocjan, Tomaz and Ngeow, Joanne and Yoel, Uri and Fraenkel, Merav and Simsir, Ilgin Yildirim and Ugurlu, Umit and Ziagaki, Athanasia and Schalin-Jäntti, Camilla and Díaz, Luis Robles and Kudlai, Inna Stepanovna and Gimm, Oliver and Scherbaum, Christina Rebecca and Barbon, Giovanni and Taschin, Elisa and Malinoc, Angelica and Khudiakova, Natalia Valeryevna and Ivanov, Nikita V. and Castinetti, Frederic and Vlček, Petr and Pfeifer, Marija and Beltsevich, Dmitry and Egorov, Viacheslav I. and Zovato, Stefania and Ploeckinger, Ursula and Makay, Özer and Grineva, Elena and Schiavi, Francesca and Jarzab, Barbara and Januszewicz, Andrzej and Opocher, Giuseppe and Shah, Nalini and Seufert, Jochen and Links, Thera P. and Larsson, Catharina and Lechan, Ronald M. and Bausch, Birke and Young, William F. and Eng, Charis and Neumann, Hartmut P. H., Prevention Medicine in Bilateral Phaeochromocytoma (November 21, 2018). Available at SSRN: https://ssrn.com/abstract=3289794

Uliana Tsoy (Contact Author)

Almazov National Medical Research Centre ( email )

St. Petersburg
Russia

Vincent Amodru

Hôpital de la Conception

Marseille, 13005
France

Martin K. Walz

Huyssens Foundation Clinics

Essen
Germany

Irina Bancos

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

200 First Street S.W
Rochester, MN 55905
United States

Ravinder Kaur Jeet

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

200 First Street S.W
Rochester, MN 55905
United States

Xiaoping Qi

Wenzhou Medical University

Zhejiang Province
China

Tushar Bandgar

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Mumbai, 400012
India

Sanjeet Kumar Jaiswal

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Mumbai, 400012
India

Roman Petrov

Bakhrushin Brothers Moscow City Hospital

Moscow
Russia

Anna Roslyakova

Endocrinology Research Center

Moscow
Russia

Marina Y. Yukina

Endocrinology Research Center

Moscow
Russia

Anouk N. A. van der Horst-Schrivers

University of Groningen - University Medical Center Groningen (UMCG)

Hanzeplein 1
Groningen, 9713
Netherlands

Annika M.A. Berends

University of Groningen - University Medical Center Groningen (UMCG)

Hanzeplein 1
Groningen, 9713
Netherlands

Ana O. Hoff

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Luciana Audi Castroneves

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Alfonso Massimiliano Ferrara

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Silvia Rizzati

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Caterina Mian

University of Padua

Via 8 Febbraio, 2
Padova, Vicenza 35122
Italy

Sarka Dvorakova

National Academy of Sciences of Ukraine - Institute of Endocrinology (Prague)

Prague
Czech Republic

Kornelia Hasse-Lazar

Maria Curie Sklodowska University

Lublin
Poland

Andrey Kvachenyuk

National Academy of Sciences of Ukraine - Institute of Endocrinology (Prague)

Prague
Czech Republic

Mariola Peczkowska

Cardinal Wyszynski National Institute of Cardiology

Warsaw
Poland

Paola Loli

Ospedale Niguarda Cà Granda

Milano
Italy

Feyza Erenler

Tufts New England Medical Center (NEMC)

750 Washington Street #63
Boston, MA 02111
United States

Stefan Zschiedrich

University of Freiburg

Freiburg
Germany

Tobias Krauss

University of Freiburg

Fahnenbergplatz
Freiburg, D-79085
Germany

Madson Q. Almeida

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Maria C. B. V. Fragoso

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Maria A. A. Pereira

University of São Paulo (USP)

Rua Luciano Gualberto, 315
São Paulo, São Paulo 14800-901
Brazil

Longfei Liu

Central South University

Changsha, Hunan 410083
China

Minghao Li

Central South University

Changsha, Hunan 410083
China

Feizhou Zhu

Central South University

Changsha, Hunan 410083
China

Mònica Recasens

University of Girona

Spain

Josefina Biarnes Costa

University of Girona

Spain

Nelson Wohllk

University of Chile

Pío Nono Nº1, Providencia
Santiago, R. Metropolitana 7520421
Chile

Eleonora Corssmit

Leiden University - Medical Center (LUMC)

Albinusdreef 2
Leiden, 2333 ZA
Netherlands

Zulfiya Shafigullina

North-western State Medical University

St. Petersburg
Russia

Jan Callissendorff

Karolinska Institutet

Granits väg 4
Solna, Stockholm 17171
Sweden

Carl Christofer Juhlin

Karolinska Institutet - Karolinska University Hospital

Solna, 17176
Sweden

Simona Grozinsky-Glasberg

Hebrew University of Jerusalem - Hadassah Medical Center

Jerusalem
Israel

David Gross

Hebrew University of Jerusalem - Hadassah Medical Center

Jerusalem
Israel

Tada Kunavisarut

Mahidol University

69 Vipawadee Rangsit Road
Phayatai, Bangkok, Nakhonpathom 10400
Thailand

Alice H. D. Violante

Universidade Federal do Rio de Janeiro (UFRJ)

Av; Pasteur, 250
terreo - Bairro Maracana
Rio de Janeiro, Rio de Janeiro 23890000
Brazil

Tomaz Kocjan

University Medical Centre Ljubljana

Zaloška cesta 7
1000 Ljubljana
Slovenia

Joanne Ngeow

Nanyang Technological University (NTU)

S3 B2-A28 Nanyang Avenue
Singapore, 639798
Singapore

Uri Yoel

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Merav Fraenkel

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Ilgin Yildirim Simsir

Ege University

Bornova
Izmir, 3504
Turkey

Umit Ugurlu

Marmara University

Goztepe Campus
Istanbul, Istanbul 34840
Turkey

Athanasia Ziagaki

Charité - Universitätsmedizin Berlin

Charitéplatz 1
Berlin, 10117
Germany

Camilla Schalin-Jäntti

University of Helsinki

University of Helsinki
Helsinki, FIN-00014
Finland

Luis Robles Díaz

Hospital Universitario 12 de Octubre

Madrid
Spain

Inna Stepanovna Kudlai

Endocrinology Center of Regional Hospital №2

Krasnodar
Russia

Oliver Gimm

Linkoping University

Överstegatan 30
Linköping, 58212
Sweden

Christina Rebecca Scherbaum

University of Duesseldorf

Universitätsstraße 1
Dusseldorf, 40225
Germany

Giovanni Barbon

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Elisa Taschin

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Angelica Malinoc

University of Freiburg

Fahnenbergplatz
Freiburg, D-79085
Germany

Natalia Valeryevna Khudiakova

North-western State Medical University

St. Petersburg
Russia

Nikita V. Ivanov

North-western State Medical University

St. Petersburg
Russia

Frederic Castinetti

Hôpital de la Conception

Marseille, 13005
France

Petr Vlček

Charles University in Prague

Celetná 13
Praha 1, 116 36
Czech Republic

Marija Pfeifer

University Medical Centre Ljubljana

Zaloška cesta 7
1000 Ljubljana
Slovenia

Dmitry Beltsevich

Endocrinology Research Center

Moscow
Russia

Viacheslav I. Egorov

Bakhrushin Brothers Moscow City Hospital

Moscow
Russia

Stefania Zovato

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Ursula Ploeckinger

University of Helsinki

University of Helsinki
Helsinki, FIN-00014
Finland

Özer Makay

Ege University

Bornova
Izmir, 3504
Turkey

Elena Grineva

Almazov National Medical Research Centre

St. Petersburg
Russia

Francesca Schiavi

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Barbara Jarzab

Maria Sklodowska-Curie Institute - Oncology Center

Gliwice
Poland

Andrzej Januszewicz

Institute of Cardiology (Poland)

Warsaw
Poland

Giuseppe Opocher

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - IRCCS Veneto Institute of Oncology (IOV-IRCCS)

Via Gattamelata, 64
Padova PD, 35128
Italy

Nalini Shah

Seth Gordhandas Sunderdas Medical College - King Edward Memorial Hospital

Mumbai, 400012
India

Jochen Seufert

University of Freiburg

Fahnenbergplatz
Freiburg, D-79085
Germany

Thera P. Links

University of Groningen - University Medical Center Groningen (UMCG)

Hanzeplein 1
Groningen, 9713
Netherlands

Catharina Larsson

Karolinska Institutet - Karolinska University Hospital

Solna, 17176
Sweden

Ronald M. Lechan

Tufts University

Birke Bausch

University of Freiburg

Fahnenbergplatz
Freiburg, D-79085
Germany

William F. Young

Mayo Clinic - Division of Endocrinology, Diabetes, Metabolism, and Nutrition

200 First Street S.W
Rochester, MN 55905
United States

Charis Eng

Cleveland Clinic, Lerner Research Institute, Genomic Medicine Institute

Cleveland, OH 44106
United States

Cleveland Clinic, Lerner College of Medicine, Department of Molecular Medicine

9500 Euclid Avenue
Cleveland, OH 44195
United States

Case Western Reserve University, School of Medicine, Case Comprehensive Cancer Center

Cleveland, OH 44195
United States

Case Western Reserve University, School of Medicine, Department of Genetics and Genome Sciences

2511 Overlook Road
Cleveland Heights, OH
United States

Cleveland Clinic - Taussig Cancer Institute

9500 Euclid Avenue
Cleveland, OH 44195
United States

Hartmut P. H. Neumann

University of Freiburg - Section for Preventive Medicine ( email )

Freiburg, 79104
Germany

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
102
Downloads
7