Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Margaret C S Boguszewski¹, Cesar L Boguszewski², Wassim Chemaitilly³, Laurie E Cohen⁴, Judith Gebauer⁵, Claire Higham⁶, Andrew R Hoffman⁷, Michel Polak⁸, Kevin C J Yuen^{9

10}, Nathalie Alos¹¹, Zoltan Antal¹², Martin Bidlingmaier¹³, Beverley M K Biller¹⁴, George Brabant¹⁵, Catherine S Y Choong^{16

17}, Stefano Cianfarani^{18

19

20}, Peter E Clayton²¹, Regis Coutant²², Adriane A Cardoso-Demartini²³, Alberto Fernandez²⁴, Adda Grimberg^{25

26}, Kolbeinn Guðmundsson²⁷, Jaime Guevara-Aguirre²⁸, Ken K Y Ho²⁹, Reiko Horikawa³⁰, Andrea M Isidori³¹, Jens Otto Lunde Jørgensen³², Peter Kamenicky³³, Niki Karavitaki^{34

35

36}, John J Kopchick³⁷, Maya Lodish³⁸, Xiaoping Luo³⁹, Ann I McCormack^{40

41

42}, Lillian Meacham⁴³, Shlomo Melmed⁴⁴, Sogol Mostoufi Moab⁴⁵, Hermann L Müller⁴⁶, Sebastian J C M M Neggers⁴⁷, Manoel H Aguiar Oliveira⁴⁸, Keiichi Ozono⁴⁹, Patricia A Pennisi⁵⁰, Vera Popovic⁵¹, Sally Radovick⁵², Lars Savendahl^{53

54}, Philippe Touraine⁵⁵, Hanneke M van Santen⁵⁶, Gudmundur Johannsson^{57

58}

Affiliations

¹ Department of Pediatrics, Federal University of Paraná, Curitiba, Brazil.
² SEMPR (Endocrine Division), Department of Internal Medicine, Federal University of Parana, Curitiba, Brazil.
³ Division of Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁴ Division of Endocrinology and Diabetes, Department of Pediatrics, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, New York, New York, USA.
⁵ Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Luebeck, Germany.
⁶ Department of Endocrinology, Christie Hospital NHS Foundation Trust, University of Manchester, and Manchester Academic Health Science Centre, Manchester, UK.
⁷ Stanford University School of Medicine, Stanford, California, USA.
⁸ Department of Pediatric Endocrinology, Gynecology and Diabetology, Hôpital Universitaire Necker Enfants Malades, AP-HP, Université de Paris, Paris, France.
⁹ Barrow Pituitary Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
¹⁰ Department of Neuroendocrinology, St. Joseph's Hospital and Medical Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, USA.
¹¹ Division of Endocrinology, Sainte-Justine University Hospital Centre, University of Montreal, Montreal, Quebec, Canada.
¹² Memorial Sloan-Kettering Cancer Center and Weill Cornel Medicine New York Presbyterian Hospital, New York, New York, USA.
¹³ Medizinische Klinik und Poliklinik IV, LMU Klinikum, Munich, Germany.
¹⁴ Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁵ Department of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK.
¹⁶ Department of Endocrinology and Diabetes, Perth Children's Hospital, Child & Adolescent Health Service, Perth, Australia.
¹⁷ Division of Paediatrics, Faculty of Health & Medical Sciences, University of Western Australia, Perth, Australia.
¹⁸ Department of Systems Medicine, University of Rome Tor Vergata, Rome Italy.
¹⁹ Dipartimento Pediatrico Universitario Ospedaliero, IRCCS 'Bambino Gesu' Children's Hospital, Rome Italy.
²⁰ Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
²¹ Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
²² Department of Pediatric Endocrinology, University Hospital, Angers, France.
²³ Pediatric Endocrinology Unit, Department of Pediatrics, Hospital de Clínicas, Federal University of Parana, Curitiba, Brazil.
²⁴ Endocrinology Department, Hospital Universitario de Mostoles, Mostoles, Spain.
²⁵ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁶ Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
²⁷ Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
²⁸ Department of Diabetes and Endocrinology, College of Medicine, Universidad San Francisco de Quito at Quito, Quito, Ecuador.
²⁹ The Garvan Institute of Medical Research and St. Vincent Hospital, Sydney, Australia.
³⁰ Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan.
³¹ Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy.
³² Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
³³ Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France.
³⁴ Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
³⁵ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
³⁶ Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³⁷ Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.
³⁸ Division of Pediatric Endocrinology and Diabetes, University of California, San Francisco, California, USA.
³⁹ Department of Pediatrics, Tongji Hospital, Tonji Medical College, Hu, China.
⁴⁰ Department of Endocrinology, St Vincent's Hospital, Sydney, Australia.
⁴¹ Hormones and Cancer Group, Garvan Institute of Medical Research, Sydney, Australia.
⁴² St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia.
⁴³ Children's Healthcare of Atlanta Aflac Cancer and Blood Disorders Service, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
⁴⁴ Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁴⁵ Divisions of Oncology and Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁴⁶ Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Carl von Ossietzki University Oldenburg, Oldenburg, Germany.
⁴⁷ Department of Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
⁴⁸ Division of Endocrinology, Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
⁴⁹ Department of Pediatrics, Osaka University Graduate School of Children, Osaka, Japan.
⁵⁰ Centro de Investigaciones Endocrinológicas 'Dr. César Bergadá', CEDIE-CONICET-FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
⁵¹ Medical Faculty, University of Belgrade, Belgrade, Serbia.
⁵² Department of Pediatrics, Rutgers Robert Wood, Johnson Medical School, New Brunswick, New Jersey, USA.
⁵³ Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
⁵⁴ Division of Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
⁵⁵ Department of Endocrinology and Reproductive Medicine, Center for Rare Endocrine and Gynecological Disorders, Pitie Salpetriere Hospital, Sorbonne Université Medecine, Paris, France.
⁵⁶ Department of Pediatric Endocrinology, Wilhelmina Chilrdren's Hospital, University Medical Center and Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁵⁷ Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵⁸ Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

PMID: 35319491
PMCID: PMC9066587
DOI: 10.1530/EJE-21-1186

Review

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Margaret C S Boguszewski et al. Eur J Endocrinol. 2022.

. 2022 Apr 21;186(6):P35-P52.

doi: 10.1530/EJE-21-1186.

Authors

Affiliations

¹ Department of Pediatrics, Federal University of Paraná, Curitiba, Brazil.
² SEMPR (Endocrine Division), Department of Internal Medicine, Federal University of Parana, Curitiba, Brazil.
³ Division of Endocrinology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁴ Division of Endocrinology and Diabetes, Department of Pediatrics, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, New York, New York, USA.
⁵ Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Luebeck, Germany.
⁶ Department of Endocrinology, Christie Hospital NHS Foundation Trust, University of Manchester, and Manchester Academic Health Science Centre, Manchester, UK.
⁷ Stanford University School of Medicine, Stanford, California, USA.
⁸ Department of Pediatric Endocrinology, Gynecology and Diabetology, Hôpital Universitaire Necker Enfants Malades, AP-HP, Université de Paris, Paris, France.
⁹ Barrow Pituitary Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
¹⁰ Department of Neuroendocrinology, St. Joseph's Hospital and Medical Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, USA.
¹¹ Division of Endocrinology, Sainte-Justine University Hospital Centre, University of Montreal, Montreal, Quebec, Canada.
¹² Memorial Sloan-Kettering Cancer Center and Weill Cornel Medicine New York Presbyterian Hospital, New York, New York, USA.
¹³ Medizinische Klinik und Poliklinik IV, LMU Klinikum, Munich, Germany.
¹⁴ Neuroendocrine & Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁵ Department of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK.
¹⁶ Department of Endocrinology and Diabetes, Perth Children's Hospital, Child & Adolescent Health Service, Perth, Australia.
¹⁷ Division of Paediatrics, Faculty of Health & Medical Sciences, University of Western Australia, Perth, Australia.
¹⁸ Department of Systems Medicine, University of Rome Tor Vergata, Rome Italy.
¹⁹ Dipartimento Pediatrico Universitario Ospedaliero, IRCCS 'Bambino Gesu' Children's Hospital, Rome Italy.
²⁰ Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
²¹ Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
²² Department of Pediatric Endocrinology, University Hospital, Angers, France.
²³ Pediatric Endocrinology Unit, Department of Pediatrics, Hospital de Clínicas, Federal University of Parana, Curitiba, Brazil.
²⁴ Endocrinology Department, Hospital Universitario de Mostoles, Mostoles, Spain.
²⁵ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁶ Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
²⁷ Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
²⁸ Department of Diabetes and Endocrinology, College of Medicine, Universidad San Francisco de Quito at Quito, Quito, Ecuador.
²⁹ The Garvan Institute of Medical Research and St. Vincent Hospital, Sydney, Australia.
³⁰ Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan.
³¹ Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy.
³² Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
³³ Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France.
³⁴ Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
³⁵ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
³⁶ Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³⁷ Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.
³⁸ Division of Pediatric Endocrinology and Diabetes, University of California, San Francisco, California, USA.
³⁹ Department of Pediatrics, Tongji Hospital, Tonji Medical College, Hu, China.
⁴⁰ Department of Endocrinology, St Vincent's Hospital, Sydney, Australia.
⁴¹ Hormones and Cancer Group, Garvan Institute of Medical Research, Sydney, Australia.
⁴² St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia.
⁴³ Children's Healthcare of Atlanta Aflac Cancer and Blood Disorders Service, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
⁴⁴ Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁴⁵ Divisions of Oncology and Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁴⁶ Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Carl von Ossietzki University Oldenburg, Oldenburg, Germany.
⁴⁷ Department of Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
⁴⁸ Division of Endocrinology, Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
⁴⁹ Department of Pediatrics, Osaka University Graduate School of Children, Osaka, Japan.
⁵⁰ Centro de Investigaciones Endocrinológicas 'Dr. César Bergadá', CEDIE-CONICET-FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
⁵¹ Medical Faculty, University of Belgrade, Belgrade, Serbia.
⁵² Department of Pediatrics, Rutgers Robert Wood, Johnson Medical School, New Brunswick, New Jersey, USA.
⁵³ Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
⁵⁴ Division of Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
⁵⁵ Department of Endocrinology and Reproductive Medicine, Center for Rare Endocrine and Gynecological Disorders, Pitie Salpetriere Hospital, Sorbonne Université Medecine, Paris, France.
⁵⁶ Department of Pediatric Endocrinology, Wilhelmina Chilrdren's Hospital, University Medical Center and Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁵⁷ Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵⁸ Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.

PMID: 35319491
PMCID: PMC9066587
DOI: 10.1530/EJE-21-1186

Abstract

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

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References

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Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Affiliations

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical