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

Author:

Boguszewski Margaret C S1,Boguszewski Cesar L2,Chemaitilly Wassim3,Cohen Laurie E4,Gebauer Judith5ORCID,Higham Claire6,Hoffman Andrew R7,Polak Michel8,Yuen Kevin C J910ORCID,Alos Nathalie11,Antal Zoltan12,Bidlingmaier Martin13,Biller Beverley M K14,Brabant George15,Choong Catherine S Y1617,Cianfarani Stefano181920,Clayton Peter E21ORCID,Coutant Regis22,Cardoso-Demartini Adriane A23,Fernandez Alberto24,Grimberg Adda2526,Guðmundsson Kolbeinn27,Guevara-Aguirre Jaime28,Ho Ken K Y29ORCID,Horikawa Reiko30ORCID,Isidori Andrea M31,Jørgensen Jens Otto Lunde32ORCID,Kamenicky Peter33ORCID,Karavitaki Niki343536ORCID,Kopchick John J37,Lodish Maya38,Luo Xiaoping39,McCormack Ann I404142,Meacham Lillian43,Melmed Shlomo44,Mostoufi Moab Sogol45,Müller Hermann L46ORCID,Neggers Sebastian J C M M47,Aguiar Oliveira Manoel H48,Ozono Keiichi49,Pennisi Patricia A50ORCID,Popovic Vera51,Radovick Sally52,Savendahl Lars5354,Touraine Philippe55ORCID,van Santen Hanneke M56,Johannsson Gudmundur5758ORCID

Affiliation:

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

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.

Publisher

Oxford University Press (OUP)

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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