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Considering GH replacement for GH-deficient adults with a previous history of cancer: a conundrum for the clinician

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Abstract

Previous studies have shown that GH and IGF-I may enhance tumorigenesis, metastasis, and cell proliferation in humans and animals. Evidence supporting this notion is derived from animal model studies, epidemiological studies, experience from patients with acromegaly, molecular therapeutic manipulation of GH and IGF-I actions, and individuals with GH receptor and congenital IGF-I deficiencies. Prior exposure to radiation therapy, aging, family history of cancer, and individual susceptibility may also contribute to increase this risk. Therefore, the use of GH replacement in patients with a history of cancer raises hypothetical safety concerns for patients, caregivers, and providers. Studies of GH therapy in GH-deficient adults with hypopituitarism and childhood cancer survivors have not convincingly demonstrated an increased cancer risk. Conversely, the risk of occurrence of a second neoplasm (SN) in childhood cancer survivors may be increased, with meningiomas being the most common tumor; however, this risk appears to decline over time. In light of these findings, if GH replacement is to be considered in patients with a previous history of cancer, we propose this consideration to be based on each individual circumstance and that such therapy should only be initiated at least 2 years after cancer remission is achieved with the understanding that in some patients (particularly those with childhood cancers), GH may potentially increase the risk of SNs. In addition, close surveillance should be undertaken working closely with the patient’s oncologist. More long-term data are thus needed to determine if GH replacement in GH-deficient adults with a history of cancer is associated with the development of de novo tumors and tumor recurrence.

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References

  1. W. Chemaitilly, C.A. Sklar, Endocrine complications in long-term survivors of childhood cancers. Endocr. Relat. Cancer 17, R141–R159 (2010)

    Article  CAS  PubMed  Google Scholar 

  2. N.M. Appelman-Dijkstra, N.E. Kokshoorn, O.M. Dekkers, K.J. Neelis, N.R. Biermasz, J.A. Romijn, J.W. Smit, A.M. Pereira, Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 96, 2330–2340 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. L. Adan, C. Sainte-Rose, J.C. Souberbielle, J.M. Zucker, C. Kalifa, R. Brauner, Adult height after growth hormone (GH) treatment for GH deficiency due to cranial irradiation. Med. Pediatr. Oncol. 34, 14–19 (2000)

    Article  CAS  PubMed  Google Scholar 

  4. H.K. Gleeson, R. Stoeter, A.L. Ogilvy-Stuart, H.R. Gattamaneni, B.M. Brennan, S.M. Shalet, Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. J. Clin. Endocrinol. Metab. 88, 3682–3689 (2003)

    Article  CAS  PubMed  Google Scholar 

  5. M.L. Reed, G.R. Merriam, A.Y. Kargi, Adult growth hormone deficiency - benefits, side effects, and risks of growth hormone replacement. Front. Endocrinol. (Lausanne) 4, 64 (2013)

    Google Scholar 

  6. P.E. Clayton, I. Banerjee, P.G. Murray, A.G. Renehan, Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat. Rev. Endocrinol. 7, 11–24 (2011)

    Article  CAS  PubMed  Google Scholar 

  7. P.J. Jenkins, A. Mukherjee, S.M. Shalet, Does growth hormone cause cancer? Clin. Endocrinol. (Oxf.) 64, 115–121 (2006)

    Article  CAS  Google Scholar 

  8. S. Pekic, V. Popovic, GH therapy and cancer risk in hypopituitarism: what we know from human studies. Eur. J. Endocrinol. 169, R89–R97 (2013)

    Article  CAS  PubMed  Google Scholar 

  9. J.R. Arnold, D.F. Arnold, A. Marland, N. Karavitaki, J.A. Wass, GH replacement in patients with non-functioning pituitary adenoma (NFA) treated solely by surgery is not associated with increased risk of tumour recurrence. Clin. Endocrinol. (Oxf.) 70, 435–438 (2009)

    Article  CAS  Google Scholar 

  10. T.T. Chung, W.M. Drake, J. Evanson, D. Walker, P.N. Plowman, S.L. Chew, A.B. Grossman, G.M. Besser, J.P. Monson, Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement. Clin. Endocrinol. (Oxf.) 63, 274–279 (2005)

    Article  CAS  Google Scholar 

  11. G. Frajese, W.M. Drake, R.A. Loureiro, J. Evanson, D. Coyte, D.F. Wood, A.B. Grossman, G.M. Besser, J.P. Monson, Hypothalamo-pituitary surveillance imaging in hypopituitary patients receiving long-term GH replacement therapy. J. Clin. Endocrinol. Metab. 86, 5172–5175 (2001)

    Article  CAS  PubMed  Google Scholar 

  12. A.G. Hatrick, P. Boghalo, J.B. Bingham, A.B. Ayres, P.H. Sonksen, D.L. Russell-Jones, Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours? Eur. J. Endocrinol. 146, 807–811 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. A. Jostel, A. Mukherjee, P.A. Hulse, S.M. Shalet, Adult growth hormone replacement therapy and neuroimaging surveillance in brain tumour survivors. Clin. Endocrinol. (Oxf.) 62, 698–705 (2005)

    Article  CAS  Google Scholar 

  14. R.M. Blizzard, History of growth hormone therapy. Indian J. Pediatr. 79, 87–91 (2012)

    Article  PubMed  Google Scholar 

  15. R. Abs, B.A. Bengtsson, E. Hernberg-Stahl, J.P. Monson, J.P. Tauber, P. Wilton, C. Wuster, GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin. Endocrinol. (Oxf.) 50, 703–713 (1999)

    Article  CAS  Google Scholar 

  16. J.C. Carel, E. Ecosse, F. Landier, D. Meguellati-Hakkas, F. Kaguelidou, G. Rey, J. Coste, Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J. Clin. Endocrinol. Metab. 97, 416–425 (2012)

    Article  CAS  PubMed  Google Scholar 

  17. L. Savendahl, M. Maes, K. Albertsson-Wikland, B. Borgstrom, J.C. Carel, S. Henrard, N. Speybroeck, M. Thomas, G. Zandwijken, A. Hokken-Koelega, Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study. J. Clin. Endocrinol. Metab. 97, E213–E217 (2012)

    Article  PubMed  CAS  Google Scholar 

  18. M.L. Hartman, R. Xu, B.J. Crowe, L.L. Robison, E.M. Erfurth, D.L. Kleinberg, A.G. Zimmermann, W.W. Woodmansee, G.B. Cutler Jr, J.J. Chipman et al., Prospective safety surveillance of GH-deficient adults: comparison of GH-treated vs untreated patients. J. Clin. Endocrinol. Metab. 98, 980–988 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. D. Mo, D.S. Hardin, E.M. Erfurth, S. Melmed, Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS). Pituitary 17, 477–485 (2013)

    Article  PubMed Central  CAS  Google Scholar 

  20. F. Darendeliler, G. Karagiannis, P. Wilton, M.B. Ranke, K. Albertsson-Wikland, D.A. Price, On Behalf of the Kigs International, Recurrence of brain tumours in patients treated with growth hormone: analysis of KIGS (Pfizer International Growth Database). Acta Paediatr. 95, 1284–1290 (2006)

    Article  PubMed  Google Scholar 

  21. R.D. Murray, K.H. Darzy, H.K. Gleeson, S.M. Shalet, GH-deficient survivors of childhood cancer: GH replacement during adult life. J. Clin. Endocrinol. Metab. 87, 129–135 (2002)

    Article  CAS  PubMed  Google Scholar 

  22. A.J. Swerdlow, C.D. Higgins, P. Adlard, M.A. Preece, Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959–1985: a cohort study. Lancet 360, 273–277 (2002)

    Article  CAS  PubMed  Google Scholar 

  23. B.C. Patterson, Y. Chen, C.A. Sklar, J. Neglia, Y. Yasui, A. Mertens, G.T. Armstrong, A. Meadows, M. Stovall, L.L. Robison et al., Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J. Clin. Endocrinol. Metab. 99, 2030–2037 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. W.W. Woodmansee, A.G. Zimmermann, C.J. Child, Q. Rong, E.M. Erfurth, P. Beck-Peccoz, W.F. Blum, L.L. Robison, GeNeSis Hypo CCSIAB incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS. Eur. J. Endocrinol. 168, 565–573 (2013)

    Article  CAS  PubMed  Google Scholar 

  25. D.M. Cook, K.C. Yuen, B.M. Biller, S.F. Kemp, M.L. Vance, American Association of Clinical Endocrinologists, American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr. Pract. 15(Suppl 2), 1–29 (2009)

    Article  PubMed  Google Scholar 

  26. K.K. Ho, GH Deficiency Consensus Workshop Participants, Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur. J. Endocrinol. 157, 695–700 (2007)

    Article  CAS  PubMed  Google Scholar 

  27. M.E. Molitch, D.R. Clemmons, S. Malozowski, G.R. Merriam, M.L. Vance, Endocrine Society, Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1587–1609 (2011)

    Article  CAS  PubMed  Google Scholar 

  28. Y. Harada, Pituitary role in the growth of metastasizing MRMT-1 mammary carcinoma in rats. Cancer Res. 36, 18–22 (1976)

    CAS  PubMed  Google Scholar 

  29. D.P. Rose, J.J. Noonan, Influence of prolactin and growth hormone on rat mammary tumors induced by N-nitrosomethylurea. Cancer Res. 42, 35–38 (1982)

    CAS  PubMed  Google Scholar 

  30. P. Bates, R. Fisher, A. Ward, L. Richardson, D.J. Hill, C.F. Graham, Mammary cancer in transgenic mice expressing insulin-like growth factor II. Br. J. Cancer 72, 1189–1193 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. J. Tornell, B. Carlsson, P. Pohjanen, H. Wennbo, L. Rymo, O. Isaksson, High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice. J. Steroid Biochem. Mol. Biol. 43, 237–242 (1992)

    Article  CAS  PubMed  Google Scholar 

  32. X.F. Yang, W.G. Beamer, H. Huynh, M. Pollak, Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation. Cancer Res. 56, 1509–1511 (1996)

    CAS  PubMed  Google Scholar 

  33. K. Hemminki, A. Forsti, J. Ji, Incidence and familial risks in pituitary adenoma and associated tumors. Endocr. Relat. Cancer 14, 103–109 (2007)

    Article  PubMed  Google Scholar 

  34. C. Frank, M. Fallah, J. Sundquist, A. Hemminki, K. Hemminki, Population landscape of familial cancer. Sci. Rep. 5, 12891 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. C.M. Perks, J.M. Holly, Insulin-like growth factors in health and disease. Preface. Endocrinol. Metab. Clin. North. Am. 41, xv–xvi (2012)

    Article  PubMed  Google Scholar 

  36. J.T. Emerman, M. Leahy, P.W. Gout, N. Bruchovsky, Elevated growth hormone levels in sera from breast cancer patients. Horm. Metab. Res. 17, 421–424 (1985)

    Article  CAS  PubMed  Google Scholar 

  37. J.P. Peyrat, J. Bonneterre, B. Hecquet, P. Vennin, M.M. Louchez, C. Fournier, J. Lefebvre, A. Demaille, Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur. J. Cancer 29A, 492–497 (1993)

    Article  CAS  PubMed  Google Scholar 

  38. G. Vitale, M.P. Brugts, G. Ogliari, D. Castaldi, L.M. Fatti, A.J. Varewijck, S.W. Lamberts, D. Monti, L. Bucci, E. Cevenini et al., Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians’ offspring. Aging. (Albany NY) 4, 580–589 (2012)

    Article  CAS  Google Scholar 

  39. C. Harding, F. Pompei, E.E. Lee, R. Wilson, Cancer suppression at old age. Cancer Res. 68, 4465–4478 (2008)

    Article  CAS  PubMed  Google Scholar 

  40. E. Giovannucci, M.N. Pollak, E.A. Platz, W.C. Willett, M.J. Stampfer, N. Majeed, G.A. Colditz, F.E. Speizer, S.E. Hankinson, A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer. Epidemiol. Biomarkers. Prev. 9, 345–349 (2000)

    CAS  PubMed  Google Scholar 

  41. S.E. Hankinson, W.C. Willett, G.A. Colditz, D.J. Hunter, D.S. Michaud, B. Deroo, B. Rosner, F.E. Speizer, M. Pollak, Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393–1396 (1998)

    Article  CAS  PubMed  Google Scholar 

  42. Y. Wu, S. Yakar, L. Zhao, L. Hennighausen, D. LeRoith, Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 62, 1030–1035 (2002)

    CAS  PubMed  Google Scholar 

  43. J.M. Chan, M.J. Stampfer, E. Giovannucci, P.H. Gann, J. Ma, P. Wilkinson, C.H. Hennekens, M. Pollak, Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563–566 (1998)

    Article  CAS  PubMed  Google Scholar 

  44. J.M. Chan, M.J. Stampfer, E. Giovannucci, J. Ma, M. Pollak, Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and prostate cancer risk: epidemiological studies. Growth. Horm. IGF. Res. 10(Suppl A), S32–S33 (2000)

    Article  PubMed  Google Scholar 

  45. J. Ma, M.N. Pollak, E. Giovannucci, J.M. Chan, Y. Tao, C.H. Hennekens, M.J. Stampfer, Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J. Natl Cancer Inst. 91, 620–625 (1999)

    Article  CAS  PubMed  Google Scholar 

  46. A.G. Renehan, M. Zwahlen, C. Minder, S.T. O’Dwyer, S.M. Shalet, M. Egger, Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363, 1346–1353 (2004)

    Article  CAS  PubMed  Google Scholar 

  47. F. el Atiq, F. Garrouste, M. Remacle-Bonnet, B. Sastre, G. Pommier, Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. Int. J. Cancer 57, 491–497 (1994)

    Article  PubMed  Google Scholar 

  48. R.C. Baxter, A.J. Butt, L.J. Schedlich, J.L. Martin, Antiproliferative and pro-apoptotic activities of insulin-like growth factor-binding protein-3. Growth. Horm. IGF. Res. 10(Suppl A), S10–S11 (2000)

    Article  PubMed  Google Scholar 

  49. Z.P. Gill, C.M. Perks, P.V. Newcomb, J.M. Holly, Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J. Biol. Chem. 272, 25602–25607 (1997)

    Article  CAS  PubMed  Google Scholar 

  50. A.P. Chokkalingam, M. Pollak, C.M. Fillmore, Y.T. Gao, F.Z. Stanczyk, J. Deng, I.A. Sesterhenn, F.K. Mostofi, T.R. Fears, M.P. Madigan et al., Insulin-like growth factors and prostate cancer: a population-based case-control study in China. Cancer. Epidemiol. Biomarkers. Prev. 10, 421–427 (2001)

    CAS  PubMed  Google Scholar 

  51. A. Ben-Shlomo, M.C. Sheppard, J.M. Stephens, S. Pulgar, S. Melmed, Clinical, quality of life, and economic value of acromegaly disease control. Pituitary. 14, 284–294 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. P.J. Jenkins, M. Besser, Clinical perspective: acromegaly and cancer: a problem. J. Clin. Endocrinol. Metab. 86, 2935–2941 (2001)

    Article  CAS  PubMed  Google Scholar 

  53. A.G. Renehan, J. O’Connell, D. O’Halloran, F. Shanahan, C.S. Potten, S.T. O’Dwyer, S.M. Shalet, Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications. Horm. Metab. Res. 35, 712–725 (2003)

    Article  CAS  PubMed  Google Scholar 

  54. A. Bhansali, R. Kochhar, Y.K. Chawla, S. Reddy, R.J. Dash, Prevalence of colonic polyps is not increased in patients with acromegaly: analysis of 60 patients from India. J. Gastroenterol. Hepatol. 19, 266–269 (2004)

    Article  PubMed  Google Scholar 

  55. P.J. Jenkins, P.D. Fairclough, T. Richards, D.G. Lowe, J. Monson, A. Grossman, J.A. Wass, M. Besser, Acromegaly, colonic polyps and carcinoma. Clin. Endocrinol. (Oxf.) 47, 17–22 (1997)

    Article  CAS  Google Scholar 

  56. A.G. Renehan, P. Bhaskar, J.E. Painter, S.T. O’Dwyer, N. Haboubi, J. Varma, S.G. Ball, S.M. Shalet, The prevalence and characteristics of colorectal neoplasia in acromegaly. J. Clin. Endocrinol. Metab. 85, 3417–3424 (2000)

    Article  CAS  PubMed  Google Scholar 

  57. P.J. Jenkins, V. Frajese, A.M. Jones, C. Camacho-Hubner, D.G. Lowe, P.D. Fairclough, S.L. Chew, A.B. Grossman, J.P. Monson, G.M. Besser, Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J. Clin. Endocrinol. Metab. 85, 3218–3221 (2000)

    CAS  PubMed  Google Scholar 

  58. N.A. Tritos, G. Johannsson, M. Korbonits, K.K. Miller, U. Feldt-Rasmussen, K.C. Yuen, D. King, A.F. Mattsson, P.J. Jonsson, M. Koltowska-Haggstrom et al., Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly: a KIMS analysis. J. Clin. Endocrinol. Metab. 99, 2018–2029 (2014)

    Article  CAS  PubMed  Google Scholar 

  59. D. Petroff, A. Tonjes, M. Grussendorf, M. Droste, C. Dimopoulou, G. Stalla, C. Jaursch-Hancke, M. Mai, J. Schopohl, C. Schofl, The incidence of cancer amongst acromegaly patients: results from the German Acromegaly Registry. J. Clin. Endocrinol. Metab. 100, 3894–3902 (2015)

    Article  CAS  PubMed  Google Scholar 

  60. C.L. Arteaga, L.J. Kitten, E.B. Coronado, S. Jacobs, F.C. Kull Jr, D.C. Allred, C.K. Osborne, Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. J. Clin. Invest. 84, 1418–1423 (1989)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. S.E. Dunn, M. Ehrlich, N.J. Sharp, K. Reiss, G. Solomon, R. Hawkins, R. Baserga, J.C. Barrett, A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer. Cancer Res. 58, 3353–3361 (1998)

    CAS  PubMed  Google Scholar 

  62. Y. Wu, K. Cui, K. Miyoshi, L. Hennighausen, J.E. Green, J. Setser, D. LeRoith, S. Yakar, Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Res. 63, 4384–4388 (2003)

    CAS  PubMed  Google Scholar 

  63. B. Wen, E. Deutsch, E. Marangoni, V. Frascona, L. Maggiorella, B. Abdulkarim, N. Chavaudra, J. Bourhis, Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells. Br. J. Cancer 85, 2017–2021 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. H.X. Chen, E. Sharon, IGF-1R as an anti-cancer target—trials and tribulations. Chin. J. Cancer. 32, 242–252 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. D. Yee, Insulin-like growth factor receptor inhibitors: baby or the bathwater? J. Natl. Cancer Inst. 104, 975–981 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. K.E. Friend, Cancer and the potential place for growth hormone receptor antagonist therapy. Growth. Horm. IGF. Res. 11(Suppl A), S121–S123 (2001)

    Article  PubMed  Google Scholar 

  67. I.E. McCutcheon, A. Flyvbjerg, H. Hill, J. Li, W.F. Bennett, J.A. Scarlett, K.E. Friend, Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice. J. Neurosurg. 94, 487–492 (2001)

    Article  CAS  PubMed  Google Scholar 

  68. P. Leporati, R. Fonte, L. de Martinis, A. Zambelli, F. Magri, L. Pavesi, M. Rotondi, L. Chiovato, A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression. BMC Cancer 15, 397 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  69. J. Guevara-Aguirre, A.L. Rosenbloom, P.J. Fielder, F.B. Diamond Jr, R.G. Rosenfeld, Growth hormone receptor deficiency in Ecuador: clinical and biochemical phenotype in two populations. J. Clin. Endocrinol. Metab. 76, 417–423 (1993)

    CAS  PubMed  Google Scholar 

  70. A.L. Rosenbloom, J. Guevara Aguirre, R.G. Rosenfeld, P.J. Fielder, The little women of Loja—growth hormone-receptor deficiency in an inbred population of southern Ecuador. N. Engl. J Med. 323, 1367–1374 (1990)

    Article  CAS  PubMed  Google Scholar 

  71. J. Guevara-Aguirre, P. Balasubramanian, M. Guevara-Aguirre, M. Wei, F. Madia, C.W. Cheng, D. Hwang, A. Martin-Montalvo, J. Saavedra, S. Ingles et al., Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci. Transl. Med. 3, 7013 (2011)

    Article  CAS  Google Scholar 

  72. O. Shevah, Z. Laron, Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report. Growth. Horm. IGF. Res. 17, 54–57 (2007)

    Article  CAS  PubMed  Google Scholar 

  73. J.A. Alvarez, R.E. Scully, T.L. Miller, F.D. Armstrong, L.S. Constine, D.L. Friedman, S.E. Lipshultz, Long-term effects of treatments for childhood cancers. Curr. Opin. Pediatr. 19, 23–31 (2007)

    Article  PubMed  Google Scholar 

  74. R.L. Mulder, L.C. Kremer, H.M. van Santen, J.L. Ket, A.S. van Trotsenburg, C.C. Koning, A.Y. Schouten-van Meeteren, H.N. Caron, S.J. Neggers, E.C. van Dalen, Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat. Rev. 35, 616–632 (2009)

    Article  CAS  PubMed  Google Scholar 

  75. M. Schmiegelow, S. Lassen, H.S. Poulsen, U. Feldt-Rasmussen, K. Schmiegelow, H. Hertz, J. Muller, Cranial radiotherapy of childhood brain tumours: growth hormone deficiency and its relation to the biological effective dose of irradiation in a large population based study. Clin. Endocrinol. (Oxf.) 53, 191–197 (2000)

    Article  CAS  Google Scholar 

  76. G.T. Armstrong, W. Liu, W. Leisenring, Y. Yasui, S. Hammond, S. Bhatia, J.P. Neglia, M. Stovall, D. Srivastava, L.L. Robison, Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J. Clin. Oncol. 29, 3056–3064 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  77. E.M. Erfurth, Update in mortality in GH-treated patients. J. Clin. Endocrinol. Metab. 98, 4219–4226 (2013)

    Article  CAS  PubMed  Google Scholar 

  78. A.J. Swerdlow, R.E. Reddingius, C.D. Higgins, H.A. Spoudeas, K. Phipps, Z. Qiao, W.D. Ryder, M. Brada, R.D. Hayward, C.G. Brook et al., Growth hormone treatment of children with brain tumors and risk of tumor recurrence. J. Clin. Endocrinol. Metab. 85, 4444–4449 (2000)

    CAS  PubMed  Google Scholar 

  79. R.J. Packer, J.M. Boyett, A.J. Janss, T. Stavrou, L. Kun, J. Wisoff, C. Russo, R. Geyer, P. Phillips, M. Kieran et al., Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J. Clin. Oncol. 19, 480–487 (2001)

    CAS  PubMed  Google Scholar 

  80. C.A. Sklar, A.C. Mertens, P. Mitby, G. Occhiogrosso, J. Qin, G. Heller, Y. Yasui, L.L. Robison, Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab. 87, 3136–3141 (2002)

    Article  CAS  PubMed  Google Scholar 

  81. B. Ergun-Longmire, A.C. Mertens, P. Mitby, J. Qin, G. Heller, W. Shi, Y. Yasui, L.L. Robison, C.A. Sklar, Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J. Clin. Endocrinol. Metab. 91, 3494–3498 (2006)

    Article  CAS  PubMed  Google Scholar 

  82. S. MacKenzie, T. Craven, H.R. Gattamaneni, R. Swindell, S.M. Shalet, G. Brabant, Long-term safety of growth hormone replacement after CNS irradiation. J. Clin. Endocrinol. Metab. 96, 2756–2761 (2011)

    Article  CAS  PubMed  Google Scholar 

  83. J.P. Neglia, L.L. Robison, M. Stovall, Y. Liu, R.J. Packer, S. Hammond, Y. Yasui, C.E. Kasper, A.C. Mertens, S.S. Donaldson et al., New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J. Natl. Cancer Inst. 98, 1528–1537 (2006)

    Article  PubMed  Google Scholar 

  84. W. Leung, S.R. Rose, Y. Zhou, M.L. Hancock, S. Burstein, E.A. Schriock, R. Lustig, R.K. Danish, W.E. Evans, M.M. Hudson et al., Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. J. Clin. Oncol. 20, 2959–2964 (2002)

    Article  CAS  PubMed  Google Scholar 

  85. E. Brignardello, F. Felicetti, A. Castiglione, N. Fortunati, P. Matarazzo, E. Biasin, C. Sacerdote, U. Ricardi, F. Fagioli, A. Corrias et al., GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution. J. Endocrinol. Invest. 38, 171–176 (2015)

    Article  CAS  PubMed  Google Scholar 

  86. T.E. Merchant, S.R. Rose, C. Bosley, S. Wu, X. Xiong, R.H. Lustig, Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J. Clin. Oncol. 29, 4776–4780 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. B. Bulow, L. Hagmar, Z. Mikoczy, C.H. Nordstrom, E.M. Erfurth, Increased cerebrovascular mortality in patients with hypopituitarism. Clin. Endocrinol. (Oxf.) 46, 75–81 (1997)

    Article  CAS  Google Scholar 

  88. J.W. Tomlinson, N. Holden, R.K. Hills, K. Wheatley, R.N. Clayton, A.S. Bates, M.C. Sheppard, P.M. Stewart, Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357, 425–431 (2001)

    Article  CAS  PubMed  Google Scholar 

  89. R.C. Gaillard, A.F. Mattsson, A.C. Akerblad, B.A. Bengtsson, J. Cara, U. Feldt-Rasmussen, M. Koltowska-Haggstrom, J.P. Monson, B. Saller, P. Wilton et al., Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur. J. Endocrinol. 166, 1069–1077 (2012)

    Article  CAS  PubMed  Google Scholar 

  90. C.J. Child, A.G. Zimmermann, W.W. Woodmansee, D.M. Green, J.J. Li, H. Jung, E.M. Erfurth, L.L. Robison, C.C.S.I.A.B. Hypo, Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study. Eur. J. Endocrinol. 165, 217–223 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. N. Karavitaki, J.T. Warner, A. Marland, B. Shine, F. Ryan, J. Arnold, H.E. Turner, J.A. Wass, GH replacement does not increase the risk of recurrence in patients with craniopharyngioma. Clin. Endocrinol. (Oxf.) 64, 556–560 (2006)

    Article  CAS  Google Scholar 

  92. D.S. Olsson, M. Buchfelder, K. Wiendieck, N. Kremenevskaja, B.A. Bengtsson, K.E. Jakobsson, M. Jarfelt, G. Johannsson, A.G. Nilsson, Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up. Eur. J. Endocrinol. 166, 1061–1068 (2012)

    Article  CAS  PubMed  Google Scholar 

  93. J. Svensson, B.A. Bengtsson, T. Rosen, A. Oden, G. Johannsson, Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J. Clin. Endocrinol. Metab. 89, 3306–3312 (2004)

    Article  CAS  PubMed  Google Scholar 

  94. C.J. Child, D. Conroy, A.G. Zimmermann, W.W. Woodmansee, E.M. Erfurth, L.L. Robison, Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study. Eur. J. Endocrinol. 172, 779–790 (2015)

    Article  CAS  PubMed  Google Scholar 

  95. T.A. Wilson, S.R. Rose, P. Cohen, A.D. Rogol, P. Backeljauw, R. Brown, D.S. Hardin, S.F. Kemp, M. Lawson, S. Radovick et al., Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J. Pediatr. 143, 415–421 (2003)

    Article  PubMed  Google Scholar 

  96. V.N. Anisimov, Biology of aging and cancer. Cancer Control 14, 23–31 (2007)

    PubMed  Google Scholar 

  97. A. Hjartaker, H. Langseth, E. Weiderpass, Obesity and diabetes epidemics: cancer repercussions. Adv. Exp. Med. Biol. 630, 72–93 (2008)

    Article  PubMed  Google Scholar 

  98. J.D. Schiffman, J.I. Geller, E. Mundt, A. Means, L. Means, V. Means, Update on pediatric cancer predisposition syndromes. Pediatr. Blood Cancer 60, 1247–1252 (2013)

    Article  PubMed  Google Scholar 

  99. B. Strahm, D. Malkin, Hereditary cancer predisposition in children: genetic basis and clinical implications. Int. J. Cancer 119, 2001–2006 (2006)

    Article  CAS  PubMed  Google Scholar 

  100. A.J. Weissberger, K.K. Ho, L. Lazarus, Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J. Clin. Endocrinol. Metab. 72, 374–381 (1991)

    Article  CAS  PubMed  Google Scholar 

  101. M. Koltowska-Haggstrom, A.F. Mattsson, S.M. Shalet, Assessment of quality of life in adult patients with GH deficiency: KIMS contribution to clinical practice and pharmacoeconomic evaluations. Eur. J. Endocrinol. 161(Suppl 1), S51–S64 (2009)

    Article  PubMed  CAS  Google Scholar 

  102. C. Hoybye, P. Cohen, A.R. Hoffman, R. Ross, B.M. Biller, J.S. Christiansen, Status of long-acting-growth hormone preparations—2015. Growth. Horm. IGF. Res. 25, 201–206 (2015)

    Article  PubMed  CAS  Google Scholar 

  103. D.B. Allen, P. Backeljauw, M. Bidlingmaier, B. Biller, M. Boguszewski, P. Burman, G. Butler, K. Chihara, J.S. Christiansen, S. Cianfarani et al., Growth Hormone Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults. Eur. J. Endocrinol. (2015). doi:10.1530/EJE-15-0873

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery and Neurology, Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, WA, 98122, USA

    Kevin C. J. Yuen

  2. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90073, USA

    Anthony P. Heaney

  3. Clinic for Endocrinology, Diabetes and Metabolic Disease, University Clinical Center Belgrade, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000, Belgrade, Serbia

    Vera Popovic

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  1. Kevin C. J. Yuen
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  2. Anthony P. Heaney
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Correspondence to Kevin C. J. Yuen.

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KCJY has received research grants from Pfizer, Novo Nordisk, and Versartis, and has served on the advisory boards for Pfizer, Novo Nordisk, Sandoz, and Versartis. APH has received research grants from Novartis and has served on advisory boards for Pfizer, Novo Nordisk, Sandoz and Ipsen. VP is a member of the International Board for Nordinet-Novo Nordisk.

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Yuen, K.C.J., Heaney, A.P. & Popovic, V. Considering GH replacement for GH-deficient adults with a previous history of cancer: a conundrum for the clinician. Endocrine 52, 194–205 (2016). https://doi.org/10.1007/s12020-015-0840-2

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