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Published in: Endocrine 2/2016

01-05-2016 | Review

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

Authors: Kevin C. J. Yuen, Anthony P. Heaney, Vera Popovic

Published in: Endocrine | Issue 2/2016

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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.
Literature
1.
go back to reference W. Chemaitilly, C.A. Sklar, Endocrine complications in long-term survivors of childhood cancers. Endocr. Relat. Cancer 17, R141–R159 (2010)PubMedCrossRef W. Chemaitilly, C.A. Sklar, Endocrine complications in long-term survivors of childhood cancers. Endocr. Relat. Cancer 17, R141–R159 (2010)PubMedCrossRef
2.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
3.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
4.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
5.
go back to reference 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) 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)
6.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
7.
go back to reference P.J. Jenkins, A. Mukherjee, S.M. Shalet, Does growth hormone cause cancer? Clin. Endocrinol. (Oxf.) 64, 115–121 (2006)CrossRef P.J. Jenkins, A. Mukherjee, S.M. Shalet, Does growth hormone cause cancer? Clin. Endocrinol. (Oxf.) 64, 115–121 (2006)CrossRef
8.
go back to reference S. Pekic, V. Popovic, GH therapy and cancer risk in hypopituitarism: what we know from human studies. Eur. J. Endocrinol. 169, R89–R97 (2013)PubMedCrossRef S. Pekic, V. Popovic, GH therapy and cancer risk in hypopituitarism: what we know from human studies. Eur. J. Endocrinol. 169, R89–R97 (2013)PubMedCrossRef
9.
go back to reference 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)CrossRef 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)CrossRef
10.
go back to reference 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)CrossRef 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)CrossRef
11.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
12.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
13.
go back to reference 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)CrossRef 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)CrossRef
14.
15.
go back to reference 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)CrossRef 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)CrossRef
16.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
17.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
18.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
19.
go back to reference 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)PubMedCentralCrossRef 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)PubMedCentralCrossRef
20.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
21.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
22.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
23.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
24.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
25.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
26.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
27.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
28.
go back to reference Y. Harada, Pituitary role in the growth of metastasizing MRMT-1 mammary carcinoma in rats. Cancer Res. 36, 18–22 (1976)PubMed Y. Harada, Pituitary role in the growth of metastasizing MRMT-1 mammary carcinoma in rats. Cancer Res. 36, 18–22 (1976)PubMed
29.
go back to reference 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)PubMed 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)PubMed
30.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
31.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
32.
go back to reference 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)PubMed 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)PubMed
33.
go back to reference K. Hemminki, A. Forsti, J. Ji, Incidence and familial risks in pituitary adenoma and associated tumors. Endocr. Relat. Cancer 14, 103–109 (2007)PubMedCrossRef K. Hemminki, A. Forsti, J. Ji, Incidence and familial risks in pituitary adenoma and associated tumors. Endocr. Relat. Cancer 14, 103–109 (2007)PubMedCrossRef
35.
go back to reference C.M. Perks, J.M. Holly, Insulin-like growth factors in health and disease. Preface. Endocrinol. Metab. Clin. North. Am. 41, xv–xvi (2012)PubMedCrossRef C.M. Perks, J.M. Holly, Insulin-like growth factors in health and disease. Preface. Endocrinol. Metab. Clin. North. Am. 41, xv–xvi (2012)PubMedCrossRef
36.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
37.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
38.
go back to reference 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)CrossRef 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)CrossRef
39.
go back to reference C. Harding, F. Pompei, E.E. Lee, R. Wilson, Cancer suppression at old age. Cancer Res. 68, 4465–4478 (2008)PubMedCrossRef C. Harding, F. Pompei, E.E. Lee, R. Wilson, Cancer suppression at old age. Cancer Res. 68, 4465–4478 (2008)PubMedCrossRef
40.
go back to reference 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)PubMed 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)PubMed
41.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
42.
go back to reference 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)PubMed 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)PubMed
43.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
44.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
45.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
46.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
47.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
48.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
49.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
50.
go back to reference 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)PubMed 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)PubMed
51.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
52.
go back to reference P.J. Jenkins, M. Besser, Clinical perspective: acromegaly and cancer: a problem. J. Clin. Endocrinol. Metab. 86, 2935–2941 (2001)PubMedCrossRef P.J. Jenkins, M. Besser, Clinical perspective: acromegaly and cancer: a problem. J. Clin. Endocrinol. Metab. 86, 2935–2941 (2001)PubMedCrossRef
53.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
54.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
55.
go back to reference 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)CrossRef 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)CrossRef
56.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
57.
go back to reference 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)PubMed 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)PubMed
58.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
59.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
60.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
61.
go back to reference 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)PubMed 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)PubMed
62.
go back to reference 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)PubMed 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)PubMed
63.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
66.
go back to reference K.E. Friend, Cancer and the potential place for growth hormone receptor antagonist therapy. Growth. Horm. IGF. Res. 11(Suppl A), S121–S123 (2001)PubMedCrossRef K.E. Friend, Cancer and the potential place for growth hormone receptor antagonist therapy. Growth. Horm. IGF. Res. 11(Suppl A), S121–S123 (2001)PubMedCrossRef
67.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
68.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
69.
go back to reference 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)PubMed 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)PubMed
70.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
71.
go back to reference 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)CrossRef 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)CrossRef
72.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
73.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
74.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
75.
go back to reference 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)CrossRef 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)CrossRef
76.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
77.
go back to reference E.M. Erfurth, Update in mortality in GH-treated patients. J. Clin. Endocrinol. Metab. 98, 4219–4226 (2013)PubMedCrossRef E.M. Erfurth, Update in mortality in GH-treated patients. J. Clin. Endocrinol. Metab. 98, 4219–4226 (2013)PubMedCrossRef
78.
go back to reference 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)PubMed 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)PubMed
79.
go back to reference 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)PubMed 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)PubMed
80.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
81.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
82.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
83.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
84.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
85.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
86.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
87.
go back to reference 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)CrossRef 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)CrossRef
88.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
89.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
90.
go back to reference 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)PubMedPubMedCentralCrossRef 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)PubMedPubMedCentralCrossRef
91.
go back to reference 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)CrossRef 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)CrossRef
92.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
93.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
94.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
95.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
96.
go back to reference V.N. Anisimov, Biology of aging and cancer. Cancer Control 14, 23–31 (2007)PubMed V.N. Anisimov, Biology of aging and cancer. Cancer Control 14, 23–31 (2007)PubMed
97.
go back to reference A. Hjartaker, H. Langseth, E. Weiderpass, Obesity and diabetes epidemics: cancer repercussions. Adv. Exp. Med. Biol. 630, 72–93 (2008)PubMedCrossRef A. Hjartaker, H. Langseth, E. Weiderpass, Obesity and diabetes epidemics: cancer repercussions. Adv. Exp. Med. Biol. 630, 72–93 (2008)PubMedCrossRef
98.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
99.
go back to reference B. Strahm, D. Malkin, Hereditary cancer predisposition in children: genetic basis and clinical implications. Int. J. Cancer 119, 2001–2006 (2006)PubMedCrossRef B. Strahm, D. Malkin, Hereditary cancer predisposition in children: genetic basis and clinical implications. Int. J. Cancer 119, 2001–2006 (2006)PubMedCrossRef
100.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
101.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
102.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
103.
go back to reference 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 PubMedPubMedCentral 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 PubMedPubMedCentral
Metadata
Title
Considering GH replacement for GH-deficient adults with a previous history of cancer: a conundrum for the clinician
Authors
Kevin C. J. Yuen
Anthony P. Heaney
Vera Popovic
Publication date
01-05-2016
Publisher
Springer US
Published in
Endocrine / Issue 2/2016
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-015-0840-2

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