Advances in the Understanding of Adult Growth Hormone Deficiency Syndrome may increase the risk of secondary malignancies.115–117 Neither has
GH treatment increased the rates of tumour regrowth in patients with previous craniopharyngeomas or with other childhood brain tumours.118,119
The risk of secondary brain tumour was calculated after a median follow-up of 12 years in a study in 426 patients with pituitary adenomas who had received radiotherapy.120
The reported cumulative risk of
secondary brain tumour was 2% after 10 years and 8.5% after 30 years; thus surveillance is recommended.85
A study in patients with childhood
cancer reported a slightly increased number of patients who developed secondary neoplasms;121
however, the risk seems to decline with time when comparing data with a previous report from the same cohort.122
A meta-analysis found that men who had serum levels of either testosterone or IGF-I in the upper quartile have double the risk of developing prostate cancer.123,124
Torben Laursen is an Associate Professor in the Department of Pharmacology at the University of Aarhus and a Consultant in the Department of Clinical Pharmacology at Aarhus University Hospital. He is a Member of the US Endocrine Society. His major research interests include growth hormone (GH) pharmacokinetics and metabolic impact of the pattern of GH administration, factors modulating the activity of the insulin-like growth factor system and clinical pharmacological aspects of
Prospective trials in pre-menopausal women reported a 4.5-fold increased relative risk
1. Raben MS, J Clin Endocrinol Metab, 1958;18(8):901–3. 2. Buchanan CR, Preece MA, Milner RD, BMJ, 1991;302(6780):824–8.
3. Beshyah SA, Freemantle C, Thomas E, et al., Clin Endocrinol (Oxf), 1995;42(2):179–89.
4. Colao A, Di SC, Pivonello R, et al., J Clin Endocrinol Metab, 2002;87(3): 1088–93.
5. Jallad RS, Liberman B, Vianna CB, et al., Growth Horm IGF Res, 2003;13(2–3): 81–8.
6. McGauley GA, Acta Paediatr Scand Suppl, 1989;356:70–2. 7. Tomlinson JW, Holden N, Hills RK, et al., Lancet, 2001;357(9254):425–31.
8. Rosén T, Bengtsson BA, Lancet, 1990;336:285–8. 9. Salomon F, Cuneo RC, Hesp R, et al., N Engl J Med, 1989;321:1797–803.
10. Jørgensen JO, Pedersen SA, Thuesen L, et al., Lancet, 1989;1:1221–5.
11. Binnerts A, Swart GR, Wilson JH, et al., Clin Endocrinol (Oxf), 1992;37:79–87.
12. Whitehead HM, Boreham C, McIlrath EM, et al., Clin Endocrinol (Oxf), 1992;36:45–52.
13. Bengtsson BA, Edén S, Lönn L, et al., J Clin Endocrinol Metab, 1993;76:309–17.
14. Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society, J Clin Endocrinol Metab, 2001;86(5):1868–70.
15. Cohen LE, Radovick S, Endocr Rev, 2002;23(4): 431–42. 16. Dattani MT, Hindmarsh PC, Brook CG, et al., J Endocrinol, 1994;140(3):445–53.
17. Moseley CT, Phillips JA 3rd, Semin Reprod Med, 2000;18(1): 21–9.
18. Wajnrajch MP, Gertner JM, Harbison MD, et al., Nat Genet, 1996;12(1):88–90.
19. Dattani MT, Clin Endocrinol (Oxf), 2005;63(2):121–30. 20. Gleeson HK, Gattamaneni HR, Smethurst L, et al., J Clin Endocrinol Metab, 2004;89(2):662–6.
21. Littley MD, Shalet SM, Beardwell CG, et al., Q J Med, 1989;70(262):145–60.
22. Snyder PJ, Fowble BF, Schatz NJ, et al., Am J Med, 1986;81(3):457–62.
23. Feigl GC, Bonelli CM, Berghold A, et al., J Neurosurg, 2002;97(5 Suppl):415–21.
24. Ho KK, Eur J Endocrinol, 2007;157(6):695–700. 25. Arafah BM, Prunty D, Ybarra J, et al., J Clin Endocrinol Metab, 2000;85:1789–93.
26. Webb SM, Rigla M, Wägner A, et al., J Clin Endocrinol Metab, 1999;84(10):3696–700.
27. Arafah BM, J Clin Endocrinol Metab, 1986;62(6):1173–9. 28. Arafah BM, Kailani SH, Nekl KE, et al., J Clin Endocrinol Metab, 1994;79(2):348–54.
29. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, et al., JAMA, 2007;298(12):1429–38.
30. Kokshoorn NE, Wassenaar MJ, Biermasz NR, et al., Eur J EUROPEAN ENDOCRINOLOGY Endocrinol, 2010;162(1):11–8.
31. Agha A, Rogers B, Sherlock M, et al., J Clin Endocrinol Metab, 2004;89(10):4929–36.
32. Leal-Cerro A, Flores JM, Rincon M, et al., Clin Endocrinol (Oxf), 2005;62(5):525–32.
33. Aimaretti G, Ambrosio MR, Di SC, et al., Clin Endocrinol (Oxf), 2004;61(3):320–6.
34. Aimaretti G, Ambrosio MR, Di SC, et al., J Clin Endocrinol Metab, 2005;90(11):6085–92.
35. Schneider HJ, Schneider M, Saller B, et al., Eur J Endocrinol, 2006;154(2):259–65.
36. Clayton PE, Price DA, Shalet SM, Arch Dis Child, 1987;62(3):222–6.
37. Cacciari E, Tassoni P, Parisi G, et al., J Clin Endocrinol Metab, 1992;74(6):1284–9.
38. Wacharasindhu S, Cotterill AM, Camacho-Hubner C, et al., Clin Endocrinol (Oxf), 1996;45(5):553–6.
39. Longobardi S, Merola B, Pivonello R, et al., J Clin Endocrinol Metab, 1996;81(3):1244–7.
40. Nicolson A, Toogood AA, Rahim A, et al., Clin Endocrinol (Oxf), 1996;44(3):311–6.
41. Tauber M, Moulin P, Pienkowski C, et al., J Clin Endocrinol Metab, 1997;82(2):352–6.
42. Vahl N, Jørgensen JO, Jurik AG, et al., J Clin Endocrinol Metab, 1996;81(6):2209–15.
43. Aimaretti G, Corneli G, Razzore P, et al., J Clin Endocrinol Metab, 1998;83(5):1615–8.
44. Biller BM, Samuels MH, Zagar A, et al., J Clin Endocrinol Metab, 2002;87(5):2067–79.
45. Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency, J Clin Endocrinol Metab, 1998;83(2):379–81.
46. Hartman ML, Crowe BJ, Biller BM, et al., J Clin Endocrinol Metab, 2002;87(2):477–85.
47. Toogood AA, Beardwell CG, Shalet SM, Clin Endocrinol (Oxf), 1994;41(4):511–6.
48. Hoffman DM, O’Sullivan AJ, Freund J, et al., J Clin Endocrinol Metab, 1995;80(1):72–7.
49. Juul A, Behrenscheer A, Tims T, et al., Clin Endocrinol (Oxf), 1993;38:237–44.
50. Bottinelli R, Narici M, Pellegrino MA, et al., J Clin Endocrinol Metab, 1997;82(12):4133–8.
51. Drake WM, Coyte D, Camacho-Hübner C, et al., J Clin Endocrinol Metab, 1998;83(11):3913–9.
52. Burman P, Johansson AG, Siegbahn A, et al., J Clin Endocrinol Metab, 1997;82(2):550–5.
53. Holmes SJ, Economou G, Whitehouse RW, et al., J Clin Endocrinol Metab, 1994;78(3): 669–74.
54. Murray RD, Columb B, Adams JE, et al., J Clin Endocrinol Metab, 2004;89(3):1124–30.
55. Rosén T, Wilhelmsen L, Landin-Wilhelmsen K, et al., Eur J Endocrinol, 1997;137(3):240–5.
56. Wüster C, Abs R, Bengtsson BA, et al., J Bone Miner Res, 2001;16(2):398–405.
57. Vestergaard P, Jorgensen JO, Hagen C, et al., Clin Endocrinol (Oxf), 2002;56(2):159–67.
58. Mazziotti G, Bianchi A, Bonadonna S, et al., J Bone Miner Res, 2006;21(4):520–8.
59. Teegarden D, Proulx WR, Martin BR, et al., J Bone Miner Res, 1995;10(5):711–5.
60. Baroncelli GI, Bertelloni S, Sodini F, et al., J Pediatr Endocrinol Metab, 2003;16 Suppl 2:327–35.
61. Hew FL, Koschmann M, Christopher M, et al., J Clin Endocrinol Metab, 1996;81(2):555–64.
62. Johansson JO, Fowelin J, Landin K, et al., Metabolism, 1995;44(9):1126–9.
63. Colao A, Vitale G, Pivonello R, et al., Eur J Endocrinol, 2004;151(Suppl. 1):S93–101.
64. Maison P, Chanson P, Circulation, 2003;108(21):2648–52. 65. Bengtsson BA, Abs R, Bennmarker H, et al., J Clin Endocrinol Metab, 1999;84(11):3929–35.
66. Leonsson M, Hulthe J, Oscarsson J, et al., Clin Endocrinol (Oxf), 2002;57(6):751–9.
67. Murata M, Kaji H, Mizuno I, et al., Eur J Endocrinol, 2003;148(3):333–8.
68. Colao A, Di SC, Filippella M, et al., Clin Endocrinol (Oxf), 2004;61(3):360–6.
69. Markussis V, Beshyah SA, Fisher C, et al., Eur J Endocrinol, 1997;136(2):157–64.
70. Hodis HN, Mack WJ, LaBree L, et al. Ann Intern Med, 1998;128(4):262–9.
71. Smith JC, Evans LM, Wilkinson I, et al., Clin Endocrinol (Oxf), 2002;56(4):493–501.
72. Maison P, Griffin S, Nicoue-Beglah M, et al., J Clin Endocrinol Metab, 2004;89(5):2192–9.
73. Böger RH, Skamira C, Bode-Böger SM, et al., J Clin Invest, 1996;98(12):2706–13.
74. Johannsson G, Sunnerhagen KS, Svensson J, Clin Endocrinol (Oxf), 2004;60(5):550–9.
75. Johansson J-O, Landin K, Tengborn L, et al., Arterioscler Thromb, 1994;14:434–7.
76. Sverrisdóttir YB, Elam M, Caidahl K, et al., J Hypertens, 2003;21(10):1905–14.
77. Johansson JO, Landin K, Johannsson G, et al., Thromb Haemost, 1996;76(3):422–8.
78. Sesmilo G, Biller BM, Llevadot J, et al., Ann Intern Med, 2000;133(2):111–22.
79. Sesmilo G, Biller BM, Llevadot J, et al., J Clin Endocrinol Metab, 2001;86(4):1518–24.
80. Leonsson M, Hulthe J, Johannsson G, et al., Clin Endocrinol (Oxf), 2003;59(2):242–50.
81. Holmes SJ, Shalet SM, Clin Endocrinol (Oxf), 1995;43(2):151–7.
82. Attanasio AF, Lamberts SW, Matranga AM, et al., J Clin Endocrinol Metab, 1997;82(1):82–8.
83. Arwert LI, Veltman DJ, Deijen JB, et al., Neuroendocrinology, 49
insulin therapy. Professor Laursen obtained a PhD in endocrinology in 1995 and a DMSci in 2004 from the University of Aarhus. Both theses concerned the impact of the pattern of GH administration. He received board approval in clinical pharmacology in 2003.
of breast cancer in subjects with serum IGF-I levels in the highest compared with the lowest quartile.125 reported for colorectal cancer in men.126
Similar results have been These studies provide a
rationale for maintaining IGF-I within the age-adjusted normal range. Overall, GH treatment is considered to be contraindicated in the presence of an active malignancy. n
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