Advances in the Understanding of Adult Growth Hormone Deficiency Syndrome – Diagnosis, Epidemiology and Management

European Endocrinology, 2010;6(2):45-50

Abstract:

Abstract
In patients with hypopituitarism, growth hormone (GH) deficiency is almost always present. Lack of other pituitary hormones may require prompt replacement, but lack of GH is also associated with several abnormalities, which can be improved by GH treatment. The aberrations include low bone mass and increased risk of fractures, abnormal body composition, e.g. increased fat mass and reduced lean body mass resulting in reduced muscle mass and strength. Decreased exercise capacity may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies, such as reduced insulin sensitivity and hyperlipidaemia, increasing the risk of cardiovascular diseases. Patients with hypopituitarism replaced with relevant hormones except GH have increased mortality due to cardiovascular diseases and increased morbidity. Thus, it is important to diagnose GH deficiency, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with an insulin tolerance test or arginine plus GH-releasing hormone can be used.

Keywords
Growth hormone, growth hormone deficiency, hypopituitarism, diagnosis, epidemiology

Disclosure: The author has no conflicts of interest to declare.
Received: 6 August 2010 Accepted: 20 September 2010 Citation: European Endocrinology, 2010;6(2):45–50
Correspondence: Torben Laursen, Department of Pharmacology, Bartholin Building, Vilhelm Meyers allé 4, University of Aarhus, DK-8000 Aarhus C, Denmark. E: tl@farm.au.dk

Citation European Endocrinology, 2010;6(2):45-50

Growth hormone (GH) therapy was introduced in the 1950s, but the initial GH preparations extracted from human cadaver pituitaries were reserved the treatment of GH deficiency (GHD) children.1 Since 1985, only recombinant DNA-derived biosynthetic human GH free from, for example, Creutzfeldt-Jakob prions has been used.2

GH has now been approved in many countries for the treatment of non-GHD patients with short stature, e.g. Turner’s syndrome, chronic renal failure, small size for gestational age, Prader-Willi syndrome and idiopathic short stature. Often GH therapy is discontinued once adult height has been achieved. Sustained GH deficiency in adult life is, however, associated with disturbances in body composition, carbohydrate and lipid metabolism, bone turnover, the cardiovascular system and quality of life.3–6 Moreover, GHD might contribute to the increased morbidity and mortality observed in hypopituitary adults.7,8

Several studies have demonstrated that GH therapy improves body composition, bone health, cardiovascular risk factors and quality of life in adult GHD (AGHD) and GH-replacement therapy has now been approved in many countries.9–13 Despite this, reductions in cardiovascular events and mortality still need to be demonstrated. Furthermore, although treatment appears to be safe, certain areas – such as risks of glucose intolerance, pituitary tumour regrowth and cancer – require long-term surveillance.14 Variable individual response to GH replacement is still a challenge, although the low GH doses used now are adjusted according to age, gender and body composition.

References:
  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 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, 2006;83(1):12–9.
  84. Bates AS, Van’t Hoff W, Jones PJ, et al., J Clin Endocrinol Metab, 1996;81(3):1169–72.
  85. Erfurth EM, Bulow B, Nordström CH, et al., Eur J Endocrinol, 2004;150(4):497–502.
  86. Bülow B, Hagmar L, Mikoczy Z, et al., Clin Endocrinol (Oxf), 1997;46(1):75–81.
  87. Nilsson B, Gustavasson-Kadaka E, Bengtsson BA, et al., J Clin Endocrinol Metab, 2000;85(4):1420–5.
  88. Bülow B, Hagmar L, Mikoczy Z, et al., Clin Endocrinol (Oxf), 1997;46(1):75–81.
  89. Stochholm K, Gravholt CH, Laursen T, et al., Eur J Endocrinol, 2007;157(1):9–18.
  90. Stochholm K, Laursen T, Green A, et al., Eur J Endocrinol, 2008;158(4): 447–57.
  91. Laursen T, Growth Horm IGF Res, 2004;14(1): 16–44.
  92. de Boer H, van der Veen E, Horm Res, 1997;48(Suppl. 5):21–30.
  93. Johannsson G, Rosén T, Bengtsson BA, Clin Endocrinol Oxf, 1997;47(5):571–81.
  94. Murray RD, Skillicorn CJ, Howell SJ, et al., Clin Endocrinol (Oxf), 1999;50(6):749–57.
  95. Murray RD, Shalet SM, J Clin Endocrinol Metab, 2002;87(10):4427–8.
  96. Hoffman AR, Strasburger CJ, Zagar A, et al., J Clin Endocrinol Metab, 2004;89(7):3224–33.
  97. Cook DM, Ludlam WH, Cook MB, J Clin Endocrinol Metab, 1999;84(11):3956–60.
  98. Underwood LE, Attie KM, Baptista J, J Clin Endocrinol Metab, 2003;88(11):5273–80.
  99. Porretti S, Giavoli C, Ronchi C, et al., J Clin Endocrinol Metab, 2002;87(5):2042–5.
  100. Giavoli C, Libé R, Corbetta S, et al., J Clin Endocrinol Metab, 2004;89(11): 5397–401.
  101. Mauras N, Pescovitz OH, Allada V, et al., J Clin Endocrinol Metab, 2005;90(7):3946–55.
  102. Orme SM, Sebastian JP, Oldroyd B, et al., Clin Endocrinol (Oxf), 1992;37:453–9.
  103. Kehely A, Bates PC, Frewer P, et al., J Clin Endocrinol Metab, 2002;87(5):1974–9.
  104. Bryant J, Loveman E, Cave C, et al., J Endocrinol, 2002;175(2):545–52.
  105. Carroll PV, Christ ER, Bengtsson BA, et al., J Clin Endocrinol Metab, 1998;83(2):382–95.
  106. Carroll PV, Littlewood R, Weissberger AJ, et al., Eur J Endocrinol, 1997;137(2):146–53.
  107. Holmes SJ, Shalet SM, Clin Endocrinol (Oxf), 1995;43(2): 143–9.
  108. Thuesen L, Jørgensen JO, Müller JR, et al., Clin Endocrinol (Oxf), 1994;41(5):615–20.
  109. Svensson J, Fowelin J, Landin K, et al., J Clin Endocrinol Metab, 2002;87(5): 2121–7.
  110. Monson JP, Bengtsson BA, Abs R, et al., Lancet, 2000;355(9216):1728–9.
  111. Hoffman AR, Kuntze JE, Baptista J, et al., J Clin Endocrinol Metab, 2004;89(5):2048–56.
  112. Hansen R, Koller EA, Malozowski S, J Clin Endocrinol Metab, 2000;85(7):2627.
  113. Yakar S, Leroith D, Brodt P, Cytokine Growth Factor Review, 2005;16:407–420.
  114. Popovic V, Damjanovic S, Micic D, et al., Clin Endocrinol (Oxf), 1998;49(4):441–5.
  115. Tuffli GA, Johanson A, Rundle AC, et al., J Clin Endocrinol Metab, 1995;80(4): 1416–22.
  116. Hatrick AG, Boghalo P, Bingham JB, et al., Eur J Endocrinol, 2002;146(6):807–11.
  117. Frajese G, Drake WM, Loureiro RA, et al., J Clin Endocrinol Metab, 2001;86(11):5172–5.
  118. Karavitaki N, Warner JT, Marland A, et al., Clin Endocrinol (Oxf), 2006;64(5):556–60.
  119. Jostel A, Mukherjee A, Hulse PA, et al., Clin Endocrinol (Oxf), 2005;62(6):698–705.
  120. Minniti G, Traish D, Ashley S, et al., J Clin Endocrinol Metab, 2005;90(2):800–4.
  121. Ergun-Longmire B, Mertens AC, Mitby P, et al., J Clin Endocrinol Metab, 2006;91(9):3494–8.
  122. Sklar CA, Mertens AC, Mitby P, et al., J Clin Endocrinol Metab, 2002;87(7):3136–41.
  123. Chan JM, Stampfer MJ, Giovannucci E, et al., Science, 1998; 279(5350):563–6.
  124. Shaneyfelt T, Husein R, Bubley G, et al., J Clin Oncol, 2000;18(4):847–53.
  125. Hankinson SE, Willett WC, Colditz GA, et al., Lancet, 1998; 351(9113):1393–6.
  126. Ma J, Pollak MN, Giovannucci E, et al., J Natl Cancer Inst, 1999;91(7):620–5.
Customize This