Management of Adults with Childhood-Onset Growth Hormone Deficiency

Chapter

Abstract

In patients with childhood-onset growth hormone (GH) deficiency, linear growth is the most evident and objective parameter to monitor GH therapy during infancy and puberty. Once adult height is achieved and the patient transits from puberty to adulthood, confirmation of the diagnosis of GH deficiency (GHD) may be needed in order to assess the need for long-term replacement therapy. Depending on the etiology of GHD, patients have different chances of having persistent deficit. Most of the children with an isolated, idiopathic GHD are likely to restore a physiological secretion during transition, whereas those with anatomic hypothalamic-pituitary damage and/or multiple pituitary hormone deficiencies have a higher likelihood of remaining GH deficient. Retesting the patient during transition from puberty to adulthood can be challenging; there are no basal laboratory tests able to confirm GHD in most of cases, and dynamic evaluation is influenced by several variables that might make it difficult to interpret the results. The decision on if, when, and how to treat with long-term GH replacement therapy (GHRT) has to be tailored on every single case. This treatment has proven benefits on bone maturation, metabolism control, and quality of life. However, it has contraindications and potential side effects as well, and the decision to restart the treatment should be discussed extensively with the patients and their families.

Keywords

GH Insulin-like growth factor 1 (IGF-1) GH deficiency GH replacement therapy Transition Bone mineral density Bone peak Body composition Metabolic syndrome Quality of life Insulin tolerance test Arginine + GHRH test Glucagon stimulation est Hypopituitarism Adrenal insufficiency Hypothyroidism 

References

  1. 1.
    Cummings DE, Merriam GR. Growth hormone therapy in adults. Annu Rev Med. 2003;54:513–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Stochholm K, Gravholt CH, Laursen T, Jorgensen JO, Laurberg P, Andersen M, et al. Incidence of GH deficiency - a nationwide study. Eur J Endocrinol. 2006;155(1):61–71.CrossRefPubMedGoogle Scholar
  3. 3.
    Clayton PE, Shalet SM. Difficulties in patient management associated with the transition period. Horm Res. 2005;64(Suppl 2):74–5.PubMedGoogle Scholar
  4. 4.
    Attanasio AF, Howell S, Bates PC, Frewer P, Chipman J, Blum WF, et al. Body composition, IGF-I and IGFBP-3 concentrations as outcome measures in severely GH-deficient (GHD) patients after childhood GH treatment: a comparison with adult onset GHD patients. J Clin Endocrinol Metab. 2002;87(7):3368–72.CrossRefPubMedGoogle Scholar
  5. 5.
    Ranke MB, Price DA, Albertsson-Wikland K, Maes M, Lindberg A. Factors determining pubertal growth and final height in growth hormone treatment of idiopathic growth hormone deficiency. Analysis of 195 patients of the Kabi Pharmacia international growth study. Horm Res. 1997;48(2):62–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, et al. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult growth hormone deficiency study group. J Clin Endocrinol Metab. 1997;82(1):82–8.PubMedGoogle Scholar
  7. 7.
    Courtillot C, Baudoin R, Du Souich T, Saatdjian L, Tejedor I, Pinto G, et al. Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition. Eur J Endocrinol. 2013;169(5):587–96.CrossRefPubMedGoogle Scholar
  8. 8.
    Godbout A, Tejedor I, Malivoir S, Polak M, Touraine P. Transition from pediatric to adult healthcare: assessment of specific needs of patients with chronic endocrine conditions. Horm Res Paediatr. 2012;78(4):247–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Downing J, Gleeson HK, Clayton PE, Davis JR, Wales JK, Callery P. Transition in endocrinology: the challenge of maintaining continuity. Clin Endocrinol. 2013;78(1):29–35.CrossRefGoogle Scholar
  10. 10.
    Mo D, Hardin DS, Erfurth EM, Melmed S. 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. 2014;17(5):477–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Prodam F, Savastio S, Genoni G, Babu D, Giordano M, Ricotti R, et al. Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height. PLoS One. 2014;9(1):e87157.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Maghnie M, Triulzi F, Larizza D, Preti P, Priora C, Scotti G, et al. Hypothalamic-pituitary dysfunction in growth hormone-deficient patients with pituitary abnormalities. J Clin Endocrinol Metab. 1991;73(1):79–83.CrossRefPubMedGoogle Scholar
  13. 13.
    Alatzoglou KS, Webb EA, Le Tissier P, Dattani MT. Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent advances. Endocr Rev. 2014;35(3):376–432.CrossRefPubMedGoogle Scholar
  14. 14.
    Webb SM, Strasburger CJ, Mo D, Hartman ML, Melmed S, Jung H, et al. Changing patterns of the adult growth hormone deficiency diagnosis documented in a decade-long global surveillance database. J Clin Endocrinol Metab. 2009;94(2):392–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298(12):1429–38.CrossRefPubMedGoogle Scholar
  16. 16.
    Einaudi S, Matarazzo P, Peretta P, Grossetti R, Giordano F, Altare F, et al. Hypothalamo-hypophysial dysfunction after traumatic brain injury in children and adolescents: a preliminary retrospective and prospective study. J Pediatr Endocrinol Metab. 2006;19(5):691–703.CrossRefPubMedGoogle Scholar
  17. 17.
    Brabant G, Poll EM, Jonsson P, Polydorou D, Kreitschmann-Andermahr I. Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations? Eur J Endocrinol. 2009;161(Suppl 1):S25–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P. Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab. 1997;82(2):352–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Secco A, di Iorgi N, Napoli F, Calandra E, Calcagno A, Ghezzi M, et al. Reassessment of the growth hormone status in young adults with childhood-onset growth hormone deficiency: reappraisal of insulin tolerance testing. J Clin Endocrinol Metab. 2009;94(11):4195–204.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Attanasio AF, Bates PC, Ho KK, Webb SM, Ross RJ, Strasburger CJ, et al. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS database. J Clin Endocrinol Metab. 2002;87(4):1600–6.PubMedGoogle Scholar
  21. 21.
    Radovick S, DiVall S. Approach to the growth hormone-deficient child during transition to adulthood. J Clin Endocrinol Metab. 2007;92(4):1195–200.CrossRefPubMedGoogle Scholar
  22. 22.
    Petkovic V, Lochmatter D, Turton J, Clayton PE, Trainer PJ, Dattani MT, et al. Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency. J Clin Endocrinol Metab. 2007;92(11):4427–35.CrossRefPubMedGoogle Scholar
  23. 23.
    Zhu YL, Conway-Campbell B, Waters MJ, Dannies PS. Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II. Endocrinology. 2002;143(11):4243–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine S. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587–609.CrossRefGoogle Scholar
  25. 25.
    Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ, et al. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab. 2002;87(2):477–85.CrossRefPubMedGoogle Scholar
  26. 26.
    Ahmid M, Fisher V, Graveling AJ, McGeoch S, McNeil E, Roach J, et al. An audit of the management of childhood-onset growth hormone deficiency during young adulthood in Scotland. Int J Pediatr Endocrinol. 2016;2016:6.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Mulder RL, Kremer LC, van Santen HM, Ket JL, van Trotsenburg AS, Koning CC, et al. Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat Rev. 2009;35(7):616–32.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gleeson HK, Gattamaneni HR, Smethurst L, Brennan BM, Shalet SM. Reassessment of growth hormone status is required at final height in children treated with growth hormone replacement after radiation therapy. J Clin Endocrinol Metab. 2004;89(2):662–6.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Darzy KH. Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nat Clin Pract Endocrinol Metab. 2009;5(2):88–99.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Leger J, Danner S, Simon D, Garel C, Czernichow P. Do all patients with childhood-onset growth hormone deficiency (GHD) and ectopic neurohypophysis have persistent GHD in adulthood? J Clin Endocrinol Metab. 2005;90(2):650–6.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    di Iorgi N, Secco A, Napoli F, Tinelli C, Calcagno A, Fratangeli N, et al. Deterioration of growth hormone (GH) response and anterior pituitary function in young adults with childhood-onset GH deficiency and ectopic posterior pituitary: a two-year prospective follow-up study. J Clin Endocrinol Metab. 2007;92(10):3875–84.CrossRefGoogle Scholar
  32. 32.
    De Bellis A, Bellastella G, Maiorino MI, Aitella E, Lucci E, Cozzolino D, et al. Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age. Eur J Endocrinol. 2016;174(3):381–7.CrossRefGoogle Scholar
  33. 33.
    Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC, Rose NR. Autoimmune hypophysitis. Endocr Rev. 2005;26(5):599–614.CrossRefGoogle Scholar
  34. 34.
    Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, et al. Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab. 1999;84(4):1324–8.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Clayton PE, Cuneo RC, Juul A, Monson JP, Shalet SM, Tauber M, et al. Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol. 2005;152(2):165–70.CrossRefGoogle Scholar
  36. 36.
    Ho KK, Participants GHDCW. 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. 2007;157(6):695–700.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML. American Association of Clinical E. 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. 2009;15(Suppl 2):1–29.CrossRefGoogle Scholar
  38. 38.
    Zucchini S, Pirazzoli P, Baronio F, Gennari M, Bal MO, Balsamo A, et al. Effect on adult height of pubertal growth hormone retesting and withdrawal of therapy in patients with previously diagnosed growth hormone deficiency. J Clin Endocrinol Metab. 2006;91(11):4271–6.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Gourmelen M. Pham-Huu-Trung MT, Girard F. Transient partial hGH deficiency in prepubertal children with delay of growth. Pediatr Res. 1979;13(4 Pt 1):221–4.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Attanasio AF, Shalet SM. Growth hormone and the transition from puberty into adulthood. Endocrinol Metab Clin N Am. 2007;36(1):187–201.CrossRefGoogle Scholar
  41. 41.
    Stein MT, Frasier SD, Stabler B, Shapiro HL, Cupoli M, Johnson D. Parent requests growth hormone for child with idiopathic short stature. J Dev Behav Pediatr. 2004;25(2):105–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Filipsson H, Johannsson GGH. Replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies. Eur J Endocrinol. 2009;161(Suppl 1):S85–95.CrossRefPubMedGoogle Scholar
  43. 43.
    Maghnie M, Aimaretti G, Bellone S, Bona G, Bellone J, Baldelli R, et al. Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement. Eur J Endocrinol. 2005;152(4):589–96.CrossRefPubMedGoogle Scholar
  44. 44.
    Barth JH, Sibley PE. Standardization of the IMMULITE systems growth hormone assay with the recombinant IS 98/574. Ann Clin Biochem. 2008;45(Pt 6):598–600.CrossRefPubMedGoogle Scholar
  45. 45.
    Giacomozzi C, Spadoni GL, Pedicelli S, Scire G, Cristofori L, Peschiaroli E, et al. Responses to GHRH plus arginine test are more concordant with IGF-I circulating levels than responses to arginine and clonidine provocative tests. J Endocrinol Investig. 2012;35(8):742–7.Google Scholar
  46. 46.
    Colao A, Di Somma C, Savastano S, Rota F, Savanelli MC, Aimaretti G, et al. A reappraisal of diagnosing GH deficiency in adults: role of gender, age, waist circumference, and body mass index. J Clin Endocrinol Metab. 2009;94(11):4414–22.CrossRefPubMedGoogle Scholar
  47. 47.
    Borson-Chazot F, Brue T. Pituitary deficiency after brain radiation therapy. Ann Endocrinol (Paris). 2006;67(4):303–9.CrossRefGoogle Scholar
  48. 48.
    Darzy KH, Aimaretti G, Wieringa G, Gattamaneni HR, Ghigo E, Shalet SM. The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab. 2003;88(1):95–102.CrossRefPubMedGoogle Scholar
  49. 49.
    Yuen KC, Biller BM, Katznelson L, Rhoads SA, Gurel MH, Chu O, et al. Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults. Pituitary. 2013;16(2):220–30.CrossRefPubMedGoogle Scholar
  50. 50.
    Dichtel LE, Yuen KC, Bredella MA, Gerweck AV, Russell BM, Riccio AD, et al. Overweight/obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency. J Clin Endocrinol Metab. 2014;99(12):4712–9.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, et al. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2002;87(5):2067–79.CrossRefPubMedGoogle Scholar
  52. 52.
    Beshyah SA, Johnston DG. Cardiovascular disease and risk factors in adults with hypopituitarism. Clin Endocrinol. 1999;50(1):1–15.CrossRefGoogle Scholar
  53. 53.
    Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336(8710):285–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Bates AS. Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169–72.PubMedGoogle Scholar
  55. 55.
    Attanasio AF, Shavrikova E, Blum WF, Cromer M, Child CJ, Paskova M, et al. Continued growth hormone (GH) treatment after final height is necessary to complete somatic development in childhood-onset GH-deficient patients. J Clin Endocrinol Metab. 2004;89(10):4857–62.CrossRefPubMedGoogle Scholar
  56. 56.
    Ahmid M, Perry CG, Ahmed SF, Shaikh MG. Growth hormone deficiency during young adulthood and the benefits of growth hormone replacement. Endocr Connect. 2016;5(3):R1–R11.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Drake WM, Carroll PV, Maher KT, Metcalfe KA, Camacho-Hubner C, Shaw NJ, et al. The effect of cessation of growth hormone (GH) therapy on bone mineral accretion in GH-deficient adolescents at the completion of linear growth. J Clin Endocrinol Metab. 2003;88(4):1658–63.CrossRefPubMedGoogle Scholar
  58. 58.
    Shalet SM, Shavrikova E, Cromer M, Child CJ, Keller E, Zapletalova J, et al. Effect of growth hormone (GH) treatment on bone in postpubertal GH-deficient patients: a 2-year randomized, controlled, dose-ranging study. J Clin Endocrinol Metab. 2003;88(9):4124–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Golden NH, Abrams SA. Committee on N. Optimizing bone health in children and adolescents. Pediatrics. 2014;134(4):e1229–43.CrossRefGoogle Scholar
  60. 60.
    Barake M, Klibanski A, Tritos NA. Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3):852–60.CrossRefPubMedGoogle Scholar
  61. 61.
    Davidson P, Milne R, Chase D, Cooper C. Growth hormone replacement in adults and bone mineral density: a systematic review and meta-analysis. Clin Endocrinol. 2004;60(1):92–8.CrossRefGoogle Scholar
  62. 62.
    Ortolani S. Bone densitometry: assessing the effects of growth hormone treatment in adults. Horm Res. 2000;54(Suppl 1):19–23.CrossRefPubMedGoogle Scholar
  63. 63.
    Hogler W, Shaw N. Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol. 2010;72(3):281–9.CrossRefGoogle Scholar
  64. 64.
    Mauras N, Pescovitz OH, Allada V, Messig M, Wajnrajch MP, Lippe B, et al. Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: a phase III multicenter, double-blind, randomized two-year trial. J Clin Endocrinol Metab. 2005;90(7):3946–55.CrossRefPubMedGoogle Scholar
  65. 65.
    Norrelund H, Vahl N, Juul A, Moller N, Alberti KG, Skakkebaek NE, et al. Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism. J Clin Endocrinol Metab. 2000;85(5):1912–7.CrossRefPubMedGoogle Scholar
  66. 66.
    Vahl N, Juul A, Jorgensen JO, Orskov H, Skakkebaek NE, Christiansen JS. Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study. J Clin Endocrinol Metab. 2000;85(5):1874–81.CrossRefPubMedGoogle Scholar
  67. 67.
    Underwood LE, Attie KM, Baptista J. Genentech collaborative study G. Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab. 2003;88(11):5273–80.CrossRefPubMedGoogle Scholar
  68. 68.
    Bazarra-Castro MA, Sievers C, Schwarz HP, Pozza SB, Stalla GK. Changes in BMI and management of patients with childhood onset growth hormone deficiency in the transition phase. Exp Clin Endocrinol Diabetes. 2012;120(9):507–10.CrossRefPubMedGoogle Scholar
  69. 69.
    Carroll PV, Drake WM, Maher KT, Metcalfe K, Shaw NJ, Dunger DB, et al. Comparison of continuation or cessation of growth hormone (GH) therapy on body composition and metabolic status in adolescents with severe GH deficiency at completion of linear growth. J Clin Endocrinol Metab. 2004;89(8):3890–5.CrossRefPubMedGoogle Scholar
  70. 70.
    Abs R, Mattsson AF, Bengtsson BA, Feldt-Rasmussen U, Goth MI, Koltowska-Haggstrom M, et al. Isolated growth hormone (GH) deficiency in adult patients: baseline clinical characteristics and responses to GH replacement in comparison with hypopituitary patients. A sub-analysis of the KIMS database. Growth Hormon IGF Res. 2005;15(5):349–59.CrossRefGoogle Scholar
  71. 71.
    Claessen KM, Appelman-Dijkstra NM, Adoptie DM, Roelfsema F, Smit JW, Biermasz NR, et al. Metabolic profile in growth hormone-deficient (GHD) adults after long-term recombinant human growth hormone (rhGH) therapy. J Clin Endocrinol Metab. 2013;98(1):352–61.CrossRefPubMedGoogle Scholar
  72. 72.
    Hulthen L, Bengtsson BA, Sunnerhagen KS, Hallberg L, Grimby G, Johannsson GGH. Is needed for the maturation of muscle mass and strength in adolescents. J Clin Endocrinol Metab. 2001;86(10):4765–70.CrossRefPubMedGoogle Scholar
  73. 73.
    Rutherford OM, Jones DA, Round JM, Buchanan CR, Preece MA. Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults. Clin Endocrinol. 1991;34(6):469–75.CrossRefGoogle Scholar
  74. 74.
    Bechtold S, Bachmann S, Putzker S, Dalla Pozza R, Schwarz HP. Early changes in body composition after cessation of growth hormone therapy in childhood-onset growth hormone deficiency. J Clin Densitom. 2011;14(4):471–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Lagrou K, Xhrouet-Heinrichs D, Massa G, Vandeweghe M, Bourguignon JP, De Schepper J, et al. Quality of life and retrospective perception of the effect of growth hormone treatment in adult patients with childhood growth hormone deficiency. J Pediatr Endocrinol Metab. 2001;14(Suppl 5):1249–60. discussion 61-2PubMedGoogle Scholar
  76. 76.
    Koltowska-Haggstrom M, Geffner ME, Jonsson P, Monson JP, Abs R, Hana V, et al. Discontinuation of growth hormone (GH) treatment during the transition phase is an important factor determining the phenotype of young adults with nonidiopathic childhood-onset GH deficiency. J Clin Endocrinol Metab. 2010;95(6):2646–54.CrossRefPubMedGoogle Scholar
  77. 77.
    Johannsson G, Albertsson-Wikland K, Bengtsson BA. Discontinuation of growth hormone (GH) treatment: metabolic effects in GH-deficient and GH-sufficient adolescent patients compared with control subjects. Swedish study Group for Growth Hormone Treatment in children. J Clin Endocrinol Metab. 1999;84(12):4516–24.PubMedGoogle Scholar
  78. 78.
    Lanes R, Gunczler P, Lopez E, Esaa S, Villaroel O, Revel-Chion R. Cardiac mass and function, carotid artery intima-media thickness, and lipoprotein levels in growth hormone-deficient adolescents. J Clin Endocrinol Metab. 2001;86(3):1061–5.CrossRefPubMedGoogle Scholar
  79. 79.
    Colao A, Di Somma C, Salerno M, Spinelli L, Orio F, Lombardi G. The cardiovascular risk of GH-deficient adolescents. J Clin Endocrinol Metab. 2002;87(8):3650–5.CrossRefPubMedGoogle Scholar
  80. 80.
    Murata M, Kaji H, Mizuno I, Sakurai T, Iida K, Okimura Y, et al. A study of carotid intima-media thickness in GH-deficient Japanese adults during onset among adults and children. Eur J Endocrinol. 2003;148(3):333–8.CrossRefPubMedGoogle Scholar
  81. 81.
    Colao A, Di Somma C, Rota F, Di Maio S, Salerno M, Klain A, et al. Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: a prospective study after GH withdrawal and restarting GH replacement. J Clin Endocrinol Metab. 2005;90(5):2659–65.CrossRefPubMedGoogle Scholar
  82. 82.
    Feinberg MS, Scheinowitz M, Laron Z. Cardiac dimension and function in patients with childhood onset growth hormone deficiency, before and after growth hormone retreatment in adult age. Am Heart J. 2003;145(3):549–53.CrossRefPubMedGoogle Scholar
  83. 83.
    Sherlock M, Stewart PM. Updates in growth hormone treatment and mortality. Curr Opin Endocrinol Diabetes Obes. 2013;20(4):314–20.CrossRefPubMedGoogle Scholar
  84. 84.
    Svensson J, Finer N, Bouloux P, Bevan J, Jonsson B, Mattsson AF, et al. Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response. Growth Hormon IGF Res. 2007;17(1):67–76.CrossRefGoogle Scholar
  85. 85.
    Feldt-Rasmussen U, Brabant G, Maiter D, Jonsson B, Toogood A, Koltowska-Haggstrom M, et al. Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak. Eur J Endocrinol. 2013;168(5):733–43.CrossRefPubMedGoogle Scholar
  86. 86.
    Schneider HJ, Buchfelder M, Wallaschofski H, Luger A, Johannsson G, Kann PH, et al. Proposal of a clinical response score and predictors of clinical response to 2 years of GH replacement therapy in adult GH deficiency. Eur J Endocrinol. 2015;173(6):843–51.CrossRefPubMedGoogle Scholar
  87. 87.
    Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, et al. 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. 2012;97(2):416–25.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Savendahl L, Maes M, Albertsson-Wikland K, Borgstrom B, Carel JC, Henrard S, et al. 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. 2012;97(2):E213–7.CrossRefGoogle Scholar
  89. 89.
    Allen DB, Backeljauw P, Bidlingmaier M, Biller BM, Boguszewski M, Burman P, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016;174(2):P1–9.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Raman S, Grimberg A, Waguespack SG, Miller BS, Sklar CA, Meacham LR, et al. Risk of neoplasia in pediatric patients receiving growth hormone therapy--a report from the pediatric Endocrine Society drug and therapeutics committee. J Clin Endocrinol Metab. 2015;100(6):2192–203.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Abs R, Mattsson AF, Thunander M, Verhelst J, Goth MI, Wilton P, et al. Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis. Eur J Endocrinol. 2013;168(3):297–305.CrossRefPubMedGoogle Scholar
  92. 92.
    Agha A, Walker D, Perry L, Drake WM, Chew SL, Jenkins PJ, et al. Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients. Clin Endocrinol. 2007;66(1):72–7.Google Scholar
  93. 93.
    Toogood AA, Taylor NF, Shalet SM, Monson JP. Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients. J Clin Endocrinol Metab. 2000;85(4):1727–30.PubMedGoogle Scholar
  94. 94.
    Birzniece V, Nelson AE, Ho KK. Growth hormone and physical performance. Trends Endocrinol Metab. 2011;22(5):171–8.CrossRefPubMedGoogle Scholar
  95. 95.
    Wilkinson-Berka JL, Wraight C, Werther G. The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. Curr Med Chem. 2006;13(27):3307–17.CrossRefPubMedGoogle Scholar
  96. 96.
    Vila G, Akerblad AC, Mattsson AF, Riedl M, Webb SM, Hana V, et al. Pregnancy outcomes in women with growth hormone deficiency. Fertil Steril. 2015;104(5):1210–7. e1CrossRefPubMedGoogle Scholar
  97. 97.
    Hoybye C, Cohen P, Hoffman AR, Ross R, Biller BM, Christiansen JS, et al. Status of long-acting-growth hormone preparations--2015. Growth Hormon IGF Res. 2015;25(5):201–6.CrossRefGoogle Scholar
  98. 98.
    Ho KK, Gibney J, Johannsson G, Wolthers T. Regulating of growth hormone sensitivity by sex steroids: implications for therapy. Front Horm Res. 2006;35:115–28.CrossRefPubMedGoogle Scholar
  99. 99.
    Gasco V, Prodam F, Grottoli S, Marzullo P, Longobardi S, Ghigo E, et al. GH therapy in adult GH deficiency: a review of treatment schedules and the evidence for low starting doses. Eur J Endocrinol. 2013;168(3):R55–66.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
  2. 2.Division of Endocrinology, Department of MedicineJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations