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Indications and strategies for continuing GH treatment during transition from late adolescence to early adulthood in patients with GH deficiency: The impact on bone mass

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Abstract

GH plays an important role in longitudinal bone growth and maturation during childhood and adolescence. However, GH has important metabolic functions other than bone growth, which become more apparent during young adulthood, when growth has been completed. Indeed, GH deficiency (GHD) in adult life is a recognized clinical syndrome which includes symptoms such as increased central adiposity, decreased lean body mass, reduced bone mineral density (BMD), increased atherogenic risk, cerebrovascular and cardiac morbidity and mortality, and reduced quality of life. As approximately one quarter of the children with GHD should continue GH administration in adulthood, it is important to reconfirm GHD at the end of growth in order to select patients with severe GHD who need to resume GH therapy with an appropriate age-related dosage. Some evidence indicates that most peak bone mass (PBM) is achieved by the end of adolescence but small increases in BMD continue during the period of transition from late adolescence to young adulthood. Some young adults with GHD show a persistent increase of lumbar BMD after the completion of growth even after discontinuation of treatment suggesting a spontaneous progression towards lumbar PBM or a continuing effect of the treatment. The data indicates that adolescents with GHD who do not reach lumbar PBM at the time of discontinuation of GH treatment can achieve a BMD lower than their genetic potential if they are not treated during the transition to young adulthood.

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References

  1. Carroll PV, Christ ER, Bengtsson BA, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998, 83: 382–95.

    Article  PubMed  CAS  Google Scholar 

  2. Hulthén L, Bengtsson BA, Stibrant Sunnerhgen K, Hallberg L, Grimby G, Johannsson G. Growth hormone is needed for the maturation of muscle mass and strength in adolescents. J Clin Endocrinol Metab 2001, 86: 4765–70.

    Article  PubMed  Google Scholar 

  3. Verhelst J, Abs R. Long-term growth hormone replacement therapy in hypopituitary adults. Drugs 2002, 62: 2399–412.

    Article  PubMed  CAS  Google Scholar 

  4. Rosenfalck AM, Maghsoudi S, Fisker S, et al. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults. J Clin Endocrinol Metab 2000, 85: 4173–81.

    Article  PubMed  CAS  Google Scholar 

  5. Matkovic V, Jelic T, Wardlaw GM, et al. Timing of peak bone mass in caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Invest 1994, 93: 799–808.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Riggs BL, Khosla S, Melton J. The assembly of the adult skeleton during growth and maturation: implications for senile osteoporosis. J Clin Invest 1999, 104: 671–2.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 1979, 46: 451–6.

    PubMed  CAS  Google Scholar 

  8. Borges O. Isometric and isokinetic knee extension and flection torque in men and women aged 20–70. Scand J Rehab Med 1989, 21: 45–53.

    CAS  Google Scholar 

  9. Rutheford OM, Jones DA, Round JM, Buchanan CR, Preece MA. Change in skeletal muscle and body composition after discontinuation of growth hormone deficient young adults. Clin Endocrinol (Oxf) 1991, 34: 469–75.

    Article  Google Scholar 

  10. Wacharasindhu AM, Cotterill AM, Camacho-Huebner C, Besser GM, Savage MO. Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth. Clin Endocrinol (Oxf) 1991, 45: 553–6.

    Article  Google Scholar 

  11. Nicolson A, Toogood AA, Rahim A, Shalet SM. The prevalence of severe growth hormone deficiency in adults who received growth hormone replacement in childhood. Clin Endocrinol (Oxf) 1996, 44: 311–6.

    Article  CAS  Google Scholar 

  12. Clayton PE, Price DA, Shalet SM. Growth hormone state after completion of treatment with growth hormone. Arch Dis Child 1997, 62: 222–8.

    Article  Google Scholar 

  13. Tauber M, Moulin P, Pienkowski C, Jouret B, Rocchiccioli P. Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab 1997, 82: 352–6.

    Article  PubMed  CAS  Google Scholar 

  14. Monson JP, Hindmarsh P. The assessment of growth hormone deficiency in children and adults with particular reference to the transitional period. Clin Endocrinol (Oxf) 2000, 53: 545–7.

    Article  CAS  Google Scholar 

  15. Aimaretti G, Baffoni C, Bellone S, et al. Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing hormone-plus-arginine test. J Clin Endocrinol Metab 2000, 85: 3693–9.

    PubMed  CAS  Google Scholar 

  16. Toogood AA, Beardwell CG, Shalet SM. The severity of growth hormone deficiency in adult pituitary disease is related to the degree of hypopituitarism. Clin Endocrinol (Oxf) 1994, 41: 511–6.

    Article  CAS  Google Scholar 

  17. Maghnie M, Strigazzi C, Tinelli C, 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: 1324–8.

    Article  PubMed  CAS  Google Scholar 

  18. Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KKY. Diagnosis of growth hormone deficiency in adults. Lancet 1994, 343: 1064–8.

    Article  PubMed  CAS  Google Scholar 

  19. Growth Hormone Research Society (GRS). Consensus guidelines for the diagnosis and treatment of growth hormone deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 2000, 85: 3990–3.

    Google Scholar 

  20. Allen D. Issues in the transition from childhood to adult growth hormone therapy. Pediatrics 1999, 104: 1004–9.

    PubMed  CAS  Google Scholar 

  21. Saenger P. A lifetime of growth hormone deficiency: a US pediatric perspective. J Pediatr Endocrinol Metab 2000, 13: 1337–42.

    PubMed  Google Scholar 

  22. Aimaretti G, Baffoni C, Di Vito L, et al. Comparison among old and new provocative tests of GH secretion in 178 normal adults. Eur J Endocrinol 2000, 142: 347–52.

    Article  PubMed  CAS  Google Scholar 

  23. Zadik Z, Chalew SA, McCarter Jr. RJ, Meistas M, Kowarski AA. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 1985, 60: 513–6.

    Article  PubMed  CAS  Google Scholar 

  24. Thorner MO, Bengtsson BA, Ho KY, et al. The diagnosis of growth hormone deficiency (GHD) in adults. J Clin Endocri-nol Metab 1995, 80: 3097–8.

    CAS  Google Scholar 

  25. Saggese G, Ranke MB, Saenger P, et al. Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Horm Res 1998, 50: 320–40.

    Article  PubMed  CAS  Google Scholar 

  26. Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing GH therapy in adults and children. Endocr Rev 2001, 22: 425–50.

    Article  PubMed  CAS  Google Scholar 

  27. Shalet SM, Rosenfeld RG. Growth hormone replacement therapy during transition of patients with childhood-onset growth hormone deficiency into adulthood: what are the issues? Growth Horm IGF Res. 1998, 8: 177–84.

    Article  PubMed  Google Scholar 

  28. Monson JP. Optimal strategy for management of pituitary disease in the growth hormone-deficient teenager. J Pediatr Endocrinol Metab 2000, 13: 1343–8.

    PubMed  Google Scholar 

  29. Maghnie M, Salati B, Bianchi S, et al. Relationship between the morphological evaluation of the pituitary and the growth hormone (GH) response to GH-releasing hormone plus arginine in children and adults with congenital hypopituitarism. J Clin Endocrinol Metab 2001, 86: 1574–9.

    PubMed  CAS  Google Scholar 

  30. Rosenfeld RG. Transitioning patients with childhood-onset growth hormone deficiency to treatment in adulthood. J Pediatr Endocrinol Metab 2002, 15: 1361–5.

    PubMed  CAS  Google Scholar 

  31. Drake WM, Coyte D, Kaltsas G, et al. Optimising growth hormone replacement by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998, 83: 3913–9.

    Article  PubMed  CAS  Google Scholar 

  32. Murray RD, Shalet SM. Adult growth hormone replacement: lessons learned and future direction. J Clin Endocrinol Metab 2002, 87: 4427–8.

    Article  PubMed  CAS  Google Scholar 

  33. Cohen P, Bright GM, Rogol A, Kappelgaard A, Rosenfeld RG. Effects of dose and gender on the growth and growth factor response to GH in GH-deficient children: implications for efficacy and safety. J Clin Endocrinol Metab 2002, 87: 90–8.

    Article  PubMed  CAS  Google Scholar 

  34. Cowell CT, Woodhead H, Brody J. Bone markers and bone mineral density during growth hormone treatment in children with growth hormone deficiency. Horm Res 2000, 54 (Suppl 1): 44–51.

    Article  PubMed  CAS  Google Scholar 

  35. Baroncelli GI, Bertelloni S, Ceccarelli C, Cupelli D, Saggese G. Dynamics of bone turnover in children with GH deficiency treated with GH until final height. Eur J Endocrinol 2000, 142: 549–56.

    Article  PubMed  CAS  Google Scholar 

  36. Van der Sluis IM, Boot AM, Hop WC, et al. Long-term effects of growth hormone therapy on bone mineral density, body composition, and serum lipid levels in growth hormone deficient children: a 6-year follow-up study. Horm Res 2002, 58: 207–14.

    Article  PubMed  Google Scholar 

  37. Shore RM, Chesney RW, Mazess RB, Rose PG, Bargman GJ. Bone mineral status in growth hormone deficiency. J Pediatr 1980, 96: 393–6.

    Article  PubMed  CAS  Google Scholar 

  38. Zamboni G, Antoniazzi F, Radetti G, Musumeci C, Tatò L. Effect of two different regimens of recombinant human growth hormone therapy on the bone mineral density of patients with growth hormone deficiency. J Pediatr 1991, 119: 483–5.

    Article  PubMed  CAS  Google Scholar 

  39. Saggese G, Baroncelli GI, Bertelloni S, Cinquanta L, Di Nero G. Effects of long-term treatment with growth hormone on bone and mineral metabolism in children with growth hormone deficiency. J Pediatr 1993, 122: 37–45.

    Article  PubMed  CAS  Google Scholar 

  40. Boot AM, Engels MAMJ, Boerma GJM, Krenning EP, De Muinck Keizer-Schrama SMPF. Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency. J Clin Endocrinol Metab 1997, 82: 2423–8.

    PubMed  CAS  Google Scholar 

  41. Baroncelli GI, Bertelloni S, Ceccarelli C, Saggese G. Measurement of volumetric bone mineral density accurately determines degree of lumbar undermineralization in children with growth hormone deficiency. J Clin Endocrinol Metab. 1998, 83: 3150–4.

    Article  PubMed  CAS  Google Scholar 

  42. Kandemir N, Gonc EN, Yordam N. Responses of bone turnover markers and bone mineral density to growth hormone therapy in children with isolated growth hormone deficiency and multiple pituitary hormone deficiencies. J Pediatr Endocrinol Metab 2002, 15, 809–16.

    Article  PubMed  CAS  Google Scholar 

  43. Saggese G, Baroncelli GI, Bertelloni S, Barsanti S. The effect of long-term growth hormone (GH) treatment on bone mineral density in children with GH deficiency. Role of GH in the attainment of peak bone mass. J Clin Endocrinol Metab 1996, 81: 3077–83.

    PubMed  CAS  Google Scholar 

  44. Battin J, Barthe N, Barat P. L’apport de l’ostéodensitométrie dans le syndrome de Turner et dans les déficit soma-totropes. Arch Pédiatr 1997, 4 (Suppl 2): 95S–101S.

    Article  PubMed  CAS  Google Scholar 

  45. Ogle GD, Moore B, Lu PW, Craighead A, Briody JN, Cowell CT. Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report. Acta Pædiatr 1994, 399 (Suppl): 3–7.

    Article  CAS  Google Scholar 

  46. Fors H, Bjarnason R, Wiren L, et al. Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents. Clin Endocrinol (Oxf) 2001, 55: 617–24.

    Article  CAS  Google Scholar 

  47. Baroncelli GI, Bertelloni S, Sodini F, Saggese G. Lumbar bone mineral density at final height and prevalence of fractures in treated children with growth hormone deficiency. J. Clin Endocrinol Metab 2002, 87: 3624–31.

    Article  PubMed  CAS  Google Scholar 

  48. Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J, The Genentech, Inc, Cooperative Study Group. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. J Clin Endocrinol Metab 2000, 85: 3653–60.

    PubMed  CAS  Google Scholar 

  49. Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int 1997, 7: 390–406.

    Article  PubMed  CAS  Google Scholar 

  50. Hyer SL, Rodin DA, Tobias JH, Leiper A, Nussey SS. Growth hormone deficiency during puberty reduces adult bone mineral density. Arch Dis Child 1992, 67: 1472–4.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Kaufman J-M, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992, 74: 118–123.

    PubMed  CAS  Google Scholar 

  52. De Boer H, Block GJ, Van Lingen A, Teule GJJ, Lips P, Van der Veen EA. Consequences of childhood-onset growth hormone deficiency for adult bone mass. J Bone Miner Res 1994, 9: 1319–26.

    Article  PubMed  Google Scholar 

  53. Bonjour J, Theintz G, Buchs B, Slosman D, Rizzoli R. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 1991, 73: 555–63.

    Article  PubMed  CAS  Google Scholar 

  54. Theintz G, Buchs B, Rizzoli R, et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab 1992, 75: 1060–5.

    PubMed  CAS  Google Scholar 

  55. Takahashi Y, Minamitani K, Kobayashi Y, Minagawa M, Yasuda T, Niimi H. Spinal and femoral bone mass accumulation during normal adolescence: comparison with female patients with sexual precocity and with hypogonadism. J Clin Endocrinol Metab 1996, 81: 1248–53.

    PubMed  CAS  Google Scholar 

  56. Lu PW, Cowell CT, Lloyd-Jones SA, Briody JN, Howman-Giles R. Volumetric bone mineral density in normal subjects, aged 5–27 years. J Clin Endocrinol Metab 1996, 81: 1586–90.

    PubMed  CAS  Google Scholar 

  57. Lu PW, Briody JN, Ogle GD, et al. Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study. J Bone Miner Res 1994, 9: 1451–8.

    Article  PubMed  CAS  Google Scholar 

  58. Fournier P-E, Rizzoli R, Slosman D-O, Theintz G, Bonjour J-P. 1997 Asynchrony between the rates of standing height gain and bone mass accumulation during puberty. Osteoporos Int 1997, 7: 525–32.

    Article  PubMed  CAS  Google Scholar 

  59. Baroncelli GI, Bertelloni S, Sodini S, Saggese G. Longitudinal changes of lumbar bone mineral density (BMD) in patients with growth hormone deficiency after discontinuation of treatment at final height. Timing and peak value of lumbar BMD Clin Endoc (Oxf) 2004, 60: 175–84.

    Article  Google Scholar 

  60. Benbassat CA, Wasserman M, Laron Z. Changes in bone mineral density after discontinuation and early reinstitution of growth hormone (GH) in patients with childhood-onset GH deficiency. Growth Horm. IGF Res 1999, 9: 290–5.

    Article  PubMed  CAS  Google Scholar 

  61. Holmes SJ, Whitehouse RW, Economou G, O’Halloran DJ, Adams JE, Shalet SM. Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement. Clin Endocrinol (Oxf) 1995, 42: 3–7.

    Article  CAS  Google Scholar 

  62. Biller BMK, Sesmilo G, Baum HBA, Hayden D, Schoenfeld D, Klibanski A. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab 2000, 85: 970–6.

    PubMed  CAS  Google Scholar 

  63. Drake WM, Carroll PV, Maher KT, 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: 1658–63.

    Article  PubMed  CAS  Google Scholar 

  64. Bouillon R, Prodonova A. Growth hormone deficiency and peak bone mass. J Pediatr Endocrinol Metab 2000, 13 (Suppl 6): 1327–36.

    PubMed  Google Scholar 

  65. Monson JP, Drake WM, Carroll PV, Weaver JU, Rodriguez-Arnao J, Savage MO. Influence of growth hormone on accretion of bone mass. Horm Res 2002, 58 (Suppl 1): 52–6.

    Article  PubMed  CAS  Google Scholar 

  66. Johannsson G, Bengtsson B-A. Growth hormone and the acquisition of bone mass. Horm Res 1997, 48 (Suppl 5): 72–7.

    Article  PubMed  Google Scholar 

  67. Colao A, Di Somma C, Pivonello R, et al. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999, 84: 1919–24.

    Article  PubMed  CAS  Google Scholar 

  68. Rosen T, Wilhemsen L, Landin-Wilhemsen K, Lappas G, Bengtsson B-Å. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 1997, 137: 240–5.

    Article  PubMed  CAS  Google Scholar 

  69. Wüster C, Abs R, Bengtsson B-Å, et al. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res 2001, 16: 398–405.

    Article  PubMed  Google Scholar 

  70. Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev 1998, 19: 55–79.

    PubMed  CAS  Google Scholar 

  71. Abrahamsen B, Hangaard J, Horn HC, et al. Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies. Clin Endocrinol (Oxf) 2002, 57: 273–81.

    Article  CAS  Google Scholar 

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  1. Endocrine Unit, Division of Pediatrics, Department of Reproductive Medicine and Pediatrics, University of Pisa, Pisa, Italy

    G. Saggese, G. I. Baroncelli, T. Vanacore, L. Fiore, S. Ruggieri & G. Federico

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  1. G. Saggese
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  2. G. I. Baroncelli
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Saggese, G., Baroncelli, G.I., Vanacore, T. et al. Indications and strategies for continuing GH treatment during transition from late adolescence to early adulthood in patients with GH deficiency: The impact on bone mass. J Endocrinol Invest 27, 596–602 (2004). https://doi.org/10.1007/BF03347486

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