Long-Term Outcome of Growth Hormone Therapy in Children and Adolescents

Treatments in Endocrinology

Volumn 3, Issue 1, 2004, Pages 53-66

  Lanes, Roberto ^a,b  

^a Hospital de Clinicas Caracas   (Venezuela)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH HORMONE; OXANDROLONE; RECOMBINANT GROWTH HORMONE; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN BINDING PROTEIN 2; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C;

ADOLESCENT; BODY GROWTH; BODY HEIGHT; BONE DENSITY; BONE MINERAL; CADAVER; CARDIOVASCULAR RISK; CARPAL TUNNEL SYNDROME; CHILD; CHILDHOOD LEUKEMIA; CHRONIC KIDNEY FAILURE; CREUTZFELDT JAKOB DISEASE; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG COST; EDEMA; EPIPHYSIOLYSIS; EVALUATION; GROWTH DISORDER; GROWTH HORMONE DEFICIENCY; GROWTH HORMONE RELEASE; GYNECOMASTIA; HORMONAL THERAPY; HUMAN; IDIOPATHIC DISEASE; INTRACRANIAL PRESSURE; INTRAUTERINE GROWTH RETARDATION; LYMPHEDEMA; MAJOR CLINICAL STUDY; MORTALITY; OUTCOMES RESEARCH; PREDICTION; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SCORING SYSTEM; SHORT STATURE; STATISTICAL SIGNIFICANCE; STRESS; TURNER SYNDROME; UREMIA;

ADOLESCENT; BODY COMPOSITION; BODY HEIGHT; CALCIFICATION, PHYSIOLOGIC; CARDIOVASCULAR DISEASES; CHILD; FETAL GROWTH RETARDATION; HUMAN GROWTH HORMONE; HUMANS; RISK FACTORS; TREATMENT OUTCOME; TURNER SYNDROME; UREMIA;

EID: 0942266135     PISSN: 11756349     EISSN: None     Source Type: Journal    
DOI: 10.2165/00024677-200403010-00006     Document Type: Review

References (108)

1. Sizonenko PC, Clayton PE, Cohen P, et al. Diagnosis and management of growth hormone deficiency in childhood and adolescence. Growth Horm IGF Res 2001; 11: 137-65
2. Raben MS. Treatment of a pituitary dwarf with human growth hormone. J Clin Endocrinol Metab 1958; 18: 901-3
3. Frasier SD. Human pituitary growth hormone (hGH) therapy in growth hormone deficiency. J Clin Endocrinol Metab 1983; 4: 155-70
4. Frasier SD, Aceto T, Hayles AB, et al. Collaborative study of the effects of human growth hormone in growth hormone deficiency: IV. Treatment with low doses of human growth hormone based on body weight. J Clin Endocrinol Metab 1977; 44: 22-31
5. Gertner JM, Tamborlane WV, Gianfredi SP, et al. Renewed catch-up growth with increased replacement doses of human growth hormone. J Pediatr 1987; 110: 425-9
6. Dean HJ, Friesen HG. Long-term growth of children with growth hormone deficiency and hypoglycemia: Therapeutic Trial of Growth Hormone Committee. Medical Research Council of Canada. J Pediatr 1989; 115: 598-600
7. Blethen SL, Baptista J, Kuntze J, et al. Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. J Clin Endocrinol Metab 1997; 82: 418-20
8. Rappaport R, Mugnier E, Limoni C, et al. A 5 year prospective study of growth hormone (GH) deficient children treated with GH before the age of 3 years. J Clin Endocrinol Metab 1997; 82: 452-6
9. Adan L, Souberbielle JC, Zucker JM, et al. Adult height in 24 patients treated for growth hormone deficiency and early puberty. J Clin Endocrinol Metab 1997; 82: 229-33
10. Mericq MV, Eggers M, Avila A, et al. Near final height in pubertal growth hormone-deficient patients treated with GH alone or in combination with luteinizing hormone releasing hormone analog: results of a prospective, randomized trial. J Clin Endocrinol Metab 2000; 85: 569-73
11. Zamboni G, Antoniazzi F, Radetti G, et al. Effects 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
12. Saggese G, Baroncelli GI, Bertelloni S, et al. The effects of long-term growth hormone treatment on bone mineral density in children with GH deficiency: role of GH in the attainment of peak bone mass. J Clin Endocrinol Metab 1986; 81: 3077-83
13. Baroncelli GI, Bertelloni S, Sodini F, et al. Lumbar bone mineral density at final height and prevalence of fractures in treated children with GH deficiency. J Clin Endocrinol Metab 2002; 87: 3624-31
14. Boot AM, Engels MAMJ, Boerma GJM, et al. Changes in bone mineral density, body composition and lipid metabolism during growth hormone treatment in children with GH-deficiency. J Clin Eudocrinol Metab 1997; 82: 2423-8
15. Koranyi J, Svensson J, Gotherstrom G, et al. Baseline characteristics and the effects of five years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset: a comparative study. J Clin Endocrinol Metab 2001; 86: 4693-9
16. Korumaru R, Kohno H, Ueyama N, et al. Long-term prospective study of body composition and lipid profiles during and after growth hormone (GH) treatment in children with GH deficiency: gender-specific effects. J Clin Endocrinol Metab 1998; 83: 3890-6
17. 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: 4516-24
18. Bengtsson BA, Christiansen JS, Cuneo RC, et al. Cardiovascular effects of GH. J Endocrinol 1997; 152: 1-3
19. Sacca L, Atteolini A, Fazio S. Growth hormone and the heart. Endocr Rev 1997; 15: 555-73
20. Abdu TAM, Neary R, Elhaad TA, et al. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities. Clin Endocrinol 2001; 55: 209-16
21. Evans LM, Davies JS, Anderson RA, et al. Elevated plasma homocysteine levels are associated with enhanced oxidative stress and endothelial dysfunction in adult hypopituitary patients with growth hormone deficiency. J Endocrinol 1999; 160 Suppl.: 22
22. Johansson JO, Landin K, Tengborn L, et al. High fibrinogen and plasminogen activator inhibitor activity in growth hormone deficient adults. Arteroscler Thromb 1999; 76: 422-8
23. Al-Shoumer KAS, Cox KH, Hughes CL, et al. Fasting and postprandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy. J Clin Endocrinol Metab 1997; 82: 2653-9
24. Murray RD, Wieringa GE, Lissett CA, et al. Low dose replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome. Clin Endocrinol (Oxf) 2002; 56: 525-32
25. Colao A, Di Somma C, Pivonello R, et al. The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12 month prospective study. J Clin Endocrinol Metab 2002; 87: 1088-93
26. Sesmilo G, Biller BM, Llevado J, et al. Effects of growth hormone (GH) administration on homocysteine levels in men with GH deficiency: a randomized controlled trial. J Clin Endocrinol Metab 2001; 86: 1518-24
27. Valcavi R, Gaddi O, Zini M, et al. Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. J Clin Endocrinol Metab 2001; 80: 659-66
28. Pfeifer M, Verhovec R, Zizek B, et al. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999; 84: 453-7
29. Lanes R, Gunczler P, Lopez E, et al. Cardiac mass and function, carotid artery intima-media thickness and lipoprotein levels in growth hormone deficient adolescents. J Clin Endocrinol Metab 2001; 86: 1061-5
30. Colao A, Di Somma C, Salerno M, et al. The cardiovascular risk of GH-deficient adolescents. J Clin Endocrinol Metab 2002; 87: 3650-5
31. Lanes R, Paoli M, Carrillo E, et al. The cardiovascular risk of young growth hormone deficient adolescents: differences in growth hormone treated and untreated subjects. Horm Res 2003; 60: 291-5
32. Aimaretti G, Cornelli G, Bellone S, et al. Growth hormone deficiency in the transition adolescent: should treatment be continued in adult life. J Pediatr Endocrinol Metab 2001; 14: 1233-42
33. Hartman ML, Crowe BJ, Biller BMK, et al. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency, J Clin Endocrinol Metab 2002; 87: 477-85
34. Attanasio AF, Howell S, Bates PC, et al. Body composition, IGF-1 and IGFBP3 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: 3368-72
35. Lyon AJ, Preece MA, Grant DB. Growth curve for girls with Turner syndrome. Arch Dis Child 1985; 60: 932-5
36. Ranke MB. Growth in Turner's syndrome [letter]. Acta Paediatr 1994; 83: 343-4
37. Zadik Z, Landau H, Chen M, et al. Assesment of growth hormone axis in Turner's syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor 1, plasma GH-binding activity, GH binding to IM9 cells and GH response to pharmacological stimulation. J Clin Endocrinol Metab 1992; 75: 412-6
38. Van Es, Massarano AA, Wit JM. 24 hour growth hormone secretion in Turner syndrome. In: Ranke MB, Rosenfeld RG, editors. Turner syndrome: growth promoting therapies. Amsterdam: Elsevier Science Publishers BV. 1991: 29-33
39. Lanes R, Brito S, Suniaga M, et al. Growth hormone secretion in pubertal age patients with Turner's syndrome. J Clin Endocrinol Metab 1992; 71: 770-2
40. Veldhuis JD, Sotos JF, Sherman BM. Decreased metabolic clearance of endogenous growth hormone and specific alterations in the pulsatile mode of growth hormone secretion occur in prepubertal girls with Turner's syndrome. J Clin Endocrinol Metab 1991; 73: 1073-80
41. Massa G, Bouillon R, Vanderschueren-Lodeweyckx M. Serum growth hormone-binding protein and insulin-like growth factor 1 levels in Turner's syndrome before and during treatment with recombinant human GH and estradiol. J Clin Endocrinol Metab 1992; 75: 1298-302
42. Rudman D, Goldsmith M, Kutner M, et al. Effect of growth hormone and oxandrolone singly or together on growth rate in girls with X chromosome abnormalities. J Pediatr 1988; 96: 132-5
43. Ross JL, Myerson L, Skerda M, et al. Growth response relationship between growth hormone dose and short term growth in patients with Turner's syndrome. J Clin Endocrinol Metab 1986; 63: 1028-30
44. Raiti S, Moore WV, Van Vliet G, et al. Growth-stimulating effects of human growth hormone therapy in patients with Turner syndrome. J Pediatr 1986; 109: 944-9
45. Rosenfeld RG, Hintz R, Johanson AJ, et al. Methyonil human growth hormone and oxandrolone in Turner syndrome: preliminary results of a prospective randomized trial. J Pediatr 1986; 109: 936-43
46. Lanes R, Gunczler P, Paoli M, et al. Bone mineral density of prepubertal age girls with Turner syndrome while on growth hormone therapy. Horm Res 1995; 44: 168-71
47. Teunenbroek AV, Muinck Keizer-Scharma SMPF, Stijnen T, et al. Yearly stepwise increments of the growth hormone dose results in a better growth response after four years in girls with Turner syndrome. J Clin Endocrinol Metab 1996; 81: 4013-21
48. Rosenfeld R, Attie KM, Frane J, et al. Growth hormone therapy of Turner's syndrome: beneficial effect on adult height, J Pediatr 1998; 132: 319-24
49. Nilsson KO, Albertsson-Wikland K, Alm J, et al. Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone. J Clin Endocrinol Metab 1996; 81: 635-40
50. Quigley CA, Crowe BJ, Anglin DG, et al. Growth hormone and low dose estrogen in Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab 2002; 87: 2033-41
51. Van den Broeck J, Massa GG, Attanasio A, et al. Final height after long term growth hormone treatment in Turner syndrome. J Pediatr 1996; 127: 729-35
52. Dacou-Voutetakis C, Karavanaki-Karanassiou K, Petrou V, et al. The growth pattern and final height of girls with Turner syndrome with and without human growth hormone treatment. Pediatrics 1998; 101: 663-8
53. Joss EE, Mullis PE, Werder EA, et al. Growth promotion and Turner-specific bone age after therapy with growth hormone and in combination with oxandrolone: when should therapy be started in Turner syndrome? Horm Res 1997; 47: 102-9
54. Chernausek SD, Attie KM, Cara JF, et al. Growth hormone therapy of Turner syndrome: the impact of age of estrogen replacement on final height. Genentech Inc., Collaborative Study Group. J Clin Endocrinol Metab 2000; 85: 2439-45
55. Ross JL, Meyerson Long L, Feuillan P, et al. Normal bone density of the wrist and spine and increased wrist fractures in girls with Turner syndrome. J Clin Endocrinol Metab 1991; 73: 355-9
56. Mora S, Weber G, Guarneri MP, et al. Effect of estrogen replacement therapy on bone mineral content in girls with Turner syndrome. Obstet Gynecol 1992; 79: 747-51
57. Neely EK, Marcus R, Rosenfeld RG, et al. Turner syndrome adolescents receiving growth hormone are not osteopenic. J Clin Endocrinol Metab 1993; 76: 861-6
58. Shaw NJ, Rehan VK, Husain S, et al. Bone mineral density in Turner syndrome: a longitudinal study. Clin Endocrinol (Oxt) 1997; 47: 367-70
59. Davies M, Gulekli B, Jacobs HS. Osteoporosis in Turner syndrome and other forms of primary amenorrhea. Clin Endocrinol 1996; 43: 741-6
60. Lanes R, Gunczler P, Esaa S, et al. Decreased trabecular bone mineral density in young women with Turner syndrome despite estrogen replacement and previously normal bone densities. Fertil Steril 1999; 72: 896-9
61. Hojbjerg C, Gravholt A, Lauridsen L, et al. Marked disproportionality in bone size and mineral, and distinct abnormalities in bone markers and calcitropic hormones in adult Turner syndrome: a cross-sectional study. J Clin Endocrinol Metab 2002; 87: 2798-808
62. Bertelloni S, Cinquata L, Baroncelli GI, et al. Volumetric bone mineral density in young women with Turner syndrome treated with estrogens or estrogens plus growth hormone. Horm Res 2000; 53: 72-6
63. Sas TC, de Muinck Keiser-Schrama SM, Stijnen T, et al. A longitudinal study on bone mineral density until adulthood in girls with Turner syndrome participating in a growth hormone injection frequency-response trial. Clin Endocrinol (Oxf) 2000; 532: 531-6
64. Veldhuis JD, Blizzard RM, Rogol AD, et al. Properties of spontaneous growth hormone secretory bursts and half life of endogenous growth hormone in boys with idiopathic short stature: the Genentech Collaborative Group. J Clin Endocrinol Metab 1993; 74: 766-73
65. Attie KM, Carlsson LMS, Rundle AC, et al. Evidence for a partial growth hormone insensitivity among patients with idiopathic short stature. J Pediatr 1995; 127: 244-50
66. Genentech Collaborative Group. Idiopathic short stature: results of a one-year controlled study of human growth hormone treatment. J Pediatr 1989; 115: 713-9
67. Lanes R. Effects of two years of growth hormone treatment in short, slowly growing non-growth hormone deficient children. J Pediatr Endocrinol Metab 1995; 8: 167-71
68. Wit JM, Fokker MH, de Muinck Keizer-Schrama MPF, et al. Effects of two years of methionyl growth hormone therapy in two dosage regimen in prepubertal children with short stature, subnormal growth rate, and normal growth hormone response to secretagogues. J Pediatr 1989; 115: 720-5
69. Loche S, Cambiaso P, Setzu S, et al. Final height after growth hormone therapy in non-growth-hormone deficient children with short stature. J Pediatr 1994; 125: 196-200
70. Rekers-Mombarg LTM, Massa GG, Wit JM, et al. Growth hormone therapy with three dosage regimens in children with idiopathic short stature: European Study Group Participating Investigators. J Pediatr 1998; 132: 455-60
71. Kawai M, Momoi T, Yorifuji T, et al. Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency. J Pediatr 1997; 130: 205-9
72. Hintz RL, Attie KM, Baptista J, et al. Effect of growth hormone treatment on adult height of children with idiopathic short stature. N Engl J Med 1999; 340: 502-7
73. Buchlis JG, Irizarry L, Crotzer BC, et al. Comparison of final heights of growth hormone treated vs untreated children with idiopathic growth failure. J Clin Endocrinol Metab 1998; 83: 1075-9
74. Lesage C, Walker J, Chatelain P, et al. Near normalization of adolescent height with growth hormone therapy in very short children without growth hormone deficiency. J Pediatr 1991; 119: 29-34
75. Wit JM, Rekers-Mombarg TM. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 2002; 87: 604-11
76. Saggese G, Cesareretti G, Barsanti S, et al. Combination treatment with growth hormone and gonadotropin-releasing hormone analogs in short normal girls. J Pediatr 1995; 126: 468-73
77. Kamp GA, Mul D, Waelkens JJJ, et al. A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation. J Clin Endocrinol Metab 2001; 86: 2969-75
78. Balducci R, Toscano V, Mangiantini A, et al. Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analog and growth hormone. J Clin Endocrinol Metab 1995; 80: 3596-600
79. Lanes R, Gunczler P. Final height after combined growth hormone and gonadotropin releasing hormone analogue therapy in short healthy children entering into normally timed puberty. Clin Endocrinol (Oxf) 1998; 49: 197-202
80. Ogle GD, Rosenberg AR, Calligeros D, et al. Effects of growth hormone treatment for short stature on calcium homeostasis, bone mineralisation and body composition. Horm Res 1994; 41: 16-20
81. Lanes R, Gunczler P, Weisinger JR. Decreased trabecular bone mineral density in children with idiopathic short stature: normalization of bone density and increased bone turnover after one year of growth hormone treatment. J Pediatr 1999; 135: 177-81
82. Lanes R, Gunczler P, Weisinger JR. The effect of short and long term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3 year study. Clin Endocrinol (Oxf) 2002; 57: 725-30
83. Fine R. Growth hormone treatment of children with chronic renal insufficiency, end-stage renal disease and following renal transplantation. J Pediatr Endocrinol Metab 1997; 10: 361-70
84. Fine R, Pyke-Grimm K, Nelson PA, et al. Recombinant human growth hormone treatment of children with chronic renal failure: long term (1 to 3 year) outcome. Pediatr Nephrol 1991; 5: 477-81
85. Fine RN, Kohaut EC, Brown D, et al. Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. Genentech Cooperative Study Group. J Pediatr 1994; 124: 374-81
86. Hokken-Koelega ACS, Stijnen T, de Muinck Keizer-Schrama SMPF, et al. Placebo-controlled, double-blind, cross over trial of growth hormone treatment in prepubertal children with chronic renal failure. Lancet 1991; 338: 585-90
87. Lanes R, Gunczler P, Orta N, et al. Changes in bone mineral density, growth velocity and renal function of prepubertal uremic children during growth hormone treatment. Horm Res 1996; 46: 263-8
88. Van Dop C, Jabs KL, Donahoue PA, et al. Accelerated growth rates in children treated with growth hormone after renal transplantation. J Pediatr 1994; 120: 244-50
89. Hokken-Koelega ACS, Stijnen T, de Jong MCJW, et al. Double blind trial comparing the effects of two doses of growth hormone in prepubertal patients with chronic renal insufficiency. J Clin Endocrinol Metab 1992; 79: 1185-90
90. Fine RN, Brown DF, Kuntze J, et al. Growth after discontinuation of recombinant human growth hormone therapy in children with chronic renal failure. J Pediatr 1996; 129: 883-91
91. Lanes R, Gunczler P, Orta N, et al. Incremento en la velocidad de crecimiento y en la mineralizacion osea de niños con insuficiencia renal cronica durante 2 años de tratamiento con hormona de crecimiento; desaceleracion marcada de su velocidad de crecimiento al descontinuar terapia. Endocrinologia 1997; 44: 355-60
92. Van Dyck M, Gyssels A, Proesmans W, et al. Growth hormone treatment enhances bone mineralisation in children with chronic renal failure. Eur J Pediatr 2001; 160: 359-63
93. Boot AM, Nauta J, de Jong MCJW, et al. Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with or without growth hormone treatment. Clin Endocrinol (Oxf) 1998; 49: 665-72
94. Feber J, Cochat P, Braillon P, et al. Bone mineral density after renal transplantation in children. J Pediatr 1994; 125: 870-5
95. De Zegher F, Francois I, van Helvirt M, et al. Small as fetus and short as child: from endogenous to exogenous growth hormone. J Clin Endocrinol Metab 1997; 82: 2021-6
96. Boguszewski M, Rosberg S, Albertsson-Wikland K. Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children. J Clin Endocrinol Metab 1995; 80: 2599-606
97. Foley TP, Thompson RG, Shaw M, et al. Growth responses to human growth hormone in patients with intrauterine growth retardation. J Pediatr 1974; 84: 635-41
98. Lanes R, Plotnick LP, Lee PA. Sustained effect of human growth hormone therapy on children with intrauterine growth retardation. Pediatrics 1979; 63: 731-5
99. Chatelain PC, Job JC, Blanchard J, et al. Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. J Clin Endocrinol Metab 1994; 78: 1454-60
100. de Zegher F, Maes M, Gargosky SE, et al. High-dose growth hormone treatment of short children born small for gestational age. J Clin Endocrinol Metab 1996; 81: 1887-92
101. Boguszewski M, Albertsson-Wikland K, Aronsson S, et al. Growth hormone treatment of short children born small-for-gestational age: the Nordic Multicentre Trial. Acta Paediatr 1998; 87: 257-63
102. de Zegher F, Albertsson-Wikland K, Wollmann HA, et al. Growth hormone treatment of short children born small for gestational age: growth responses with continuous and discontinuous regimens over 6 years. J Clin Endocrinol Metab 2000; 85: 2816-21
103. Sas T, Waal W, Mulder P, et al. Growth hormone treatment in children with short stature born small for gestational age: 5 years results of a randomized, double blind, dose-response trial. J Clin Endocrinol Metab 1999; 84: 3064-70
104. Coutant R, Carel JC, Letrait M, et al. Short stature associated with intrauterine growth retardation: final height of untreated and growth hormone-treated children. J Clin Endocrinol Metab 1998; 83: 1070-4
105. Blethen S, Allen DB, Graves D, et al. Safety of recombinant deoxyribonucleic acid-derived growth hormone: the national cooperative growth study experience. J Clin Endocrinol Metab 1996; 81: 1704-10
106. Cutfield WS, Wilton P, Bennmarker H, et al. Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 2000; 355: 610-3
107. Swerdlow AJ, Higgins CD, Adlard P, et al. Risk of cancer in patients treated with human pituitary growth hormone in the United Kingdom, 1959-1985: a cohort study. Lancet 2002; 360: 273-7
108. Sperling MA, Saenger PH, Hintz R, et al. Special editorial: growth hormone treatment and neoplasia-coincidence or consequence. Lawson Wilkins Pediatric Endocrine Society (LWPES) Executive Committee and LWPES Drug and Therapeutics Committee. J Clin Endocrinol Metab 2002; 87: 5351-2