The role of insulin-like growth factors in growth hormone deficiency

Growth Hormone Therapy in Pediatrics-20 Years of KIGS

Volumn , Issue , 2007, Pages 70-82

  Juul, Anders ^a  

^a Rigshospitalet   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 80054975455     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1159/000101721     Document Type: Chapter

References (126)

1. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT: Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995; 16: 143-163.
2. Siebler T, Lopaczynski W, Terry CL, Casella SJ, Munson P, De Leon DD, Phang L, Blakemore KJ, McEvoy RC, Kelley RI: Insulin-like growth factor I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15. J Clin Endocrinol Metab 1995; 80: 3447-3457.
3. Hattori Y, Vera JC, Rivas CI, Bersch N, Bailey RC, Geffner ME, Golde DW: Decreased insulin-like growth factor I receptor expression and function in immortalized African Pygmy T cells. J Clin Endocrinol Metab 1996; 81: 2257-2263.
4. Nielsen FC: The molecular and cellular biology of insulin-like growth factor II. Prog Growth Factor Res 1992; 4: 257-290.
5. Steele-Perkins G, Turner J, Edman JC, Hari J, Pierce SB, Stover C, Rutter WJ, Roth RA: Expression and characterization of a functional human insulin-like growth factor I receptor. J Biol Chem 1988; 263: 11486-11492.
6. Baxter RC, Binoux MA, Clemmons DR, Conover CA, Drop SL, Holly JM, Mohan S, Oh Y, Rosenfeld RG: Recommendations for nomenclature of the insulin-like growth factor binding protein superfamily. J Clin Endocrinol Metab 1998; 83: 3213.
7. Baxter RC: Circulating levels and molecular distribution of the acid-labile (alpha) subunit of the high molecular weight insulin-like growth factor-binding protein complex. J Clin Endocrinol Metab 1990; 70: 1347-1353.
8. Arany E, Afford S, Strain AJ, Winwood PJ, Arthur MJ, Hill DJ: Differential cellular synthesis of insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 within human liver. J Clin Endocrinol Metab 1994; 79: 1871-1876.
9. Chin E, Zhou J, Dai J, Baxter RC, Bondy CA: Cellular localization and regulation of gene expression for components of the insulin-like growth factor ternary binding protein complex. Endocrinology 1994; 134: 2498-2504.
10. Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, Muller J, Skakkebaek NE: Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995; 80: 2534-2542.
11. Holman SR, Baxter RC: Insulin-like growth factor binding protein-3: factors affecting binary and ternary complex formation. Growth Regul 1996; 6: 42-47.
12. Baxter RC: Glycosaminoglycans inhibit formation of the 140 kDa insulin-like growth factor-binding protein complex. Biochem J 1990; 271: 773-777.
13. Cook JS, Hoffman RP, Stene MA, Hansen JR: Effects of maturational stage on insulin sensitivity during puberty. J Clin Endocrinol Metab 1993; 77: 725-730.
14. Luna AM, Wilson DM, Wibbelsman CJ, Brown RC, Nagashima RJ, Hintz RL, Rosenfeld RG: Somatomedins in adolescence: a cross-sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels. J Clin Endocrinol Metab 1983; 57: 268-271.
15. Argente J, Barrios V, Pozo J, Munoz MT, Hervas F, Stene M, Hernandez M: Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age- and sex-related changes. J Clin Endocrinol Metab 1993; 77: 1522-1528.
16. Blumsohn A, Hannon RA, Wrate R, Barton J, al-Dehaimi AW, Colwell A, Eastell R: Biochemical markers of bone turnover in girls during puberty. Clin Endocrinol (Oxf) 1994; 40: 663-670
17. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994; 78: 744-752.
18. Lofqvist C, Andersson E, Gelander L, Rosberg S, Blum WF, Albertsson WK: Reference values for IGF-I throughout childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty. J Clin Endocrinol Metab 2001; 86: 5870-5876.
19. Wilson DM, Stene MA, Killen JD, Hammer LD, Litt IF, Hayward C, Taylor CB: Insulin-like growth factor binding protein-3 in normal pubertal girls. Acta Endocrinol (Copenh) 1992; 126: 381-386.
20. Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR: A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin- binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 1990; 70: 1292-1298.
21. Juul A, Scheike T, Nielsen CT, Krabbe S, Muller J, Skakkebaek NE: Serum insulin- like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate). J Clin Endocrinol Metab 1995; 80: 3059-3067.
22. Juul A, Moller S, Mosfeldt-Laursen E, Rasmussen MH, Scheike T, Pedersen SA, Kastrup KW, Yu H, Mistry J, Rasmussen S, Muller J, Henriksen J, Skakkebaek NE: The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum: hepatosplanchnic release, diurnal variation, circulating concentrations in healthy subjects, and diagnostic use in patients with growth hormone deficiency. J Clin Endocrinol Metab 1998; 83: 4408-4415.
23. Nimura A, Katsumata N, Horikawa R, Tanae A, Tanaka T: Acid-labile subunit (ALS) measurements in children. Endocr J 2000; 47(suppl):S111-S114.
24. Barrios V, Pozo J, Munoz MT, Buno M, Argente J: Normative data for total and free acid-labile subunit of the human insulin-like growth factor-binding protein complex in pre- and full-term newborns and healthy boys and girls throughout postnatal development. Horm Res 2000; 53: 148-153.
25. Juul A, Flyvbjerg A, Frystyk J, Muller J, Skakkebaek NE: Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins-1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty. Clin Endocrinol (Oxf) 1996; 44: 515-523.
26. Blum WF, Horn N, Kratzsch J, Jorgensen JO, Juul A, Teale D, Mohnike K, Ranke MB: Clinical studies of IGFBP-2 by radioimmunoassay. Growth Regul 1993; 3: 100-104.
27. Juul A, Holm K, Kastrup KW, Pedersen SA, Michaelsen KF, Scheike T, Rasmussen S, Muller J, Skakkebaek NE: Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 2497-2502.
28. Giwercman B, Giwercman A, Kastrup KW, Skakkebaek NE: Age- and sexrelated variations in the serum concentration of somatomedin C in normal children and adults. Ugeskr Laeger 1987; 149: 1320-1323.
29. Rikken B, van Doorn J, Ringeling A, van den Brande JL, Massa G, Wit JM: Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res 1998; 50: 166-176.
30. Rasat R, Livesey JL, Espiner EA, Abbott GD, Donald RA: IGF-1 and IGFBP-3 screening for disorders of growth hormone secretion. N Z Med J 1996; 109: 156-159.
31. Suwa S, Katsumata N, Maesaka H, Tokuhiro E, Yokoya S: Serum insulinlike growth factor I (somatomedin-C) level in normal subjects from infancy to adulthood, pituitary dwarfs and normal variant short children. Endocrinol Jpn 1988; 35: 857-864.
32. Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA: Significance of basal IGF-I, IGFBP-3 and IGFBP-2 measurements in the diagnostics of short stature in children. Horm Res 2000; 54: 60-68.
33. Hall CM, Gill MS, Foster P, Pennells L, Tillmann V, Jones J, Price DA, Clayton PE: Relationship between serum and urinary insulin-like growth factor-I through childhood and adolescence: their use in the assessment of disordered growth. Clin Endocrinol (Oxf) 1999; 50: 611-618.
34. Mitchell H, Dattani MT, Nanduri V, Hindmarsh PC, Preece MA, Brook CG: Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency. Arch Dis Child 1999; 80: 443-447.
35. Rosenfeld RG, Wilson DM, Lee PD, Hintz RL: Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr 1986; 109: 428-433.
36. Rose SR, Ross JL, Uriarte M, Barnes KM, Cassorla FG, Cutler GB: The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency. N Engl J Med 1988; 319: 201-207.
37. Albertsson-Wikland K, Rosberg S, Hall K: Spontaneous secretion of growth hormone and serum levels of insulinlike growth factor I and somatomedin binding protein in children of different growth rates; in Isaksson O, Binder C, Hall K, Hökfelt B (eds): Growth Hormone - Basic and Clinical Aspects. Amsterdam, Elsevier Science Publishers BV (Biomedical Division), 1987, pp 163-175.
38. Saggese G, Cesaretti G, Cioni C, Cinguanta L, Ginanessi N: Relationship between plasma somatomedin C levels and 24-hour spontaneous growth hormone secretion in short children. J Pediatr Endocrinol Metab 1991; 4: 159-166.
39. Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB: Serum levels of insulin- like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 1993; 76: 1610-1616.
40. Achermann JC, Brook CG, Robinson IC, Matthews DR, Hindmarsh PC: Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF- 1) concentrations in short children. Clin Endocrinol (Oxf) 1999; 50: 301-308.
41. Achermann JC, Hindmarsh PC, Brook CG: The relationship between the growth hormone and insulin-like growth factor axis in long-term survivors of childhood brain tumours. Clin Endocrinol (Oxf) 1998; 49: 639-645.
42. Phillip M, Chalew SA, Kowarski AA, Stene MA: Plasma IGFBP-3 and its relationship with quantitative growth hormone ecretion in short children. Clin Endocrinol (Oxf) 1993; 39: 427-432.
43. Nunez SB, Municchi G, Barnes KM, Rose SR: Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations compared to stimulated and night growth hormone in the evaluation of short children - a clinical research center study. J Clin Endocrinol Metab 1996; 81: 1927-1932.
44. Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP: Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981; 67: 1361-1369.
45. Reutens AT, Hoffman DM, Leung KC, Ho KK: Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency. J Clin Endocrinol Metab 1995; 80: 480-485.
46. Vahl N, Jorgensen JO, Jurik AG, Christiansen JS: Abdominal adiposity and physical fitness are major determinants of the age associated decline in stimulated GH secretion in healthy adults. J Clin Endocrinol Metab 1996; 81: 2209-2215.
47. Baum HB, Biller BM, Katznelson L, Oppenheim DS, Clemmons DR, Cannistraro KB, Schoenfeld DA, Best SA, Klibanski A: Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men - a clinical research center study. J Clin EndocrinolMetab 1996; 81: 84-92.
48. Corpas E, Harman SM, Blackman MR: Serum IGF-binding protein-3 is related to IGF-I, but not to spontaneous GH release, in healthy old men. Horm Metab Res 1992; 24: 543-545.
49. Marin G, Domene HM, Barnes KM, Blackwell BJ, Cassorla FG, Cutler GB: The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab 1994; 79: 537-541.
50. Martinez AS, Domene HM, Ropelato MG, Jasper HG, Pennisi PA, Escobar ME, Heinrich JJ: Estrogen priming effect on growth hormone (GH) provocative test: a useful tool for the diagnosis of GH deficiency. J Clin Endocrinol Metab 2000; 85: 4168-4172.
51. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, Bartolotta E, Dammacco F, Camanni F: Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab 1996; 81: 3323-3327.
52. Granada ML, Sanmarti A, Lucas A, Salinas I, Carrascosa A, Foz M, Audi L: Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children. Acta Paediatr Scand Suppl 1990; 370: 63-70; discussion 71.
53. Andersson AM, Orskov H, Ranke MB, Shalet S, Skakkebaek NE: Interpretation of growth hormone provocative tests: comparison of cut-off values in four European laboratories. Eur J Endocrinol 1995; 132: 340-343.
54. Zapf J, Walter H, Froesch ER: Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 1981; 68: 1321-1330.
55. Furlanetto RW, Underwood LE, Van Wyk JJ, D'Ercole AJ: Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest 1977; 60: 648-657.
56. Bala RM, Bhaumick B: Radioimmunoassay of a basic somatomedin: comparison of various assay techniques and somatomedin levels in various sera. J Clin Endocrinol Metab 1979; 49: 770-777.
57. Juul A, Skakkebaek NE: Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin- like growth factor I and insulin-like growth factor binding protein 3. J Pediatr 1997; 130: 197-204.
58. Boquete HR, Sobrado PG, Fideleff HL, Sequera AM, Giaccio AV, Suarez MG, Ruibal GF, Miras M: Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Metab 2003; 88: 4702-4708.
59. Lee PD, Wilson DM, Rountree L, Hintz RL, Rosenfeld RG: Efficacy of insulinlike growth factor I levels in predicting the response to provocative growth hormone testing. Pediatr Res 1990; 27: 45-51.
60. Smith WJ, Nam TJ, Underwood LE, Busby WH, Celnicker A, Clemmons DR: Use of insulin-like growth factorbinding protein-2 (IGFBP-2), IGFBP-3, and IGF-I for assessing growth hormone status in short children. J Clin Endocrinol Metab 1993; 77: 1294-1299.
61. Cianfarani S, Boemi S, Spagnoli A, Cappa M, Argiro G, Vaccaro F, Manca BM, Boscherini B: Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency? Clin Endocrinol (Oxf) 1995; 43: 43-47.
62. Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y: Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996; 134: 184-189.
63. Bussieres L, Souberbielle JC, Pinto G, Adan L, Noel M, Brauner R: The use of insulin-like growth factor 1 reference values for the diagnosis of growth hormone deficiency in prepubertal children. Clin Endocrinol (Oxf) 2000; 52: 735-739.
64. Tillmann V, Buckler JM, Kibirige MS, Price DA, Shalet SM, Wales JK, Addison MG, Gill MS, Whatmore AJ, Clayton PE: Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 531-535.
65. Sklar C, Sarafoglou K, Whittam E: Efficacy of insulin-like growth factor binding protein 3 in predicting the growth hormone response to provocative testing in children treated with cranial irradiation. Acta Endocrinol (Copenh) 1993; 129: 511-515.
66. Weinzimer SA, Homan SA, Ferry RJ, Moshang T: Serum IGF-I and IGFBP-3 concentrations do not accurately predict growth hormone deficiency in children with brain tumours. Clin Endocrinol (Oxf) 1999; 51: 339-345.
67. Oerter KE, Sobel AM, Rose SR, Cristiano A, Malley JD, Cutler GB, Baron J: Combining insulin-like growth factor-I and mean spontaneous nighttime growth hormone levels for the diagnosis of growth hormone deficiency. J Clin Endocrinol Metab 1992; 75: 1413-1420.
68. Ranke MB, Schweizer R, Lindberg A, Price DA, Reiter EO, Albertsson-Wikland K, Darendeliler F: Insulin-like growth factors as diagnostic tools in growth hormone deficiency during childhood and adolescence: the KIGS experience. Horm Res 2004; 62(suppl 1):17-25.
69. Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Nose O, Ohyama Y, Araki K, Tanaka T, Saisyo S, Yokoya S: Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency. Eur J Endocrinol 1994; 131: 27-32.
70. Aguiar-Oliveira MH, Gill MS, de A Barrett ES, Alcantara MR, Miraki-Moud F, Menezes CA, Souza AH, Martinelli CE, Pereira FA, Salvatori R, Levine MA, Shalet SM, Camacho-Hubner C, Clayton PE: Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding proteins, and ternary complex formation throughout life. J Clin Endocrinol Metab 1999; 84: 4118-4126.
71. Barrios V, Argente J, Munoz MT, Pozo J, Chowen JA, Hernandez M: Diagnostic interest of acid-labile subunit measurement in relationship to other components of the IGF system in pediatric patients with growth or eating disorders. Eur J Endocrinol 2001; 144: 245-250.
72. Rosenfeld RG: Is growth hormone deficiency a viable diagnosis? J Clin Endocrinol Metab 1997; 82: 349-351.
73. Hoffman DM, O'Sullivan AJ, Baxter RC, Ho KK: Diagnosis of growth-hormone deficiency in adults. Lancet 1994; 343: 1064-1068.
74. de Boer H, Blok GJ, Popp-Snijders C, van der Veen EA: Diagnosis of growth hormone deficiency in adults. Lancet 1994; 343: 1645-1646.
75. Janssen YJ, Frolich M, Roelfsema F: A low starting dose of genotropin in growth hormone-deficient adults. J Clin Endocrinol Metab 1997; 82: 129-135.
76. Juul A, Kastrup KW, Pedersen SA, Skakkebaek NE: Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3. J Clin Endocrinol Metab 1997; 82: 1195-1201.
77. Rahim A, Toogood AA, Shalet SM: The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf) 1996; 45: 557-562.
78. Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P: Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 1995; 133: 305-312.
79. Anonymous: Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 2000; 85: 3990-3993.
80. Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, Severi F: 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: 1324-1328.
81. Granada ML, Murillo J, Lucas A, Salinas I, Llopis MA, Castells I, Foz M, Sanmarti A: Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol 2000; 142: 243-253.
82. Hilding A, Hall K, Wivall-Helleryd IL, Saaf M, Melin AL, Thoren M: Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19-82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 1999; 84: 2013-2019.
83. Aimaretti G, Baffoni C, Bellone S, Di Vito L, Corneli G, Arvat E, Benso L, Camanni F, Ghigo E: Retesting young adults with childhood-onset growth hormone (GH) deficiency with GHreleasing-hormone-plus-arginine test. J Clin Endocrinol Metab 2000; 85: 3693-3699.
84. Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Bellone J, Camanni F, Ghigo E: Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults. J Endocrinol Invest 1998; 21: 506-511.
85. Svensson J, Johannsson G, Bengtsson BA: Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test. Clin Endocrinol (Oxf) 1997; 46: 579-586.
86. Cuneo RC, Judd S, Wallace JD, Perry- Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley D: The Australian multicenter trial of growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 1998; 83: 107-116.
87. Bates AS, Evans AJ, Jones P, Clayton RN: Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin-like growth factor-I and urinary growth hormone excretion. Clin Endocrinol (Oxf) 1995; 42: 425-430.
88. Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA: Highaffinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormonedeficiency. Eur J Endocrinol 1996; 135: 82-86.
89. Andersen M, Hansen TB, Støving K, et al: The pyridostigmine-growth hormone-releasing hormone test in adults. The reference interval and a comparison with the insulin tolerance test. Endocrinol Metab 1996; 3: 197-206.
90. Span JP, Pieters GF, Sweep CG, Swinkels LM, Smals AG: Plasma IGF-I is a useful marker of growth hormone deficiency in adults. J Endocrinol Invest 1999; 22: 446-450.
91. Toogood AA, Jones J, O'Neill PA, Thorner MO, Shalet SM: The diagnosis of severe growth hormone deficiency in elderly patients with hypothalamicpituitary disease. Clin Endocrinol (Oxf) 1998; 48: 569-576.
92. Sassolas G, Chazot FB, Jaquet P, Bachelot I, Chanson P, Rudelli CC, Tauber JP, Allannic H, Bringer J, Roudaut N, Rohmer V, Roger P, Latapie JL, Reville P, Leutenegger M: GH deficiency in adults: an epidemiological approach. Eur J Endocrinol 1999; 141: 595-600.
93. Musolino NR, Da Cunha N, Marino JR, Giannella-Neto D, Bronstein MD: Evaluation of free insulin-like growth factor-I measurement on the diagnosis and follow-up treatment of growth hormone-deficient adult patients. Clin Endocrinol (Oxf) 1999; 50: 441-449.
94. Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G: The growth hormone (GH) response to the arginine plus GHreleasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab 1999; 84: 1277-1282.
95. Marzullo P, Di Somma C, Pratt KL, Khosravi J, Diamandis A, Lombardi G, Colao A, Rosenfeld RG: Usefulness of different biochemical markers of the insulin-like growth factor (IGF) family in diagnosing growth hormone excess and deficiency in adults. J Clin Endocrinol Metab 2001; 86: 3001-3008.
96. Kim HJ, Kwon SH, Kim SW, Park DJ, Shin CS, Park KS, Kim SY, Cho BY, Lee HK: Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults. Horm Res 2001; 56: 117-123.
97. Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ: Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 2002; 87: 477-485.
98. Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F: New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996; 134: 352-356.
99. Attanasio AF, Howell S, Bates PC, Blum WF, Frewer P, Quigley C, Shalet SM: Confirmation of severe GH deficiency after final height in patients diagnosed as GH deficient during childhood. Clin Endocrinol (Oxf) 2002; 56: 503-507.
100. Fisker S, Jorgensen JO, Vahl N, Orskov H, Christiansen JS: Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults. Eur J Endocrinol 1999; 141: 601-608.
101. Maghnie M, Aimaretti G, Bellone S, Bona G, Bellone J, Baldelli R, de Sanctis C, Gargantini L, Gastaldi R, Ghizzoni L, Secco A, Tinelli C, Ghigo E: 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: 589-596.
102. Ono T, Kanzaki S, Seino Y, Baylink DJ, Mohan S: Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme. J Clin Endocrinol Metab 1996; 81: 2111-2116.
103. de Muinck K, Rikken B, Wynne HJ, Hokken-Koelega AC, Wit JM, Bot A, Drop SL: Dose-response study of biosynthetic human growth hormone (GH) in GH-deficient children: effects on auxological and biochemical parameters. Dutch Growth Hormone Working Group. J Clin Endocrinol Metab 1992; 74: 898-905.
104. Cohen P, Bright GM, Rogol AD, Kappelgaard AM, Rosenfeld RG: Effects of dose and gender on the growth and growth factor response to GH in GHdeficient children: implications for efficacy and safety. J Clin Endocrinol Metab 2002; 87: 90-98.
105. Coutant R, Boux dC, Rouleau S, Douay O, Mathieu E, Audran M, Limal JM: Body composition, fasting leptin, and sex steroid administration determine GH sensitivity in peripubertal short children. J Clin Endocrinol Metab 2001; 86: 5805-5812.
106. Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA: Relevance of IGFI, IGFBP-3, and IGFBP-2 measurements during GH treatment of GHdeficient and non-GH-deficient children and adolescents. Horm Res 2001; 55: 115-124.
107. Ghigo E, Aimaretti G, Maccario M, Fanciulli G, Arvat E, Minuto F, Giordano G, Delitala G, Camanni F: Doseresponse study of GH effects on circulating IGF-I and IGFBP-3 levels in healthy young men and women. Am J Physiol 1999; 276:E1009-E1013.
108. Yuen K, Ong K, Husbands S, Chatelain P, Fryklund L, Gluckman P, Ranke M, Cook D, Rosenfeld R, Wass J, Dunger D: The effects of short-term administration of two low doses versus the standard GH replacement dose on insulin sensitivity and fasting glucose levels in young healthy adults. J Clin Endocrinol Metab 2002; 87: 1989-1995.
109. Jorgensen JO, Blum WF, Moller N, Ranke MB, Christiansen JS: Shortterm changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GH-deficient patients. J Clin Endocrinol Metab 1991; 72: 582-587.
110. Jorgensen JO, Pedersen SA, Thuesen L, Jorgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS: Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989;i:1221-1225.
111. Juul A, Andersson AM, Pedersen SA, Jorgensen JO, Christiansen JS, Groome NP, Skakkebaek NE: Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebocontrolled crossover study. Horm Res 1998; 49: 269-278.
112. de Boer H, Blok GJ, Popp-Snijders C, Stuurman L, Baxter RC, van der Veen E: Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. J Clin Endocrinol Metab 1996; 81: 1371-1377.
113. Abs R, Bengtsson BA, Hernberg-Stahl E, Monson JP, Tauber JP, Wilton P, Wuster C: GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin Endocrinol (Oxf) 1999; 50: 703-713.
114. Kehely A, Bates PC, Frewer P, Birkett M, Blum WF, Mamessier P, Ezzat S, Ho KK, Lombardi G, Luger A, Marek J, Russell-Jones D, Sonksen P, Attanasio AF: Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms. J Clin Endocrinol Metab 2002; 87: 1974-1979.
115. Chipman JJ, Attanasio AF, Birkett MA, Bates PC, Webb S, Lamberts SW: The safety profile of GH replacement therapy in adults. Clin Endocrinol (Oxf) 1997; 46: 473-481.
116. Johannsson G, Bjarnason R, Bramnert M, Carlsson LM, Degerblad M, Manhem P, Rosen T, Thoren M, Bengtsson BA: The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender. J Clin Endocrinol Metab 1996; 81: 1575-1581
117. Florkowski CM, Barnard R, Livesey JH, Veveris T, Espiner EA, Donald RA: Growth hormone binding protein correlates strongly with leptin and percentage body fat in GH-deficient adults, is increased by GH replacement but does not predict IGF-I response. Growth Horm IGF Res 1999; 9: 35-40.
118. Toogood AA, Shalet SM: Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study. J Clin Endocrinol Metab 1999; 84: 131-136.
119. Juul A, Pedersen SA, Sorensen S, Winkler K, Jorgensen JO, Christiansen JS, Skakkebaek NE: Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. Eur J Endocrinol 1994; 131: 41-49.
120. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA: Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 1997; 82: 550-555.
121. Johansson AG, Engstrom BE, Ljunghall S, Karlsson FA, Burman P: Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency. J Clin Endocrinol Metab 1999; 84: 2002-2007.
122. Hayes FJ, Fiad TM, McKenna TJ: Gender difference in the response of growth hormone (GH)-deficient adults to GH therapy. Metabolism 1999; 48: 308-313.
123. Drake WM, Coyte D, Camacho-Hubner C, Jivanji NM, Kaltsas G, Wood DF, Trainer PJ, Grossman AB, Besser GM, Monson JP: Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998; 83: 3913-3919.
124. Bengtsson BA, Abs R, Bennmarker H, Monson JP, Feldt-Rasmussen U, Hernberg-Stahl E, Westberg B, Wilton P, Wuster C: The effects of treatment and the individual responsiveness to growth hormone (GH) replacement therapy in 665 GH-deficient adults. KIMS Study Group and the KIMS International Board. J Clin Endocrinol Metab 1999; 84: 3929-3935.
125. Ekman B, Lindstrom T, Nystrom F, Olsson AG, Toss G, Arnqvist HJ: A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults. Eur J Endocrinol 2002; 147: 49-57.
126. Murray RD, Howell SJ, Lissett CA, Shalet SM: Pre-treatment IGF-I level is the major determinant of GH dosage in adult GH deficiency. Clin Endocrinol (Oxf) 2000; 52: 537-542.