Long-term efficacy and safety of somatropin for adult growth hormone deficiency

Treatments in Endocrinology

Volumn 2, Issue 2, 2003, Pages 109-120

  Svensson, Johan ^a   Johannson, Gudmundur ^a  

^a SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN GROWTH HORMONE; INSULIN; LIPOPROTEIN; SOMATOMEDIN C;

ARTHRALGIA; BODY COMPOSITION; BONE DENSITY; BONE MASS; CANCER RISK; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CONCENTRATION RESPONSE; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; GLUCOSE METABOLISM; GROWTH HORMONE DEFICIENCY; HUMAN; HYPOPHYSIS DISEASE; HYPOPHYSIS TUMOR; LIPOPROTEIN METABOLISM; LONG TERM EXPOSURE; MORBIDITY; MORTALITY; MUSCLE STRENGTH; MYALGIA; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; PROSTATE CANCER; QUALITY OF LIFE; REVIEW; SIDE EFFECT; WELLBEING;

ADULT; ARTERIOSCLEROSIS; BIOMECHANICS; BODY COMPOSITION; BONE AND BONES; FRACTURES, BONE; HEART; HEART DISEASES; HUMAN GROWTH HORMONE; HUMANS; HYPOTHALAMIC NEOPLASMS; MORTALITY; MUSCLE, SKELETAL; NEOPLASMS; PITUITARY NEOPLASMS; QUALITY OF LIFE;

EID: 0041825737     PISSN: 11756349     EISSN: None     Source Type: Journal    
DOI: 10.2165/00024677-200302020-00004     Document Type: Review

References (148)

1. Jørgensen JOL, Pedersen SA, Thuesen L, et al. Beneficial effect of growth hormone treatment in GH-deficient adults. Lancet 1989; I: 1221-5
2. Salomon F, Cuneo R, Hesp R, et al. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321: 1221-5
3. Binnerts A, Swart G, Wilson J, et al. The effects of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate, and lipid homeostasis, as well as on body composition. Clin Endocrinol 1992; 37: 79-87
4. Whitehead H, Boreman C, McIlrath E, et al. Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo-controlled cross-over study. Clin Endocrinol 1992; 36: 45-52
5. Bengtsson B-Å, Edén S, Lönn L, et al. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 1993; 76: 309-17
6. De Boer H, Blok G-J, Voerman B, et al. The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis. J Clin Endocrinol Metab 1995; 80: 2069-76
7. Janssen Y, Fröhlich M, Roelfsema F. A low starting dose of genotropin in growth hormone deficient adults. J Clin Endocrinol Metab 1997; 82: 129-35
8. Johannsson G, Rosén T, Bengtsson B-A. Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol 1997; 47: 571-81
9. Carroll P, Christ E, Bengtsson B-Å, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998; 83: 382-95
10. Lönn L, Johansson G, Sjöström L, et al. Body composition and tissue distributions in growth hormone deficient adults before and after growth hormone treatment. Obes Res 1996; 4: 45-54
11. Bosaeus I, Johannsson G, Rosén T, et al. Comparison of methods to estimate body fat in growth hormone deficient adults. Clin Endocrinol 1996; 44: 395-402
12. Götherström G, Svensson J, Koranyi J, et al. A prospective study of five years of growth hormone (GH) replacement therapy in GH deficient adults; sustained effects on body composition, bone mass, and metabolic indices. J Clin Endocrinol Metab 2001; 86: 4657-65
13. De Boer H, Blok G-J, Van Der Veen E. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995; 16: 63-86
14. ter Maaten J, de Boer H, Kamp O, et al. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab 1999; 84: 2373-80
15. Burman P, Johansson AG, Siegbahn A, et al. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 1997; 82: 550-5
16. Johansson A, Engström B, Ljunghall S, et al. 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: 2002-7
17. Välimäki M, Salmela P, Salmi J, et al. Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 1999; 140: 545-54
18. Cuneo R, Salomon F, Wiles C, et al. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 1991; 70: 688-94
19. Johannsson G, Grimby G, Stibrant Sunnerhagen K, et al. Two years of growth hormone (GH) treatment increase isometric and isokinetic muscle stregth in GH-deficient adults. J Clin Endocrinol Metab 1997; 82: 2877-84
20. Jørgensen J, Pedersen S, Thuesen L, et al. Long-term growth hormone treatment in growth hormone deficient adults. Acta Endocrinol 1991; 125: 449-53
21. Rutherford O, Beshyah S, Johnston D. Quadriceps strength before and after growth hormone replacement in hypopituitary adults; relationship to changes in lean body mass and IGF-I. Endocrinol Metab 1994; 1: 41-7
22. Beshyah S, Freemantle C, Shahi M, et al. Replacement therapy with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults. Clin Endocrinol 1995; 42: 73-84
23. Wallymahmed M, Foy P, Shaw D, et al. Quality of life, body composition and muscle strength in adult with growth hormone deficiency: the influence of growth hormone replacement therapy for up to 3 years. Clin Endocrinol 1997; 47: 439-46
24. Janssen Y, Doornbos J, Roelfsema F. Changes in muscle volume, strength, and bioenergetics during recombinant human growth hormone (GH) therapy in adults with GH deficiency. J Clin Endocrinol Metab 1999; 84: 279-84
25. Koranyi J, Svensson J, Götherström G, et al. Baseline characteristics and the effects of five years of growth hormone (GH) replacement therapy in adults with GH deficiency of childhood or adulthood onset: a comparative, prospective study. J Clin Endocrinol Metab 2001; 86: 4693-9
26. Ayling C, Moreland B, Zanelli J, et al. Human growth hormone treatment of hypophysectomized rats increases the proportion of type-I fibres in skeletal muscle. J Endocrinol 1989; 123: 429-35
27. Mayoux E, Ventura-Clapier R, Timsit J, et al. Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion. Circ Res 1993; 72: 57-64
28. Daugaard J, Laustsen J, Hansen B, et al. Growth hormone induces muscle fibre type transformation in growth hormone-deficient rats. Acta Physiol Scand 1998; 164: 119-26
29. Ameredes B, Watchko J, Daood M, et al. Growth hormone restores aged diaphragm myosin composition and performance after chronic undernutrition. J Appl Physiol 1999; 87: 1253-9
30. Lange K, Andersen J, Beyer N, et al. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab 2002; 87: 513-23
31. Bottinelli R, Narici M, Pellegrino M. et al. Contractile properties and fiber type distribution of quadriceps muscles in adults with childhood-onset growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 4133-8
32. Daugaard J, Bramnert M, Manhem P, et al. Effect of 6 months of GH replacement on myosin heavy chain composition in GH-deficient patients. Eur J Endocrinol 1999; 141: 342-9
33. Rutherford O, Beshyah S, Schott J, et al. Contractile properties of the quadriceps muscle in growth hormone-deficient hypopituitary adults. Clin Sci 1995; 88: 67-71
34. Sunnerhagen K, Hedberg M, Henning G-B, et al. Muscle performance in an urban population sample of 40- to 79-year-old men and women. Scand J Rehab Med 2000; 32: 159-67
35. Ohlsson C, Bengtsson B-Å, Isaksson O, et al. Growth hormone and bone. Endocr Rev 1998; 19: 55-79
36. Schlemmer A, Johansen J, Pedersen S, et al. The effect of growth hormone (GH) therapy on urinary pyridinoline cross-links in GH-deficient adults. Clin Endocrinol 1991; 35: 471-6
37. Amato G, Carella C, Fazio S, et al. Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993; 77: 1671-6
38. Bravenboer N, Holzmann P, de Boer H, et al. The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men. J Clin Endocrinol Metab 1997; 82: 551-7
39. Degerblad M, Bengtsson B-Å, Bramnert M, et al. Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. Eur J Endocrinol 1995; 133: 180-8
40. Hansen T, Brixen K, Vahl N, et al. Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J Clin Endocrinol Metab 1996; 81: 3352-9
41. Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism. Ann Intern Med 1989; 111: 567-73
42. Ho P, Fig L, Barkan A, et al. Bone mineral density of the axial skeleton in acromegaly. J Nucl Med 1992; 33: 1608-12
43. Kotzmann H, Bernecker P, Hubsch P, et al. Bone mineral density and parameters of bone metabolism in patients with acromegaly. J Bone Miner Res 1993; 8: 459-65
44. O'Halloran D, Tsatsoulis A, Whitehouse R, et al. Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. J Clin Endocrinol Metab 1993; 76: 1344-8
45. Rosén T, Hansson T, Granhed H, et al. Reduced bone mineral content in adult patients with growth hormone deficiency. Acta Endocrinol 1993; 129: 201-8
46. Holmes S, Economou G, Whitehouse R, et al. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994; 78: 669-74
47. Toogood A, Adams J, O'Neill P, et al. Elderly patients with adult-onset growth hormone deficiency are not osteopenic. J Clin Endocrinol Metab 1997; 82: 1462-6
48. Fernholm R, Bramnert M, Hagg E, et al. Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 2000; 85: 4104-12
49. Thoren M, Soop M, Degerblad M, et al. Preliminary study of the effects of growth hormone substitution therapy on bone mineral density and serum osteocalcin levels in adults with growth hormone deficiency. Acta Endocrinol (Copenh) 1993; 128: 41-3
50. Vandeweghe M, Taelman P, Kaufman J. Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males. Clin Endocrinol (Oxf) 1993; 39: 409-15
51. Degerblad M, Elgindy N, Hall K, et al. Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. Acta Endocrinol (Copenh) 1992; 126: 387-93
52. Johannsson G, Rosen T, Bosaeus I, et al. Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1996; 81: 2865-73
53. Rahim A, Holmes S, Adams J, et al. Long-term change in the bone mineral density of adults with adult onset growth hormone (GH) deficiency in response to short or long-term GH replacement therapy. Clin Endocrinol 1998; 48: 463-9
54. Biller B, Sesmilo G, Baum H, et al. 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
55. Gomez J, Gomez N, Fiter J, et al. Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res 2000; 32: 66-70
56. Wüter C, Slenczka E, Ziegler R. Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: need for additional growth hormone substitution? Klinische Wochenschrift 1991; 69: 769-73
57. Rosén T, Wilhelmsen L, Landin-Wilhelmsen K, et al. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 1997; 137: 240-5
58. Wuster 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 Mineral Res 2001; 16: 398-405
59. Cummings S, Black D, Nevitt M, et al. Bone density at various sites for prediction of hip fracture. Lancet 1993; 341: 72-5
60. Melton III L, Atkinson E, O'Fallon W, et al. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993; 8: 1227-33
61. Cummings S, Nevitt M, Browner W, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332: 767-73
62. Johansson J-O, Larson G, Andersson M, et al. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmittors. Neuroendocrinology 1995; 61: 57-66
63. Burman P, Hetta J, Wide L, et al. Growth hormone treatment affects brain neurotransmittors and thyroxine. Clin Endocrinol 1996; 44: 319-24
64. McGauley G. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta Paediatr Scand 1989; 356 Suppl.: 70-2
65. Astöm C, Lindholm J. Growth hormone-deficient young adults have decreased deep sleep. Neuroendocrinology 1990; 51: 82-4
66. Deijen J, de Boer H, Blok G, et al. Cognitive impairments and mood disturbances in growth hormone deficient men. Psychoneuroendocrinology 1996; 21: 313-22
67. Hunt S, McKenna S, McEwen J, et al. The Nottingham Health Profile: subjective health status and medication consultations. Soc Sci Med 1981; 15 Suppl. A: 221-9
68. Dupuy H. The psychological general well-being (PGWB) index. In: Wenger NK, editor. Association of quality of life in clinical trials of cardiovascular therapies. New York: Le Jacq Publications, 1984: 170-83
69. Doward L. The development of the AGHDA: a measure to assess quality of life in adults with growth hormone deficiency. QoL Life Res 1995; 4: 420-1
70. Carroll P, Littlewood R, Weissberger A, et al. The effects of two doses of replacement growth hormone on the biochemical, body composition, and psychological profiles of growth-hormone-deficient adults. Eur J Endocrinol 1997; 137: 146-53
71. Murray R, Skillicorn C, Howell S, et al. Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults. Clin Endocrinol 1999; 50: 749-57
72. Cuneo R, Judd S, Wallace J, et al. The Australian multicenter trial of growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 1998; 83: 107-16
73. Gibney J, Wallace J, Spinks T, et al. The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Metab 1999; 84: 2596-602
74. Hernberg-Ståhl E, Luger A, Abs R, et al. Healthcare consumption decreases in parallell with improvements in quality of life during GH replacement in hypopittiitary adults with GH deficiency. J Clin Endocrinol Metab 2001; 86: 5277-81
75. Wirén L, Bengtsson B-A, Johannsson G. Beneficial effects of long-term GH replacement therapy on quality of life in adults with GH deficiency. Clin Endocrinol 1998; 48: 613-20
76. Johansson J-O, Fowelin J, Landin K, et al. Growth hormone-deficient adults are insulin-resistant. Metabolism 1995; 44: 1126-9
77. Hew F, Koschmann M, Christopher M, et al. Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity. J Clin Endocrinol Metab 1996; 81: 555-64
78. Fowelin J, Attvall S, Lager I, et al. Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency. Metabolism 1993; 42: 1443-7
79. Nørrelund H, Vahl N, Juul A, et al. Continuation of growth hormone treatment in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism. J Clin Endocrinol Metab 2000; 85: 1912-7
80. Al-Shoumer K, Gray R, Anyaoku V, et al. Effects of four years treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults. Clin Endocrinol 1998; 48: 795-802
81. Bülow B, Erfurth E. A low individualized GH dose in young patients with childhood onset GH deficiency normalized serum IGF-I without significant deterioration in glucose tolerance. Clin Endocrinol 1999; 50: 45-55
82. Weaver J, Monson J, Noonan K, et al. The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. J Clin Endocrinol Metab 1995; 80: 153-9
83. Rosenfalck A, 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
84. Christopher M, Hew F, Oakley M, et al. Defects of insulin action and skeletal muscle glucose metabolism in growth hormone-deficient adults persist after 24 months of recombinant human growth hormone therapy. J Clin Endocrinol Metab 1998; 83: 1668-81
85. Hwu C-M, Kwok C, Lai T-Y, et al. Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience. J Clin Endocrinol Metab 1997; 82: 3285-92
86. Jørgensen J, Vahl N, Nyholm B, et al. Substrate metabolism and insulin sensitivity following long-term growth hormone (GH) replacement therapy in GH-deficient adults. Endocr Metab 1996; 3: 281-6
87. Svensson J, Fowelin J, Landin K, et al. Effects of 7 years of GH-replacement therapy on insulin sensitivity in GH-deficient adults. J Clin Endocrinol Metab 2002; 87: 2121-7
88. Howard B, Howard W. Dyslipidemia in non-insulin-dependent diabetes mellitus. Endocr Rev 1994; 15: 263-74
89. Elam M, Simkevich C, Solomon S, et al. Stimulation of in vitro triglyceride synthesis in the rat hepatocyte by growth hormone treatment in vivo. Endocrinology 1988; 122: 1397-402
90. Elam M, Wilcox H, Salomon S, et al. In vivo growth hormone treatment stimulates secretion of low density lipoproteins by the perfused rat liver. Endocrinology 1992; 131: 2717-22
91. Sjöberg A, Oscarsson J, Edén S, et al. Continuous but not intermittent administration of growth hormone to hypophysectomized increases apolipoprotein-E secretion from cultured hepatocytes. Endocrinology 1994; 134: 790-8
92. Rudling M, Norstedt G, Olivecrona H, et al. Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci USA 1992; 89: 6983-7
93. Cummings M, Christ E, Umpleby A, et al. Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism contibute to the dyslipidaemia of adult growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 2010-3
94. Christ E, Cummings M, Albany E, et al. Effects of growth hormone (GH) therapy on very low density lipoprotein apolipoprtotein B100 kinetics in patients with adult GH deficiencey: a stable isotope study. J Clin Endocrinol Metab 1999; 84: 307-16
95. Angelin B, Rudling M. Growth hormone and hepatic lipoprotein metabolism. Curr Opin Lipidol 1994; 5: 160-5
96. Rosengren A, Wilhelmsen L, Eriksson E, et al. Lipoprotein(a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ 1990; 301: 1248-51
97. Edén S, Wiklund O, Oscarsson J, et al. Growth hormone treatment of growth hormone-deficient adults results in a marked increase in Lp(a) and HDL cholesterol concentrations. Arterioscler Thromb 1993; 13: 296-301
98. Johannsson G, Oscarsson J, Rosén T, et al. Effects of 1 year of growth hormone therapy on serum lipoprotein levels in growth hormone-deficient adults; influence of gender and and apo(a) and apoE phenotypes. Areterioscler Thromb Vasc Biol 1995; 15: 2142-50
99. O'Halloran D, Wieringa G, Tsatsoulis A, et al. Increased serum lipoprotein(a) concentrations after growth hormone (GH) treatment in patients with isolated GH deficiency. Ann Clin Biochem 1996; 33: 330-4
100. Nolte W, Rädisch C, Armstrong V, et al. The effect of recombinant human GH replacement therapy on liprotein(a) and other lipid parameters in adults with acquired GH deficiency: results of a double-blind and placebo-controlled trial. Eur J Endocrinol 1997; 137: 459-66
101. Krauss R, Burke D. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res 1982; 23: 97-104
102. Fisher W. Heterogeneity of low density lipoprotein: manifestations of the physiologic phenomenon in man. Metabolism 1983; 32: 283-91
103. Austin M, Breslow J, Hennekens C, et al. Low-density lipoprotein subclass patterns and risk of myocardial infarction. J Am Med Assoc 1988; 260: 1917-21
104. O'Neal D, Hew F, Sikaris K, et al. Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy. J Clin Endocrinol Metab 1996; 81: 2448-54
105. Tan K, Shiu S, Janus E, et al. LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-1. Atherosclerosis 1997; 129: 59-65
106. O'Neal D, Hew F, Best J, et al. The effect of 24 months recombinant human growth hormone (rh-GH) on LDL cholesterol, triglyceride-rich lipoproteins and apo [a] in hypopituitary adults previously treated with conventional replacement therapy. GH IGF Res 1999; 9: 165-73
107. Hew F, Alford F, Christopher M, et al. Effects of growth hormone deficiency and therapy in adults on skeletal muscle glucose metabolism, lipid profiles and regional body composition. Endocrinol Metab 1996; 3 Suppl. A: 55-60
108. Johansson J-O, Landin K, Tengborn L, et al. High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adults. Arterioscler Thromb 1994; 14: 434-7
109. Sverrisdóttir Y, Elam M, Bengtsson B-Å, et al. Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. J Clin Endocrinol Metab 1998; 83: 1881-5
110. Rosén T, Bengtsson B-Å. Premature mortality due to cardiovascular diseases in hypopituitarism. Lancet 1990; 336: 285-8
111. Bülow B, Hagmar L, Mikoczy Z, et al. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 1997; 46: 75-81
112. Bates A, Van't Hoff W, Jones P, et al. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996; 81: 1169-72
113. Tomlinson J, Holden N, Hills R, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 2001; 357: 425-31
114. Markussis V, Beshyah S, Fisher C, et al. Detection of premature atherosclerosis by high-resolution ultrasonography in symtom-free hypopituitary adults. Lancet 1992; 340: 1188-92
115. Böger R, Skamira C, Bode-Bòger S, et al. Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. J Clin Invest 1996; 98: 2706-13
116. Caidahl K, Edén S, Bengtsson B-Å. Cardiovascular and renal effects of growth hormone. Clin Endocrinol 1994; 40: 93-400
117. Borson-Chazot F, Serusclat A, Kalfallah Y, et al. Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab 1999; 84: 1329-33
118. Pfeifer M, Verhovec M, Zi Zek B, et al. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999; 84: 453-7
119. Svensson J, Johannsson G, Bengtsson B-Å. Body composition and quality of life as markers of the efficacy of growth hormone replacement therapy in adults. Horm Res 2001; 55 Suppl. 2: 55-60
120. de Boer H, Blok G, Popp-Sniders C, et al. Monitoring of growth hormone replacement therapy in adults, based on measurements of serum markers. J Clin Endocrinol Metab 1996; 81: 1371-7
121. Svensson J, Johannsson G, Bengtsson B-Å. Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test. Clin Endocrinol 1997; 46: 579-86
122. Drake W, Coyte D, Camacho-Hubner C, et al. Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998; 83: 3913-9
123. Kaklamani V, Linos A, Kaklamani E, et al. Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 concentrations in healthy adults. J Clin Oncol 1999; 17: 3291-8
124. Oscarsson J, Johannsson G, Johansson J-O, et al. Diurnal variation in serum insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations during daily subcutaneous injections of recombinant human growth hormone in GH-deficient adults. Clin Endocrinol 1997; 46: 63-8
125. Bates A, Van't Hoff W, Jones P, et al. An audit of outcome of treatment in acromegaly. Q J Med 1993; 86: 293-9
126. Chan J, Stampfer M, Giovannuci F, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563-6
127. Takala J, Ruokonen E, Webster N, et al. Increased mortality associated with growth hormone treatment in critically ill patients. N Engl J Med 1999; 341: 785-92
128. Saccà L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev 1994; 15: 555-73
129. Cuneo R, Salomon F, Wiles C, et al. Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol 1991; 70: 695-700
130. Beshyah S, Shahi M, Skinner E, et al. Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults. Eur J Endocrinol 1994; 130: 451-8
131. Fort S, Weaver J, Monson J, et al. The effects of low dose recombinant human growth hormone on cardiovascular structure and function in hypopituitary adults growth hormone-deficient adults. Endocrinol Metab 1995; 2: 119-26
132. Thuesen L, Jørgensen J, Müller J, et al. Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults. Clin Endocrinol 1994; 41: 615-20
133. Johannsson G, Bengtsson B-Å, Andersson B, et al. Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults: preliminary data in a small group of patients. Clin Endocrinol 1996; 45: 305-14
134. Ogilvy-Stuart A, Ryder W, Gattamaneni H, et al. Growth hormone and tumour recurrence. BMJ 1992; 304: 1601-5
135. Attanasio A, Lamberts S, Matranga A, et al. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrinol Metab 1997; 82: 82-8
136. Abs R, Bengtsson B-A, Hernberg-Stahl E, et al. The effects of treatment in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin Endocrinol 1999; 50: 703-13
137. Freier S, Weiss O, Eran M, et al. Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon. Gut 1999; 44: 704-8
138. Bengtsson B. Acromegaly and neoplasia. J Pediatr Endocrinol 1992; 6: 73-8
139. Jenkins P, Besser M. Clinical perspective: acromegaly and cancer: a problem. J Clin Endocrinol Metab 2001; 86: 2935-41
140. Orme S, MCNally R, Cartwright R, et al. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 1998; 83: 2730-4
141. Shaneyfelt T, Husein R, Bubley G, et al. Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol 2000; 18: 847-53
142. Hankinson S, Willett W, Colditz G, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998; 351: 1393-6
143. Corpas E, Harman S, Blackman M. Human growth hormone and human aging. Endocr Rev 1993; 14: 20-38
144. Sjögren K, Liu J, Blad K, et al. Liver-derived insulin-like growth factor I (IGF-I) is the principle source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 1999; 96: 7088-92
145. Popovic V, Damjanovic S, Mimic D, et al. Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group. Clin Endocrinol 1998; 49: 441-5
146. Nilsson B, Gustavsson-Kadaka E, Bengtsson B, et al. Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab 2000; 85: 1420-5
147. Bengtsson B-Å, Koppeschaar H, Abs R, et al. Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group. J Clin Endocrinol Metab 1999; 84: 4291-2
148. Cutfield W, 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