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Vol 69, No 5 (2018)
Guidelines / Expert consensus
Published online: 2018-08-17

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National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy

Andrzej Lewiński12, Joanna Smyczyńska2, Renata Stawerska2, Maciej Hilczer3, Magdalena Stasiak2, Tomasz Bednarczuk4, Marek Bolanowski5, Roman Junik6, Marek Ruchała7, Anhelli Syrenicz8, Mieczysław Walczak9, Wojciech Zgliczyński10, Małgorzata Karbownik-Lewińska211
DOI: 10.5603/EP.a2018.0054
Pubmed: 30117531
Endokrynol Pol 2018;69(5):468-524.

Abstract

Growth hormone (GH) has been used in the treatment of short stature in children with GH deficiency (GHD) for 60 years, and for about 30 years also in the treatment of adults with GHD, in whom such treatment is carried out due to metabolic indications. In Poland, GH treatment is reimbursed only in children with GHD, while so far it has not been refunded in adults with GHD. There are two groups of adults (or adolescents after growth completion) with GHD, who require GH therapy: patients with GHD that occurred in childhood (childhood-onset GHD — CO-GHD) and patients with GHD acquired in adulthood (adulthood-onset GHD — AO-GHD). This review presents a brief outline of the history of GH treatment in humans, the latest data on the causes and symptoms of GHD in adults, and the complications of untreated GHD. Current recommendations regarding diagnosis, treatment and monitoring of GH therapy in adults are also discussed. Moreover, the review paper presents the objectives, assumptions, and plans of implementation of the “National Treatment Program for Severe Growth Hormone Deficiency in Adults and Adolescents after Completion of the Growth Promoting Therapy”, as well as the expected health and economic effects of introduction of GH treatment in adults with GHD in Poland.

Keywords: treatment programgrowth hormone treatmentgrowth hormone deficiency that occurred in childhood (childhood-onset GHD)growth hormone deficiency acquired in adulthood (adulthood-onset GHD)

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References

  1. Mauras N, O'Brien KO, Welch S, et al. Insulin-like growth factor I and growth hormone (GH) treatment in GH-deficient humans: differential effects on protein, glucose, lipid, and calcium metabolism. J Clin Endocrinol Metab. 2000; 85(4): 1686–1694.
    CrossRefPubMed
  2. Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab. 1998; 83(2): 379–381.
    CrossRefPubMed
  3. Hokken-Koelega A, van der Lely AJ, Hauffa B, et al. Bridging the gap: metabolic and endocrine care of patients during transition. Endocr Connect. 2016; 5(6): R44–R54.
    CrossRefPubMed
  4. Ho KKY. 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007; 157(6): 695–700.
    CrossRefPubMed
  5. Lewiński A, Hilczer M, Pniewska-Siark B, et al. Ogólnoposlki program leczenia niedoboru hormonu wzrostu u ludzi dorosłych. Endokrynol Pol. 2000; 51: 645–691.
  6. Clayton PE, Cuneo RC, Juul A, et al. European Society of Paediatric Endocrinology. Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol. 2005; 152(2): 165–170.
    CrossRefPubMed
  7. Regal M, Páramo C, Sierra SM, et al. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001; 55(6): 735–740.
    CrossRefPubMed
  8. Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, et al. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf). 2013; 78(2): 278–284.
    CrossRefPubMed
  9. Stochholm K, Laursen T, Green A, et al. Incidence of GH deficiency - a nationwide study. Eur J Endocrinol. 2006; 155(1): 61–71.
    CrossRefPubMed
  10. Sassolas G, Chazot FB, Jaquet P, et al. GH deficiency in adults: an epidemiological approach. Eur J Endocrinol. 1999; 141(6): 595–600.
    PubMed
  11. Attanasio AF, Howell S, Bates PC, et al. Confirmation of severe GH deficiency after final height in patients diagnosed as GH deficient during childhood. Clin Endocrinol (Oxf). 2002; 56(4): 503–507.
    PubMed
  12. Johannsson G, Rosén T, Bengtsson BA. Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol (Oxf). 1997; 47(5): 571–581.
    PubMed
  13. Meazza C, Gertosio C, Pagani S, et al. Is retesting in growth hormone deficient children really useful? Minerva Endocrinol. 2017; 42(4): 325–330.
    CrossRefPubMed
  14. Smyczyńska J, Stawerska R, Lewiński A, et al. Incidence and predictors of persistent growth hormone deficiency (GHD) in patients with isolated, childhood-onset GHD. Endokrynol Pol. 2014; 65(5): 334–341.
    CrossRefPubMed
  15. Hilczer M, Smyczynska J, Stawerska R, et al. Final height and growth hormone secretion after completion of growth hormone therapy in patients with idiopathic growth hormone deficiency and with abnormalities of the hypothalamic-pituitary region. Neuro Endocrinol Lett. 2005; 26(1): 19–24.
    PubMed
  16. Brabant G, Poll EM, Jönsson P, et al. Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations? Eur J Endocrinol. 2009; 161 Suppl 1: S25–S31.
    CrossRefPubMed
  17. Webb SM, Strasburger CJ, Mo D, et al. HypoCCS International Advisory Board. Changing patterns of the adult growth hormone deficiency diagnosis documented in a decade-long global surveillance database. J Clin Endocrinol Metab. 2009; 94(2): 392–399.
    CrossRefPubMed
  18. Abs R, Bengtsson BA, Hernberg-Stâhl E, et al. GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin Endocrinol (Oxf). 1999; 50(6): 703–713.
    CrossRefPubMed
  19. Abs R, Mattsson AF, Bengtsson BA, et al. KIMS Study Group. Isolated growth hormone (GH) deficiency in adult patients: baseline clinical characteristics and responses to GH replacement in comparison with hypopituitary patients. A sub-analysis of the KIMS database. Growth Horm IGF Res. 2005; 15(5): 349–359.
    CrossRefPubMed
  20. Littley MD, Shalet SM, Beardwell CG, et al. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989; 70(262): 145–160.
    CrossRefPubMed
  21. Tritos NA, Johannsson G, Korbonits M, et al. Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly: a KIMS analysis. J Clin Endocrinol Metab. 2014; 99(6): 2018–2029.
    CrossRefPubMed
  22. Kosowicz J. Nabyty niedobór hormonu wzrostu (GH) u dorosłych — przyczyny, objawy kliniczne. Endokrynol Pol. 1999; 50(Supl 2): 39–45.
  23. Caidahl K, Edén S, Bengtsson BA. Cardiovascular and renal effects of growth hormone. Clin Endocrinol (Oxf). 1994; 40(3): 393–400.
    PubMed
  24. Carroll PV, Christ ER, Bengtsson BA, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab. 1998; 83(2): 382–395.
    CrossRefPubMed
  25. Kokoszko A, Karbownik M, Lewiński A. Increased lipid peroxidation in growth hormone-deficient adult patients. Neuro Endocrinol Lett. 2006; 27(1-2): 225–230.
    PubMed
  26. Cuneo RC, Salomon F, Watts GF, et al. Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism. 1993; 42(12): 1519–1523.
    CrossRefPubMed
  27. de Boer H, Blok GJ, Van der Veen EA. Clinical aspects of growth hormone deficiency in adults. Endocr Rev. 1995; 16(1): 63–86.
    CrossRefPubMed
  28. Giovannini L, Tirabassi G, Muscogiuri G, et al. Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]. Endocr J. 2015; 62(12): 1037–1048.
    CrossRefPubMed
  29. Ikeda H, Kudo M. Long-term follow-up results of growth hormone therapy for patients with adult growth hormone deficiency. Hormones (Athens). 2016; 15(1): 45–53.
    CrossRefPubMed
  30. Karbownik-Lewinska M, Kokoszko A, Lewandowski KC, et al. GH replacement reduces increased lipid peroxidation in GH-deficient adults. Clin Endocrinol (Oxf). 2008; 68(6): 957–964.
    CrossRefPubMed
  31. Johannsson G, Albertsson-Wikland K, Bengtsson BA. Discontinuation of growth hormone (GH) treatment: metabolic effects in GH-deficient and GH-sufficient adolescent patients compared with control subjects. Swedish Study Group for Growth Hormone Treatment in Children. J Clin Endocrinol Metab. 1999; 84(12): 4516–4524.
    CrossRefPubMed
  32. Hilczer M, Smyczyńska J, Stawerska R, et al. Effects of one-year low-dose growth hormone (GH) therapy on body composition, lipid profile and carbohydrate metabolism in young adults with childhood-onset severe GH deficiency confirmed after completion of growth promotion. Endokrynol Pol. 2008; 59(4): 292–300.
    PubMed
  33. Wollmann HA, Ranke MB. Metabolic effects of growth hormone in children. Metabolism. 1995; 44(10 Suppl 4): 97–102.
    PubMed
  34. Johansson JO, Fowelin J, Landin K, et al. Growth hormone-deficient adults are insulin-resistant. Metabolism. 1995; 44(9): 1126–1129.
    CrossRefPubMed
  35. Abs R, Mattsson AF, Thunander M, et al. Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis. Eur J Endocrinol. 2013; 168(3): 297–305.
    CrossRefPubMed
  36. Gazzaruso C, Gola M, Karamouzis I, et al. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH--an update. J Clin Endocrinol Metab. 2014; 99(1): 18–29.
    CrossRefPubMed
  37. Yuen KCJ, Frystyk J, White DK, et al. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005; 63(4): 428–436.
    CrossRefPubMed
  38. Beshyah SA, Sharp PS, Gelding SV, et al. Whole-body leucine turnover in adults on conventional treatment for hypopituitarism. Acta Endocrinol (Copenh). 1993; 129(2): 158–164.
    PubMed
  39. Herlitz H, Jonsson O, Bengtsson BA. Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly. Acta Endocrinol (Copenh). 1992; 127(1): 38–43.
    PubMed
  40. Ho KY, Weissberger AJ. The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system. Metabolism. 1990; 39(2): 133–137.
    CrossRefPubMed
  41. Kamenický P, Mazziotti G, Lombès M, et al. Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical implications. Endocr Rev. 2014; 35(2): 234–281.
    CrossRefPubMed
  42. Di Somma C, Scarano E, Savastano S, et al. Cardiovascular alterations in adult GH deficiency. Best Pract Res Clin Endocrinol Metab. 2017; 31(1): 25–34.
    CrossRefPubMed
  43. Moisey R, Orme S, Barker D, et al. Cardiac functional reserve is diminished in growth hormone-deficient adults. Cardiovasc Ther. 2009; 27(1): 34–41.
    CrossRefPubMed
  44. Bolanowski M, Milewicz A. Substytucyjne leczenie hormonem wzrostu (GH) u dorosłych : wyniki, powikłania. Endokrynol Pol. 1999; 50(Supl 2): 55–61.
  45. Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev. 1996; 17(5): 481–517.
    CrossRefPubMed
  46. Cuneo RC, Salomon F, Wiles CM, et al. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol (1985). 1991; 70(2): 688–694.
    CrossRefPubMed
  47. Appelman-Dijkstra NM, Claessen KM, Hamdy NAT, et al. Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study. Clin Endocrinol (Oxf). 2014; 81(5): 727–735.
    CrossRefPubMed
  48. Ohlsson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev. 1998; 19(1): 55–79.
    CrossRefPubMed
  49. Nishiyama K, Sugimoto T, Kaji H, et al. Stimulatory effect of growth hormone on bone resorption and osteoclast differentiation. Endocrinology. 1996; 137(1): 35–41.
    CrossRefPubMed
  50. O'Halloran DJ, Tsatsoulis A, Whitehouse RW, et al. Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. J Clin Endocrinol Metab. 1993; 76(5): 1344–1348.
    CrossRefPubMed
  51. Gasińska T. Kliniczne i metaboliczne efekty działania GH – IGF-1 u dorosłych – układ mięśniowy i kostny, gonady. Endokrynol Pol. 1999; 50(Supl 2): 63–68.
  52. Isaksson OG, Lindahl A, Nilsson A, et al. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev. 1987; 8(4): 426–438.
    CrossRefPubMed
  53. Johannsson G, Rosén 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(8): 2865–2873.
    CrossRefPubMed
  54. Cuneo RC, Salomon F, Wiles CM, et al. Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol (1985). 1991; 70(2): 695–700.
    CrossRefPubMed
  55. Mason HD, Martikainen H, Beard RW, et al. Direct gonadotrophic effect of growth hormone on oestradiol production by human granulosa cells in vitro. J Endocrinol. 1990; 126(3): R1–R4.
    PubMed
  56. Sharara FI, Giudice LC. Role of growth hormone in ovarian physiology and onset of puberty. J Soc Gynecol Investig. 1997; 4(1): 2–7.
    CrossRefPubMed
  57. Bonjour JP, Theintz G, Buchs B, et al. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab. 1991; 73(3): 555–563.
    CrossRefPubMed
  58. 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(2): 799–808.
    CrossRefPubMed
  59. Conway GS, Szarras-Czapnik M, Racz K, et al. 1369 GHD to GHDA Transition Study Group. Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency. Eur J Endocrinol. 2009; 160(6): 899–907.
    CrossRefPubMed
  60. Wüster C, Abs R, Bengtsson BA, et al. KIMS Study Group and the KIMS International Board. Pharmacia & Upjohn International Metabolic Database. 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(2): 398–405.
    CrossRefPubMed
  61. Giampietro A, Milardi D, Bianchi A, et al. The effect of treatment with growth hormone on fertility outcome in eugonadal women with growth hormone deficiency: report of four cases and review of the literature. Fertil Steril. 2009; 91(3): 930.e7–930.11.
    CrossRefPubMed
  62. Yoshizawa M, Ieki Y, Takazakura E, et al. Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement. Intern Med. 2017; 56(5): 527–530.
    CrossRefPubMed
  63. Molitch ME, Clemmons DR, Malozowski S, et al. Endocrine Society, Endocrine Society's Clinical Guidelines Subcommittee. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006; 91(5): 1621–1634.
    CrossRefPubMed
  64. Gasco V, Corneli G, Beccuti G, et al. Retesting the childhood-onset GH-deficient patient. Eur J Endocrinol. 2008; 159 Suppl 1: S45–S52.
    CrossRefPubMed
  65. Grimberg A, DiVall SA, Polychronakos C, et al. Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. Horm Res Paediatr. 2016; 86(6): 361–397.
    CrossRefPubMed
  66. Mahajan T, Lightman SL. A simple test for growth hormone deficiency in adults. J Clin Endocrinol Metab. 2000; 85(4): 1473–1476.
    CrossRefPubMed
  67. Gómez JM, Espadero RM, Escobar-Jiménez F, et al. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf). 2002; 56(3): 329–334.
    CrossRefPubMed
  68. Wit J-M, Ranke MB, Kelnar CJH. The ESPE classification of paediatric endocrine diagnoses. Horm Res. 2007; 68: 1–120.
  69. Gibney J, Wallace JD, 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(8): 2596–2602.
    CrossRefPubMed
  70. Schuetz P, Müller B, Nusbaumer C, et al. Circulating levels of GH predict mortality and complement prognostic scores in critically ill medical patients. Eur J Endocrinol. 2009; 160(2): 157–163.
    CrossRefPubMed
  71. Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med. 1999; 341(11): 785–792.
    CrossRefPubMed
  72. Wu TE, Chen HS. Increased prevalence of proliferative retinopathy in patients with acromegaly. J Chin Med Assoc. 2018; 81(3): 230–235.
    CrossRefPubMed
  73. Hansen R, Koller EA, Malozowski S. Full remission of growth hormone (GH)-induced retinopathy after GH treatment discontinuation: long-term follow-up. J Clin Endocrinol Metab. 2000; 85(7): 2627.
    CrossRefPubMed
  74. Koller EA, Green L, Gertner JM, et al. Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients. J Clin Endocrinol Metab. 1998; 83(7): 2380–2383.
    CrossRefPubMed
  75. Urban B, Gardziejczyk M, Urban M, et al. Ocena wpływu terapii ludzkim hormonem wzrostu na narzad wzroku pacjentów z somatotropinowa niedoczynnościa przysadki i pacjentek z zespołem Turnera [Effect of human growth hormone treatment on the eyes of patients with somatotropic pituitary insufficiency and in girls with Turner’s syndrome]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2005; 11: 9–12.
  76. Darendeliler F, Karagiannis G, Wilton P. Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. Horm Res. 2007; 68 Suppl 5: 41–47.
    CrossRefPubMed
  77. Malozowski S, Tanner LA, Wysowski D, et al. Growth hormone, insulin-like growth factor I, and benign intracranial hypertension. N Engl J Med. 1993; 329(9): 665–666.
    CrossRefPubMed
  78. Wirén L, Boguszewski CL, Johannsson G. Growth hormone (GH) replacement therapy in GH-deficient women during pregnancy. Clin Endocrinol (Oxf). 2002; 57(2): 235–239.
    CrossRefPubMed
  79. Verhelst J, Abs R, Vandeweghe M, et al. Two years of replacement therapy in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1997; 47(4): 485–494.
    CrossRefPubMed
  80. Elbornsson M, Götherström G, Bengtsson BÅ, et al. Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation. Growth Horm IGF Res. 2013; 23(6): 249–255.
    CrossRefPubMed
  81. Elbornsson M, Horvath A, Götherström G, et al. Seven years of growth hormone (GH) replacement improves quality of life in hypopituitary patients with adult-onset GH deficiency. Eur J Endocrinol. 2017; 176(2): 99–109.
    CrossRefPubMed
  82. Bengtsson BA, Abs R, Bennmarker H, et al. 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(11): 3929–3935.
    CrossRefPubMed
  83. Iranmanesh A, Lizarralde G, Veldhuis JD. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab. 1991; 73(5): 1081–1088.
    CrossRefPubMed
  84. Florini JR, Prinz PN, Vitiello MV, et al. Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. J Gerontol. 1985; 40(1): 2–7.
    PubMed
  85. Höybye C, Weber MM, Pournara E, et al. Is GH dosing optimal in female patients with adult-onset GH deficiency? An analysis from the NordiNet International Outcome Study. Clin Endocrinol (Oxf). 2017; 86(6): 798–805.
    CrossRefPubMed
  86. Pilarska K, Kulig G. Kliniczne i metaboliczne efekty działania GH–IGF-1: wydatkowanie energii, interakcje z TSH i hormonami tarczycy. Endokrynol Pol. 1999; 50(Supl 2): 33–38.
  87. Karbownik-Lewińska M, Lewiński A, McKenna S, et al. The Polish version of the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) - four-stage translation and validation. Endokrynol Pol. 2008; 59(5): 374–384.
    PubMed
  88. Cohn L, Feller AG, Draper MW, et al. Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations. Clin Endocrinol (Oxf). 1993; 39(4): 417–425.
    CrossRefPubMed
  89. Trinconi AF, Filassi JR, Soares JM, et al. Evaluation of the insulin-like growth factors (IGF) IGF-I and IGF binding protein 3 in patients at high risk for breast cancer. Fertil Steril. 2011; 95(8): 2753–2755.
    CrossRefPubMed
  90. Neuhouser ML, Platz EA, Till C, et al. Insulin-like growth factors and insulin-like growth factor-binding proteins and prostate cancer risk: results from the prostate cancer prevention trial. Cancer Prev Res (Phila). 2013; 6(2): 91–99.
    CrossRefPubMed
  91. Carel JC, Ecosse E, Landier F, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012; 97(2): 416–425.
    CrossRefPubMed
  92. Swerdlow AJ, Cooke R, Beckers D, et al. Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study. J Clin Endocrinol Metab. 2017; 102(5): 1661–1672.
    CrossRefPubMed
  93. Johannsson G. Treatment of growth hormone deficiency in adults. Horm Res. 2009; 71 Suppl 1: 116–122.
    CrossRefPubMed
  94. Gaillard RC, Mattsson AF, Akerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012; 166(6): 1069–1077.
    CrossRefPubMed
  95. Krzyzanowska-Mittermayer K, Mattsson AF, Maiter D, et al. New Neoplasm During GH Replacement in Adults With Pituitary Deficiency Following Malignancy: A KIMS Analysis. J Clin Endocrinol Metab. 2018; 103(2): 523–531.
    CrossRefPubMed
  96. Pekic S, Popovic V. GH therapy and cancer risk in hypopituitarism: what we know from human studies. Eur J Endocrinol. 2013; 169(5): R89–R97.
    CrossRefPubMed
  97. Pekic S, Stojanovic M, Popovic V. Controversies in the risk of neoplasia in GH deficiency. Best Pract Res Clin Endocrinol Metab. 2017; 31(1): 35–47.
    CrossRefPubMed
  98. Sowiński J. Diagnostyka niedoboru hormonu wzrostu u osób dorosłych. Endokrynol Pol. 1999; 50(Supl 2): 47–53.
  99. Schneider HJ, Buchfelder M, Wallaschofski H, et al. Proposal of a clinical response score and predictors of clinical response to 2 years of GH replacement therapy in adult GH deficiency. Eur J Endocrinol. 2015; 173(6): 843–851.
    CrossRefPubMed

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