Lo normal y lo patológico | 22 SEP 19

Deficiencia de hormona de crecimiento en el adulto

La hormona del crecimiento en el adulto es importante para el metabolismo de lípidos y carbohidratos, es esencial para el funcionamiento normal del organismo en estados de ayuno y tiene un papel predominante en el equilibrio energético
Autor: Melmed M. N Engl J Med 2019;380:2551-62.
INDICE:  1. Página 1 | 2. Referencias bibliográficas
Referencias bibliográficas

1. Raben MS. Growth hormone — physiologic aspects. N Engl J Med 1962; 266:31-5.

2. Tsai YC, Cooke NE, Liebhaber SA. Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster. Nucleic Acids Res 2016; 44: 4651-64.

3. Murray PG, Higham CE, Clayton PE. 60 Years of neuroendocrinology: the hypothalamo-GH axis: the past 60 years. J Endocrinol 2015; 226: T123-T140.

4. Perry JK, Wu ZS, Mertani HC, Zhu T, Lobie PE. Tumour-derived human growth hormone as a therapeutic target in oncology. Trends Endocrinol Metab 2017; 28:587-96.

5. Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest 2009; 119: 3189-202.

6. Casanueva FF, Camina JP, Carreira MC, Pazos Y, Varga JL, Schally AV. Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a. Proc Natl Acad Sci U S A 2008; 105: 20452-7.

7. Leung K, Rajkovic IA, Peters E, Markus I, Van Wyk JJ, Ho KK. Insulin-like growth factor I and insulin down-regulate growth hormone (GH) receptors in rat osteoblasts: evidence for a peripheral feedback loop regulating GH action. Endocrinology 1996; 137: 2694-702.

8. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998; 19:717-97.

9. Bonert VS, Elashoff JD, Barnett P, Melmed S. Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 2004; 89: 3397-401.

10. Colao A, Di Somma C, Savastano S, et al. A reappraisal of diagnosing GH deficiency in adults: role of gender, age, waist circumference, and body mass index. J Clin Endocrinol Metab 2009; 94: 4414-22.

11. 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: 1081-8.

12. Russell-Aulet M, Jaffe CA, Demott-Friberg R, Barkan AL. In vivo semiquantification of hypothalamic growth hormone-releasing hormone (GHRH) output in humans: evidence for relative GHRH deficiency in aging. J Clin Endocrinol Metab 1999; 84: 3490-7.

13. Jessup SK, Dimaraki EV, Symons KV, Barkan AL. Sexual dimorphism of growth hormone (GH) regulation in humans: endogenous GH-releasing hormone maintains basal GH in women but not in men. J Clin Endocrinol Metab 2003; 88: 4776-80.

14. van den Berg G, Veldhuis JD, Frolich M, Roelfsema F. An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women. J Clin Endocrinol Metab 1996;81: 2460-7.

15. Waters MJ, Conway-Campbell BL. The oncogenic potential of autocrine human growth hormone in breast cancer. Proc Natl Acad Sci U S A 2004; 101: 14992-3. 16. Melmed S. Idiopathic adult growth hormone deficiency. J Clin Endocrinol Metab 2013; 98: 2187-97.

17. Brooks AJ, Dai W, O’Mara ML, et al. Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 2014; 344: 1249783.

18. Carter-Su C, Schwartz J, Argetsinger LS. Growth hormone signaling pathways. Growth Horm IGF Res 2016; 28: 11-5.

19. Rotwein P. Mapping the growth hormone–Stat5b–IGF-I transcriptional circuit. Trends Endocrinol Metab 2012; 23: 186-93.

20. Kofoed EM, Hwa V, Little B, et al. Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 2003; 349: 1139-47.

21. Yakar S, Liu JL, Stannard B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A 1999; 96:7324-9.

22. Surya S, Horowitz JF, Goldenberg N, et al. The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab 2009; 94: 2828-34.

23. Glad CAM, Svensson PA, Nystrom FH, et al. Expression of GHR and downstream signaling genes in human adipose tissue — relation to obesity and weight change. J Clin Endocrinol Metab 2019; 104: 1459-70.

24. Gan Y, Paterson AJ, Zhang Y, Jiang J, Frank SJ. Functional collaboration of insulin-like growth factor-1 receptor (IGF-1R), but not insulin receptor (IR), with acute GH signaling in mouse calvarial cells. Endocrinology 2014; 155: 1000-9.

25. Kupfer SR, Underwood LE, Baxter RC, Clemmons DR. Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously. J Clin Invest 1993;91: 391-6.

26. Chikani V, Ho KK. Action of GH on skeletal muscle function: molecular and metabolic mechanisms. J Mol Endocrinol 2013; 52: R107-R123.

27. Vijayakumar A, Yakar S, Leroith D. The intricate role of growth hormone in metabolism. Front Endocrinol (Lausanne) 2011; 2: 32.

28. Zhao JT, Cowley MJ, Lee P, Birzniece V, Kaplan W, Ho KK. Identification of novel GH-regulated pathway of lipid metabolism in adipose tissue: a gene expression study in hypopituitary men. J Clin Endocrinol Metab 2011; 96: E1188-E1196.

29. Mazziotti G, Frara S, Giustina A. Pituitary diseases and bone. Endocr Rev 2018;39: 440-88.

30. Sklar CA, Antal Z, Chemaitilly W, et al. Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2018;103: 2761-84.

31. Yuen KC, Tritos NA, Samson SL, Hoffman AR, Katznelson L. American Association of Clinical Endocrinologists and American College of Endocrinology disease state clinical review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency. Endocr Pract 2016; 22: 1235-44.

32. Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab 2018; 103: 3083-93.

33. Biller BM, Samuels MH, Zagar A, et al. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 2002; 87: 2067-79.

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

35. Alba-Roth J, Muller OA, Schopohl J, von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab 1988; 67: 1186-9.

36. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine S. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1587-609.

37. Chanson P, Cailleux-Bounacer A, Kuhn JM, et al. Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations. J Clin Endocrinol Metab 2010; 95: 3684-92.

38. Hamrahian AH, Yuen KC, Gordon MB, Pulaski-Liebert KJ, Bena J, Biller BM. Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitaryadrenal axes in adults: results from a prospective randomized multicenter study. Pituitary 2016; 19: 332-41.

39. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem 2011; 57: 555-9.

40. Junnila RK, Strasburger CJ, Bidlingmaier M. Pitfalls of insulin-like growth factor-I and growth hormone assays. Endocrinol Metab Clin North Am 2015; 44:27-34.

41. 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; 87:477-85.

42. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 3888-921.

43. Mavromati M, Kuhn E, Agostini H, et al. Classification of patients with GH disorders may vary according to the IGF-I assay. J Clin Endocrinol Metab 2017; 102:2844-52.

44. Cuneo RC, Salomon F, McGauley GA, Sonksen PH. The growth hormone deficiency syndrome in adults. Clin Endocrinol (Oxf) 1992; 37: 387-97.

45. Attanasio AF, Lamberts SWJ, Matranga AMC, 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.

46. Gazzaruso C, Gola M, Karamouzis I, Giubbini R, Giustina A. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH — an update. J Clin Endocrinol Metab 2014; 99: 18-29.

47. Mazziotti G, Doga M, Frara S, et al. Incidence of morphometric vertebral fractures in adult patients with growth hormone deficiency. Endocrine 2016; 52: 103-10.

48. Jorgensen JOL, Pedersen SA, Thuesen L, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; 1: 1221-5.

49. Salomon F, Cuneo RC, Hesp R, Sonksen PH. 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: 1797-803.

50. Elbornsson M, Gotherstrom G, Bosaus I, Bengtsson BA, Johannsson G, Svensson J. Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol 2013; 168: 745-53.

51. Hoffman AR, Kuntze JE, Baptista J, et al. Growth hormone (GH) replacement therapy in adult-onset GH deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004; 89: 2048-56.

52. Hartman ML, Xu R, Crowe BJ, et al. Prospective safety surveillance of GHdeficient adults: comparison of GH-treated vs untreated patients. J Clin Endocrinol Metab 2013; 98: 980-8.

53. Carvalho LR, de Faria ME, Osorio MG, et al. Acromegalic features in growth hormone (GH)-deficient patients after long-term GH therapy. Clin Endocrinol (Oxf) 2003; 59: 788-92.

54. Karges B, Pfaffle R, Boehm BO, Karges W. Acromegaly induced by growth hormone replacement therapy. Horm Res 2004;61: 165-9.

55. Claessen KM, Appelman-Dijkstra NM, Adoptie DM, et al. Metabolic profile in growth hormone-deficient (GHD) adults after long-term recombinant human growth hormone (rhGH) therapy. J Clin Endocrinol Metab 2013; 98: 352-61.

56. Child CJ, Conroy D, Zimmermann AG, Woodmansee WW, Erfurth EM, Robison LL. Incidence of primary cancers and intracranial tumour recurrences in GHtreated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study. Eur J Endocrinol 2015; 172: 779-90.

57. van Varsseveld NC, van Bunderen CC, Franken AA, Koppeschaar HP, van der Lely AJ, Drent ML. Tumor recurrence or regrowth in adults with nonfunctioning pituitary adenomas using GH replacement therapy. J Clin Endocrinol Metab 2015; 100:3132-9.

58. Olsson DS, Buchfelder M, Schlaffer S, et al. Comparing progression of nonfunctioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy. Eur J Endocrinol 2009; 161: 663-9.

59. 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: 523-31.

60. Clemmons DR, Molitch M, Hoffman AR, et al. Growth hormone should be used only for approved indications. J Clin Endocrinol Metab 2014; 99: 409-11.

61. Corcoran C, Grinspoon S. Treatments for wasting in patients with the acquired immunodeficiency syndrome. N Engl J Med 1999; 340: 1740-50.

62. Lo J, You SM, Canavan B, et al. Lowdose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial.JAMA 2008; 300: 509-19.

63. Stanley TL, Feldpausch MN, Oh J, et al.Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA 2014; 312: 380-9.

64. Baumann GP. Growth hormone doping in sports: a critical review of use and detection strategies. Endocr Rev 2012; 33: 155-86.

65. Oh JH, Chung SW, Oh KS, et al. Effect of recombinant human growth hormone on rotator cuff healing after arthroscopic repair: preliminary result of a multicenter, prospective, randomized, open-label blinded end point clinical exploratory trial. J Shoulder Elbow Surg 2018; 27: 777-85.

66. Meinhardt U, Nelson AE, Hansen JL, et al. The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial. Ann Intern Med 2010; 152: 568-77.

67. Liu H, Bravata DM, Olkin I, et al. Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med 2008; 148: 747-58.

68. Hermansen K, Bengtsen M, Kjar M,Vestergaard P, Jorgensen JOL. Impact of GH administration on athletic performance in healthy young adults: a systematic review and meta-analysis of placebocontrolled trials. Growth Horm IGF Res 2017; 34: 38-44.

69. Nelson AE, Meinhardt U, Hansen JL, et al. Pharmacodynamics of growth hormone abuse biomarkers and the influence of gender and testosterone: a randomized double-blind placebo-controlled study in young recreational athletes. J Clin Endocrinol Metab 2008; 93: 2213-22.

70. Melmed S. Acromegaly. N Engl J Med 2006; 355: 2558-73.

71. Sonksen PH, Cowan D, Holt RI. Use and misuse of hormones in sport. Lancet Diabetes Endocrinol 2016; 4: 882-3.

72. Ehrnborg C, Ellegard L, Bosaeus I, Bengtsson BA, Rosen T. Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults. Clin Endocrinol (Oxf) 2005; 62: 449-57.

73. Giannoulis MG, Martin FC, Nair KS, Umpleby AM, Sonksen P. Hormone replacement therapy and physical function in healthy older men: time to talk hormones? Endocr Rev 2012; 33: 314-77.

74. Liu H, Bravata DM, Olkin I, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med 2007; 146: 104-15.

75. Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 2002; 288: 2282-92.

76. Papadakis MA, Grady D, Black D, et al. Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 1996; 124: 708-16.

77. Milman S, Atzmon G, Huffman DM, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 2014; 13: 769-71.

78. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature 1996; 384: 33.

79. Aguiar-Oliveira MH, Bartke A. Growth hormone deficiency: health and longevity. Endocr Rev 2019; 40: 575-601.

80. Milman S, Huffman DM, Barzilai N. The somatotropic axis in human aging: framework for the current state of knowledge and future research. Cell Metab 2016; 23: 980-9.

81. Junnila RK, List EO, Berryman DE, Murrey JW, Kopchick JJ. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 2013; 9: 366-76.

82. Bartke A, Sun LY, Longo V. Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 2013; 93: 571-98.

83. Spadaro O, Goldberg EL, Camell CD, et al. Growth hormone receptor deficiency protects against age-related NLRP3 inflammasome activation and immune senescence.Cell Rep 2016; 14: 1571-80.

84. Ben-Avraham D, Govindaraju DR, Budagov T, et al. The GH receptor exon 3 deletion is a marker of male-specific ex ceptional longevity associated with increased GH sensitivity and taller stature. Sci Adv 2017;3(6):e1602025.

85. van der Spoel E, Jansen SW, Akintola AA, et al. Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity. Aging Cell 2016;15:1126-31.

86. Dal J, Leisner MZ, Hermansen K, et al. Cancer incidence in patients with

acromegaly: a cohort study and meta-analysis of the literature. J Clin Endocrinol Metab

2018; 103:2182-8.

87. Chen YJ, Zhang X, Wu ZS, et al. Autocrine human growth hormone stimulates the tumor initiating capacity and metastasis of estrogen receptor-negative mammary carcinoma cells. Cancer Lett 2015; 365:182-9.

88. Wu ZS, Yang K, Wan Y, et al. Tumor expression of human growth hormone and human prolactin predict a worse survival outcome in patients with mammary or endometrial carcinoma. J Clin Endocrinol Metab 2011;96:E1619-E1629.

89. Chesnokova V, Zhou C, Ben-Shlomo A, et al. Growth hormone is a cellular senescence target in pituitary and nonpituitary cells. Proc Natl Acad Sci U S A 2016;


90. Brittain AL, Basu R, Qian Y, Kopchick JJ. Growth hormone and the epithelial to- mesenchymal transition. J Clin Endocrinol Metab 2017; 102:3662-73.

91. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in proaging signaling, cancer, and diabetes in humans. Sci Transl Med 2011; 3:70ra13.

92. Cittadini A, Berggren A, Longobardi S, et al. Supraphysiological doses of GH induce rapid changes in cardiac morphology and function. J Clin Endocrinol Metab 2002;87:1654-9.

93. Thorner MO. Statement by the Growth Hormone Research Society on the GH/ IGF-I axis in extending health span. J Ger- ontol A Biol Sci Med Sci 2009;64:1039-44.

94. Perls TT, Reisman NR, Olshansky SJ. Provision or distribution of growth hormone for “antiaging”: clinical and legal issues. JAMA 2005;294-:2086-90



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