Abstrakt
Niedobór hormonu wzrostu (GHD) u dorosłych jest skutkiem spadku produkcji i sekrecji tego hormonu przez komórki somatotropowe przedniego płata przysadki, który nie wynika z fizjologicznego procesu starzenia. Konsekwencjami GHD są: niekorzystna zmiana składu ciała, zaburzenia metabolizmu węglowodanów i lipidów, powikłania dotyczące układu sercowo-naczyniowego oraz upośledzona jakość życia. Wiele z tych następstw może być, przynajmniej częściowo odwracalnych podczas leczenia rekombinowanym ludzkim hormonem wzrostu (rhGH). Dlatego lekarze wielu specjalności, w szczególności endokrynologii powinni diagnozować pacjentów z podejrzeniem GHD, a w przypadku potwierdzenia diagnozy rozważyć substytucję rhGH.
Bibliografia
1. Molitch, M.E., D.R. Clemmons, S. Malozowski, et al., Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2011. 96(6): p. 1587-609.
2. Lewinski, A., J. Smyczynska, R. Stawerska, et al., National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy. Endokrynol Pol, 2018. 69(5): p. 468-524.
3. Yuen, K.C.J., B.M.K. Biller, S. Radovick, et al., American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care. Endocr Pract, 2019. 25(11): p. 1191-1232.
4. Gazzaruso, C., M. Gola, I. Karamouzis, 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): p. 18-29.
5. Underwood, L.E., K.M. Attie, J. Baptista, and G. Genentech Collaborative Study, Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab, 2003. 88(11): p. 5273-80.
6. Ayyar, V.S., History of growth hormone therapy. Indian J Endocrinol Metab, 2011. 15 Suppl 3(Suppl3): p. S162-5.
7. Elbornsson, M., G. Gotherstrom, I. Bosaeus, et al., Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol, 2013. 168(5): p. 745-53.
8. Fernandez-Rodriguez, E., M. Lopez-Raton, P. Andujar, et al., Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf), 2013. 78(2): p. 278-84.
9. Sassolas, G., F.B. Chazot, P. Jaquet, et al., GH deficiency in adults: an epidemiological approach. Eur J Endocrinol, 1999. 141(6): p. 595-600.
10. Stochholm, K., C.H. Gravholt, T. Laursen, et al., Incidence of GH deficiency - a nationwide study. Eur J Endocrinol, 2006. 155(1): p. 61-71.
11. Stelmachowska-Banas, M. and I. Czajka-Oraniec, Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review. Endocr Connect, 2020. 9(10): p. R207-R228.
12. Brabant, G., E.M. Poll, P. Jonsson, 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: p. S25-31.
13. Martel-Duguech, L.M., J.O.L. Jorgensen, M. Korbonits, et al., ESE audit on management of Adult Growth Hormone Deficiency in clinical practice. Eur J Endocrinol, 2020.
14. Tritos, N.A. and B.M.K. Biller, Current concepts of the diagnosis of adult growth hormone deficiency. Rev Endocr Metab Disord, 2021. 22(1): p. 109-116.
15. Isgaard, J., Cardiovascular disease and risk factors: the role of growth hormone. Horm Res, 2004. 62 Suppl 4: p. 31-8.
16. Weaver, J.U., J.P. Monson, K. Noonan, 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(1): p. 153-9.
17. Carroll, P.V., E.R. Christ, B.A. Bengtsson, 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): p. 382-95.
18. Kim, S.H. and M.J. Park, Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab, 2017. 22(3): p. 145-152.
19. Hoffman, A.R., J.E. Kuntze, J. Baptista, 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(5): p. 2048-56.
20. Appelman-Dijkstra, N.M., K.M. Claessen, F. Roelfsema, et al., Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. Eur J Endocrinol, 2013. 169(1): p. R1-14.
21. Filipsson Nystrom, H., E.J. Barbosa, A.G. Nilsson, et al., Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency. J Clin Endocrinol Metab, 2012. 97(9): p. 3185-95.
22. Bouillon, R., E. Koledova, O. Bezlepkina, et al., Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency. J Clin Endocrinol Metab, 2004. 89(10): p. 4993-8.
23. Bonadonna, S., G. Mazziotti, M. Nuzzo, et al., Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res, 2005. 20(10): p. 1837-44.
24. Mazziotti, G., S. Chiavistelli, and A. Giustina, Pituitary diseases and bone. Endocrinol Metab Clin North Am, 2015. 44(1): p. 171-80.
25. Hogler, W. and N. Shaw, Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol (Oxf), 2010. 72(3): p. 281-9.
26. Olney, R.C., Regulation of bone mass by growth hormone. Med Pediatr Oncol, 2003. 41(3): p. 228-34.
27. Hansen, T.B., K. Brixen, N. Vahl, 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(9): p. 3352-9.
28. Degerblad, M., B.A. Bengtsson, M. Bramnert, 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(2): p. 180-8.
29. Elbornsson, M., G. Gotherstrom, I. Bosaeus, et al., Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency. Eur J Endocrinol, 2012. 166(5): p. 787-95.
30. Appelman-Dijkstra, N.M., K.M. Claessen, N.A. Hamdy, 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): p. 727-35.
31. Mo, D., M. Fleseriu, R. Qi, et al., Fracture risk in adult patients treated with growth hormone replacement therapy for growth hormone deficiency: a prospective observational cohort study. Lancet Diabetes Endocrinol, 2015. 3(5): p. 331-8.
32. van Varsseveld, N.C., C.C. van Bunderen, A.A. Franken, et al., Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults. Pituitary, 2016. 19(4): p. 381-90.
33. Radcliffe, D.J., J.S. Pliskin, J.B. Silvers, and L. Cuttler, Growth hormone therapy and quality of life in adults and children. Pharmacoeconomics, 2004. 22(8): p. 499-524.
34. Walser, M., J. Svensson, L. Karlsson, et al., Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases. Front Endocrinol (Lausanne), 2020. 11: p. 606089.
35. Sin, N.L., The Protective Role of Positive Well-Being in Cardiovascular Disease: Review of Current Evidence, Mechanisms, and Clinical Implications. Curr Cardiol Rep, 2016. 18(11): p. 106.
36. Levine, G.N., B.E. Cohen, Y. Commodore-Mensah, et al., Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association. Circulation, 2021. 143(10): p. e763-e783.
37. McGauley, G., The psychological consequences and quality of life in adults with growth hormone deficiency. Growth Horm IGF Res, 2000. 10 Suppl B: p. S63-8.
38. Roemmler, J., M. Kuenkler, H.J. Schneider, et al., Comparison of glucose and lipid metabolism and bone mineralization in patients with growth hormone deficiency with and without long-term growth hormone replacement. Metabolism, 2010. 59(3): p. 350-8.
39. Ukropec, J., A. Penesova, M. Skopkova, et al., Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J Clin Endocrinol Metab, 2008. 93(6): p. 2255-62.
40. Szalecki, M., A. Malinowska, M. Prokop-Piotrkowska, and R. Janas, Interactions between the growth hormone and cytokines - A review. Adv Med Sci, 2018. 63(2): p. 285-289.
41. Maison, P., S. Griffin, M. Nicoue-Beglah, et al., Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. J Clin Endocrinol Metab, 2004. 89(5): p. 2192-9.
42. Giagulli, V.A., M. Castellana, R. Perrone, et al., GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis. Endocr Metab Immune Disord Drug Targets, 2017. 17(4): p. 285-296.
43. Wollmann, H.A. and M.B. Ranke, Metabolic effects of growth hormone in children. Metabolism, 1995. 44(10 Suppl 4): p. 97-102.
44. Cutfield, W.S., P. Wilton, H. Bennmarker, et al., Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet, 2000. 355(9204): p. 610-3.
45. Zhou, H., L. Sun, S. Zhang, et al., Effect of long-term growth hormone replacement on glucose metabolism in adults with growth hormone deficiency: a systematic review and meta-analysis. Pituitary, 2021. 24(1): p. 130-142.
46. Ratku, B., V. Sebestyen, A. Erdei, et al., Effects of adult growth hormone deficiency and replacement therapy on the cardiometabolic risk profile. Pituitary, 2022. 25(2): p. 211-228.
47. Isgaard, J., M. Arcopinto, K. Karason, and A. Cittadini, GH and the cardiovascular system: an update on a topic at heart. Endocrine, 2015. 48(1): p. 25-35.
48. Chanson, P., The heart in growth hormone (GH) deficiency and the cardiovascular effects of GH. Ann Endocrinol (Paris), 2021. 82(3-4): p. 210-213.
49. Boger, R.H., C. Skamira, S.M. Bode-Boger, et al., Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest, 1996. 98(12): p. 2706-13.
50. Levine, A.B., D. Punihaole, and T.B. Levine, Characterization of the role of nitric oxide and its clinical applications. Cardiology, 2012. 122(1): p. 55-68.
51. Zhang, S., Z. Li, Y. Lv, et al., Cardiovascular effects of growth hormone (GH) treatment on GH-deficient adults: a meta-analysis update. Pituitary, 2020. 23(4): p. 467-475.
52. Lekakis, J.P., C.M. Papamichael, A.T. Cimponeriu, et al., Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis. Am J Cardiol, 2000. 85(8): p. 949-52.
53. Di Somma, C., E. Scarano, S. Savastano, et al., Cardiovascular alterations in adult GH deficiency. Best Pract Res Clin Endocrinol Metab, 2017. 31(1): p. 25-34.
54. Borson-Chazot, F., A. Serusclat, Y. Kalfallah, 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(4): p. 1329-33.
55. Andreassen, M., J. Faber, A. Kjaer, et al., Cardiac function in growth hormone deficient patients before and after 1 year with replacement therapy: a magnetic resonance imaging study. Pituitary, 2011. 14(1): p. 1-10.
56. Olsson, D.S., A.G. Nilsson, I.L. Bryngelsson, et al., Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study. J Clin Endocrinol Metab, 2015. 100(7): p. 2651-8.
57. Bates, A.S., W. Van't Hoff, P.J. Jones, and R.N. Clayton, The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab, 1996. 81(3): p. 1169-72.
58. van Bunderen, C.C. and D.S. Olsson, Growth hormone deficiency and replacement therapy in adults: Impact on survival. Rev Endocr Metab Disord, 2021. 22(1): p. 125-133.
59. Burman, P., A.F. Mattsson, G. Johannsson, et al., Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. J Clin Endocrinol Metab, 2013. 98(4): p. 1466-75.
60. Sanmarti, A., A. Lucas, F. Hawkins, et al., Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol, 1999. 141(5): p. 481-9.
2. Lewinski, A., J. Smyczynska, R. Stawerska, et al., National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy. Endokrynol Pol, 2018. 69(5): p. 468-524.
3. Yuen, K.C.J., B.M.K. Biller, S. Radovick, et al., American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Growth Hormone Deficiency in Adults and Patients Transitioning from Pediatric to Adult Care. Endocr Pract, 2019. 25(11): p. 1191-1232.
4. Gazzaruso, C., M. Gola, I. Karamouzis, 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): p. 18-29.
5. Underwood, L.E., K.M. Attie, J. Baptista, and G. Genentech Collaborative Study, Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab, 2003. 88(11): p. 5273-80.
6. Ayyar, V.S., History of growth hormone therapy. Indian J Endocrinol Metab, 2011. 15 Suppl 3(Suppl3): p. S162-5.
7. Elbornsson, M., G. Gotherstrom, I. Bosaeus, et al., Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol, 2013. 168(5): p. 745-53.
8. Fernandez-Rodriguez, E., M. Lopez-Raton, P. Andujar, et al., Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf), 2013. 78(2): p. 278-84.
9. Sassolas, G., F.B. Chazot, P. Jaquet, et al., GH deficiency in adults: an epidemiological approach. Eur J Endocrinol, 1999. 141(6): p. 595-600.
10. Stochholm, K., C.H. Gravholt, T. Laursen, et al., Incidence of GH deficiency - a nationwide study. Eur J Endocrinol, 2006. 155(1): p. 61-71.
11. Stelmachowska-Banas, M. and I. Czajka-Oraniec, Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review. Endocr Connect, 2020. 9(10): p. R207-R228.
12. Brabant, G., E.M. Poll, P. Jonsson, 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: p. S25-31.
13. Martel-Duguech, L.M., J.O.L. Jorgensen, M. Korbonits, et al., ESE audit on management of Adult Growth Hormone Deficiency in clinical practice. Eur J Endocrinol, 2020.
14. Tritos, N.A. and B.M.K. Biller, Current concepts of the diagnosis of adult growth hormone deficiency. Rev Endocr Metab Disord, 2021. 22(1): p. 109-116.
15. Isgaard, J., Cardiovascular disease and risk factors: the role of growth hormone. Horm Res, 2004. 62 Suppl 4: p. 31-8.
16. Weaver, J.U., J.P. Monson, K. Noonan, 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(1): p. 153-9.
17. Carroll, P.V., E.R. Christ, B.A. Bengtsson, 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): p. 382-95.
18. Kim, S.H. and M.J. Park, Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab, 2017. 22(3): p. 145-152.
19. Hoffman, A.R., J.E. Kuntze, J. Baptista, 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(5): p. 2048-56.
20. Appelman-Dijkstra, N.M., K.M. Claessen, F. Roelfsema, et al., Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. Eur J Endocrinol, 2013. 169(1): p. R1-14.
21. Filipsson Nystrom, H., E.J. Barbosa, A.G. Nilsson, et al., Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency. J Clin Endocrinol Metab, 2012. 97(9): p. 3185-95.
22. Bouillon, R., E. Koledova, O. Bezlepkina, et al., Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency. J Clin Endocrinol Metab, 2004. 89(10): p. 4993-8.
23. Bonadonna, S., G. Mazziotti, M. Nuzzo, et al., Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res, 2005. 20(10): p. 1837-44.
24. Mazziotti, G., S. Chiavistelli, and A. Giustina, Pituitary diseases and bone. Endocrinol Metab Clin North Am, 2015. 44(1): p. 171-80.
25. Hogler, W. and N. Shaw, Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol (Oxf), 2010. 72(3): p. 281-9.
26. Olney, R.C., Regulation of bone mass by growth hormone. Med Pediatr Oncol, 2003. 41(3): p. 228-34.
27. Hansen, T.B., K. Brixen, N. Vahl, 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(9): p. 3352-9.
28. Degerblad, M., B.A. Bengtsson, M. Bramnert, 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(2): p. 180-8.
29. Elbornsson, M., G. Gotherstrom, I. Bosaeus, et al., Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency. Eur J Endocrinol, 2012. 166(5): p. 787-95.
30. Appelman-Dijkstra, N.M., K.M. Claessen, N.A. Hamdy, 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): p. 727-35.
31. Mo, D., M. Fleseriu, R. Qi, et al., Fracture risk in adult patients treated with growth hormone replacement therapy for growth hormone deficiency: a prospective observational cohort study. Lancet Diabetes Endocrinol, 2015. 3(5): p. 331-8.
32. van Varsseveld, N.C., C.C. van Bunderen, A.A. Franken, et al., Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults. Pituitary, 2016. 19(4): p. 381-90.
33. Radcliffe, D.J., J.S. Pliskin, J.B. Silvers, and L. Cuttler, Growth hormone therapy and quality of life in adults and children. Pharmacoeconomics, 2004. 22(8): p. 499-524.
34. Walser, M., J. Svensson, L. Karlsson, et al., Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases. Front Endocrinol (Lausanne), 2020. 11: p. 606089.
35. Sin, N.L., The Protective Role of Positive Well-Being in Cardiovascular Disease: Review of Current Evidence, Mechanisms, and Clinical Implications. Curr Cardiol Rep, 2016. 18(11): p. 106.
36. Levine, G.N., B.E. Cohen, Y. Commodore-Mensah, et al., Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association. Circulation, 2021. 143(10): p. e763-e783.
37. McGauley, G., The psychological consequences and quality of life in adults with growth hormone deficiency. Growth Horm IGF Res, 2000. 10 Suppl B: p. S63-8.
38. Roemmler, J., M. Kuenkler, H.J. Schneider, et al., Comparison of glucose and lipid metabolism and bone mineralization in patients with growth hormone deficiency with and without long-term growth hormone replacement. Metabolism, 2010. 59(3): p. 350-8.
39. Ukropec, J., A. Penesova, M. Skopkova, et al., Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J Clin Endocrinol Metab, 2008. 93(6): p. 2255-62.
40. Szalecki, M., A. Malinowska, M. Prokop-Piotrkowska, and R. Janas, Interactions between the growth hormone and cytokines - A review. Adv Med Sci, 2018. 63(2): p. 285-289.
41. Maison, P., S. Griffin, M. Nicoue-Beglah, et al., Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. J Clin Endocrinol Metab, 2004. 89(5): p. 2192-9.
42. Giagulli, V.A., M. Castellana, R. Perrone, et al., GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis. Endocr Metab Immune Disord Drug Targets, 2017. 17(4): p. 285-296.
43. Wollmann, H.A. and M.B. Ranke, Metabolic effects of growth hormone in children. Metabolism, 1995. 44(10 Suppl 4): p. 97-102.
44. Cutfield, W.S., P. Wilton, H. Bennmarker, et al., Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet, 2000. 355(9204): p. 610-3.
45. Zhou, H., L. Sun, S. Zhang, et al., Effect of long-term growth hormone replacement on glucose metabolism in adults with growth hormone deficiency: a systematic review and meta-analysis. Pituitary, 2021. 24(1): p. 130-142.
46. Ratku, B., V. Sebestyen, A. Erdei, et al., Effects of adult growth hormone deficiency and replacement therapy on the cardiometabolic risk profile. Pituitary, 2022. 25(2): p. 211-228.
47. Isgaard, J., M. Arcopinto, K. Karason, and A. Cittadini, GH and the cardiovascular system: an update on a topic at heart. Endocrine, 2015. 48(1): p. 25-35.
48. Chanson, P., The heart in growth hormone (GH) deficiency and the cardiovascular effects of GH. Ann Endocrinol (Paris), 2021. 82(3-4): p. 210-213.
49. Boger, R.H., C. Skamira, S.M. Bode-Boger, et al., Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest, 1996. 98(12): p. 2706-13.
50. Levine, A.B., D. Punihaole, and T.B. Levine, Characterization of the role of nitric oxide and its clinical applications. Cardiology, 2012. 122(1): p. 55-68.
51. Zhang, S., Z. Li, Y. Lv, et al., Cardiovascular effects of growth hormone (GH) treatment on GH-deficient adults: a meta-analysis update. Pituitary, 2020. 23(4): p. 467-475.
52. Lekakis, J.P., C.M. Papamichael, A.T. Cimponeriu, et al., Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis. Am J Cardiol, 2000. 85(8): p. 949-52.
53. Di Somma, C., E. Scarano, S. Savastano, et al., Cardiovascular alterations in adult GH deficiency. Best Pract Res Clin Endocrinol Metab, 2017. 31(1): p. 25-34.
54. Borson-Chazot, F., A. Serusclat, Y. Kalfallah, 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(4): p. 1329-33.
55. Andreassen, M., J. Faber, A. Kjaer, et al., Cardiac function in growth hormone deficient patients before and after 1 year with replacement therapy: a magnetic resonance imaging study. Pituitary, 2011. 14(1): p. 1-10.
56. Olsson, D.S., A.G. Nilsson, I.L. Bryngelsson, et al., Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study. J Clin Endocrinol Metab, 2015. 100(7): p. 2651-8.
57. Bates, A.S., W. Van't Hoff, P.J. Jones, and R.N. Clayton, The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab, 1996. 81(3): p. 1169-72.
58. van Bunderen, C.C. and D.S. Olsson, Growth hormone deficiency and replacement therapy in adults: Impact on survival. Rev Endocr Metab Disord, 2021. 22(1): p. 125-133.
59. Burman, P., A.F. Mattsson, G. Johannsson, et al., Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. J Clin Endocrinol Metab, 2013. 98(4): p. 1466-75.
60. Sanmarti, A., A. Lucas, F. Hawkins, et al., Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol, 1999. 141(5): p. 481-9.
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