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Growth Hormone Excess and Other Conditions of Overgrowth

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Pediatric Endocrinology

Abstract

Tall stature is characterized by increased height velocity and height greater than 2 SDs than predicted for age and sex. The most common cause of tall stature is familial and should be considered after a detailed history, physical examination, and selected laboratory evaluation has ruled out syndromic and non-syndromic causes of tall stature.

Pituitary gigantism is the most common cause of growth hormone (GH) excess. Besides tall stature, clinical features such as coarse facial features, prognathism, arthralgias, and skeletal deformities may suggest GH excess. IGF-1 levels and the nadir GH level after glucose administration help confirm the diagnosis. Subsequent radiologic investigations and visual field testing can provide the location, size, and invasiveness of the GH-secreting somatotroph tumor and help plan further management. Surgery is the first line of therapy. However, multimodal therapy (surgical, medical, and radiologic) may be necessary to control tumor size and GH excess. Somatostatin analogs are used when surgery is not successful in removing the entire tumor and sometimes preoperatively to reduce tumor size and decrease IGF-1 levels, which may improve surgical outcomes. Dopamine agonists and the growth hormone receptor blocker (pegvisomant) are other options available for medical therapy. Radiation therapy may be necessary to control tumor size and IGF-1 levels if surgery and medical therapy are not effective.

Long-term complications related to GH excess and treatment should be monitored and adequately addressed. Glucose intolerance, hypertension, sleep apnea, cardiovascular complications, and vertebral fractures can be seen in patients with prolonged GH excess.

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References

  1. Martinelli CE, Keogh JM, Greenfield JR, Henning E, van der Klaauw AA, Blackwood A, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab. 2011;96(1):E181–8.

    Article  CAS  Google Scholar 

  2. de Waal WJ, Greyn-Fokker MH, Stijnen T, van Gurp EA, Toolens AM, de Munick Keizer-Schrama SM, et al. Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children. J Clin Endocrinol Metab. 1996;81(3):1206–16.

    Google Scholar 

  3. Upners EN, Juul A. Evaluation and phenotypic characteristics of 293 Danish girls with tall stature: effects of oral administration of natural 17beta-estradiol. Pediatr Res. 2016;80(5):693–701.

    Article  CAS  Google Scholar 

  4. Venn A, Bruinsma F, Werther G, Pyett P, Baird D, Jones P, et al. Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility. Lancet. 2004;364(9444):1513–8.

    Article  CAS  Google Scholar 

  5. Hendriks AE, Laven JS, Valkenburg O, Fong SL, Fauser BC, de Ridder MA, et al. Fertility and ovarian function in high-dose estrogen-treated tall women. J Clin Endocrinol Metab. 2011;96(4):1098–105.

    Article  CAS  Google Scholar 

  6. Benyi E, Kieler H, Linder M, Ritzen M, Carlstedt-Duke J, Tuvemo T, et al. Risks of malignant and non-malignant tumours in tall women treated with high-dose oestrogen during adolescence. Horm Res Paediatr. 2014;82(2):89–96.

    Article  CAS  Google Scholar 

  7. Reinehr T, Gueldensupp M, Wunsch R, Bramswig JH. Treatment of tall stature in boys: comparison of two different treatment regimens. Horm Res Paediatr. 2011;76(5):343–7.

    Article  CAS  Google Scholar 

  8. Odink RJ, Gerver WJ, Heeg M, Rouwe CW, van Waarde WM, Sauer PJ. Reduction of excessive height in boys by bilateral percutaneous epiphysiodesis around the knee. Eur J Pediatr. 2006;165(1):50–4.

    Article  Google Scholar 

  9. Benyi E, Berner M, Bjernekull I, Boman A, Chrysis D, Nilsson O, et al. Efficacy and safety of percutaneous epiphysiodesis operation around the knee to reduce adult height in extremely tall adolescent girls and boys. Int J Pediatr Endocrinol. 2010;2010:740629.

    Article  PubMed  Google Scholar 

  10. Manski TJ, Haworth CS, Duval-Arnould BJ, Rushing EJ. Optic pathway glioma infiltrating into somatostatinergic pathways in a young boy with gigantism. Case report. J Neurosurg. 1994;81(4):595–600.

    Article  CAS  Google Scholar 

  11. Pandey P, Ojha BK, Mahapatra AK. Pediatric pituitary adenoma: a series of 42 patients. J Clin Neurosci. 2005;12(2):124–7.

    Article  CAS  Google Scholar 

  12. Cannavo S, Venturino M, Curto L, De Menis E, D’Arrigo C, Tita P, et al. Clinical presentation and outcome of pituitary adenomas in teenagers. Clin Endocrinol. 2003;58(4):519–27.

    Article  CAS  Google Scholar 

  13. Burton T, Le Nestour E, Neary M, Ludlam WH. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016;19(3):262–7.

    Article  PubMed  Google Scholar 

  14. Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4–9.

    Article  Google Scholar 

  15. Rostomyan L, Daly AF, Petrossians P, Nachev E, Lila AR, Lecoq AL, et al. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer. 2015;22(5):745–57.

    Article  CAS  Google Scholar 

  16. Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386(1–2):2–15.

    Article  CAS  PubMed  Google Scholar 

  17. Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014;371(25):2363–74.

    Article  CAS  PubMed  Google Scholar 

  18. Faje AT, Barkan AL. Basal, but not pulsatile, growth hormone secretion determines the ambient circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab. 2010;95(5):2486–91.

    Article  CAS  PubMed  Google Scholar 

  19. Barkan AL, Beitins IZ, Kelch RP. Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab. 1988;67(1):69–73.

    Article  CAS  Google Scholar 

  20. Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WF, Barkan AL. Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab. 2002;87(8):3537–42.

    Article  CAS  Google Scholar 

  21. Grinspoon S, Clemmons D, Swearingen B, Klibanski A. Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly. J Clin Endocrinol Metab. 1995;80(3):927–32.

    CAS  Google Scholar 

  22. Costa AC, Rossi A, Martinelli CE Jr, Machado HR, Moreira AC. Assessment of disease activity in treated acromegalic patients using a sensitive GH assay: should we achieve strict normal GH levels for a biochemical cure? J Clin Endocrinol Metab. 2002;87(7):3142–7.

    Article  CAS  Google Scholar 

  23. Cazabat L, Libe R, Perlemoine K, Rene-Corail F, Burnichon N, Gimenez-Roqueplo AP, et al. Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. Eur J Endocrinol/Eur Fed Endocr Soc. 2007;157(1):1–8.

    Article  CAS  Google Scholar 

  24. Shimon I, Jallad RS, Fleseriu M, Yedinak CG, Greenman Y, Bronstein MD. Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors. Eur J Endocrinol/Eur Fed Endocr Soc. 2015;172(6):707–13.

    Article  CAS  Google Scholar 

  25. Biermasz NR, Dekker FW, Pereira AM, van Thiel SW, Schutte PJ, van Dulken H, et al. Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab. 2004;89(6):2789–96.

    Article  CAS  Google Scholar 

  26. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89(2):667–74.

    Article  CAS  Google Scholar 

  27. Sherlock M, Reulen RC, Aragon-Alonso A, Ayuk J, Clayton RN, Sheppard MC, et al. A paradigm shift in the monitoring of patients with acromegaly: last available growth hormone may overestimate risk. J Clin Endocrinol Metab. 2014;99(2):478–85.

    Article  CAS  Google Scholar 

  28. Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab. 2008;93(8):2957–68.

    Article  CAS  Google Scholar 

  29. Gatto F, Feelders RA, Franck SE, van Koetsveld PM, Dogan F, Kros JM, et al. In vitro head-to-head comparison between octreotide and pasireotide in GH-secreting pituitary adenomas. J Clin Endocrinol Metab. 2017;102(6):2009–18.

    Article  Google Scholar 

  30. Ezzat S, Kontogeorgos G, Redelmeier DA, Horvath E, Harris AG, Kovacs K. In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. Eur J Endocrinol/Eur Fed Endocr Soc. 1995;133(6):686–90.

    Article  CAS  Google Scholar 

  31. Puig-Domingo M, Resmini E, Gomez-Anson B, Nicolau J, Mora M, Palomera E, et al. Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J Clin Endocrinol Metab. 2010;95(11):4973–8.

    Article  CAS  PubMed  Google Scholar 

  32. Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S. The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J Clin Endocrinol Metab. 2005;90(11):6290–5.

    Article  CAS  PubMed  Google Scholar 

  33. Mercado M, Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, et al. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol. 2007;66(6):859–68.

    Article  CAS  Google Scholar 

  34. Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS One. 2012;7(5):e36411.

    Article  CAS  PubMed  Google Scholar 

  35. Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791–9.

    Article  CAS  PubMed  Google Scholar 

  36. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011;96(5):1327–35.

    Article  CAS  PubMed  Google Scholar 

  37. Abs R, Verhelst J, Maiter D, Van Acker K, Nobels F, Coolens JL, et al. Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab. 1998;83(2):374–8.

    Article  CAS  PubMed  Google Scholar 

  38. Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Khandji AG, Post KD. Cabergoline therapy of growth hormone & growth hormone/prolactin secreting pituitary tumors. Pituitary. 2004;7(1):21–30.

    Article  CAS  PubMed  Google Scholar 

  39. Maione L, Garcia C, Bouchachi A, Kallel N, Maison P, Salenave S, et al. No evidence of a detrimental effect of cabergoline therapy on cardiac valves in patients with acromegaly. J Clin Endocrinol Metab. 2012;97(9):E1714–9.

    Article  CAS  PubMed  Google Scholar 

  40. Marazuela M, Paniagua AE, Gahete MD, Lucas T, Alvarez-Escola C, Manzanares R, et al. Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study. J Clin Endocrinol Metab. 2011;96(2):E251–9.

    Article  CAS  Google Scholar 

  41. Rix M, Laurberg P, Hoejberg AS, Brock-Jacobsen B. Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl. Eur J Endocrinol/Eur Fed Endocr Soc. 2005;153(2):195–201.

    Article  CAS  Google Scholar 

  42. Buhk JH, Jung S, Psychogios MN, Goricke S, Hartz S, Schulz-Heise S, et al. Tumor volume of growth hormone-secreting pituitary adenomas during treatment with pegvisomant: a prospective multicenter study. J Clin Endocrinol Metab. 2010;95(2):552–8.

    Article  CAS  Google Scholar 

  43. Neggers SJ, de Herder WW, Feelders RA, van der Lely AJ. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients. Pituitary. 2011;14(3):253–8.

    Article  CAS  PubMed  Google Scholar 

  44. van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012;97(5):1589–97.

    Article  Google Scholar 

  45. McLaughlin N, Laws ER, Oyesiku NM, Katznelson L, Kelly DF. Pituitary centers of excellence. Neurosurgery. 2012;71(5):916–24. discussion 24–6.

    Article  Google Scholar 

  46. Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab. 2011;96(9):2732–40.

    Article  CAS  Google Scholar 

  47. Briceno V, Zaidi HA, Doucette JA, Onomichi KB, Alreshidi A, Mekary RA, et al. Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis. Neurol Res. 2017;39(5):387–98.

    Article  Google Scholar 

  48. Zada G, Sivakumar W, Fishback D, Singer PA, Weiss MH. Significance of postoperative fluid diuresis in patients undergoing transsphenoidal surgery for growth hormone-secreting pituitary adenomas. J Neurosurg. 2010;112(4):744–9.

    Article  CAS  Google Scholar 

  49. Freda PU. Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Clin Endocrinol. 2009;71(2):166–70.

    Article  CAS  Google Scholar 

  50. Molitch ME, Grossman AB. Pituitary radiotherapy. Pituitary. 2009;12(1):1–2.

    Article  Google Scholar 

  51. Minniti G, Jaffrain-Rea ML, Osti M, Esposito V, Santoro A, Solda F, et al. The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas. Clin Endocrinol. 2005;62(2):210–6.

    Article  Google Scholar 

  52. Gheorghiu ML. Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary. 2017;20(1):154–68.

    Article  Google Scholar 

  53. Ross DA, Wilson CB. Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients. J Neurosurg. 1988;68(6):854–67.

    Article  CAS  Google Scholar 

  54. Biermasz NR, van Dulken H, Roelfsema F. Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly. J Clin Endocrinol Metab. 2000;85(7):2476–82.

    Article  CAS  Google Scholar 

  55. Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S, Klibanski A, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab. 1998;83(10):3419–26.

    CAS  Google Scholar 

  56. Ritvonen E, Loyttyniemi E, Jaatinen P, Ebeling T, Moilanen L, Nuutila P, et al. Mortality in acromegaly: a 20-year follow-up study. Endocr Relat Cancer. 2015;23(6):469–80.

    Article  Google Scholar 

  57. Mercado M, Gonzalez B, Vargas G, Ramirez C, de los Monteros AL, Sosa E, et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438–46.

    Article  CAS  Google Scholar 

  58. Maione L, Brue T, Beckers A, Delemer B, Petrossians P, Borson-Chazot F, et al. Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry. Eur J Endocrinol/Eur Fed Endocr Soc. 2017;176(5):645–55.

    Article  CAS  Google Scholar 

  59. Clayton RN. Cardiovascular function in acromegaly. Endocr Rev. 2003;24(3):272–7.

    Article  CAS  Google Scholar 

  60. Colao A, Baldelli R, Marzullo P, Ferretti E, Ferone D, Gargiulo P, et al. Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy. J Clin Endocrinol Metab. 2000;85(1):193–9.

    CAS  Google Scholar 

  61. Akutsu H, Kreutzer J, Wasmeier G, Ropers D, Rost C, Mohlig M, et al. Acromegaly per se does not increase the risk for coronary artery disease. Eur J Endocrinol/Eur Fed Endocr Soc. 2010;162(5):879–86.

    Article  CAS  Google Scholar 

  62. Davi MV, Dalle Carbonare L, Giustina A, Ferrari M, Frigo A, Lo Cascio V, et al. Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease. Eur J Endocrinol/Eur Fed Endocr Soc. 2008;159(5):533–40.

    Article  CAS  Google Scholar 

  63. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102–52.

    Article  CAS  Google Scholar 

  64. Frara S, Maffezzoni F, Mazziotti G, Giustina A. Current and emerging aspects of diabetes mellitus in acromegaly. Trends Endocrinol Metab. 2016;27(7):470–83.

    Article  CAS  Google Scholar 

  65. Jonas C, Maiter D, Alexopoulou O. Evolution of glucose tolerance after treatment of acromegaly: a study in 57 patients. Horm Metab Res. 2016;48(5):299–305.

    Article  CAS  Google Scholar 

  66. Maffezzoni F, Maddalo M, Frara S, Mezzone M, Zorza I, Baruffaldi F, et al. High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures. Endocrine. 2016;54(2):532–42.

    Article  CAS  Google Scholar 

  67. Mazziotti G, Maffezzoni F, Frara S, Giustina A. Acromegalic osteopathy. Pituitary. 2017;20(1):63–9.

    Article  CAS  Google Scholar 

  68. Wassenaar MJ, Cazemier M, Biermasz NR, Pereira AM, Roelfsema F, Smit JW, et al. Acromegaly is associated with an increased prevalence of colonic diverticula: a case-control study. J Clin Endocrinol Metab. 2010;95(5):2073–9.

    Article  CAS  Google Scholar 

  69. Wolinski K, Stangierski A, Dyrda K, Nowicka K, Pelka M, Iqbal A, et al. Risk of malignant neoplasms in acromegaly: a case-control study. J Endocrinol Investig. 2017;40(3):319–22.

    Article  CAS  Google Scholar 

  70. Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998;83(8):2730–4.

    CAS  Google Scholar 

  71. Petroff D, Tonjes A, Grussendorf M, Droste M, Dimopoulou C, Stalla G, et al. The incidence of cancer among acromegaly patients: results from the german acromegaly registry. J Clin Endocrinol Metab. 2015;100(10):3894–902.

    Article  CAS  Google Scholar 

  72. Tirosh A, Shimon I. Complications of acromegaly: thyroid and colon. Pituitary. 2017;20(1):70–5.

    Article  Google Scholar 

  73. Jenkins PJ, Besser M. Clinical perspective: acromegaly and cancer: a problem. J Clin Endocrinol Metab. 2001;86(7):2935–41.

    Article  CAS  Google Scholar 

  74. Melmed S. Acromegaly and cancer: not a problem? J Clin Endocrinol Metab. 2001;86(7):2929–34.

    Article  CAS  Google Scholar 

  75. Geraedts VJ, Andela CD, Stalla GK, Pereira AM, van Furth WR, Sievers C, et al. Predictors of quality of life in acromegaly: no consensus on biochemical parameters. Front Endocrinol (Lausanne). 2017;8:40.

    Google Scholar 

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Singhal, V., Misra, M. (2018). Growth Hormone Excess and Other Conditions of Overgrowth. In: Radovick, S., Misra, M. (eds) Pediatric Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73782-9_9

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