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Growth hormone- and growth-hormone-releasing hormone-producing tumors

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Endocrine Neoplasms

Part of the book series: Cancer Treatment and Research ((CTAR,volume 89))

Abstract

Acromegaly, a clinical syndrome of disordered somatic growth and proportion, is usually caused by the unrestrained secretion of growth hormone (GH) by a pituitary adenoma and rarely may result from GH-releasing hormone (GHRH) secretion by an extrapituitary tumor. The disease was first described more than a century ago and was the earliest pituitary disorder to be recognized. The clinical features of acromegaly are caused by elevated GH and insulin-like growth factor-I (IGF-I) levels.

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References

  1. Miller WL, Eberhardt NL. 1983. Structure and evaluation of growth hormone gene family. Endocr Rev 4:97–130.

    Article  PubMed  CAS  Google Scholar 

  2. Lewis UJ, Bonewald LF, Lewis VJ. 1980. The 20,000-dalton variant of human growth hormone: Location of the amino acid deletions. Biochem Biophys Res Commun 92:511–516.

    Article  PubMed  CAS  Google Scholar 

  3. Baumann G. 1991. Growth hormone heterogeneity: Genes, isohormones, variants, and binding proteins. Endocr Rev 12:235–251.

    Article  Google Scholar 

  4. Barinaga M, Yamanoto G, Rivier G, Vale W, Evans R, Rosenfeld MG. 1983. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature 306:84–86.

    Article  PubMed  CAS  Google Scholar 

  5. Fukata J, Diamond DJ, Martin JB. 1985. Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells. Endocrinology 117:457–467.

    Article  PubMed  CAS  Google Scholar 

  6. Yamashita S, Weiss M, Melmed S. 1986. Insulin-growth factor I regulates growth hormone secretion and messenger ribonucleic acid levels in human pituitary tumor cells. J Clin Endocrinol Metab 63:730–735.

    Article  PubMed  CAS  Google Scholar 

  7. Herman V, Weiss M, Becker D, Melmed S. 1990. Hypothalamic hormonal regulation of human growth hormane gene expression in somatotroph adenoma cell cultures. Endocr Pathol 1:236–244.

    Article  Google Scholar 

  8. Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WG, Barnard R, Waters MJ, Wood EI. 1987. Growth hormone receptor and serum binding protein: Purification, cloning and expression. Nature 330:537–543.

    Article  PubMed  CAS  Google Scholar 

  9. Mannor DA, Winer LM, Shaw MA, Baumann G. 1991. Plasma growth hormone (GH)-binding proteins: Effect on GH binding to receptors and GH action. J Clin Endocrinol Metab 73:30–34.

    Article  PubMed  CAS  Google Scholar 

  10. Salomon F, Cuneo RC, Hesp R, Sonksen PH. 1989. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321:1797–1803.

    Article  PubMed  CAS  Google Scholar 

  11. Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S. 1990. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 71:1427–1433.

    Article  PubMed  CAS  Google Scholar 

  12. Vallar L, Spada A, Giannattasio G. 1987. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 330:566–568.

    Article  PubMed  CAS  Google Scholar 

  13. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. 1989. GTPase inhibiting mutations activate the a chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340:692–696.

    Article  PubMed  CAS  Google Scholar 

  14. Landis CA, Harsh G, Lyons J, Davis RL, McCormick F, Bourne HR. 1990. Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. J Clin Endocrinol Metab 71:1416–1420.

    Article  PubMed  CAS  Google Scholar 

  15. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. 1991. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 325:1688–1695.

    Article  PubMed  CAS  Google Scholar 

  16. Bertherat J, Chanson P, Montminy M. 1995. The cyclic adenosine 3′,5′-monophosphate-responsive factor CREB is constitutively activated in human somatotroph adenomas. Mol Endocrinol 9:777–783.

    Article  PubMed  CAS  Google Scholar 

  17. Thakker RV, Pook MA, Wooding C, Boscaro M, Scanarini M, Clayton RN. 1993. Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations. J Clin Invest 91:2815–2821.

    Article  PubMed  CAS  Google Scholar 

  18. Billestrup N, Swanson LW, Vale W. 1986. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc Natl Acad Sci USA 83:6854–6857.

    Article  PubMed  CAS  Google Scholar 

  19. Joubert (Bression) D, Benlot C, Lagoguey A, Gamier P, Brandi AM, Gautron JP, Legrand JC, Peillon F. 1989. Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone. J Clin Endocrinol Metab 68:572–577.

    Article  Google Scholar 

  20. Lloyd RV, Cano M, Chandler WF, Barkan AL, Horvath E, Kovacs K. 1989. Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization. Am J Pathol 134:605–613.

    PubMed  CAS  Google Scholar 

  21. Kovacs K, Horvath E, Asa SL, Stefaneanu L, Sano T. 1989. Pituitary cells producing more than one hormone. Trends Endocrinol Metab 1:104–107.

    Article  PubMed  CAS  Google Scholar 

  22. Rasmussen P, Lindholm J. 1979. Ectopic pituitary adenomas. Clin Endocrinol 11:69–74.

    Article  CAS  Google Scholar 

  23. Mountcastle RB, Roof BS, Mayfield RK, Mordes DB, Sagel J, Biggs PJ, Rawe SE. 1989. Case report: Pituitary adenocarcinoma in an acromegalic patient: Response to bromocriptine and pituitary testing: A review of the literature on 36 cases of pituitary carcinoma. Am J Med Sci 298:109–118.

    Article  PubMed  CAS  Google Scholar 

  24. Greenman Y, Woolf P, Congilio J, O’Mara R, Pei L, Said JW, Melmed S. 1996. Remission of acromegaly caused by pituitary carcinoma after surgical excision of growth hormone secreting metastasis detected by Ill-indium pentetreotide scan. J Clin Endocrinol Metab, in press.

    Google Scholar 

  25. Melmed S, Ezrin C, Kovacs K, Goodman RS, Frohman LA. 1985. Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor. N Engl J Med 312:9–17.

    Article  PubMed  CAS  Google Scholar 

  26. Scheithauer BW, Carpenter PC, Bloch B, Brazeau P. 1984. Ectopic secretion of a growth hormone-releasing factor. Report of a case of acromegaly with bronchial carcinoid tumor. Am J Med 76:605–615.

    Article  PubMed  CAS  Google Scholar 

  27. Schulte HM, Benker G, Windeck R, Olbricht T, Reinwein D. 1985. Failure to respond to growth hormone releasing hormone (GHRH) in acromegaly due to a GHRH secreting pancreatic tumor: Dynamics of multiple endocrine testing. J Clin Endocrinol Metab 61:585–587.

    Article  PubMed  CAS  Google Scholar 

  28. Asa SL, Scheithauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Laws ER Jr, Singer W, Linfoot JA, Thorner MO, Vale W. 1984. A case for hypothalamic acromegaly: A clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 58:796–803.

    Article  PubMed  CAS  Google Scholar 

  29. Asa SL, Bilbao JM, Kovacs K, Linfoot JA. 1980. Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly. Acta Neuropathol 53:231–234.

    Article  Google Scholar 

  30. Ashcraft MW, Hartzband PI, Van Herle AJ, Bersch N, Golde DW. 1983. A unique growth factor in patients with acromegaloidism. J Clin Endocrinol Metab 57:272–276.

    Article  PubMed  CAS  Google Scholar 

  31. Molitch ME. 1992. Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am 21:597–614.

    PubMed  CAS  Google Scholar 

  32. Nabarro JDN. 1987. Acromegaly. Clin Endocrinol 26:481–512.

    Article  CAS  Google Scholar 

  33. Grunstein RR, Ho KY, Sullivan CE. 1991. Sleep apnea in acromegaly. Ann Intern Med 115:527–532.

    PubMed  CAS  Google Scholar 

  34. Bengtsson B-A, Eden S, Ernest I, Oden A, Sjogren B. 1988. Epidemiology and long-term survival in acromegaly. Acta Med Scand 223:327–335.

    Article  PubMed  CAS  Google Scholar 

  35. Rajasoorya C, Holdaway MI, Wrightson P, Scott DJ, Ibbertson HK. 1994. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol 41:95–102.

    Article  CAS  Google Scholar 

  36. Ezzat S, Melmed S. 1991. Are patients with acromegaly at increased risk for neoplasia? J Clin Endocrinol Metab 72:245–2249.

    Article  PubMed  CAS  Google Scholar 

  37. Ituarte EA, Petrini J, Hershman JM. 1984. Acromegaly and colon cancer. Ann Intern Med 101:627–628.

    PubMed  CAS  Google Scholar 

  38. Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni JJ. 1991. Acromegaly and gastrointestinal cancer. Cancer 68:1673–1677.

    Article  PubMed  CAS  Google Scholar 

  39. Klein I, Parveen G, Gavaler JS, Vanthiel DH. 1982. Colonic polyps in patients with acromegaly. Ann Intern Med 97:27–30.

    PubMed  CAS  Google Scholar 

  40. Ezzat S, Storm C, Melmed S. 1991. Colon polyps in acromegaly. Ann Intern Med 114:754–758.

    PubMed  CAS  Google Scholar 

  41. Hartman ML, Veldhuis JD, Vance ML, Faria AC, Furlanetto RW, Thorner MO. 1990. Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy. J Clin Endocrinol Metab 70:1375–1384.

    Article  PubMed  CAS  Google Scholar 

  42. Melmed S. 1990. Acromegaly. N Engl J Med 322:966–977.

    Article  PubMed  CAS  Google Scholar 

  43. Clemmons DR, Van Wyk JJ, Ridgway EC, Kliman B, Kjellberg RN, Underwood KE. 1979. Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 301:1138–1142.

    Article  PubMed  CAS  Google Scholar 

  44. Rieu M, Girard F, Bricaire H, Binoux M. 1982. The importance of insulin-like growth factor (somatomedin) measurements in the diagnosis and surveillance of acromegaly. J Clin Endocrinol Metab 55:147–153.

    Article  PubMed  CAS  Google Scholar 

  45. Chang-DeMoranville BM, Jackson IM. 1992. Diagnosis and endocrine testing in acromegaly. Endocrinol Metab Clin North Am 21:649–668.

    PubMed  CAS  Google Scholar 

  46. Grinspoon S, Clemmons D, Swearingen B, Klibanski A. 1995. Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly. J Clin Endocrinol Metab 80:927–932.

    Article  PubMed  CAS  Google Scholar 

  47. Ezzat S, Ren S, Braunstein GD, Melmed S. 1991. Octreotide stimulates insulin-like growth factor binding protein-1 (IGFBP-1) levels in acromegaly. J Clin Endocrinol Metab 73:441–443.

    Article  PubMed  CAS  Google Scholar 

  48. Irie M, Tsushima T. 1972. Increase of serum growth hormone concentration following thyrotropin-releasing hormone injection in patients with acromegaly or gigantism. J Clin Endocrinol Metab 35:97–100.

    Article  PubMed  CAS  Google Scholar 

  49. Acromegaly Therapy Consensus Development Panel. 1994. Consensus statement: Benefits versus risks of medical therapy for acromegaly. Am J Med 97:468–473.

    Article  Google Scholar 

  50. Frohman LA. 1984. Ectopic hormone production by tumors. Clin Neuroendocr Perspect 3:201–224.

    CAS  Google Scholar 

  51. Bates AS, Van’t Hoff W, Jones JM, Clayton RN. 1993. An audit of outcome of treatment in acromegaly. Q J Med 86:293–299.

    PubMed  CAS  Google Scholar 

  52. Ross DA, Wilson CB. 1988. Results of transsphenoidal microsurgery for growth hormonesecreting pituitary adenomas in a series of 214 patients. J Neurosurg 68:854–867.

    Article  PubMed  CAS  Google Scholar 

  53. Fahlbusch R, Honegger J, Buchfelder M. 1992. Surgical management of acromegaly. Endocrinol Metab Clin North Am 21:669–692.

    PubMed  CAS  Google Scholar 

  54. Tindall GT, Oyesiku NM, Watts NB, Clark RV, Christy JH, Adams DA. 1993. Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: Outcome analysis and determinants of failure. J Neurosurg 78:205–215.

    Article  PubMed  CAS  Google Scholar 

  55. Zervas NT. 1987. Multicenter surgical results in acromegaly. In Ludecke DK, Tolis G, eds. Growth Hormone, Growth Factors, and Acromegaly. New York: Raven Press, p 253.

    Google Scholar 

  56. Melmed S, Ho K, Thorner M, Klibanski A, Reichlin S. 1995. Recent advances in pathogenesis, diagnosis and management of acromegaly. J Clin Endocrinol Metab 80:3395–3402.

    Article  PubMed  CAS  Google Scholar 

  57. Faglia G, Arosio M, Bazzoni N. 1992. Ectopic acromegaly. Endocrinol Metab Clin North Am 21:575–595.

    PubMed  CAS  Google Scholar 

  58. Eastman RC, Gorden P, Glatstein E, Roth J. 1992. Radiation therapy of acromegaly. Endocrinol Metab Clin North Am 21:693–712.

    PubMed  CAS  Google Scholar 

  59. Eastman RC, Gorden P, Roth J. 1979. Conventional supervoltage irradiation is an effective treatment for acromegaly. J Clin Endocrinol Metab 48:931–940.

    Article  PubMed  CAS  Google Scholar 

  60. Gorden P, Glatstein E, Oldfield E, Roth J. 1987. Conventional supervoltage radiation in the treatment of acromegaly. In Robbins RJ, Melmed S, eds. Acromegaly. A Century of Scientific and Clinical Progress. New York: Plenum, pp 211–228.

    Google Scholar 

  61. Dowsett RJ, Fowble B, Sergott RC, Savino PJ, Bosley TM, Snyder PJ, Gennarelli TA. 1990. Results of radiotherapy in the treatment of acromegaly: Lack of ophthalmologic complications. Int J Radiat Oncol Biol Phys 19:453–459.

    Article  PubMed  CAS  Google Scholar 

  62. Brada M, Ford D, Ashley S, Bliss JM, Crowley S, Mason M, Rajan B, Traish D. 1992. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br Med J 304:1343–1346.

    Article  CAS  Google Scholar 

  63. Tsang RW, Laperriere NJ, Simpson WJ, Brierley J, Panzarella T, Smyth HS. 1993. Glioma arising after radiation therapy for pituitary adenoma. Cancer 72:2227–2233.

    Article  PubMed  CAS  Google Scholar 

  64. Jaffe CA, Barkan AL. 1992. Treatment of acromegaly with dopamine agonists. Endocrinol Metab Clin North Am 21:713–735.

    PubMed  CAS  Google Scholar 

  65. Reubi JC, Landolt AM. 1984. High density of somatostatin receptors in pituitary tumors from acromegalic patients. J Clin Endocrinol Metab 59:1148–1151.

    Article  PubMed  CAS  Google Scholar 

  66. Reubi JC, Landolt AM. 1989. The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status. J Clin Endocrinol Metab 68:844–850.

    Article  PubMed  CAS  Google Scholar 

  67. Ur E, Mather SJ, Bomanji J, Ellison D, Britton KE, Grossman AB, Wass JAH, Besser GM. 1992. Pituitary imaging using a labelled somatostatin analogue in acromegaly. Clin Endocrinol 36:147–150.

    Article  CAS  Google Scholar 

  68. Greenman Y, Melmed S. 1994. Heterogeneous expression of two somatostatin receptor subtypes in pituitary tumors. J Clin Endocrinol Metab 78:398–403.

    Article  PubMed  CAS  Google Scholar 

  69. Greenman Y, Melmed S. 1994. Expression of three somatostatin receptor subtypes in pituitary adenomas: Evidence for preferential SSTR5 expression in the mammosomatotroph lineage. J Clin Endocrinol Metab 79:724–729.

    Article  PubMed  CAS  Google Scholar 

  70. Lamberts SWJ. 1988. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocr Rev 9:417–436.

    Article  PubMed  CAS  Google Scholar 

  71. Ezzat S, Snyder PJ, Young WF, Boyajy LD, Newman C, Klibanski A, Molitch ME, Boyd AE, Sheeler L, Cook DM, Malarkey WB, Jackson I, Lee Vance M, Thorner MO, Barkan A, Frohman LA, Melmed S. 1992. Octreotide treatment of acromegaly: A randomized, multicenter study. Ann Intern Med 117:711–718.

    PubMed  CAS  Google Scholar 

  72. Newman CB, Melmed S, Snyder PJ, Yound WF, Boyajy LD, Levy R, Stewart WN, Klibanski A, Molitch ME, Gagel RF, Boyd AE, Sheeler L, Cook D, Malarkey WB, Jackson IMD, Lee Vance M, Thorner MO, Ho PJ, Jaffe CA, Frohman LA, Kleinberg DL. 1995. Safety and efficacy of long term octreotide therapy of acromegaly: Results of a multicenter trial in 103 patients — a clinical research center study. J Clin Endocrinol Metab 80:2768–2775.

    Article  PubMed  CAS  Google Scholar 

  73. Lamberts SWJ, Zweens M, Verschoor L, del Pozo E. 1986. A comparison among the growth hormone-lowering effects in acromegaly of the somatostatin analog SMS 201–995, bromocriptine, and the combination of both drugs. J Clin Endocrinol Metab 63:16–20.

    Article  PubMed  CAS  Google Scholar 

  74. Grunstein RR, Ho KY, Sullivan CE. 1994. Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly. Ann Intern Med 121:478–483.

    PubMed  CAS  Google Scholar 

  75. Lim MJ, Barkan AL, Buda AJ. 1992. Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion. Ann Intern Med 117:719–726.

    PubMed  CAS  Google Scholar 

  76. von Werder K, Losa M, Muller OA, Schweiberer L, Fahlbusch R, del Poso E. 1984. Treatment of metastasing GRH-producing tumor with a long-acting somatostatin analogue. Lancet 2:282–283.

    Article  Google Scholar 

  77. Flogstad AK, Halse J, Haldorsen T, Lancranjan I, Marbach P, Bruns C, Jervell J. 1995. Sandostatin LAR in acromegalic patients: A dose-range study. J Clin Endocrinol Metab 80:3601–3607.

    Article  PubMed  CAS  Google Scholar 

  78. Chen WY, Chen N, Yun J, Wagner TE, Kopcnick JJ. 1994. In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. J Biol Chem 269:15892–15897.

    PubMed  CAS  Google Scholar 

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Authors
  1. Ilan Shimon
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  2. Shlomo Melmed
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Editors and Affiliations

  1. Laboratory of Endocrine Oncology Massachusetts General Hospital, Harvard Medical School, Jackson 1021, Boston, MA, 02114, USA

    Andrew Arnold M.D. (Chief, Associate Professor of Medicine) (Chief, Associate Professor of Medicine)

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Shimon, I., Melmed, S. (1997). Growth hormone- and growth-hormone-releasing hormone-producing tumors. In: Arnold, A. (eds) Endocrine Neoplasms. Cancer Treatment and Research, vol 89. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6355-6_1

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  • DOI: https://doi.org/10.1007/978-1-4615-6355-6_1

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