Advertisement

Current diagnosis of acromegaly

  • Rocio A. Cordero
  • Ariel L. BarkanEmail author
Article

Abstract

Acromegaly is a rare and chronic condition that is characterized by sustained unregulated hypersecretion of growth hormone (GH). More than 99% of the cases of acromegaly are due to a pathologic proliferation of pituitary somatotrophs presenting in the form of a pituitary adenoma. The excessive amounts of GH and its target hormone, insulin like growth factor-1 (IGF-1) cause metabolic changes and tissue enlargement that, collectively, lead to significant morbidity and a two to threefold increase in mortality. Thus, early diagnosis has proved to be crucial to improve survival and quality of life in this condition. The development of radioimmunoassay (RIA) in the 1960s provided clinicians with a biochemical tool to diagnose acromegaly. Many limitations were inherent to this methodology which necessitated the development of more sensitive tools, such as immunoradiometric (IRMA) or immunoluminometric (ILMA) assays for GH and IGF-1 measurements. These newer assays have not come without imperfections. The reference ranges to describe normalcy of the somatotropic axis and the biochemical criteria of “cure” of acromegaly are areas of great debate. Nevertheless, the current international consensus agrees that the diagnosis of acromegaly should be based on both clinical presentation and biochemical data.

Keywords

Acromegaly Diagnosis Growth hormone (GH) Insulin like growth factor (IGF-1) 

References

  1. 1.
    Bengtsoon BA, Eden S, Ernest I, Oden A, Sjogren B. Epidemilogy and long term survival in acromegaly: a study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 1988;223:327–5.CrossRefGoogle Scholar
  2. 2.
    Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary 1999;2(1):29–41. (Jun).PubMedCrossRefGoogle Scholar
  3. 3.
    Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 1994;41(1):95–102. (Jul).Google Scholar
  4. 4.
    Etxabe J, Gaztambide S, Latorre P, Vazquez JA. Acromegaly: an epidemiological study. J Endocrinol Invest 1993;16(3):181–7. (Mar).PubMedGoogle Scholar
  5. 5.
    Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, et al. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol 1993;151(4):439–6. Oct.CrossRefGoogle Scholar
  6. 6.
    Melmed S. Acromegaly. N Engl J Med 1993;322(14):966–77. (Apr 5).CrossRefGoogle Scholar
  7. 7.
    Burgess JR, Shepherd JJ, Parameswaran V, Hoffman L, Greenaway TM. Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred. J Clin Endocrinol Metab 1996;81:2642–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Weinstein LS, Yu S, Warner DR, Liu J. Endocrine manifestations of stimulatory G protein α-subunit mutations and the role of genomic imprinting. Endocr Rev 2001;22:675–705.PubMedCrossRefGoogle Scholar
  9. 9.
    Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome: analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996;97:699–705.PubMedCrossRefGoogle Scholar
  10. 10.
    Gadelha MR, Prezant TR, Une KN, Glick RP, Moskal SF 2nd, Vaisman M, et al. Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene. J Clin Endocrinol Metab 1999;84:249–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations. Endocr Rev 1988;9(3):357–73. (Aug).PubMedGoogle Scholar
  12. 12.
    Barkan AL, Stred SE, Reno K, Markovs M, Hopwood NJ, Kelch RP, et al. Increased growth hormone pulse frequency in acromegaly. J Clin Endocrinol Metab 1989;69(6):1225–33. (Dec).PubMedGoogle Scholar
  13. 13.
    Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004;25(1):102–52. (Feb).PubMedCrossRefGoogle Scholar
  14. 14.
    Künzler A, Farmand M. Typical changes in the viscerocranium in acromegaly. J Craniomaxillofac Surg 1991;19(8):332–40.PubMedGoogle Scholar
  15. 15.
    Lombardi G, Galdiero M, Auriemma RS, Pivonello R, Colao A. Acromegaly and the cardiovascular system. Neuroendocrinology 2006;83(3–4):211–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Minniti G, Jaffrain-Rea ML, Moroni C, Baldelli R, Ferretti E, Cassone R, et al. Echocardiographic evidence for a direct effect of GH/IGF-I hypersecretion on cardiac mass and function in young acromegalics. Clin Endocrinol (Oxf) 1998;49(1):101–6. (Jul).CrossRefGoogle Scholar
  17. 17.
    Fazio S, Cittadini A, Biondi B, Palmieri EA, Riccio G, Bone F, et al. Cardiovascular effects of short-term growth hormone hypersecretion. J Clin Endocrinol Metab 2000;85(1):179–82. (Jan).PubMedCrossRefGoogle Scholar
  18. 18.
    Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Della Morte AM, et al. Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance. J Clin Endocrinol Metab 2001;86(4):1551–7. (Apr).PubMedCrossRefGoogle Scholar
  19. 19.
    Sacca L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev 1994;15(5):555–73. (Oct).PubMedCrossRefGoogle Scholar
  20. 20.
    Hansen I, Tsalikian E, Beaufrere B, Gerich J, Haymond M, Rizza R. Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action. Am J Physiol 1986;250(3 Pt 1):E269–73. (Mar).PubMedGoogle Scholar
  21. 21.
    Moller N, Schmitz O, Joorgensen JO, Astrup J, Bak JF, Christensen SE, et al. Basal- and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy. J Clin Endocrinol Metab 1992;74(5):1012–9. (May).PubMedCrossRefGoogle Scholar
  22. 22.
    Davidson MB. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 1987;8(2):115–31. (May).PubMedGoogle Scholar
  23. 23.
    Grunstein RR, Ho KK, Sullivan CE. Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly. Ann Intern Med 1994;121(7):478–83. (Oct 1).PubMedGoogle Scholar
  24. 24.
    Layton MW, Fudman EJ, Barkan A, Braunstein EM, Fox IH. Acromegalic arthropathy. Characteristics and response to therapy. Arthritis Rheum 1988;31(8):1022–7. (Aug).PubMedCrossRefGoogle Scholar
  25. 25.
    Colao A, Marzullo P, Vallone G, Giaccio A, Ferone D, Rossi E, et al. Ultrasonographic evidence of joint thickening reversibility in acromegalic patients treated with lanreotide for 12 months. Clin Endocrinol (Oxf) 1999;51(5):611–8. (Nov).CrossRefGoogle Scholar
  26. 26.
    Jenkins PJ. Acromegaly and cancer. Horm Res 1999;62(Suppl 1):108–5.Google Scholar
  27. 27.
    Melmed S. Acromegaly and cancer: not a problem? J Clin Endocrinol Metab 2001;86(7):2929–34. (Jul).PubMedCrossRefGoogle Scholar
  28. 28.
    Renehan AG, Shalet SM. Acromegaly and colorectal cancer: risk assessment should be based on population-based studies. J Clin Endocrinol Metab 2002;87(4):1909. (Apr).PubMedCrossRefGoogle Scholar
  29. 29.
    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. (Aug).PubMedCrossRefGoogle Scholar
  30. 30.
    Duncan E, Wass JA. Investigation protocol: acromegaly and its investigation. Clin Endocrinol (Oxf) 1999;50(3):285–93. (Mar).CrossRefGoogle Scholar
  31. 31.
    Barkan AL, Beitins IZ, Kelch RP. Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. Clin Endocrinol Metab 1988;67(1):69–73. (Jul).CrossRefGoogle Scholar
  32. 32.
    Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997;278(5337):419–24. (Oct 17).PubMedCrossRefGoogle Scholar
  33. 33.
    Desailloud R, Crepin-Hemon S, Simovic-Corroyer B. Acromegaly in elderly people. Ann Endocrinol (Paris) 2005;66(6):540–4. (Dec).Google Scholar
  34. 34.
    Glick AM, Roth J, Yalow RF, Berson SA. Immunoassay of human growth hormone in plasma. Nature 1963;199:784–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Ho PJ, Friberg RD, Barkan AL. Regulation of pulsatile growth hormone secretion by fasting in normal subjects and patients with acromegaly. J Clin Endocrinol Metab 1992;75(3):812–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Ho PJ, Jaffe CA, Friberg RD, Chandler WF, Barkan AL. Persistence of rapid growth hormone (GH) pulsatility after successful removal of GH-producing pituitary tumors. J Clin Endocrinol Metab 1994;78(6):1403–10.PubMedCrossRefGoogle Scholar
  37. 37.
    Granada ML, Sanmarti A, Lucas A, Salinas I, Carrascosa A, Foz M, et al. Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children. Acta Paediatr Scand Suppl 1994;379:63–70.Google Scholar
  38. 38.
    Baumann G, Shaw M, Amburn K, Jan T, Davila N, Mercado M, et al. Heterogeneity of circulating growth hormone. Nucl Med Biol 1994;21(3):369–79. (Apr).PubMedCrossRefGoogle Scholar
  39. 39.
    Ebdrup L, Fisker S, Rensen HH, Ranke MB, Orskov H. Variety in growth hormone determinations due to use of different immunoassays and to the interference of growth hormone-binding protein. Horm Res 1994;51(Suppl 1):20–6.Google Scholar
  40. 40.
    Pokrajac A, Wark G, Ellis AR, Wear J, Wieringa GE, Trainer PJ. Variation in GH and IGF-1 assays limits the applicability of international consensus criteria for local practice. Clin Endocrinol (Oxf) 2007;67(1):65–70. (Jul).CrossRefGoogle Scholar
  41. 41.
    Christy NP. Pituitary-adrenal function during corticosteroid therapy. Learning to live with uncertainty. N Engl J Med 1992;326(4):266–7. (Jan 23).PubMedCrossRefGoogle Scholar
  42. 42.
    Tindall GT, Oyesiku NM, Watts NB, Clark RV, Christy JH, Adams DA. Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure. J Neurosurg 1993;78(2):205–15. (Feb).PubMedGoogle Scholar
  43. 43.
    Bates AS, Van't Hoff W, Jones JM, Clayton RN. An audit of outcome of treatment in acromegaly. Q J Med 1993;86(5):293–9. (May).PubMedGoogle Scholar
  44. 44.
    Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 2000;85(2):526–9. (Feb).PubMedCrossRefGoogle Scholar
  45. 45.
    Freda PU, Post KD, Powell JS, Wardlaw SL. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 1998;83:3808–16.PubMedCrossRefGoogle Scholar
  46. 46.
    Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD. Significance of “abnormal” nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 2004;89(2):495–500. (Feb).PubMedCrossRefGoogle Scholar
  47. 47.
    Ronchi CL, Varca V, Giavoli C, Epaminonda P, Beck-Peccoz P, Spada A, et al. Long-term evaluation of postoperative acromegalic patients in remission with previous and newly proposed criteria. J Clin Endocrinol Metab 2005;90(3):1377–82. (Mar).PubMedCrossRefGoogle Scholar
  48. 48.
    Costas ACF, 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.CrossRefGoogle Scholar
  49. 49.
    Serri O, Beauregard C, Hardy J. Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly. Clin Endocrinol Metab 2004;89(2):658–1. (Feb).CrossRefGoogle Scholar
  50. 50.
    Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WL, Barkan AL. Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 2002;87(8):3537–42.PubMedCrossRefGoogle Scholar
  51. 51.
    Melmed S. Medical progress: acromegaly. N Engl J Med 2006;355(24):2558–73. (Dec 14).PubMedCrossRefGoogle Scholar
  52. 52.
    Clemmons DR, Van Wyk JJ, Ridgway EC, Kliman B, Kjellberg RN, Underwood LE. Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 1979;301(21):1138–42.PubMedCrossRefGoogle Scholar
  53. 53.
    Walker JL, Crock PA, Behncken SN, Rowlinson SW, Nicholson LM, Boulton TJC, et al. A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-i and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab 1998;83:2554–61.PubMedCrossRefGoogle Scholar
  54. 54.
    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;83:3419–26.PubMedCrossRefGoogle Scholar
  55. 55.
    Beauregard C, Truong U, Hardy J, Serri O. Long-term outcome and mortality after Transsphenoidal adenomectomy for acromegaly. Clin Endocrinol (Oxf) 2003;58(1):86–91.CrossRefGoogle Scholar
  56. 56.
    Holdaway IM, Rajasoorya CR, Gamble GD, Stewart AW. Long-term treatment outcome in acromegaly. Growth Horm IGF Res 2003;13(4):185–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Biermasz NR, Dekker FW, Pereira AM, van Thiel SW, Scutte 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;89:2789–96.PubMedCrossRefGoogle Scholar
  58. 58.
    Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996;134(3):352–6. (Mar).PubMedGoogle Scholar
  59. 59.
    Brabant G, von zur Mühlen A, Wüster C, Ranke MB, Kratzsch J, Kiess W, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res 2003;60(2):53–60.PubMedCrossRefGoogle Scholar
  60. 60.
    Freda PU. Pitfalls in the biochemical assessment of acromegaly. Pituitary 2003;6(3):135–40.PubMedCrossRefGoogle Scholar
  61. 61.
    Ho KK, O'Sullivan AJ, Wolthers T, Leung KC. Metabolic effects of estrogens: impact of the route of administration. Ann Endocrinol (Paris) 2003;64(2):170–7.Google Scholar
  62. 62.
    Katznelson L, Kleinberg D, Vance ML, Stavrou S, Pulaski KJ, Schoenfeld DA, et al. Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study. Clin Endocrinol (Oxf) 2001;54(2):183–8. (Feb).CrossRefGoogle Scholar
  63. 63.
    Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, et al. Consensus statement: medical management of acromegaly. Eur J Endocrinol 2005;153(6):737–40. (Dec).PubMedCrossRefGoogle Scholar
  64. 64.
    Losa M, von Werder K. Pathophysiology and clinical aspects of the ectopic GH-releasing hormone syndrome. Clin Endocrinol (Oxf) 1997;47(2):123–35. (Aug).CrossRefGoogle Scholar
  65. 65.
    Vieira Neto L, Taboada GF, Corrêa LL, Polo J, Nascimento AF, Chimelli L, et al. Acromegaly secondary to growth hormone-releasing hormone secreted by an incidentally discovered pheochromocytoma. Endocr Pathol 2007;18(1):46–52. (Spring).PubMedCrossRefGoogle Scholar
  66. 66.
    Sugihara H, Shibasaki T, Tatsuguchi A, Okajima F, Wakita S, Nakajima Y, et al. A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor. J Endocrinol Invest 2007;30(5):421–7. (May).PubMedGoogle Scholar
  67. 67.
    Fainstein Day P, Frohman L, Garcia Rivello H, Reubi JC, Sevlever G, Glerean M, et al. Ectopic growth hormone-releasing hormone secretion by a metastatic bronchial carcinoid tumor: a case with a non hypophysial intracranial tumor that shrank during long acting octreotide treatment. Pituitary 2007;10:311–19.PubMedCrossRefGoogle Scholar
  68. 68.
    Nasr C, Mason A, Mayberg M, Staugaitis SM, Asa SL. Acromegaly and somatotroph hyperplasia with adenomatous transformation due to pituitary metastasis of a growth hormone-releasing hormone-secreting pulmonary endocrine carcinoma. J Clin Endocrinol Metab 2006;91(12):4776–80. (Dec).PubMedCrossRefGoogle Scholar
  69. 69.
    Bolanowski M, Kos-Kudła B, Rzeszutko M, Marciniak M, Zatońska K. Five year remission of GHRH secreting bronchial neuroendocrine tumor with symptoms of acromegaly. Utility of chromogranin A in the monitoring of the disease. Endokrynol Pol 2006;57(1):32–6. (Jan–Feb).PubMedGoogle Scholar
  70. 70.
    Jansson JO, Svensson J, Bengtsson BA, Frohman LA, Ahlman H, Wängberg B, et al. Acromegaly and Cushing’s syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6. Clin Endocrinol 1998;48:243–50.CrossRefGoogle Scholar
  71. 71.
    Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Kooy PPM, Lamberts SWJ. Somatostatin analogue scintigraphy in carcinoid tumours. Eur J Nucl Med 1993;20:283–92.PubMedCrossRefGoogle Scholar
  72. 72.
    Drange MR, Melmed S. Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. J Clin Endocrinol Metab 1998;83:3104–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Division of Metabolism, Endocrinology and Diabetes, Department of NeurosurgeryThe University of Michigan and the DVA Medical CenterAnn ArborUSA

Personalised recommendations