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Medical consequences of acromegaly: What are the effects of biochemical control?

  • Annamaria ColaoEmail author
  • Renata S. Auriemma
  • Rosario Pivonello
  • Mariano Galdiero
  • Gaetano Lombardi
Article

Abstract

This chapter discusses the effects of biochemical control of acromegaly on cardiovascular diseases, metabolic complications, respiratory abnormalities, malignancies and bone alterations. Acromegaly is associated with increased morbidity and mortality for cardiovascular and respiratory complications, whereas neoplasms seem to be a minor cause of increased risk of death. Other associated diseases are osteoarthritis, carpal tunnel syndrome, fatigue, visual abnormalities and reproductive disorders. Acromegaly results in premature death because of prolonged elevation of GH an IGF-I levels, and a strong biochemical control improves well-being and restores life expectancy to normal. The main goals of medical treatment of acromegaly include normalization of biochemical markers of disease activity, improvement in signs and symptoms of the disease, removal or reduction of tumor mass and preservation of pituitary function.

Keywords

Acromegaly GH IGF-I Biochemical control Cardiovascular Joints Respiratory diseases Neoplasms Dyslipidemia Diabetes 

References

  1. 1.
    Melmed S. Acromegaly. N Engl J Med. 2006;355:2558–73.PubMedCrossRefGoogle Scholar
  2. 2.
    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;85:526–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Petrossians P, Borges-Martin L, Espinoza C, Daly A, Betea D, Valdes-Socin H, et al. Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs. Eur J Endocrinol. 2005;152:61–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Colao A, Attanasio R, Pivonello R, Cappabianca P, Cavallo LM, Lasio G, et al. Partila surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2006;91(1):85–92.PubMedCrossRefGoogle Scholar
  5. 5.
    Jenkins PJ, Bates P, Carson MN, Stewart PM, Wass JA. Conventional pituitary irradiation is effective in lowering serum growth hormone and insuline-like growth factor-I in patients with acromegaly. J Clin Endocrinol Metab. 2006;91:1239–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Minniti G, Traish D, Ashley S, Gonsalves A, Brada M. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab. 2005;90:800–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Cozzi R, Attanasio R, Lodrini S, Lasio G. Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf). 2004;61:209–15.CrossRefGoogle Scholar
  8. 8.
    Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, et al. Primary treatment of acromegaly with octreotide LAR: long-term (up to nine years) prospective study af its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab. 2006;91:1397–403.PubMedCrossRefGoogle Scholar
  9. 9.
    Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, et al. Predictors of tumor shrinkage ater primari therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab. 2006;91(6):2112–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Murray RD, Kim K, Ren SG, Lewis I, Weckbecker G, Bruns C, et al. The novel somatostatin ligand (SOM 230) regulates human and rat anterior pituitary hormone secretion. J Clin Endocrinol Metab. 2004;89(6):3027–32.PubMedCrossRefGoogle Scholar
  11. 11.
    van der Hoek J, de Herder WW, Feelders RA, van der Lely AJ, Uitterlinden P, Boerlin V, et al. A single-dose comparison of the acute effects between the new somatostatin analog SOM 230 and octreotide in acromegalic patients. J Clin Endocrinol Metab. 2004;89:638–45.PubMedCrossRefGoogle Scholar
  12. 12.
    Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonet V, van der Lely AJ, et al. Treatment of acromegaly with the growth hormone-receptor anatgonist pegvisomant. N Engl J Med. 2000;342:1171–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, et al. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol. 2006;154:467–77.PubMedCrossRefGoogle Scholar
  14. 14.
    Jorgensen JO, Feldt-Rasmussen U, Frystyk J, Chen JW, Kristensen LO, Hagen C, et al. Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist. J Clin Endocrinol Metab. 2005;90(10):5627–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Feenstra J, de Herder WW, ten Have SM, van der Beld AW, Feelders RA, Janssen JA, et al. Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 2005;365:1644–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Colao A, Marzullo P, Di Somma C, Lombardi G. Growth hormone and the heart. Clin Endocrinol (Oxf). 2001;54:137–54.CrossRefGoogle Scholar
  17. 17.
    Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. N Engl J Med. 1999;341:1276–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Hejtmancik MR, Bradfield JY, Herrmann GR. Acromegaly and the heart: a clinical and pathologic study. Ann Intern Med. 1951;34:1445–56.PubMedGoogle Scholar
  19. 19.
    Lie JT, Grossman SJ. Pathology of the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J. 1980;100:41–52.PubMedCrossRefGoogle Scholar
  20. 20.
    Colao A, Merola B, Ferone D, Lombardi G. Acromegaly. J Clin Endocrinol Metab. 1997;82:2777–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Clayton RN. Cardiovascular function in acromegaly. Endocr Rev. 2003;24:272–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kahaly G, Olshausen KV, Mohr-Kahaly S, Erbel R, Boor S, Beyer J, et al. Arrhythmia profile in acromegaly. Eur Heart J. 1992;13:51–6.PubMedGoogle Scholar
  23. 23.
    Rodrigues EA, Caruana MP, Lahiri A, Nabarro JD, Jacobs HS, Raftery EB. Subclinical cardiac dysfunction in acromegaly evidence for a specific disease of heart muscle. Br Heart J. 1989;62:185–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Colao A, Spinelli L, Marzullo P, Pivonello R, Petretta M, Di Somma C, et al. High prevalence of cardiac valve disease in acromegaly: an observational analytical prospective case-control study. J Clin Endocrinol Metab 2003;88:3196–201.PubMedCrossRefGoogle Scholar
  25. 25.
    Colao A, Spiezia S, Cerbone G, Pivonello R, Marzullo P, Ferone D, et al. Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography in acromegaly. Clin Endocrinol (Oxf). 2001;54:515–24.CrossRefGoogle Scholar
  26. 26.
    Otsuki M, Kasayama S, Yamamoto H, Saito H, Sumitami S, Kouhara H, et al. Characterization of premature atherosclerosis of carotid arteries in acromegalic patients. Clin Endocrinol (Oxf). 2001;54:791–6.CrossRefGoogle Scholar
  27. 27.
    Brevetti G, Marzullo P, Silvestro A, Pivonello R, Oliva G, Di Somma C, et al. Early vascular alterations in acromegaly. J Clin Endocrinol Metab. 2002;87:3174–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Minniti G, Moroni C, Jaffrain-Rea ML, Esposito V, Santoro A, Affricano C, et al. Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients. Clin Endocrinol (Oxf). 2001;55:307–13.CrossRefGoogle Scholar
  29. 29.
    Colao A, Cuocolo A, Marzullo P, Nicolai M, 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;86:1551–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Pereira J, Rodriguez-Puras MJ, Leal-Cerro A, Martinez A, Garcia-Luna PP, Gavilan I, et al. Acromegalic cardiopathy improves after treatment with increasing doses of octreotide. J Endocrinol Invest. 1991;14:17–23.PubMedGoogle Scholar
  31. 31.
    Lim MJ, Barkan AL, Buda AJ. Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion. Ann Intern Med. 1992;117:719–26.PubMedGoogle Scholar
  32. 32.
    Merola B, Cittadini A, Colao A, Ferone D, Fazio S, Sabatini D, et al. Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly. J Clin Endocrinol Metab. 1993;77:790–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Baldelli R, Ferretti E, Jaffrain-Rea ML, Iacobellis G, Minniti G, Caracciolo B, et al. Cardiac effects of lanreotide, a slow release somatostatin analog in acromegalic patients. J Clin Endocrinol Metab. 1999;4:527–32.CrossRefGoogle Scholar
  34. 34.
    Manelli F, Desenzani P, Boni E, Bulgari G, Negrini F, Romanelli G, et al. Cardiovascular effects of a single slow release lanreotide injection in patients with acromegaly and left ventricular hypertrophy. Pituitary 1999;2:205–10.PubMedCrossRefGoogle Scholar
  35. 35.
    Colao A, Marzullo P, Ferone D, Spinelli L, Cuocolo A, Bonaduce D, et al. Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab. 2000;86:3132–40.CrossRefGoogle Scholar
  36. 36.
    Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Florimonte L, et al. Effects of one-year treatment with octreotide on cardiac performance in patients with acromegaly. J Clin Endocrinol Metab. 1999;84:17–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Colao A, Marzullo P, Cuocolo A, Spinelli L, Pivonello R, Bonaduce D, et al. Reversal of acromegalic cardiomyopathy in young but not in middle-aged patients after 12 months of treatment with the depot long-acting somatostatin analogue Octreotide. Clin Endocrinol (Oxf). 2003;58:169–76.CrossRefGoogle Scholar
  38. 38.
    Lombardi G, Colao A, Marzullo P, Biondi B, Palmieri E, Fazio S, Multicenter Italian Study Group on Lanreotide. Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced growth hormone and insulin-like growth factor-I decrease in acromegaly: a prospective multicenter study. J Endocrinol Invest. 2002;25:971–6.PubMedGoogle Scholar
  39. 39.
    Colao A, Ferone D, Cappabianca P, Del Basso De Caro ML, Marzullo P, et al. Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 1997;82:3308–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Herrington AM, George KW, Moulds CC. Octreotide-induced bradycardia. Pharmacotherapy 1998;18:413–6.PubMedGoogle Scholar
  41. 41.
    Pivonello R, Galderisi M, Auriemma RS, De Martino MC, Galdiero M, Ciccarelli A, et al. Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance. J Clin Endocrinol Metab. 2007;92(2):476–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res. 2001;34:1429–33.PubMedCrossRefGoogle Scholar
  43. 43.
    Biering H, Knappe G, Gerl H, Lochs H. Prevalence of diabetes in acromegaly and Cushing syndrome. Acta Med Austriaca. 2000;27:27–31.PubMedCrossRefGoogle Scholar
  44. 44.
    Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, et al. Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf). 2000;52:549–55.CrossRefGoogle Scholar
  45. 45.
    Puder JJ, Nilavar S, Post KD, Freda PU. Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly. J Clin Endocrinol Metab. 2005;90(4):1972–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Nikkila EA, Pelkonen R. Serum lipids in acromegaly. Metabolism 1975;24:829–38.PubMedCrossRefGoogle Scholar
  47. 47.
    Wildbrett J, Hanefeld M, Fucker K, Pinzer T, Bergmann S, Siegert G, et al. Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I. Exp Clin Endocrinol Diabetes. 1997;105:331–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Maldonado Castro GF, Escobar-Morreale HF, Ortega H, Gomez-Coronado D, Balsa Barro JA, Varela C, et al. Effects of normalization of GH hypersecretion on lipoprotein (a) and other lipoprotein serum levels in acromegaly. Clin Endocrinol (Oxf). 2000;53(3):313–9.CrossRefGoogle Scholar
  49. 49.
    Ronchi CL, Orsi E, Giavoli C, Cappiello V, Epaminonda P, Beck-Peccoz P, et al. Evaluation of insuline resistance in acromegalic patients bifore and after treatment with somatostatin analogues. J Endocrinol Invest. 2003;26(6):533–8.PubMedGoogle Scholar
  50. 50.
    Ferone D, Colao A, van der Lely A-J, Lamberts SWJ. Pharmacotherapy or surgery as primary treatment for acromegaly? Drugs Aging. 2000;17:81–92.PubMedCrossRefGoogle Scholar
  51. 51.
    Colao A, Ferone D, Marzullo P, Cappabianca P, Cirillo S, Boerlin V, et al. Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly. J Clin Endocrinol Metab. 2001;86:2779–86.PubMedCrossRefGoogle Scholar
  52. 52.
    Colao A, Pivonello R, Auriemma RS, Galdiero G, Savastano S, et al. Beneficial effects of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007;157:1–10.CrossRefGoogle Scholar
  53. 53.
    Drake WM, Rowles SV, Roberts ME, Fode FK, Besser GM, Monson JP, et al. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol 2003;149:521–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005;90(10):5684–91.PubMedCrossRefGoogle Scholar
  55. 55.
    Linberg-Larsen R, Moller N, Schmitz O, Nielsen S, Andersen M, Orskov H, et al. The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab. 2007;92(5):1724–28.CrossRefGoogle Scholar
  56. 56.
    Arosio M, Sartore G, Rossi CM, Casati G, Faglia G, Manzato E. LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients. Effects of octreotide therapy. Italian Multicenter Octreotide Study Group. Atherosclerosis 2000;151:551–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis and management. Endocr Rev. 2004;25(1):102–52.PubMedCrossRefGoogle Scholar
  58. 58.
    Sesmilo G, Fairfield WP, Katznelson L, Pulaski K, Freda PU, Bonert V, et al. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocrinol Metab. 2002;87(4):1692–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Melmed S. Acromegaly and cancer: not a problem. J Clin Endocrinol Metab. 2001;86:2929–34.PubMedCrossRefGoogle Scholar
  60. 60.
    Grunstein RR, Ho KY, Sullivan CE. Sleep apnea in acromegaly. Ann Intern Med. 1991;115:527–32.PubMedGoogle Scholar
  61. 61.
    Luboshitzky R, Barzilai D. Hypoxemia and pulmonary function in acromegaly. Am Rev Respir Dis. 1980;121:471–5.PubMedGoogle Scholar
  62. 62.
    Donnelly PM, Grunstein RR, Peat JK, Woolcock AJ, Bye PT. Large lungs and growth hormone: an increased alveolar number? Eur Respir J. 1995;8:938–47.PubMedGoogle Scholar
  63. 63.
    Rosenow F, Reuter S, Deuss U, Szelies B, Hilgers RD, Winkelmann W, et al. Sleep apnoea in treated acromegaly: relaite frequency and predisposing factors. Clin Endocrinol (Oxf). 1996;45:563–9.CrossRefGoogle Scholar
  64. 64.
    Chanson P, Timsit J, Benoit O, Augendre B, Moulonguet M, Guillausseau PG, et al. Rapid improvement of sleep apnoea of acromegaly after short term treatment with somatostatin analogue SMS 201-995. Lancet. 1986;1:1270–1.PubMedCrossRefGoogle Scholar
  65. 65.
    Ip MSM, Tan KCB, Peh WCG, Lam KSL. Effects of Sandostatin LAR on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity. Clin Endocrinol (Oxf). 2001;55:477–83.CrossRefGoogle Scholar
  66. 66.
    Thomas SG, Woodhouse LJ, Pagura SM, Ezzat S. Ventilation threshold as a measure of impaired physical performance in adults with growth hormone excess. Clin Endocrinol (Oxf). 2002;56:351–8.CrossRefGoogle Scholar
  67. 67.
    Orme SM, McNally RJQ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. J Clin Endocrinol Metab. 1998;83:2730–4.PubMedCrossRefGoogle Scholar
  68. 68.
    Renehan AG, Bhaskar P, Painter JE, O’Dwyer ST, Haboubi N, Varma J, et al. The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85:3417–24.PubMedCrossRefGoogle Scholar
  69. 69.
    Cats A, Dullaart RP, Kleibeuker JH, Kuipers F, Sluiter WT, Hardonk MJ, et al. Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res. 1996;56:523–6.PubMedGoogle Scholar
  70. 70.
    Ma J, Pollack MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999;91:620–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Colao A, Balzano A, Ferone D, Panza N, Grande G, Marzullo P, et al. Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly. Clin Endocrinol (Oxf) 1997;47:23–8.CrossRefGoogle Scholar
  72. 72.
    Ochsenkuhn T, Bayerdorffer E, Meining A, Schinkel M, Thiede C, Nussler V, et al. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer 1999;85:1664–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Burt RW, Samowitz WS. The adenomatous polyp and the hereditary polyposis syndromes. Gastroenterol Clin North Am. 1988;17:657–78.PubMedGoogle Scholar
  74. 74.
    Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer. 1975;36:2251–70.PubMedCrossRefGoogle Scholar
  75. 75.
    Bogazzi F, Ultimieri F, Raggi F, Costa A, Gasperi M, Cecconi E, et al. Peroxisome proliferator activated receptor gamma expression is reduced in the colonic mucosa of acromegalic patients. J Clin Endocrinol Metab. 2002;87:2403–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Colao A, Pivonello R, Auriemma RS, Galdiero M, Ferone D, Minuto F, et al. The association of fasting insulin concentrations and colonic neoplasm in acromegaly: a colonoscopy-based study in 210 patients. J Clin Endocrinol Metab. 2007;92:3854–60.PubMedCrossRefGoogle Scholar
  77. 77.
    Renehan AG, Bhaskar P, Painter JE, O’Dwyer ST, Haboubi N, Varma J, et al. The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85:3417–24.PubMedCrossRefGoogle Scholar
  78. 78.
    Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, et al. Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85:3218–21.PubMedCrossRefGoogle Scholar
  79. 79.
    Cheung NW, Boyages SC. The thyroid gland in acromegaly: an ultrasonographic study. Clin Endocrinol (Oxf). 1997;46:545–9.CrossRefGoogle Scholar
  80. 80.
    Gasperi M, Martino E, Manetti L, Arosio M, Porretti S, Faglia G, Acromegaly Study Group of the Italian Society of Endocrinology, et al. Prevalence of thyroid diseases in patients with acromegaly: results of an Italian multi-center study. J Endocrinol Invest. 2002;25:240–5.PubMedGoogle Scholar
  81. 81.
    Tita P, Ambrosio MR, Scollo C, Carta A, Gangemi P, Bondanelli M, et al. High prevalence of differentiated thyroid carcinoma in acromegaly. Clin Endocrinol. 2005;63:161–7.CrossRefGoogle Scholar
  82. 82.
    Balkany C, Cushing GW. An association between acromegaly and thyroid carcinoma. Thyroid. 1995;5:47–50.PubMedCrossRefGoogle Scholar
  83. 83.
    Webb SM, Casanueva F, Wass JA. Oncological complications of excess GH in acromegaly. Pituitary 2002;5(1):21–5.PubMedCrossRefGoogle Scholar
  84. 84.
    Chan JM, Stampfer MJ, Ma J, Gann P, Gaziano JM, Pollak M, et al. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced stage prostate cancer. J Natl Cancer Inst. 2002;94:1099–106.PubMedGoogle Scholar
  85. 85.
    Colao A, Marzullo P, Ferone D, Spiezia S, Cerbone G, Marino V, et al. Prostatic hyperplasia: an unknown feature of acromegaly. J Clin Endocrinol Metab. 1998;83:775–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Colao A, Marzullo P, Spiezia S, Ferone D, Giaccio A, Cerbone G, et al. Effect of growth hormone (GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab. 1999;84:1986–91.PubMedCrossRefGoogle Scholar
  87. 87.
    Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3–34.PubMedCrossRefGoogle Scholar
  88. 88.
    Colao A, Marzullo P, Spiezia S, Giaccio A, Ferone D, Cerbone G, et al. Effect of two years of growth hormone/insulin-like growth factor-I suppression on prostate diseases in acromegalic patients. J Clin Endocrinol Metab. 2000;85:3754–61.PubMedCrossRefGoogle Scholar
  89. 89.
    Detenbeck L, Tressler H, O’Duffy J, Randall RV. Peripheral joint manifestations of acromegaly. Clin Orthoped. 1973;91:119–27.CrossRefGoogle Scholar
  90. 90.
    Lieberman SA, Bjorkengren AG, Hoffman AR. Rheumatologic and skeletal changes in acromegaly. Endocrinol Metab North Am. 1992;21:615–31.Google Scholar
  91. 91.
    Scarpa R, De Brasi D, Pivonello R, Marzullo P, Manguso F, Sodano A, et al. Acromegalic axial arthropathy: a clinical case-control study. J Clin Endocrinol Metab 2004;89:598–603.PubMedCrossRefGoogle Scholar
  92. 92.
    Kameyama S, Tanaka R, Hasegawa A, Tamura T, Kuroki M. Subclinical carpal tunnel syndrome in acromegaly. Neurol Med Chir (Tokyo). 1993;33:547–51.Google Scholar
  93. 93.
    Jenkins PJ, Sohaib SA, Akker S, Phillips RR, Spillane K, Wass JA, et al. The pathology of median neuropathy in acromegaly. Ann Intern Med. 2000;133:197–201.PubMedGoogle Scholar
  94. 94.
    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.CrossRefGoogle Scholar
  95. 95.
    Colao A, Cannavò, S, Marzullo P, Pivonello R, Squadrito S, Vallone G, et al. Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly. Eur J Endocrinol. 2003;148:31–8.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Annamaria Colao
    • 1
    Email author
  • Renata S. Auriemma
    • 1
  • Rosario Pivonello
    • 1
  • Mariano Galdiero
    • 1
  • Gaetano Lombardi
    • 1
  1. 1.Department of Molecular and Clinical Endocrinology and Oncology“Federico II” University of NaplesNaplesItaly

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