Skip to main content
SpringerLink
Log in

Current Status and Future Opportunities for Controlling Acromegaly

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Growth-hormone (GH) secreting adenomas, including acromegaly, account for approximately one-sixth of all pituitary adenomas and are associated with mortality rates at least twice that of the general population. The ultimate goal of therapy for acromegaly is normalization of morbidity and mortality rates achieved through removal or reduction of the tumor mass and normalization of insulin-like growth factor I (IGF-I) levels. Previously published efficacy results of current treatment modalities (surgery, conventional radiation, and medical therapy with dopamine agonists and somatostatin analogs) are often difficult to compare because of the different criteria used to define cure (some of which are now considered inadequate). For each of these modalities, pooled data from a series of acromegaly studies were reviewed for rates of IGF-I normalization, a currently accepted definition of cure. The results showed overall cure rates of approximately 10% for bromocriptine, 34% for cabergoline, 36% for conventional radiation, 50–90% for surgery for microadenomas and less than 50% for macroadenomas, and 54–66% for octreotide. These cure rates based on IGF-I normalization are generally less than those reported for cure based solely on GH levels. Novel new therapies for acromegaly include the somatostatin analog, lanreotide, Gamma Knife radiosurgery, and pegvisomant, the first in its class of new GH receptor antagonists. Although it does not appear that Gamma Knife radiosurgery results in significantly higher cure rates or fewer complications, it does provide a notable improvement in delivery compared with conventional radiation. Early studies have reported IGF-I normalization in 48% of lanreotide-treated patients and up to 97% of pegvisomant-treated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: Occult adenomas in general population. Ann Intern Med 1994;120:817–820.

    Google Scholar 

  2. Sutherland GR, Florell R, Louw D, Choi NW, Sima AA. Epidemiology of primary intracranial neoplasms in Manitoba, Canada. Can J Neurol Sci 1987;14:586–592.

    Google Scholar 

  3. Bengtsson BA, Eden S, Ernest I, Oden A, Sjogren B. Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 1988;223:327–335.

    Google Scholar 

  4. Clayton RN. Sporadic pituitary tumours: From epidemiology to use of databases. Baillieres Best Pract Res Clin Endocrinol Metab 1999;13:451–460.

    Google Scholar 

  5. Mindermann T, Wilson CB. Age-related and gender-related occurrence of pituitary adenomas. Clin Endocrinol (Oxf) 1994;41:359–364.

    Google Scholar 

  6. Alexander L, Appleton D, Hall R, Ross WM, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol (Oxf) 1980;12:71–79.

    Google Scholar 

  7. Ritchie CM, Atkinson AB, Kennedy AL, Lyons AR, Gordon DS, Fannin T, Hadden DR. Ascertainment and natural history of treated acromegaly in Northern Ireland. Ulster Med J 1990;59:55–62.

    Google Scholar 

  8. Etxabe J, Gaztambide S, Latorre P, Vazquez JA. Acromegaly: An epidemiological study. J Endocrinol Invest 1993;16:181–187.

    Google Scholar 

  9. Swedish Tumor Registry. Data available upon request.

  10. Lindholm J, Juul S, Jørgensen JOL et al. Incidence and late prognosis of Cushing's syndrome: A population-based study. J Clin Endocrinol Metab 2001;86(1):117–123.

    Google Scholar 

  11. Drange MR, Fram NR, Herman-Bonert V, Melmed S. Pituitary tumor registry: A novel clinical resource. J Clin Endocrinol Metab 2000;85:168–174.

    Google Scholar 

  12. Wright AD, Hill DM, Lowy C, Fraser TR. Mortality in acromegaly. Q J Med 1970;34:1–16.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  15. 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;301:1138–1142.

    Google Scholar 

  16. Freda PU. Advances in the diagnosis of acromegaly. The Endocrinologist 2000;10:237–244.

    Google Scholar 

  17. Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L et al. Criteria for cure of acromegaly: A consensus statement. J Clin Endocrinol Metab 2000;85:526–529.

    Google Scholar 

  18. Kreutzer J, Vance ML, Lopes MB, Laws ER Jr. Surgical management of GH-secreting pituitary adenomas: An outcome study using modern remission criteria. J Clin Endocrinol Metab 2001;86:4072–4077.

    Google Scholar 

  19. Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 1998;89:353–358.

    Google Scholar 

  20. Swearingen B, Barker FG II, Katznelson L, Biller BMK, Grinspoon S, Klibanski A, Moayeri N, Black P MCL, Zervas NT. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998;83:3419–3426.

    Google Scholar 

  21. Minniti G, Jaffrain-Rea ML, Esposito V, Santoro A, Moroni C, Lenzi J, Tamburrano G, Cassone R, Cantore G. Surgical treatment and clinical outcome of GH-secreting adenomas in elderly patients. Acta Neurochir 2001;143:1205–1211.

    Google Scholar 

  22. Ikeda H, Jokura H, Yoshimoto T. Transsphenoidal surgery and adjuvant gamma knife treatment for growth hormonesecreting pituitary adenoma. J Neurosurg 2001;95:285–291.

    Google Scholar 

  23. Shimon I, Cohen ZR, Ram Z, Hadani M, Basso A, Fahlbusch R, Laws ER Jr, Post KD, Singer PA. Transsphenoidal surgery for acromegaly: Endocrinological follow-up of 98 patients. Neurosurg 2001;48:1239–1245.

    Google Scholar 

  24. Biermasz NR, van Dulken H, Roelfsema F. Ten-year follow-up results of transsphenoidal microsurgery in acromegaly. J Clin Endocrinol Metab 2000;85:4596–4602.

    Google Scholar 

  25. Laws ER, Vance ML, Thapar K. Pituitary surgery for the management of acromegaly. Hormone Research 2000;50:71–75.

    Google Scholar 

  26. Valdemarsson S, Ljunggren S, Bramnert M, Norrham O, Nordstrom CH. Early postoperative growth hormone levels: High predictive value for long-term outcome after surgery for acromegaly. J Intern Med 2000;247:640–650.

    Google Scholar 

  27. Yamada S, Takada K, Ozawa Y, Shimizu T, Sawano S, Shishiba Y, Sano T, Usui M. The results of transsphenoidal surgery for 44 consecutive acromegalic patients. Clin Endo 1996;45:291–298.

    Google Scholar 

  28. Jackson IM, Noren G. Role of gamma-knife radiosurgery in acromegaly. Pituitary 1999;2:71–77.

    Google Scholar 

  29. Barkan AL. Efficacy of radiotherapy in acromegaly: The re-appraisal (In press-Clin Endocrinol).

  30. Alfaro JJ, Lucas T, Lamas C, Estrada J, Garcia-Uria J, Magaelon R, Barcelo B. Conventional pituitary irradiation after transphenoidal surgery in acromegaly: Report of 91 cases. 11th Intl. Congress of Endocrinology, Sydney, 2000: P1274.

  31. Barkan AL, Halasz I, Dornfield KJ, Jaffe CA, Friberg RD, Chandler WE, Sandler HM. Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 1999;82:3187–3191.

    Google Scholar 

  32. Barrande G, Pittino-Lungo M, Coste J, Ponvert D, Bertagna X, Luton JP, Bertherat J. Hormonal and metabolic effects of radiotherapy in acromegaly: Long-term results in 128 patients followed in a single center. J Clin Endocrinol Metab 2000;85:3779–3785.

    Google Scholar 

  33. Bezerra AK, Seidenberger K, Charf A, Knoepfelmacher M, Liberman B, Musolino NC, Bronstein MD. Radiotherapy for acromegaly: Long-term results. 11th Intl. Congress of Endocrinology, Sydney, 2000: P1334.

  34. Cozzi R, Barausse M, Asnaghi D, Dallabonzana D, Lodrini S, Attanasio R. Failure of radiotherapy in acromegaly. Eur J Endocrinol 2001;145:717–726.

    Google Scholar 

  35. Epaminonda P, Motti ED, Ventrella L, Giugni E, Cappiello V, Ferrante E, Beck-Peccoz P, Fagia G, Arosio M. Effects of gamma-knife on GH and IGF-I levels in acromegaly. 83rd Meeting of the Endocrine Society, Denver, 2001. Abstract P2-185.

  36. Gianella-Neto D, Wajchenberg BL, Mendonca BB, Almeida SF, Macchione M, Spencer EM. Criteria for the cure of acromegaly: Comparison between basal growth hormone and somatomedin C plasma concentrations in active and nonactive acromegalic patients. J Endocrinol Invest 1988;11:57–60.

    Google Scholar 

  37. Gutt B, Hatzack C, Morrison K, Pollinger B, Schopohl J. Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly. Eur J Endocrinol 2001;144:109–116.

    Google Scholar 

  38. Powell JS, Wardlaw SL, Post KD, Freda PU. Outcome of radiotherapy for acromegaly using normalization of insulinlike growth factor I to define cure. J Clin Endocrinol Metab 2000;85:2068–2071.

    Google Scholar 

  39. Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT. Long-term mortality after transphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998;83:3419–3426.

    Google Scholar 

  40. Thalassinos NC, Tsagarakis S, Ioannides G, Tzavara I, Papavasiliou C. Megavoltage pituitary irradiation lowers but seldom leads to safe GH levels in acromegaly: A long-term follow-up study. Eur J Endocrinol 1998;138:160–163.

    Google Scholar 

  41. van der Lely AJ, de Herder WW, Lamberts SW. The role of radiotherapy in acromegaly. J Clin Endocrinol Metab 1997;82:3185–3186.

    Google Scholar 

  42. Plowman PN. Pituitary adenoma radiotherapy-when, who and how? Clin Endocrinol 1999;51:265–271.

    Google Scholar 

  43. Erfuth EM, Bulow B, Mikoczy Z, Svahn-Tappert G, Hagmar L. Is there an increase in second brain tumors after surgery and irradiation for a pituitary tumor? Clin Endocrinol 2001;55:613–616.

    Google Scholar 

  44. Jalali R, Brada M, Perks JR et al. Stereotactic conformal radiotherapy for pituitary adenomas: Technique and preliminary experience. Clin Endocrinol 2000;52:695–702.

    Google Scholar 

  45. Jaffe CA, Barkan AL. Acromegaly: Recognition and treatment. Drugs 1994;47:425–445.

    Google Scholar 

  46. Clayton RN, Vrionides Y, Lynch SS, Butt WR, London DR. Response of acromegaly to long term bromocriptine therapy: A biochemical and clinical assessment. Acta Endocrinol 1978;89:469–482.

    Google Scholar 

  47. Gross DJ, Halperin Y, Gomori JM, Glaser B. Bromocriptine treatment of acromegaly: Possible dose dependency of the tumor size-reducing effect. Israel J Med Sciences 1989;25:256–260.

    Google Scholar 

  48. Sachdev Y, Gomez-Pan A, Tunbridge WM, Duns A, Weightman DR et al. Bromocriptine therapy in acromegaly. Lancet 1975;2:1164–1168.

    Google Scholar 

  49. Belforte L, Camanni F, Chiodini PG, Liuzzi A, Massara F et al. Long-term treatment with 2-Br-alpha-ergocryptine in acromegaly. Acta Endocrinol 1977;85:235–248.

    Google Scholar 

  50. Bell PM, Atkinson AB, Hadden DR, Kennedy L, Leslie H et al. Bromocriptine reduces growth hormone in acromegaly. Arch Intern Med 1986;146:1145–1149.

    Google Scholar 

  51. Besser GM, Wass JAH, Thorner MO. Bromocriptine in the medical management of acromegaly. In: Goldstein et al., eds. Advances in Biochemical Psychopharmacology, New York: Raven Press 1980:191–198.

    Google Scholar 

  52. Carlson HE, Levin SR, Braunstein GD, Spencer EM, Wilson SE et al. Effect of bromocriptine on serum hormones in acromegaly. Hormone Research 1984;19:142–152.

    Google Scholar 

  53. Cassar J, Mashiter K, Joplin GF. Bromocriptine treatment of acromegaly. Metabolism 1977;26:539–546.

    Google Scholar 

  54. Chiba T, Chihara K, Miniamitani N, Goto B, Kadowaki S et al. Effects of long term bromocriptine treatment on glucose intolerance in acromegaly. Hormone and Metabolic Research 1982;14:57–61.

    Google Scholar 

  55. Chiodini PG, Cozzi R, Dallabonzana D, Oppizzi G et al. Medical treatment of acromegaly with SMS 201-995, a somatostatin analog: A comparison with bromocriptine. J Clin Endocrinol Metab 1987;64:447–453.

    Google Scholar 

  56. Chiodini PG, Liuzzi A, Botalla L, Oppizzi G, Muller EE et al. Stable reduction of plasma growth hormone (hGH) levels during chronic administration of 2-Br-alpha-ergocryptine (CB-154) in acromegalic subjects. J Clin Endocrinol Metab 1975;40:705–708.

    Google Scholar 

  57. Cozzi R, Dallabonzana D, Oppizzi G, Verde G, Liuzzi A et al. Bromocriptine does not alter growth hormone (GH) responsiveness to GH-releasing hormone in acromegaly. J Clin Endocrinol Metab 1986;62:601–604.

    Google Scholar 

  58. Dunn PJ, Donald RA, Espiner EA. Bromocriptine suppression of plasma growth hormone in acromegaly. Clin Endocrin 1977;7:273–281.

    Google Scholar 

  59. Eskildsen PC, Lund B, Sorensen OH, Bishop JE et al. Acromegaly and vitamin D metabolism: Effect of bromocriptine treatment. J Clin Endocrinol Metab 1979;49:484–486.

    Google Scholar 

  60. Giustina A, Doga M, Bussi AR, Licini M, Schettino M. Effect of long-term treatment with bromocriptine on the growth hormone response to galanin in patients with acromegaly. Acta Endocrinol 1993;128:131–135.

    Google Scholar 

  61. Halse J, Harris AG, Kvistborg A, Kjartansson O, Hanssen E et al. A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: Clinical and biochemical effects. J Clin Endocrinol Metab 1990;70:1254–1261.

    Google Scholar 

  62. Halse J, Haugen HN, Bohmer T. Bromocriptine treatment in acromegaly: Clinical and biochemical effects. Acta Endocrinol 1977;86:464–472.

    Google Scholar 

  63. Hanew K, Sugawara A, Shimizu Y, Sato S, Sasaki A et al. The combination therapy with bromocriptine and cyproheptadine in patients with acromegaly. Endocrinol Japonica 1989;36:429–438.

    Google Scholar 

  64. Holdaway IM, Frengley PA, Scott DJ, Ibbertson HK. Bromoergocryptin treatment of acromegaly persisting following conventional therapy. Clin Endocrinol 1978;8:45–54.

    Google Scholar 

  65. Karashima T, Kato K, Nawata H, Ikuyama S, Ibayashi H et al. Long-term bromocriptine therapy and predictive tests in acromegaly. Endocrinol Japonica 1986;33:163–167.

    Google Scholar 

  66. Lindholm J, Riishede J, Verstergaard S, Hummer L, Faber O et al. No effect of bromocriptine in acromegaly: A controlled trial. N Engl J Med 1981;304:1450–1454.

    Google Scholar 

  67. Lundin L, Ljunghall S, Wide L, Bostrom H. Bromocriptine therapy in eleven patients with acromegaly. Acta Endocrinol 1978;216(Suppl):207–216.

    Google Scholar 

  68. Maneschi F. Reappraisal of bromocriptine treatment for acromegaly. Horm Res 1980:12;195–205.

    Google Scholar 

  69. Moses AC, Molitch ME, Sawin CT, Jackson IM, Biller BJ et al. Bromocriptine therapy in acromegaly: Use in patients resistant to conventional therapy and effect on serum levels of somatomedin C. J Clin Endocrinol Metab 1981;53:752–758.

    Google Scholar 

  70. Nortier JWR, Croughs RJM, Thijsen JHH, Schwarz F. Bromocriptine therapy in acromegaly: Effects on plasma GH levels, somatomedin-C levels and clinical activity. Clin Endocrinol 1985;22:209–217.

    Google Scholar 

  71. Oppizzi G, Liuzzi A, Chiodini P, Dallabonzana D, Spelta B et al. Dopaminergic treatment of acromegaly: Different effects on hormone secretion and tumor size. J Clin Endocrinol Metab 1984;58:988–992.

    Google Scholar 

  72. Oppizzi G, Petroncini MM, Dallabonzana D. Relationship between somatomedin-C and growth hormone levels in acromegaly: Basal and dynamic evaluation. J Clin Endocrinol Metab 1986;63:1348–1353.

    Google Scholar 

  73. Pelkonen R, Ylikahri R, Karonen SL. Bromocriptine treatment of patients with acromegaly resistant to conventional therapy. Clin Endocrinol 1980;12:219–224.

    Google Scholar 

  74. Quabbe HJ. Treatment of acromegaly by trans-sphenoidal operation, 90-yttrium implantation and bromcriptine. Results in 230 patients. Clin Endocrinol 1982;16:107–119.

    Google Scholar 

  75. Roelfsema F, Goslings BM, Frolich M, Moolenaar AJ, Seters AP. The influence of bromocriptine on serum levels of growth hormone and other pituitary hormones and its metabolic effects in active acromegaly. Clin Endocrinol 1979;11: 235–244.

    Google Scholar 

  76. Schwinn G, Dirks H, McIntosh C, Kobberling J. Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months. Eur J Clin Invest 1977;7:101–107.

    Google Scholar 

  77. Summers VK, Hipkin LJ, Diver MH, Davis JC. Treatment of acromegaly with bromocriptine. J Clin Endocrinol Metab 1975;40:904–906.

    Google Scholar 

  78. Wass JAH, Clemmons DR, Underwood LE, Barrow I, Besser GM et al. Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly. Clin Endocrinol 1982;17:360–377.

    Google Scholar 

  79. Werner S, Hall K, Sjoberg HE. Bromocriptine therapy in patients with acromegaly: Effects on growth hormone, somatomedin A and prolactin. Acta Endocrinol 1978;216 (Suppl):199–206.

    Google Scholar 

  80. RxList-The Internet Drug Index. Bromocriptine. Available at: http://www.rxlist.com/cgi/generic3/bromocriptine ad. htm. Accessed June 6, 2002.

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

    Google Scholar 

  82. Jackson SN, Fowler J, Howlett TA. Cabergoline treatment of acromegaly: A preliminary dose finding study. Clin Endocrinol 1997;46:745–749.

    Google Scholar 

  83. Ferrari C, Paracchi A, Romano C, Gerevini G, Boghen M, Barreca A, Fortini P, Dubini A. Long lasting lowering of serum growth hormone and prolactin levels by single and repetitive cabergoline administration in dopamine-responsive acromegalic patients. Clin Endocrinol 1988;29: 467–476.

    Google Scholar 

  84. Colao A, Ferone D, Marzullo P, Di Sarno A, Cerbone G, Sarnacchiaro F, Cirillo S, Merola B, Lombardi G. Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab 1997;82:518–523.

    Google Scholar 

  85. Cozzi R, Attanasio R, Barausse M, Dallabonzana D, Orlandi P, Da Re N, Branca V, Oppizzi G, Gelli D. Cabergoline in acromegaly: A renewed role for dopamine agonist treatment? Eur J Endocrinol 1998;139:516–521.

    Google Scholar 

  86. Abs R, Verhelst J, Maiter D, van Acker K, Nobels F, Coolens J-L, Mahler C, Beckers A. Cabergoline in the treatment of acromegaly: A study in 64 patients. J Clin Endocrinol Metab 1998;83:374–378.

    Google Scholar 

  87. Muratori M, Arosio M, Gambino G, Romano C, Biella O, Faglia G. Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients. J Endocrinol Invest 1997;20:537–546.

    Google Scholar 

  88. RxList-The Internet Drug Index. Cabergoline. Available at: http://www.rxlist.com/cgi/generic3/cabergoline ad.htm. Accessed June 6, 2002.

  89. RxList-The Internet Drug Index. Octreotide. Available at: http://www.rxlist.com/cgi/generic3/octreotide2 ids.htm. Accessed June 6, 2002.

  90. Barkan A, Lloyd RV, Chandler WF et al. Treatment of acromegaly with SMS 201-995 (Sandostatin): Clinical, biochemical, and morphological study. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:103–108.

    Google Scholar 

  91. Ch'ng LJ, Sandler LM, Kraenzlin ME, Burrin MJ, Joplin GF et al. Long-term treatment of acromegaly with a longacting analogue of somatostatin. Br Med J (Clin Res Ed) 1985;290:284–285.

    Google Scholar 

  92. Comi RJ, Gorden P. The response of serum GH levels to the long-acting somatostatin analog SMS 201-995 in acromegaly. J Clin Endocrinol Metab 1987;64:37–42.

    Google Scholar 

  93. Ezzat S, Snyder PJ, YoungWF, Boyajy LD, Newman C et al. Octreotide treatment of acromegaly: A randomized, multicenter study. Annals Intern Med 1992;117:711–718.

    Google Scholar 

  94. Fredstorp L, Harris A, Haas G, Werner S. Short term treatment of acromegaly with the somatostatin analog octreotide: The first double-blind randomized placebo-controlled study on its effects. J Clin Endocrinol Metab 1990;71:1189–1194.

    Google Scholar 

  95. Harris AG, Prestele H, Herold K et al. Long-term efficacy of Sandostatin (SMS 201-995, octreotide) in 178 acromegalic patients: Results from the international multicentre acromegaly study group. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:117–125.

    Google Scholar 

  96. Ho KY, Weissberger MB, Marbach P, Lazarus L. Therapeutic efficacy of the somatostatin analog SMS 201-995 (octreotide) in acromegaly: Effects of dose and frequency and long-term safety. Annals Intern Med 1990;112:173–181.

    Google Scholar 

  97. Horikawa R, Takano K, Hizuka N, Asakawa K, Sukegawa I et al. Treatment of acromegaly with long acting somatostatin analogue SMS 201-995. Endocrinol Japon 1988;35:741–751.

    Google Scholar 

  98. Jackson IMD, Barnard L, Cobb W et al. Long-term treatment of resistant acromegaly with a somatostatin analog (SMS 201-995, Sandostatin). In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988: 133–139.

    Google Scholar 

  99. James RA, Moller N, Chatterjee S, White M, Kendall-Taylor P. Carbohydrate intolerance and serum lipids in acromegaly before and during treatment with high dose octreotide. Diabetic Med 1991;6:517–523.

    Google Scholar 

  100. Lamberts SWJ, Uitterlinden P, Schuijff PC, Klijn JG. Therapy of acromegaly with Sandostatin: The predictive value of an acute test, the value of serum somatomedin C measurements in dose adjustment and the definition of a biochemical 'cure'. Clin Endocrinol 1988;29:411–420.

    Google Scholar 

  101. Liuzzi A, Chiodini PG, Cozzi R et al. Medical treatment of acromegaly. Dopaminergic agonists and long-term somatostatin. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:75–79.

    Google Scholar 

  102. McKnight JA, McCance DR, Sheridan B et al. A long-term dose response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly. Clin Endocrinol 1991;34:119–125.

    Google Scholar 

  103. Mehltretter G, Heinz S, Schopohl J, von Werder K, Müller OA. Long-term treatment with SMS 201-995 in resistant acromegaly: Effectiveness of high doses and continuous subcutaneous infusion. Klinische Wochenschrift 1991;69:83–90.

    Google Scholar 

  104. Newman CB, Melmed S, Snyder PJ, Young WF, Boyajy LD et al. 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 1995;80:2768–2775.

    Google Scholar 

  105. Page MD, Millward ME, Taylor A, Preece M, Hourihan M et al. Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide. Quarterly J Med 1990;274:189–201.

    Google Scholar 

  106. Pieters GF, van Liessum PA, Smals AG, van Gennep JA, Benraad TJ et al. Long-term treatment of acromegaly with Sandostatin (SMS 201-995). Normalization of most anomalous GH responses. Acta Endocrinol 1987;216(Suppl):9–18.

    Google Scholar 

  107. Plewe G, Schrezenmeir J, Nölken G, Krause U, Beyer J et al. Long-term therapy of acromegaly with the somatostatin analogue SMS 201-995 over 6 months. Klinische Wochenschrift 1986;64:389–392.

    Google Scholar 

  108. Quabbe HJ, Plöckinger U. Dose-response study and longterm effect on the somatostatin analog octreotide in patient with therapy-resistant acromegaly. J Clin Endocrinol Metab 1989;68:873–881.

    Google Scholar 

  109. Roelfsema F, Frölich M, de Boer H, Harris AG. Octreotide treatment in acromegaly: A comparison between pen-treated and pump-treated patients in a cross-over study. Acta Endocrinol 1991;125:43–48.

    Google Scholar 

  110. Salmela PI, Juustila H, Pyhtinen J, Jokinen K, Alavaikko M et al. Effective clinical response to long term octreotide treatment with reduced serum concentrations of growth hormone, insulin-like growth factor-I, and the amino-terminal propeptide of type III procollagen in acromegaly. J Clin Endocrinol Metab 1990;70:1193–1201.

    Google Scholar 

  111. Sandler LM, Burrin JM, Williams G, Joplin GF, Carr DH et al. Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995). Clin Endocrinol 1987;26:85–95.

    Google Scholar 

  112. Sassolas G, Fossati P, Chanson P. Effects of long-term administration of Sandostatin (SMS 201-995) at increasing doses in 40 acromegalic patients: Results from the French Sandostatin acromegaly study group. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:89–94.

    Google Scholar 

  113. Schatz H, Stracke H, Hildebrandt G. Treatment of prolactinomas and growth-hormone-producing adenomas with an injectable bromocriptine retard preparation and a somatostatin analogue delivered by an implantable pump. Pathol Res Pract 1988;183:546–551.

    Google Scholar 

  114. Schopohl J, Müller OA, von Werder K. SMS 201-994 (Sandostatin) treatment of therapy-resistant acromegaly. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:153–156.

    Google Scholar 

  115. Spinas GA, Zapf J, Landolt AM. Preoperative treatment of 5 acromegalics with a somatostatin analogue: Endocrine and clinical observations. Acta Endocrinol 1987;114:249–256.

    Google Scholar 

  116. Stevenaert A, Beckers A, Kovacs K. Experience with Sandostatin in various groups of acromegalic patients. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:95–101.

    Google Scholar 

  117. Tauber P, Babin T, Tauber MT, Vigoni F, Bonafe A et al. Long term effects of continuous subcutaneous infusion of the somatostatin analog octreotide in the treatment of acromegaly. J Clin Endocrinol Metab 1989;68:917–924.

    Google Scholar 

  118. Timsit J, Chanson P, Larger E, Duet M, Mosse A et al. The effect of subcutaneous infusion versus subcutaneous injections of a somatostatin analogue (SMS 201-995) on the diurnal GH profile in acromegaly. Acta Endocrinol 1987;116:108–112.

    Google Scholar 

  119. Vance ML, Harris AG. Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide: Results of the international multicentre acromegaly study group. Arch Intern Med 1991;151:1573–1578.

    Google Scholar 

  120. Vance ML, Kaiser DL, Thorner MO. Sandostatin (SMS 201-995) in the treatment of acromegaly. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:149–150.

    Google Scholar 

  121. Verde GG, Santi I, Chiodini P, Cozzi R, Dallabonzana D et al. Serum type II procollagen propeptide levels in acromegalic patients. J Clin Endocrinol Metab 1986;63:1406–1410.

    Google Scholar 

  122. Wang C, Lam KSL, Arceo E, Chan FL. Comparison of the effectiveness of 2-hourly versus 8-hourly subcutaneous injections of a somatostatin analog (SMS 201-995) in the treatment of acromegaly. J Clin Endocrinol Metab 1989;69:670–677.

    Google Scholar 

  123. Wass JAH, Davidson K, Medbak S et al. Somatostatin octapeptide (SMS 201-995, Sandostatin) in the medical treatment of acromegaly. In: Lamberts SWJ, ed. Sandostatin in the Treatment of Acromegaly, New York: Springer 1988:151–152.

    Google Scholar 

  124. Stewart PM, Kane KF, Stewart SE, Lancranjan I, Sheppard MC. Depot long-acting somatostatin analog (Sandostatin-LAR) is an effective treatment for acromegaly. J Clin Endocrinol Metab 1995;80:3267–3272.

    Google Scholar 

  125. Lancranjan I, Bruns C, Grass P, Jaquet P, Jervell J et al. Sandostatin LAR:Apromising therapeutic tool in the management of acromegalic patients. Metab 1996;45(8 Suppl 1):67–71.

    Google Scholar 

  126. Fløgstad AK, Halse J, Bakke S, Lancranjan I, Marbach P, Bruns CH, Jervell J. Sandostatin LAR in acromegalic patients: Long term treatment. J Clin Endocrinol Metab 1996;82:23–28.

    Google Scholar 

  127. Davies PH, Stewart SE, Lancranjan I, Sheppard MC, Stewart PM. Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the management of acromegaly. Clin Endocrinol 1998;48:311–316.

    Google Scholar 

  128. Turner HE, Vadivale A, Keenan J, Wass JA. A comparison of lanreotide and octreotide LAR for treatment of acromegaly. Clin Endocrinol 1999;51:275–280.

    Google Scholar 

  129. Cozzi R, Dallabonzana D, Attanasio R, Barausse M, Oppizzi G. A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly. Eur J Endocrinol 1999;141:267–271.

    Google Scholar 

  130. Colao A, Marzullo P, Ferone D, Spinelli L, Cuocolo A et al. Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab 2000;85:3132–3140.

    Google Scholar 

  131. Chanson P, Boerlin V, Ajzenberg C, Bachelot Y, Benito P et al. Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly. Clin Endocrinol 2000;53:577–586.

    Google Scholar 

  132. Kendall-Taylor P, Miller M, Gebbie J, Turner S, Al-Maskari M. Long-acting octreotide LAR compared with lanreotide SR in the treatment of acromegaly. Pituitary 2000;3:61–65.

    Google Scholar 

  133. Summary of Product Characteristics, Somatuline® LA 30 mg, Ipsen Ltd, 1 Bath Road, Maidenhead, Berkshire, SL6 4UH, UK. Revised January 1998.

  134. Attanasio R, Barausse M, Cozzi R. GH/IGF-I normalization and tumor shrinkage during long-term treatment of acromegaly by lanreotide. J Endocrinol Invest 2001;24.209–216.

    Google Scholar 

  135. Jenkins PJ, Akker S, Chew SL, Besser GM, Monson JP, Grossman AB. Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration. Clin Endocrinol 2000;53:719–724.

    Google Scholar 

  136. Summary of Product Characteristics, Somatuline® Autogel, Ipsen Ltd, 190 Bath Road, Slough, Berkshire, SL1 3XE, UK. October 2001.

  137. Gutt B, Biering H, Bullmann C, Caird D, Ertekin A, Gerl H, Jockenhoevel F, Saller B, Vogel E, Schopohl J. Treatment of 23 patients with acromegaly with lanreotide autogel-A new long-acting somatostatin analogue for subcutaneous injection. Exp Clin Endocrinol Diabetes 2000;108(Suppl 1): Abstract pFr213.

  138. Caron P, Beckers A, Cullen DR, Goth MI, Gutt B, Laurberg P et al. Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly. J Clin Endocrinol Metab 2002;87:99–104.

    Google Scholar 

  139. Chen WY, Wight DC, Wagner TE et al. Expression of a mutated bovine growth hormone gene suppresses growth on transgenic mice. Proc Natl Acad Sci USA 1990;87:5061–5065.

    Google Scholar 

  140. Fuh G, Cunningham BC, Fukunaga R et al. Rational design of potent atagonists to the human growth hormone receptor. Science 1992;256:1677–1680.

    Google Scholar 

  141. Cunningham BC, Ultsch M, De Vos AM et al. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991;254:821–825.

    Google Scholar 

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

    Google Scholar 

  143. Bertherat J, Chanson P, Dewailly D, Dupuy M, Jaquet P, Peillon F, Epelbaum J. Somatostatin receptors, adenylate cyclase activity and GH response to octreotide in GH-secreting adenomas. J Clin Endocrinol Metab 1993;77:1577–1583.

    Google Scholar 

  144. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000;342:1171–1177.

    Google Scholar 

  145. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001;358:1754–1759.

    Google Scholar 

  146. Leksell L. The stereotactic method and radiosurgery of the brain. Acta Chir Scand 1951;1102:316–319.

    Google Scholar 

  147. Lim YL, Leem W, Kim TS, Rhee BA, Kim GK. Four years' experiences in the treatment of pituitary adenomas with gamma knife radiosurgery. Stereotactic Funct Neurosurg (Switzerland) 1998;70(Suppl 1):95–109.

    Google Scholar 

  148. Laws ER, Vance ML. Conventional radiotherapy for pituitary tumors. Neurosurg Clin N Am 2000;11:617–625.

    Google Scholar 

  149. Kim MS, Lee SI, Sim JH. Gamma-knife radiosurgery for functioning pituitary microadenoma. Stereotactic Funct Neurosurg 1999;72:199–124.

    Google Scholar 

  150. Landholt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G. Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 2000;85:1287–1289.

    Google Scholar 

  151. Mokry M, Ramschak-Schwarzer S, Simbrunner J, Ganz JC, Pendl G. A six year experience with the postoperative radiosurgical management of pituitary adenomas. Stereotactic Funct Neurosurg 1999;72:88–100.

    Google Scholar 

  152. Morange-Ramos I,Taieb D,Vallette-Kasic S, Regis J, Dufour H, JacquetP, BrueT. Evaluation of gamma-knife radiosurgery for secreting pituitary adenomas: An 8-year experience in 73 patients. 7th Intl. Pituitary Congress, Phoenix, 2001. Abstract #70.

  153. Shin M, Kurita H, Sasaki T, Tago M, Morita A, Ueki K, Kirino T. Stereotactic radiosurgery for pituitary adenoma invading the cavernous sinus. Nuerosurg 2000;3:2–5.

    Google Scholar 

  154. Vladyka V, Liscak R, Simonova G, Chytka T, Novotny J Jr, Vymazal J, Marek J, Hana V, Vavros D. Radiosurgical treatment of hypophyseal adenomas with the gamma knife: Results in a group of 163 patients during a 5-year period. Cas Lek Cesk 2000;139:757–766.

    Google Scholar 

  155. Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G. Stereotactic radiosurgery for recurrent surgically treated acromegaly: Comparison with fractionated radiotherapy. J Neurosurg 1998;88:1002–1008.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ceder-Sinai Medical Center, Los Angeles, CA, USA

    Shlomo Melmed

  2. University of Virginia, Charlottesville, VA, USA

    Mary Lee Vance

  3. University of Michigan, Ann Arbor, MI, USA

    Ariel L. Barkan

  4. Research Centre for Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, Göteborg, Sweden

    Bengt-Åke Bengtsson

  5. New York University Medical Center, New York, NY, USA

    David Kleinberg

  6. Massachusetts General Hospital, Boston, MA, USA

    Anne Klibanski

  7. Christie and South Manchester University Hospitals, Manchester, UK

    Peter J. Trainer

Authors
  1. Shlomo Melmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary Lee Vance
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ariel L. Barkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bengt-Åke Bengtsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Kleinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Klibanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter J. Trainer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melmed, S., Vance, M.L., Barkan, A.L. et al. Current Status and Future Opportunities for Controlling Acromegaly. Pituitary 5, 185–196 (2002). https://doi.org/10.1023/A:1023369317275

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1023369317275

Search

Navigation