Journal of Endocrinological Investigation

, Volume 19, Issue 8, pp 548–555 | Cite as

Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients

  • C. Invitti
  • L. Fatti
  • M. G. Camboni
  • L. Porcu
  • L. Danesi
  • G. Delitala
  • F. Cavagnini


Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 μg/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 μg/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients’ compliance was excellent.


Octreotide nasal powder GH IGF-I IGFBP-1 IGFBP-3 acromegaly somatostatin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ezzat S., Redelmeier D.A., Gnehm M., Harris A.G. A prospective multicenter octreotide dose response study in the treatment of acromegaly. J. Endocrinol. Invest. 18: 364, 1995.PubMedCrossRefGoogle Scholar
  2. 2.
    Lee Vance M., Harris A.G. Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Arch. Intern. Med. 151: 1573, 1991.PubMedCrossRefGoogle Scholar
  3. 3.
    Lamberts S.W.J., Hofland L.J., de Herder W.W., Kwekkeboom D.J., Reubi J.C., Krenning E.P. Octreotide and related somatostatin analogs in the diagnosis and treatment of pituitary disease and somatostatin receptor scintigraphy. Frontiers Neuroendocrinol. 14: 27, 1993.CrossRefGoogle Scholar
  4. 4.
    Chang-DeMoranville B.M., Jackson I. Diagnosis and endocrine testing in acromegaly. Endocrinol. Metab. Clin. North Am. 21: 649, 1992.PubMedGoogle Scholar
  5. 5.
    Baxter R.C. Insulin-like growth factor binding proteins in the human circulation: a review. Horm. Res. 42: 140, 1994.PubMedCrossRefGoogle Scholar
  6. 6.
    Jorgensen J.O.L., Moller N., Moller J., Weeke J., Blum W.F. Insulin-like growth factors (IGF)-I and -II and IGF binding protein −2, and −3 in patients with acromegaly before and after adenomectomy. Metabolism 43: 579, 1994.PubMedCrossRefGoogle Scholar
  7. 7.
    Fredstorp L., Werner S., Bang P., Hall K. Inverse correlation between insulin-like growth factor binding protein-1 and insulin in patients with acromegaly during treatment with the somatostatin analogue octreotide. Clin. Endocrinol. (Oxf.) 41: 495, 1994.CrossRefGoogle Scholar
  8. 8.
    Grinspoon S., Clemmons D., Swearingen B., Klibanski A. Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly. J. Clin. Endocrinol. Metab. 80: 927, 1995.PubMedGoogle Scholar
  9. 9.
    Harris A.G., Weeke J., Christensen S.E., Kaal A., Ilium P., Orskov H. Preliminary results with sandostatin nasal powder in acromegalic patients. Metabolism 41: 72, 1992.PubMedCrossRefGoogle Scholar
  10. 10.
    Daughaday W.H., Starkey R.H., Saltman S., Gavin J.R., Mills-Dunlap B., Heath-Monnig E. Characterization of serum growth hormone (GH) and insulin-like growth factor I in active acromegaly with minimal elevation of serum GH. J. Clin. Endocrinol. Metab. 65: 617, 1987.PubMedCrossRefGoogle Scholar
  11. 11.
    Giannella-Neto D., Wajchenberg B.L., Mendonca B.B., Almeida S.F., Macchione M., Spencer E.M. 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. 11: 57, 1988.PubMedCrossRefGoogle Scholar
  12. 12.
    der Herder W.W., Uitterlinden P., van der Lely A.J., Lamberts S.W.J. Octreotide, but not bromocriptine, increases circulating insulin-like growth factor binding protein 1 levels in acromegaly. Eur. J. Endocrinol. 133: 195, 1995.PubMedCrossRefGoogle Scholar
  13. 13.
    Rieu M., Girard F., Bricaire H., Binoux M. The importance of insulin-like growth factor (somatomedin) measurements in the diagnosis and surveillance of acromegaly. J. Clin. Endocrinol. Metab. 55: 147, 1982.PubMedCrossRefGoogle Scholar
  14. 14.
    Holly J.M.P., Cotterill A.M., Jemmott R.C., Shears D., Al-Othman S., Chard T., Wass J.A.H. Inter-relations between growth hormone, insulin, insulin-like growth factor-l (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly. Clin. Endocrinol. (Oxf.) 34: 275, 1991.CrossRefGoogle Scholar
  15. 15.
    Moses A.C., Molitch M.E., Sawin C.T., Jackson I.M.D., Biller B.J., Furlanetto R., Reichlin S. Bromocriptine therapy in acromegaly: use in patients resistant to conventional therapy and effect on serum levels of somatomedin C. J. Clin. Endocrinol. Metab. 53: 752, 1981.PubMedCrossRefGoogle Scholar
  16. 16.
    Oppizzi G., Petroncini M.M., Dallabonzana D., Cozzi R., Verde G., Chiodini P.G., Liuzzi A. Relationship between somatomedin-C and growth hormone levels in acromegaly: basal and dynamic evaluation. J. Clin. Endocrinol. Metab. 63: 1348, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Lamberts S.W.J., Uitterlinden P., Schuijff P.C., Klijn J.G.M. Therapy of acromegaly with sandostatin: the predictive value of an acute test, the value of somatomedin measurements in dose adjustment and the definition of a biochemical “cure”. Clin. Endocrinol. (Oxf.) 29: 411, 1988.CrossRefGoogle Scholar
  18. 18.
    Dobrashian R.D., O’Halloran D.J., Hunt A., Beardwell C.G., Shalet S.M. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin. Endocrinol. (Oxf.) 38: 589, 1993.CrossRefGoogle Scholar
  19. 19.
    Barreca A., Cariola G. Effect of octreotide on circulating IGF-I chromatographic profile: evidence for an inhibitory action on the formation of the 1 50-kDa ternary complex. Clin. Endocrinol. (Oxf.) 42: 161, 1995.CrossRefGoogle Scholar
  20. 20.
    Sugisaki T., Yamada T., Takamatsu K., Noguchi T. The influence of endocrine factors on the serum concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding proteins. J. Endocrinol. 138: 467, 1993.PubMedCrossRefGoogle Scholar
  21. 21.
    Philip M., Chalew S.A., Kowarski A.A., Stene M.A. Plasma IGFBP-3 and its relationship with quantitative growth hormone secretion in short children. Clin. Endocrinol. (Oxf.) 39: 427, 1993.CrossRefGoogle Scholar
  22. 22.
    Quin J.D., Checkley A., Gallagher A., Jones J., MacCuish A.C., Miell J.P. Response of insulin-like growth factor (IGF) -binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance. J. Endocrinol. 141: 177, 1994.PubMedCrossRefGoogle Scholar
  23. 23.
    Rasmussen M.H., Frystyk J., Andersen T., Breum L., Christiansen J.S., Hilsted J. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone. Metabolism 43: 315, 1994.PubMedCrossRefGoogle Scholar
  24. 24.
    Villafuerte B.C., Koop B.L., Pao C., Gu L., Birdsong G.G., Phillips L.S. Coculture of primary rat hepatocytes and non-parenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro. Endocrinology 134: 2044, 1994.PubMedGoogle Scholar
  25. 25.
    Laursen T., Jorgensen J.O.L., Orskov H., Moller J., Harris A.G., Cristiansen J.S. Effects of octreotide on insulin-like growth factor I and metabolic indices in growth hormone-treated growth hormone-deficient patients. Acta Endocrinol. (Copenh.) 129: 399, 1993.Google Scholar
  26. 26.
    Conover C.A., Lee P.D.K. Insulin regulation of insulin-like growth factor-binding protein production in culture HepG2 cells. J. Clin. Endocrinol. Metab. 70: 1062, 1990.PubMedCrossRefGoogle Scholar
  27. 27.
    Cotterill A.M., Holly J.M., Amiel S., Wass J.A. Suppression of endogenous insulin secretion regulates the rapid rise of insulin-like growth factor binding protein (IGFBP)-1 levels following acute hypoglycaemia. Clin. Endocrinol. (Oxf.) 38: 633, 1993.CrossRefGoogle Scholar
  28. 28.
    Ezzat S., Ren S.G., Braunstein G.D., Melmed S. Octreotide stimulates insulin-like growth factor binding protein-1 (IGFBP1) levels in acromegaly. J. Clin. Endocrinol. Metab. 73: 441, 1991.PubMedCrossRefGoogle Scholar
  29. 29.
    Ezzat S., Re S.G., Braunstein G.D., Melmed S. Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action. J. Clin. Endocrinol. Metab. 75: 1459, 1992.PubMedGoogle Scholar
  30. 30.
    Orskov H., Wolthers T., Grofte T., Flyvbjerg A., Vilstrup H. Somatostatin-stimulated insulin-like growth factor binding protein-1 release is abolished by hyperinsulinemia. J. Clin. Endocrinol. Metab. 78: 138, 1994.PubMedGoogle Scholar
  31. 31.
    Ren S.G., Ezzat S., Melmed S., Braunstein G.D. Somatostatin analog induces insulin-like growth binding protein-1 (IGFBP-1) expression in human hepatoma cells. Endocrinology 131: 2479, 1992.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1996

Authors and Affiliations

  • C. Invitti
    • 1
  • L. Fatti
    • 1
  • M. G. Camboni
    • 2
  • L. Porcu
    • 3
  • L. Danesi
    • 1
  • G. Delitala
    • 3
  • F. Cavagnini
    • 1
  1. 1.Cattedra di Endocrinologia IIUniversità di Milano, IRCCS Ospedale San LucaMilano
  2. 2.Sandoz Prodotti FarmaceuticiItaly
  3. 3.Dipartimento di MedicinaUniversità di SassariItaly

Personalised recommendations