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The role of octreotide (Sandostatin®) in non-growth hormone-, non-thyroid-stimulating hormone-, and non-prolactin-secreting adenomas
The Role of Octreotide (Sandostatin@) in Non-Growth Hormone-, NonThyroid-Stimulating Hormone-, and Non-Prolactin-Secreting Adenomas A.
Warnet
Octreotide may act on non-growth hormone-, non-thyroid-stimulating hormone, and non-prolactin-secreting adenomas. Its efficacy was reported in some cotticotropin-secreting adenomas from Nelson’s syndrome and from Cushing’s disease. In gonadotropinsecreting adenomas. octreotide was shown to be effective in twoof eight cases. In nonfunctioning adenomas. visual improvement was observed with octreotide in 14 of 23 cases in a French multicenter study. Among the 33 patients whose tumor volume was checked, shrinkage occurred in seven, but an increase in tumor volume was observed in another seven patients. Mechanism(s) and prediction of efficacy of octreotide remain to be documented. Copyright
0 1992
by W.B. Saunders
Company
P
ITUITARY ADENOMAS that do not secrete growth hornlone, thyroid-stimulating hormone, or prolactin are usually invasive and/or extensive tumors, the treatment of which is not always satisfactory. The benefit derived from conventional pituitary irradiation alone or from surgical resection is not apparent in nearly one half of the small number of patients with Nelson’s syndrome in the literature.’ Among patients with nonfunctioning adenomas treated by surgery and irradiation, 18% showed radiographic evidence of tumor recurrence during a 2- to 8-year follow-up period,* and the incidence of recurrence is presumably higher with conventional radiation therapy. Hence, the development of additional adjunctive medical therapies is of the utmost importance. It was necessary to investigate whether octreotide, the recently developed, long-acting somatostatin analogue, could be of help in such cases. CORTICOTROPIN-SECRETING ADENOMAS In
Gushing’s Disease
The effect of a single dose of octreotide on corticotropin levels was studied in 18 cases, with no response occurring in any patient, neither on basal levels in 13 patients3-5 nor on the corticotropin response to corticotropin-releasing hormone (CRH).4.5 Treatment with octreotide was given in eight or nine cases and was effective in five. In two of four patients treated by Lorcy et aL6,’ normalization of corticotropin levels within 48 hours of a 0. 1-mg subcutaneous (SC) treatment three times a day was achieved in one case, while in the other, corticotropin deficiency occurred when the dose reached 1.5 mg/d. In one other patient’ whose corticotropin level did not respond to CRH while the cortisol level responded to corticotropin during a treatment with 0.05 mg twice a day, a dose of 0.05 mg three times a day caused corticotropin deficiency. Octreotide (0.40 mg/d) induced a sustained decrease of urinary free cortisol in only one of the three patients treated by Invitti,’ while in the other two it was minimal and transient; however, in this study, corticotropin levels did not decrease. In an additional case of Cushing’s syndrome presumably due to a pituitary adenoma, octreotide (0.1 mg three times a day) normalized clinical and biological features within 15 days, and prolonged remission was observed after a 2-month treatment.‘O In Nelson ‘s Syndrome Native somatostatin is known to suppress corticotropin secretion.“,” Octreotide efficacy was reported in at least four Metabolism.
L’ol 41, No 9, Suppl 2 (September),
1992: pp 59-61
cases; in two cases,’ a single dose was effective, with the decrease being significant in both. In another, short-term octreotide treatment decreased corticotropin levels by more than 50%. An additional 1O-day treatment with 0.5 mg/d continuous SC injection proved effective.13 In one other case, longterm treatment was dramatically effective, with normalization of corticotropin levels within 6 weeks, normalization of the visual field and acuity, and no tumor extension during the 2-year treatment.3
GONADOTROPIN-SECRETING ADENOMAS
In three cases, a 0. I-mg single dose of octreotide was administered, with luteinizing hormone (LH); a-subunit suppression greater than 50% occurred in one ca.se,14but there was no effect at all on follicle-stimulating hormone (FSH) and a-subunit levels in two othersI A 2-day treatment with 0.1 mg (continuous SC infusion) was ineffective on FSH and LH hypersecretion in one case.16 Long-term treatment was given in five cases, again with good control of LH and (Ysubunit secretion being achieved in a 6-week trial in one,‘4 a 92% suppression of a-subunit levels and tumor shrinkage in another patient,15 but no effect on FSH levels in two other cases. The O-Subunit decrease was actually due to partial necrosis of the adenoma in the other patient.16 Altogether, octreotide had a suppressive effect in only two of eight cases of functioning gonadotropin-secreting adenomas. Nonfunctioning Adenomas In vitro studies have shown that some nonfunctioning adenomas had somatostatin receptors,‘7-‘9 which could also be detected by in vivo imaging.‘9.20 A dramatic improvement in chiasm dysfunction from a nonfunctioning adenoma,2’ which was actually a silent corticotropin-secreting adenoma,** was observed, and there were also two additional cases with negative immunocytochemistry.23 Several reports have now been published that evaluate octreotide’s effects on visual defects or tumor size.
From the Service MJdecine B, H6pital LariboisiPre et Universith Paris VII, France. Address reprint requests to A. Warnet. MD. Service de Mbdecine B-H6pital Lariboisitire, F- 75475 Paris CPdex 10. France. Copyright 0 1992 by U’.B. Saunders Company 00260495/92/4109-2009$03.00/O
59
A. WARNET
60
Octreotide’s Effects
011
Visual Defects
In addition to our three cases,22an impressive improvement in chiasm dysfunction was observed in one patient.23 Visual field improvement was also observed in one of four patientsz4 In a French multicenter, open-labeled trial, visual improvement occurred in 14 of 23 nonfunctioning adenomas,” in the first hours to days of treatment in most cases, and it was sustained in most patients. No somatostatin receptors could be detected in vitro in one of these cases. Visual evoked potentials also improved in two of our cases.22 In addition, an improvement in pattern-reversal, visual evoked potentials was observed 1 hour after a single dose of 0.1 mg of octreotide in some patients, 26demonstrating the rapidity of octreotide effectiveness.
Eflect on Tumor Size No tumor shrinkage was demonstrable in our three patier@ or in seven othersz4 Among 20 patients treated with octreotide at doses of 0.3 to 0.5 mg/d for 6 months, three adenomas shrank and three others increased.27 Octreotide did not induce any change in the volume of two adenomas with negative receptor imaging, but one of two adenomas with positive somatostatin-receptor imaging shrank significantly, whereas the other had a significant increase in size that was shown to be due to partial necrosis.28 In the
French multicenter trial, of eleven patients, a shrinkage was observed in three patients, but an increase in tumor volume was seen in three patients who had visual improvement. CONCLUSION
In adenomas as various as corticotropin-secreting adenomas from Nelson’s syndrome or even Cushing’s disease, gonadotropin-secreting adenomas, and nonfunctioning adenomas, the effect of octreotide is valuable and may be of great help in the difficult management of the tumors either before or at various times after surgery and/or irradiation therapy. A better characterization of nonfunctioning adenomas is needed to determine if octreotide is effective in any type. Octreotide efficacy might rely on the existence of somatostatin receptors on adenoma-cell membranes. Prediction of efficacy might then be made by in vivo somatostatin-receptor imaging, provided this technique is sensitive enough. However, whether the visual improvement in chiasmal dysfunction is related to somatostatin receptors or to other mechanisms such as a change in blood supply or in neurotransmission of visual pathways remains to be documented. ACKNOWLEDGMENT 1 wish to thank the participants Group.
of the French SandostatinB
Study
REFERENCES I. Halberg FE, Sheline GE: Radiotherapy of pituitary turnours. Endocrinol Metab Clin North Am 16:667-684, 1987 2. Ebersold MJ. Quast LM, Laws ER Jr. et al: Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 64:7 13-7 19, 1986 3. Lamberts SWJ, Uitterlinden P, Klijn JMG: The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson’s syndrome and Cushing’s disease. Acta Endocrinol (Copenh) 120:760-766, 1989 4. Ambrosi B, Bochicchio D, Fadin C, et al: Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-adrenal function in patients with corticotropin hypersecretion. J Endocrinol Invest 13:257-26 1, 1990 S. Woodhouse NJY. Dagogo-Jack S, Ahmed M: Acute and longterm effects of octreotide in patients with ACTH dependent Cushing’s syndrome. J Endocrinol Invest 14:121, 1991 (suppl 1, abstr) 6. Lorcy Y, Derennes V, Delambre C, et al: Remission d’une maladie de Cushing recidivante par un analogue de la somatostatine. Presse Med 17:1217. 1988 (letter) 7. Lorcy Y. Delambre C, Le Guerrier AM. et al: Use of longacting somatostatin analog octreotide (SMS 201-995) in the treatment of Cushing’s syndrome. J Endocrinol Invest 14: I2 1, 199 1 (suppl 1. abstr) 8. Graziano E. Chiarini V, Cremonini N, et al: Cushing’s disease successfully treated with SMS 201-995: A case report. J Endocrinol Invest 14: 122. 199 1 (suppl 1, abstr) 9. lnvitti C, De Martin M, Brunani A, et al: Treatment of Cushing’s syndrome with the long-acting somatostatin analogue SMS 201-995 (Sandostatin). Clin Endocrinol (0x0 32:275-281, 1990 10. Gross A, Grulet H, Durlach V, et al: Remission prolongee d’un syndrome de Cushing apres traitement par octreotide. Presse Med 20:915-916, 1991 (letter) 1I. Tyrrell JB, Lorenzi M. Gerich JE, et al: lnhibition by so-
matostatin of ACTH secretion in Nelson’s syndrome. J Clin Endocrinol Metab 40:1125-l 127, 1975 12. Benker G, Hackenberg K, Hamburger B, et al: Effects of growth hormone release-inhibiting hormone and bromocriptine (CB 154) in states of abnormal pituitary-adrenal function. Clin Endocrinol (0x0 5:187-190, 1976 13. Guerin V. Ortega F. James-Deidier A, et al: Continuous infusion of SMS 20 l-995 in Nelson’s syndrome. J Endocrinol Invest 13: 153, 1990 (suppl 2, abstr) 14. Vos P, Croughs RJM, Thijssen JHH. et al: Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue. Acta Endocrinol (Copenh) I I8:587-590, 1988 15. Sassolas G. Serusclat P, Claustrat B. et al: Plasma alpha-subunit levels during the treatment of pituitary adenomas with the somatostatin analog (SMS 201-995). Harm Res 29: l24- 128, 1988 16. Wamet A, Chanson P: Octreotide (Sandostatine@) et adenomes non somatotropes. Sandostatine: Symposium de Paris, Paris, France. February 6. 1990 17. Ikuyama S, Nawata H. Kato K. et al: Specific somatostatin receptors on human pituitary adenoma cell membranes. J Clin Endocrinol Metab 6 1:666-67 1. 1985 18. Reubi JC, Heitz PU, Landolt AM: Visualisation of somatostatin receptors and correlation with immunoreactive growth hormone and prolactin in human pituitary adenomas: Evidence for different tumour subclasses. J Clin Endocrinol Metab 65:65-73, 1987 19. Faglia G, Bazzoni N, Spada A. et al: In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([‘?I SDZ 204990). J Clin Endocrinol Metab 73:850-856, 1991 20. Lamberts SWJ. Bakker WH, Reubi JC, et al: Somatostatinreceptor imaging in the localization of endocrine turnours. N Engl J Med 323:1246-1249, 1990 2 1. Warnet A. Thurel C, Duet M. et al: Somatostatin analog SMS 20 I-995 (Sandostatin@) can improve chiasmatic compression due to
ROLE OF OCTREOTIDE IN NONSECRETING
ADENOMAS
nonfunctioning pituitary adenoma. First European Congress of Endocrinology, Copenhagen, Denmark, June 2 l-25, 1987 22. Warnet A, Timsit J, Chanson P. et al: The effect ofsomatostatin analogue on chiasmal dysfunction from pituitary macroadenomas. J Neurosurg 7 I :687-690. 1989 23. Riinzi M, Jaspers C, Benker G, et al: Dramastische Besserung eines Chiasmasyndromes bei endokrin inaktivem Makroadenom der Hypophyse unter Therapie mit dem Somatostatin-Analogon SMS 201-995. Klin Wochenschr 67:284, 1989 (suppl 16, abstr) 24. Petrini L, Pilosu R, Marcello A, et al: Treatment of non functional pituitary tumors with octreotide. J Endocrinol Invest 14:119, 199 I (suppl I, abstr)
61
25. Wamet A: Effect of Sandostatin on optic chiasm compression due to non GH-, non TSH-secreting pituitary adenomas. J Endocrinol Invest 13:74, 1990 (suppl 2, abstr) 26. Ducati A, Losa M. Fava E, et al: Acute effects on visual hmction of a somatostatin analog (SMS 201-995) evaluated using a neurophysi01ogicaJapproach. J Endocrinol Invest 14:120, 199I (suppl 1, abstr) 27. Liuzzi A, Dallabonzana D, Oppizzi G, et al: Is there a real medical treatment for the “non-secreting” pituitary adenomas? J Endocrinol Invest 14:18, 199 1 (suppl 1,abstr) 28. Bazzoni N, Farabola M, Arosio M, et al: Is the effect of octreotide therapy in patients with functionless pituitary adenomas predictable? J Endocrinol Invest 14:53. I99 I (suppl 2)
Warnet
Octreotide may act on non-growth hormone-, non-thyroid-stimulating hormone, and non-prolactin-secreting adenomas. Its efficacy was reported in some cotticotropin-secreting adenomas from Nelson’s syndrome and from Cushing’s disease. In gonadotropinsecreting adenomas. octreotide was shown to be effective in twoof eight cases. In nonfunctioning adenomas. visual improvement was observed with octreotide in 14 of 23 cases in a French multicenter study. Among the 33 patients whose tumor volume was checked, shrinkage occurred in seven, but an increase in tumor volume was observed in another seven patients. Mechanism(s) and prediction of efficacy of octreotide remain to be documented. Copyright
0 1992
by W.B. Saunders
Company
P
ITUITARY ADENOMAS that do not secrete growth hornlone, thyroid-stimulating hormone, or prolactin are usually invasive and/or extensive tumors, the treatment of which is not always satisfactory. The benefit derived from conventional pituitary irradiation alone or from surgical resection is not apparent in nearly one half of the small number of patients with Nelson’s syndrome in the literature.’ Among patients with nonfunctioning adenomas treated by surgery and irradiation, 18% showed radiographic evidence of tumor recurrence during a 2- to 8-year follow-up period,* and the incidence of recurrence is presumably higher with conventional radiation therapy. Hence, the development of additional adjunctive medical therapies is of the utmost importance. It was necessary to investigate whether octreotide, the recently developed, long-acting somatostatin analogue, could be of help in such cases. CORTICOTROPIN-SECRETING ADENOMAS In
Gushing’s Disease
The effect of a single dose of octreotide on corticotropin levels was studied in 18 cases, with no response occurring in any patient, neither on basal levels in 13 patients3-5 nor on the corticotropin response to corticotropin-releasing hormone (CRH).4.5 Treatment with octreotide was given in eight or nine cases and was effective in five. In two of four patients treated by Lorcy et aL6,’ normalization of corticotropin levels within 48 hours of a 0. 1-mg subcutaneous (SC) treatment three times a day was achieved in one case, while in the other, corticotropin deficiency occurred when the dose reached 1.5 mg/d. In one other patient’ whose corticotropin level did not respond to CRH while the cortisol level responded to corticotropin during a treatment with 0.05 mg twice a day, a dose of 0.05 mg three times a day caused corticotropin deficiency. Octreotide (0.40 mg/d) induced a sustained decrease of urinary free cortisol in only one of the three patients treated by Invitti,’ while in the other two it was minimal and transient; however, in this study, corticotropin levels did not decrease. In an additional case of Cushing’s syndrome presumably due to a pituitary adenoma, octreotide (0.1 mg three times a day) normalized clinical and biological features within 15 days, and prolonged remission was observed after a 2-month treatment.‘O In Nelson ‘s Syndrome Native somatostatin is known to suppress corticotropin secretion.“,” Octreotide efficacy was reported in at least four Metabolism.
L’ol 41, No 9, Suppl 2 (September),
1992: pp 59-61
cases; in two cases,’ a single dose was effective, with the decrease being significant in both. In another, short-term octreotide treatment decreased corticotropin levels by more than 50%. An additional 1O-day treatment with 0.5 mg/d continuous SC injection proved effective.13 In one other case, longterm treatment was dramatically effective, with normalization of corticotropin levels within 6 weeks, normalization of the visual field and acuity, and no tumor extension during the 2-year treatment.3
GONADOTROPIN-SECRETING ADENOMAS
In three cases, a 0. I-mg single dose of octreotide was administered, with luteinizing hormone (LH); a-subunit suppression greater than 50% occurred in one ca.se,14but there was no effect at all on follicle-stimulating hormone (FSH) and a-subunit levels in two othersI A 2-day treatment with 0.1 mg (continuous SC infusion) was ineffective on FSH and LH hypersecretion in one case.16 Long-term treatment was given in five cases, again with good control of LH and (Ysubunit secretion being achieved in a 6-week trial in one,‘4 a 92% suppression of a-subunit levels and tumor shrinkage in another patient,15 but no effect on FSH levels in two other cases. The O-Subunit decrease was actually due to partial necrosis of the adenoma in the other patient.16 Altogether, octreotide had a suppressive effect in only two of eight cases of functioning gonadotropin-secreting adenomas. Nonfunctioning Adenomas In vitro studies have shown that some nonfunctioning adenomas had somatostatin receptors,‘7-‘9 which could also be detected by in vivo imaging.‘9.20 A dramatic improvement in chiasm dysfunction from a nonfunctioning adenoma,2’ which was actually a silent corticotropin-secreting adenoma,** was observed, and there were also two additional cases with negative immunocytochemistry.23 Several reports have now been published that evaluate octreotide’s effects on visual defects or tumor size.
From the Service MJdecine B, H6pital LariboisiPre et Universith Paris VII, France. Address reprint requests to A. Warnet. MD. Service de Mbdecine B-H6pital Lariboisitire, F- 75475 Paris CPdex 10. France. Copyright 0 1992 by U’.B. Saunders Company 00260495/92/4109-2009$03.00/O
59
A. WARNET
60
Octreotide’s Effects
011
Visual Defects
In addition to our three cases,22an impressive improvement in chiasm dysfunction was observed in one patient.23 Visual field improvement was also observed in one of four patientsz4 In a French multicenter, open-labeled trial, visual improvement occurred in 14 of 23 nonfunctioning adenomas,” in the first hours to days of treatment in most cases, and it was sustained in most patients. No somatostatin receptors could be detected in vitro in one of these cases. Visual evoked potentials also improved in two of our cases.22 In addition, an improvement in pattern-reversal, visual evoked potentials was observed 1 hour after a single dose of 0.1 mg of octreotide in some patients, 26demonstrating the rapidity of octreotide effectiveness.
Eflect on Tumor Size No tumor shrinkage was demonstrable in our three patier@ or in seven othersz4 Among 20 patients treated with octreotide at doses of 0.3 to 0.5 mg/d for 6 months, three adenomas shrank and three others increased.27 Octreotide did not induce any change in the volume of two adenomas with negative receptor imaging, but one of two adenomas with positive somatostatin-receptor imaging shrank significantly, whereas the other had a significant increase in size that was shown to be due to partial necrosis.28 In the
French multicenter trial, of eleven patients, a shrinkage was observed in three patients, but an increase in tumor volume was seen in three patients who had visual improvement. CONCLUSION
In adenomas as various as corticotropin-secreting adenomas from Nelson’s syndrome or even Cushing’s disease, gonadotropin-secreting adenomas, and nonfunctioning adenomas, the effect of octreotide is valuable and may be of great help in the difficult management of the tumors either before or at various times after surgery and/or irradiation therapy. A better characterization of nonfunctioning adenomas is needed to determine if octreotide is effective in any type. Octreotide efficacy might rely on the existence of somatostatin receptors on adenoma-cell membranes. Prediction of efficacy might then be made by in vivo somatostatin-receptor imaging, provided this technique is sensitive enough. However, whether the visual improvement in chiasmal dysfunction is related to somatostatin receptors or to other mechanisms such as a change in blood supply or in neurotransmission of visual pathways remains to be documented. ACKNOWLEDGMENT 1 wish to thank the participants Group.
of the French SandostatinB
Study
REFERENCES I. Halberg FE, Sheline GE: Radiotherapy of pituitary turnours. Endocrinol Metab Clin North Am 16:667-684, 1987 2. Ebersold MJ. Quast LM, Laws ER Jr. et al: Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 64:7 13-7 19, 1986 3. Lamberts SWJ, Uitterlinden P, Klijn JMG: The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson’s syndrome and Cushing’s disease. Acta Endocrinol (Copenh) 120:760-766, 1989 4. Ambrosi B, Bochicchio D, Fadin C, et al: Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-adrenal function in patients with corticotropin hypersecretion. J Endocrinol Invest 13:257-26 1, 1990 S. Woodhouse NJY. Dagogo-Jack S, Ahmed M: Acute and longterm effects of octreotide in patients with ACTH dependent Cushing’s syndrome. J Endocrinol Invest 14:121, 1991 (suppl 1, abstr) 6. Lorcy Y, Derennes V, Delambre C, et al: Remission d’une maladie de Cushing recidivante par un analogue de la somatostatine. Presse Med 17:1217. 1988 (letter) 7. Lorcy Y. Delambre C, Le Guerrier AM. et al: Use of longacting somatostatin analog octreotide (SMS 201-995) in the treatment of Cushing’s syndrome. J Endocrinol Invest 14: I2 1, 199 1 (suppl 1. abstr) 8. Graziano E. Chiarini V, Cremonini N, et al: Cushing’s disease successfully treated with SMS 201-995: A case report. J Endocrinol Invest 14: 122. 199 1 (suppl 1, abstr) 9. lnvitti C, De Martin M, Brunani A, et al: Treatment of Cushing’s syndrome with the long-acting somatostatin analogue SMS 201-995 (Sandostatin). Clin Endocrinol (0x0 32:275-281, 1990 10. Gross A, Grulet H, Durlach V, et al: Remission prolongee d’un syndrome de Cushing apres traitement par octreotide. Presse Med 20:915-916, 1991 (letter) 1I. Tyrrell JB, Lorenzi M. Gerich JE, et al: lnhibition by so-
matostatin of ACTH secretion in Nelson’s syndrome. J Clin Endocrinol Metab 40:1125-l 127, 1975 12. Benker G, Hackenberg K, Hamburger B, et al: Effects of growth hormone release-inhibiting hormone and bromocriptine (CB 154) in states of abnormal pituitary-adrenal function. Clin Endocrinol (0x0 5:187-190, 1976 13. Guerin V. Ortega F. James-Deidier A, et al: Continuous infusion of SMS 20 l-995 in Nelson’s syndrome. J Endocrinol Invest 13: 153, 1990 (suppl 2, abstr) 14. Vos P, Croughs RJM, Thijssen JHH. et al: Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue. Acta Endocrinol (Copenh) I I8:587-590, 1988 15. Sassolas G. Serusclat P, Claustrat B. et al: Plasma alpha-subunit levels during the treatment of pituitary adenomas with the somatostatin analog (SMS 201-995). Harm Res 29: l24- 128, 1988 16. Wamet A, Chanson P: Octreotide (Sandostatine@) et adenomes non somatotropes. Sandostatine: Symposium de Paris, Paris, France. February 6. 1990 17. Ikuyama S, Nawata H. Kato K. et al: Specific somatostatin receptors on human pituitary adenoma cell membranes. J Clin Endocrinol Metab 6 1:666-67 1. 1985 18. Reubi JC, Heitz PU, Landolt AM: Visualisation of somatostatin receptors and correlation with immunoreactive growth hormone and prolactin in human pituitary adenomas: Evidence for different tumour subclasses. J Clin Endocrinol Metab 65:65-73, 1987 19. Faglia G, Bazzoni N, Spada A. et al: In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([‘?I SDZ 204990). J Clin Endocrinol Metab 73:850-856, 1991 20. Lamberts SWJ. Bakker WH, Reubi JC, et al: Somatostatinreceptor imaging in the localization of endocrine turnours. N Engl J Med 323:1246-1249, 1990 2 1. Warnet A. Thurel C, Duet M. et al: Somatostatin analog SMS 20 I-995 (Sandostatin@) can improve chiasmatic compression due to
ROLE OF OCTREOTIDE IN NONSECRETING
ADENOMAS
nonfunctioning pituitary adenoma. First European Congress of Endocrinology, Copenhagen, Denmark, June 2 l-25, 1987 22. Warnet A, Timsit J, Chanson P. et al: The effect ofsomatostatin analogue on chiasmal dysfunction from pituitary macroadenomas. J Neurosurg 7 I :687-690. 1989 23. Riinzi M, Jaspers C, Benker G, et al: Dramastische Besserung eines Chiasmasyndromes bei endokrin inaktivem Makroadenom der Hypophyse unter Therapie mit dem Somatostatin-Analogon SMS 201-995. Klin Wochenschr 67:284, 1989 (suppl 16, abstr) 24. Petrini L, Pilosu R, Marcello A, et al: Treatment of non functional pituitary tumors with octreotide. J Endocrinol Invest 14:119, 199 I (suppl I, abstr)
61
25. Wamet A: Effect of Sandostatin on optic chiasm compression due to non GH-, non TSH-secreting pituitary adenomas. J Endocrinol Invest 13:74, 1990 (suppl 2, abstr) 26. Ducati A, Losa M. Fava E, et al: Acute effects on visual hmction of a somatostatin analog (SMS 201-995) evaluated using a neurophysi01ogicaJapproach. J Endocrinol Invest 14:120, 199I (suppl 1, abstr) 27. Liuzzi A, Dallabonzana D, Oppizzi G, et al: Is there a real medical treatment for the “non-secreting” pituitary adenomas? J Endocrinol Invest 14:18, 199 1 (suppl 1,abstr) 28. Bazzoni N, Farabola M, Arosio M, et al: Is the effect of octreotide therapy in patients with functionless pituitary adenomas predictable? J Endocrinol Invest 14:53. I99 I (suppl 2)