RSS-Feed abonnieren
DOI: 10.1055/s-2002-33601
© Georg Thieme Verlag Stuttgart · New York
Varying Additive Effects of Bromocriptine with Two Somatostatin Analogs in Cultures of GH-Secreting Adenomas
Publikationsverlauf
Received: 13 November 2001
Accepted after revision: 18 April 2002
Publikationsdatum:
25. September 2002 (online)
![](https://www.thieme-connect.de/media/hmr/200208/lookinside/thumbnails/10.1055-s-2002-33601-1.jpg)
Abstract
In this study, we have investigated the effect of combined treatment using two somatostatin analogs, lanreotide or octreotide, with bromocriptine on GH release in cultures of GH-secreting pituitary tumors. Sixteen acromegalic patients were included in the study. All patients had been treated with lanreotide prior to the surgery. Five patients (31.2 %) reached GH levels below 2.0 µg/l and normal IGF-I levels according to age and sex after lanreotide treatment. A positive correlation was observed between the lanreotide-induced inhibition of GH release in vitro and serum GH decrease after lanreotide treatment (r = 0.52; p = 0.03). Combined treatment significantly inhibited GH release in vitro in 8 of the 16 tumors (50 %). However, only 5 (31.2 %) of the respective patients had been resistant to presurgical treatment with lanreotide. Three of these 5 patients (18.7 %) responded to a BC concentration similar to that achieved with therapeutic doses, and in 2 patients only when a pharmacological dose of BC was used in the combined treatment. The additive effect was observed with the combination of lanreotide and BC in 6 tumors and with octreotide and BC in 3. Only one tumor showed simultaneous response to both types of combination. These results suggest that the additive effect under the combined treatment might be found between 18 and 30 % of patients who are resistant to these drugs, and that different combinations of somatostatin analogs and dopamine agonists should be tested in resistant patients.
Key words
Acromegaly - Bromocriptine - Somatostatin Analogs
References
- 1 Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol. Metab1998; 83 2646-2652
- 2 Lamberts S WJ, Zweens M, Verschoor L, del Pozo E. A comparison among the growth hormone-lowering effects in acromegaly of the somatostatin analog SMS 201-995, bromocriptine, and combination of both drugs. J Clin Endocrinol Metab. 1986; 63 16-19
- 3 Chiodini P G, Cozzi R, Dallabonanza D, Oppizzi G, Verde G, Petroncini M, Liuzzi A, del Pozo E. Medical treatment of acromegaly with SMS 201 - 995, a somatostatin analog: A comparison with bromocriptine. J Clin Endocrinol Metab. 1987; 64 447-453
- 4 Wagenaar A H, Harris A G, van der Lely A J, Lamberts S WJ. Dynamics of the acute effects of octeotride, bromocriptine and both drugs in combination on growth hormone secretion in acromegaly. Acta Endocrinol (Copenh). 1991; 125 637-642
- 5 Flogstad A K, Halse J, Grass P, Abisch E, Djoseland O, Kutz K, Bodd E, Jervell J. A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly. J Clin Endocrinol Metab. 1994; 79 461-465
- 6 Fredstorp L, Kutz K, Werner S. Treatment with octreotide and bromocriptine in patients with acromegaly: An open pharmacodynamic interaction study. Clin Endocrinol (Oxf). 1994; 41 103-108
- 7 Lombardi G, Colao A, Ferone D, Sarnacchiaro F, Marzullo P, di Sarno A, Rossi E, Merola B. CV 205-502 treatment in therapy-resistant acromegalic patients. Eur J Endocrinol. 1995; 132 559-564
- 8 Lamberts S WJ, Verleun T, Hofland L, del Pozo E. A comparison between the effects of SMS 201-995, bromocriptine, and a combination of both drugs on hormone release by the cultured pituitary tumour cells of acromegalic patients. Clin Endocrinol (Oxf). 1987; 27 11-23
- 9 Patel Y C, Srikant C B. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr1-5). Endocrinology. 1994; 135 2814-2817
- 10 Reisine T, Bell G I. Molecular biology of somatostatin receptors. Endocr Rev. 1995; 16 427-442
- 11 Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M, Faglia G. Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl ciclase. J Clin Endocrinol Metab. 1990; 71 1421-1426
- 12 Adams E F, Lei T, Buchfelder M, Petersen B, Fahlbusch R. Biochemical characteristics of human pituitary somatotropinomas with and without gsp mutations: in vitro cell culture studies. J Clin Endocrinol Metab. 1995; 80 2077-2081
- 13 Chen C, Vincent J D, Clarke I J. Ion channels and the signal transduction pathways in the regulation of growth hormone secretion. Trends Endocrinol Metab. 1994; 5 227-233
- 14 Chen Z P, Xu S, Lightman S L, Hall L, Levy A. Intracellular calcium ion responses to somatostatin in cells from human somatotroph adenomas. Clin Endocrinol (Oxf). 1997; 46 45-53
- 15 Dubuis J M, Deal C L, Drews R T, Goodyer C G, Lagace G, Asa S L, van Vliet G, Collu R. Mammosomatotroph adenoma causing gigantism in an 8-year-old boy: A possible pathogenetic mechanism. Clin Endocrinol (Oxf). 1995; 42 539-549
- 16 Takano K, Asano S, Yamashita N. Activation of G protein-coupled K+ channels by dopamine in human GH-producing cells. Am J Physiol. 1994; 266 E318-E325
- 17 Spada A, Bassetti M, Reza Elani F, Arosio M, Gil del Alamo P, Vallar L. Differential transduction of dopamine signal in different subtypes of human growth hormone secreting adenomas. J Clin Endocrinol Metab. 1994; 78 411-417
- 18 Lucas T, García-Uría J. Preoperative treatment of growth hormone pituitary adenomas with lanreotide. J Endocrinol Invest. 1997; 20 90
- 19 Cannavò S, Squadrito S, Curtò L, Almoto B, Trimarchi F. Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma. Horm Metab Res. 2001; 33 618-624
- 20 Lowry O H, Rosenbrough N J, Farr A L, Randall R J. Protein measurement with folin phenol reagents. J Biol Chem. 1951; 193 265-275
- 21 Kelijman M, Williams T C, Downs T R, Frohman L A. Comparison of the sensitivity of growth hormone secretion to somatostatin in vivo and in vitro in acromegaly. J Clin Endocrinol Metab. 1988; 67 958-963
- 22 Barlier A, Gunz G, Zamora A J, Morange-Ramos I, Figarella-Branger D, Dufour H, Enjalbert A, Jaquet P. Prognostic and therapeutic consequences of Gsα mutations in somatotroph adenomas. J Clin Endocrinol Metab. 1998; 83 1604-1610
- 23 Corbetta S, Ballare E, Mantovani G, Lania A, Losa M, di Blasio A M, Spada A. Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: Analysis of gene sequence and mRNA expression. Eur J Clin Invest . 2001; 31 208-214
- 24 Rocheville M, Lange D C, Kumar U, Patel S C, Patel Y C. Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity. Science. 2000; 288 154-157
J. Antonio Balsa, M.D.
Servicio de Endocrinología · Hospital Ramón y Cajal
Carretera de Colmenar Km 9 · 28034 Madrid · Spain ·
Telefon: + 34 (91) 336 80 56
Fax: + 34 (91) 336 88 23
eMail: jbalsa@hrc.insalud.es