Effects of somatostatin analogs on a growth hormone-releasing hormone secreting bronchial carcinoid, in vivo and in vitro studies.
BACKGROUND
A 56-yr-old woman presented with acromegaly, a pulmonary mass, and elevated levels of GHRH, GH, and IGF-I. Histological examination revealed a bronchial carcinoid with positive staining for GHRH. Somatostatin analogs (SAs) can play an important role in the treatment of neuroendocrine tumors, dependent on the somatostatin receptor subtype (sst) expression pattern. The sst pattern in bronchial carcinoids and effects of SAs have not been extensively investigated, particularly not for the recently developed universal SA SOM230 (Pasireotide) that has high affinity for sst1, 2, 3, and 5.


OBJECTIVE
Our objective was to investigate the in vivo response of a GHRH-producing bronchial carcinoid to octreotide (OCT), its sst-expression profile, and in vitro responses to different SAs, including SOM230.


METHODS
In vivo, 50 microg OCT was administered, and plasma GH and GHRH responses were determined. In vitro, the expression of ssts was analyzed by quantitative PCR. Furthermore, the effects of SOM230 and OCT on GHRH secretion were evaluated in primary cell cultures of the carcinoid tissue.


RESULTS
In vivo, OCT administration fully suppressed GH and GHRH levels. In vitro, sst1 mRNA was most abundant, followed by sst2 and sst5. Both SOM230 and OCT inhibited GHRH production dose dependently (SOM230 100 nm vs. control, P = 0.01; OCT 110 nm vs. control, P = 0.05).


CONCLUSIONS
In this case of a GHRH-producing bronchial carcinoid, we demonstrated that SOM230 was a potent inhibitor of GHRH production in vitro and was at least equally potent compared with OCT. Therefore, SOM230 may be a potential therapeutic agent to control GHRH secretion in ectopic acromegaly.
van Hoek
M
M
Department of Internal Medicine-Bd289, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. m.vanhoek@erasmusmc.nl
Hofland
L J
LJ
de Rijke
Y B
YB
van Nederveen
F H
FH
de Krijger
R R
RR
van Koetsveld
P M
PM
Lamberts
S W J
SW
van der Lely
A J
AJ
de Herder
W W
WW
Feelders
R A
RA
D000172:Acromegaly / Q000188:drug therapy / Q000209:etiology; D001984:Bronchial Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002276:Carcinoid Tumor / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D006729:Hormones, Ectopic; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; C517782:pasireotide