In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy.
OBJECTIVE
GH and PRL cosecretion frequently occurs in acromegaly and the sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists (DA) alone or in combination, is still debated. This study was designed to evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemical findings.


METHODS
Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and 123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly and high circulating GH, PRL and IGF-I levels. The results were correlated with the response to long-term treatment with octreotide (OCT), quinagolide (QN) and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in primary cultures from the pituitary tumors and to the immunohistochemical findings.


RESULTS
The first patient showed high tumour uptake of 111In-OCT and 123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment induced circulating GH, IGF-I and PRL normalization. In the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels only. In the third patient both OCT and QN, alone or in combination, failed to normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QN than OCT treatment. After medical therapy, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT significantly suppressed GH secretion in the four primary pituitary tumor cultures, while PRL secretion was significantly suppressed only in the second and the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in all the cultures, while GH secretion was significantly suppressed in three out of four.


CONCLUSIONS
These four acromegalics, presenting similar clinical findings and comparable peripheral hormone levels, showed different responsiveness to SA and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT and DA displayed an inhibiting activity on GH and PRL secretion positively correlated with the response observed in vivo. This evidence together with the in vivo receptor imaging study suggest the existence of somatostatin and/or dopamine D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA might be primarily considered in the medical treatment of hyperprolactinemic acromegalics, while SA alone or in combination with DA in case of ineffective hormone suppression.
Ferone
D
D
Department of Molecular and Clinical Endocrinology, Federico II, University of Naples, Italy.
Pivonello
R
R
Lastoria
S
S
Faggiano
A
A
Del Basso de Caro
M L
ML
Cappabianca
P
P
Lombardi
G
G
Colao
A
A
D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004873:Ergolines / Q000627:therapeutic use; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D013006:Growth Hormone / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007457:Iodine Radioisotopes / Q000378:metabolism; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D015282:Octreotide / Q000378:metabolism / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000032:analysis; D015175:Prolactinoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013972:Thyrotropin / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000634:Aminoquinolines; D018931:Antineoplastic Agents, Hormonal; D018491:Dopamine Agonists; D004873:Ergolines; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D011954:Receptors, Dopamine; D017481:Receptors, Somatostatin; D007334:Insulin-Like Growth Factor I; C046650:quinagolide; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D000077465:Cabergoline; D015282:Octreotide