In vivo and in vitro effects of octreotide, quinagolide and cabergoline infour hyperprolactinaemic acromegalics: Correlation with somatostatin and dopamine D-2 receptor scintigraphy

OBJECTIVE GH and PRL cosecretion frequently occurs in acromegaly and the se nsitivity of both hormones to somatostatin analogs (SA) and dopamine agonis ts (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 correl ate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemi cal findings. DESIGN AND PATIENTS Scintigraphy using In-111-DTPA-Phe(1)-OCT (In-111-OCT) and I-123-methoxybenzamide (I-123-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 suppres sion 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 In-111-OCT and I-123 -IBZM, the second high uptake of only In-111-OCT, while the third one showe d faint tumour uptake of only I-123-IBZM, and the fourth a faint uptake of In-111-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment indu ced circulating GH, IGF-I and PRL normalization. in the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels on ly. In the third patient both OCT and QN, alone or in combination. failed t o normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QM than OCT treatment. After medical thera py, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, white diffuse GH and PRL st aining in the remaining three. In vitro, OCT significantly suppressed GH se cretion in the four primary pituitary tumor cultures, while PRL secretion w as significantly suppressed only In the second and the fourth cases. Dopami ne agonists (DA) significantly suppressed PRL release in ail the cultures, while GH secretion was significantly suppressed In three out of four. CONCLUSIONS These four acromegalics, presenting similar clinical findings a nd comparable peripheral hormone levels, showed different responsiveness to SA and DB. Moreover, during the in vitro study on primary tumor cell cultu res, OCT and DA displayed an inhibiting activity on GH and PRL secretion po sitively correlated with the response observed in vivo. This evidence toget her with the in vivo receptor imaging study suggest the existence of somato statin and/or dopamine D-2 receptor heterogeneity in this class of pituitar y tumors. The new potent DA might be primarily considered in the medical tr eatment of hyperprolactinemic acromegalics, while SA alone or In combinatio n with DA in case of ineffective hormone suppression.