Varying Additive Effects of Bromocriptine with Two Somatostatin Analogs in Cultures of GH-Secreting Adenomas

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 microg/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.

Effect of Opiates on Growth Hormone Secretion in Acromegaly

“…While SST release in response to acute hyperglycemia is impaired in acromegalics, GH levels re− main non−suppressible in these patients as observed in our study [8]. Decrease in GH with SST is mediated through either reduc− tion in cyclic AMP (cAMP) or its effect on Ca ++ /K + channels on so− matotrophes [9].…”

“…Other GH secretagogues include dopamine, estrogen, galanin, neuropep− tide Y, opiates and serotonin [2]. Effects of dopamine agonist Original Clinical and somatostatin analogues have been shown to have additive effects in vitro on GH secreting adenomas suggesting variable role of GH modulators [9]. Glucose−induced inhibition of GH se− cretion in healthy subjects is mediated through stimulation of SST from the hypothalamus.…”

Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells

“…However, the mechanism of action underlying the efficaciousness of the combined treatment has been uncertain. Balsa and colleagues reported interesting findings regarding the effects of combination therapy on GH release in cultures of surgically removed GH-producing adenomas (Balsa et al 2002). In their study, the combination treatment with somatostatin analogs and BRC was found to be effective in 18-30% tumor cell cultures.…”

A Short Acute Octreotide Test for Response Prediction of Long-term Treatment with Somatostatin Analogues in Acromegalic Patients

“…However, response to SDA is variable, and fully optimized treatment achieving normal IGF1 levels is obtained only in 50 % of patients depending of the series, as has been recently revised by Freda [2] , while signifi cant tumor shrinkage is observed in at least one third of all treated patients, being more frequent and greater in na ï ve patients [3] . Dopamine agonists only occasionally induce signifi cant control of GH secretion on their own, while their association with SDA may improve therapeutic response [4] . The development of new pharmacological tools, such as the GH receptor antagonist pegvisomant [5] , may eventually raise the need of a discriminatory test for the election of the best medical The usefulness of the acute octreotide test in the selection of acromegalic patients for chronic somatostatin depot analogues treatment is controversial.…”