Characteristics of acromegalic patients with a good response to octreotide, a somatostatin analogue

Abstract

In GH-secreting pituitary tumours somatostatin receptor density has been correlated with octreotide responsiveness. Little is known about the other endocrine characteristics of patients with good responses to octreotide. The purpose of this study was to determine the characteristics of these patients. We studied 30 patients with active acromegaly. Five had been treated with either transsphenoidal adenomectomy or conventional radiotherapy without cure of GH excess. Patients were divided into good or poor octreotide responders. Patients whose GH level decreased to less than 20% of basal and below 20 mU/I after a subcutaneous injection of 100 micrograms of octreotide were defined as good octreotide responders. We compared tumour size, basal GH secretory pattern, responses to TRH, GnRH and bromocriptine, and mutation of the alpha-subunit of stimulatory GTP-binding protein (G alpha s) between the two groups. Tumour size was determined by CT or MRI. Basal GH level was measured hourly between 0800 and 1600 h. GH responses to TRH and GnRH were measured every 30 minutes for 2 hours, and the GH response to oral bromocriptine was measured hourly for 6 hours. The mutation of G alpha s gene between codons 184 and 251 was examined by direct sequencing using PCR in 5 patients of each group whose tumour tissues were available for the genomic DNA extraction. Seventeen patients (57%) were good octreotide responders (group I) and 13 (43%) were poor responders (group II). The mean age, sex, tumour size, tumour grade and the basal GH secretory pattern were not significant different between the two groups. Group I responded more frequently than group II to TRH (65 vs 25%). Fifty-three per cent of group I patients and none of group II were good bromocriptine responders. Forty-one per cent of group I patients responded to both TRH and bromocriptine. Three of 5 group I tumours had point mutations at codon 201 of the G alpha s gene, none of 5 group II tumours had mutations. CGT(Arg) was replaced with TGT(Cys) in two tumours and with AGT(Ser) in one. No mutations were found at codon 227. All three tumours with mutations were from patients responsive to TRH. Two of the three were also good bromocriptine responders. These data suggest that good octreotide responders are more likely to respond to TRH or bromocriptine. Good octreotide responders may include subgroups with different levels of TRH and dopamine receptor expression. A possible relation between octreotide response and the mutation of G alpha s gene should be investigated.