CHARACTERISTICS OF ACROMEGALIC PATIENTS WITH A GOOD RESPONSE TO OCTREOTIDE, A SOMATOSTATIN ANALOG

BACKGROUND AND OBJECTIVES In GH-secreting pituitary tumours somatostat in receptor density has been correlated with octreotide responsiveness . Little is known about the other endocrine characteristics of patient s with good responses to octreotide. The purpose of this study was to determine the characteristics of these patients. PATIENTS We studied 3 0 patients with active acromegaly, Five had been treated with either t ranssphenoidal adenomectomy or conventional radiotherapy without cure of GH excess. DESIGN Patients were divided into good or poor octreotid e responders, Patients whose GH level decreased to less than 20% of ba sal and below 20 mU/l after a subcutaneous injection of 100 mu g of oc treotide were defined as good octreotide responders. We compared tumou r sire, basal GH secretory pattern, responses to TRH, GnRH and bromocr iptine, and mutation of the alpha-subunit of stimulatory GTP-binding p rotein (G alpha(s)) between the two groups. MEASUREMENT Tumour size wa s 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 m inutes for 2 hours, and the GH response to oral bromocriptine was meas ured hourly for 6 hours. The mutation of G alpha(s) gene between codon s 184 and 251 was examined by direct sequencing using PCR in 5 patient s of each group whose tumour tissues were available for the genomic DN A extraction. RESULTS Seventeen patients (57%) were good octreotide re sponders (group I) and 13 (43%) were poor responders (group II). The m ean age, sex, tumour size, tumour grade and the basal GH secretory pat tern were not significantly different between the two groups. Group I responded more frequently than group II to TRH (65 vs 25%), Fifty-thre e per cent of group I patients and none of group II were good bromocri ptine responders, Forty-one per cent of group I patients responded to both TRH and bromocriptine. Three of 5 group I tumours had point mutat ions at codon 201 of the G alpha(s) gene, none of 5 group II tumours h ad mutations. CGT(Arg) was replaced with TGT(Cys) in two tumours and w ith AGT(Ser) in one. No mutations were found at codon 227. All three t umours with mutations were from patients responsive to TRH. Two of the three were also good bromocriptine responders. CONCLUSIONS These data suggest that good octreotide responders are more likely to respond to TRH or bromocriptine. Good octreotide responders may include subgroup s with different levels of TRH and dopamine receptor expression. A pos sible relation between octreotide response and the mutation of G alpha (s) gene should be investigated.