Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients.
Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.
Shi
Y F
YF
Department of Endocrinology, Peking Union Medical College Hospital, PR China.
Harris
A G
AG
Zhu
X F
XF
Deng
J Y
JY
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000236:Adenoma / Q000150:complications / Q000473:pathology; D000328:Adult; D004562:Electrocardiography; D005260:Female; D005704:Gallbladder / Q000503:physiopathology; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000150:complications / Q000473:pathology; D012867:Skin / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D014465:Ultrasonics
D007328:Insulin; D013006:Growth Hormone; D015282:Octreotide