We treated four patients with acromegaly for 8 to 24 weeks with SMS 201-995, the long-acting somatostatin analogue, in dosages of 100 to 300 micrograms a day given subcutaneously. A rapid amelioration of the clinical signs and symptoms and near normalization of laboratory test results occurred in all patients. Mean plasma growth hormone concentrations (+/- S.E.M.), as measured over 24 hours, fell from an initial value of 57 +/- 18 micrograms per liter to 7.5 +/- 2 micrograms per liter at the end of the investigational period. Likewise, levels of plasma somatomedin-C, which were originally elevated in all patients, dropped to the normal or nearly normal range. The suppression of insulin secretion and the resulting hyperglycemia that were observed at the beginning of treatment became less marked as therapy progressed. There was evidence of slight tumor shrinkage in three of the subjects. No side effects were recorded throughout the treatment period. These preliminary results suggest that SMS 201-995 represents an additional option for the management of acromegaly, especially in patients who do not benefit sufficiently from surgery or radiotherapy and do not respond well to treatment with dopaminergic drugs.

Chronic therapy of a patient with Nelson's syndrome for 2 years with 300 \g=m\g SMS 201\p=n-\995 per day resulted in a significant decrease in circulating ACTH levels, normalization of the visual field defect and of loss of visual acuity of one eye, and stabilization of tumour growth, without radiological evidence of shrinkage of the pituitary tumour. In two other patients with Nelson's syndrome, SMS 201\p=n-\995 acutely inhibited circulating ACTH levels. This effect could be shown best if cortisol replacement was temporarily withheld. SMS 201\p=n-\995 did not affect plasma ACTH and cortisol levels in three patients with untreated Cushing's disease.

Treatment with the somatostatin receptor (sst) subtype 2 predominant analogs octreotide and lanreotide induces clinical and biochemical cure in approximately 65% of acromegalic patients. GH-secreting pituitary adenomas, which are not controlled, also express sst(5). We compared the acute effects of octreotide and SOM230, a new somatostatin analog with high affinity for sst(1,2,3,5) on hormone release in acromegalic patients. In a single-dose, proof-of-concept study, 100 microg octreotide and 100 and 250 microg SOM230 were given s.c. to 12 patients with active acromegaly. Doses of 100 and 250 microg SOM230 dose-dependently suppressed GH levels from 2-8 h after administration (-38 +/- 7.7 vs. -61 +/- 6.7%, respectively; P < 0.01). A comparable suppression of GH levels by octreotide and 250 microg SOM230 was observed in eight patients (-65 +/- 7 vs. -72 +/- 7%, respectively). In three patients, the acute GH-lowering effect of 250 microg SOM230 was significantly superior to that of octreotide (-70 +/- 2 vs. -17 +/- 15%, respectively; P < 0.01). In one patient, the GH-lowering effect of octreotide was better than that of SOM230. Tolerability for SOM230 was good. Glucose levels were initially slightly elevated after octreotide and SOM230, compared with control day, whereas insulin levels were only significantly suppressed by octreotide. We conclude that SOM230 is an effective GH-lowering drug in acromegalic patients with the potential to increase the number of patients controlled during long-term medical treatment.

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.

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