1 The aims of the study were to assess the pharmacokinetic parameters and the hormonal effects of the slow-release formulation of the somatostatin analogue (SR-L) in normal male volunteers. 2 Eight healthy males were studied. For the determination of basal values blood was sampled before the injection of vehicle and then every other hour for 8 h in order to measure plasma GH, prolactin (PRL), TSH, free thyroxin (fT4), insulin and glucagon levels. Plasma insulin-like growth factor 1 (IGF-1) levels were measured on a single sample. On day 1 of the study, 30 mg SR-L was administered intramuscularly. Blood was drawn just before injection and then every other hour for a period of 8 h. Thereafter, blood was sampled three times a week for 3 weeks in order to measure lanreotide, IGF-1, TSH, ff4 and PRL concentrations. Plasma GH was determined on days 6 and 11 of the study.3 Plasma lanreotide concentrations rose to 38.3 ± 4.1 ng ml-' 2 h following injection. The levels then progressively decreased, remaining above 1.5 ng ml-' until day 11 and reaching 0.92 ± 0.28 ng ml-' 2 weeks after injection. The apparent plasma half-life and mean residence time were 4.52 ± 0.50 and 5.48 ± 0.51 days respectively. 4 By comparison with the control day, plasma insulin concentrations only decreased 2 h following injection, whereas plasma glucagon did not change at any time. 5 Plasma TSH concentrations were significantly (P < 0.01) reduced from 2 h to day 4 following SR-L injection. ff4 concentrations dropped significantly (P < 0.01) from day 2 to day 4 but always remained within the normal adult range.6 Plasma GH concentrations were constantly below 0.2 ng ml-' whereas plasma IGF-l concentrations were significantly (P < 0.05) reduced from day 4 to day 14 following SR-L injection. No significant changes in plasma PRL levels were observed. 7 These results show that lanreotide administered in slow-release formulation to normal healthy males decreases transiently plasma insulin and TSH, and consecutively fT4 levels, without affecting either PRL or glucagon secretion. In contrast, SR-L reduces IGF-I levels (likely through a decrease in GH secretion) for at least 14 days. This indicates that SR-L could be injected every 14 days to decrease IGF-1 levels. 8 This slow-release formulation may be very convenient for the treatment of diseases for which a lowering of IGF-1 levels is essential, without side effects on glucose homeostasis and thyroid function.

We have recently shown that serotonin (5-HT) stimulates cortisol secretion from human adrenocortical tissue in vitro through activation of 5-HT4 receptors. The aim of the present study was to investigate the effect of the 5-HT4 agonist racemic zacopride on aldosterone secretion from the human adrenal gland in vivo and in vitro. In vivo studies were conducted on 28 healthy volunteers pretreated with dexamethasone. The subjects received a single oral dose of placebo, 10 micrograms zacopride, or 400 micrograms zacopride. Plasma aldosterone levels increased significantly within 90 min after the administration of 400 micrograms zacopride, remained elevated for 60 min, and gradually returned to the baseline within 180 min. In contrast, the administration of 10 micrograms zacopride or placebo did not modify the aldosterone concentration. No significant changes were observed in renin, ACTH, or cortisol levels. In vitro studies were conducted on perifused human adrenocortical slices. Administration of 20-min pulses of zacopride (from 10(-11) - 10(-6) mol/L) induced a dose-dependent increase in aldosterone secretion. The minimal effective dose was 10(-10) mol/L, and half-maximal stimulation was obtained with a dose of 7 x 10(-8) mol/L. Zacopride was 100 times more potent in stimulating aldosterone than cortisol release. Taken together, the present data suggest that 5-HT-evoked aldosterone secretion involves the activation of 5-HT4 receptors.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.

We report 3 sisters treated for cerebrotendinous xanthomatosis. We treated one, with a severe neurologic form of the illness, with chenodeoxycholic acid, then lovastatin and simvastatin. These drugs had different efficacy and tolerance, but induced no clinical improvement. Her sisters, without neurologic symptoms, received chenodeoxycholic acid, which normalized the cholestanol level. Optimal treatment of this illness must begin before there is significant clinical symptomatology.

OBJECTIVE Somatostatin analogues have been proposed for the treatment of thyrotrophinomas. However, this treatment requires several S. C. injections a day to be