Objective: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. Design: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30 mg intramuscular every 7±14 days. Methods: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year.
OBJECTIVE The aims of this study were (I) to evaluate gall-bladder form and contents, (ii) to assess the prevalence of gallstones in acromegalic patients before octreotide treatment end the Incidence of gallstone formation in patients with acromegaly during long-term (6-90 months, mean 44 months) octreotide treatment, and (ill) to test the efficacy of ursodeoxycholic ecld In preventing and treating octreotide-induced cholelithiasls. DESIGN Forty-nine patients (23 men and 26 women, aged 19-81 years) were studied by repeated gall-bladder ultrasonography performed at baseline and then every 6 months during octreotide therapy. All ultrasound scans were evaluated by the same radiologist. Statistical analy-$18 was performed using the Chi-squared and regression analysis tests. RESULTS Asymptomatic stones were recorded in 13/49 patients (26.5%) prior to octreotide treatment (the prevalence of cholellthlasls in the Italian population IS 9.5% In men and 18.9% In women). During octreotide therapy gallStOnes developed in 10/36 patients (27.7%). No signlfl-can1 correfations with sex, age, body mass Index. duration Of the disease, daily dose and duration of octreotlde therapy, altered gall-bladder form, family history of gallbladder stones, basal plasma values of cholesterol and triglycerides were found between the patients (10136) who developed stones during octreotide treatment and the ones who did not (26136). Fourteen patients (10 with newly developed stones and four with cholelithiasis diagnosed prior to octreotide) were put on ursodeoxychoiic acid at the dally dose of 10 mgkg. Gallstones completely diwP peared in 6/14 patients (42.8%; five patients with newly developed stones and one with stones prior to octreotide Cormpondena: Dr Marcella Montini. Division Of Endocrinology. Ospedali Rsuniti Largo Barom, 1-24100-Bergamo. Italy. therapy) after a mean of 30.8 months of ursodeoxycholic acid treatment. In addition, seven patients were treated with ursodeoxychoiic acid at the preventive dose of 450 mg, administered as a once-a-day oral preparation in the evening. However, stones developed In one of these seven patients who was thereafter cured (gallstones completely disappeared) by the therapeutic dose of ursodeoxycholic acid of 10 mglkglday after 23 months of treatment. CONCLUSIONS This study indicates that (I) acromegaly by itself is correlated with a hlgh prevalence of gallbladder stones, (11) the long-term treatment with octreotlde increases the incidence of cholelithiasis, and (iii) ursodeoxychollc acid Is useful In the treatment of gallstones In acromegalic patients but its prophylactic effect In patients on octreotide treatment requires further assessment.
Since Corenblum reported in 1975 the first documented reduction of tumor size in two patients with macroprolactinoma, evidence has accumulated that bromocriptine causes shrinkage of PRL-secreting adenomas in most patients. Recently a long-acting form of bromocriptine (bromocriptine LA) was developed. A single dose of 50 mg i.m. decreases basal and sleep-related PRL secretion in normal subjects for 28 days. We treated 13 patients (8 women, 5 men) with PRL secreting tumors (5 macroadenomas and 8 microadenomas) with a single dose (50 mg) of bromocriptine LA. In the 5 patients with macroprolactinomas plasma PRL levels decreased markedly within 12 hours, reaching normal levels in only one patient. In all patients the suppression of PRL secretion lasted at least 28 days and the tumor size was reduced by 20% to 59% within 21 days after the injection. Visual fields improved in all 3 patients with abnormal vision prior to the injection. In one patient with bitemporal hemianopsia an almost normalization of the visual field was noted 24 hours after bromocriptine LA administration. In 7/8 patients with microprolactinomas plasma PRL levels decreased to within the normal range within 12 hours after the administration of bromocriptine LA. The normalization of PRL secretion lasted for at least 28 days. Menses resumed in all 6 women 7 to 41 days after the injection, galactorrhea disappeared in all 4 patients, and libido and potency become normal in both men with microprolactinomas. Patients treated with bromocriptine LA reported only short-lasting (1 hour - 2 days) mild or moderate adverse effects, consisting of dizziness (4 patients) and nausea (4 patients). Long-acting bromocriptine should be considered as the initial management for patients with PRL-secreting tumors. The use of bromocriptine LA could also overcome the compliance problems that occur in many patients soon after the initiation of oral bromocriptine therapy.
The effect of nifedipine 40 mg.day-1 for 3 months on glucose tolerance, insulin and C-peptide secretion after an oral glucose tolerance test (OGTT), intra-venous glucose tolerance test (IVGTT) and glucagon stimulatory test, has been studied in 8 moderately hypertensive women suffering from non-insulin dependent diabetes mellitus (NIDDM). No significant variation in glucose metabolism was noted after nifedipine treatment, except for a slight improvement in insulin secretion after OGTT at the end of the study. There was an increase in cholesterol as a collateral effect.
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