RESUMEN
BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.
Asunto(s)
Acromegalia/tratamiento farmacológico , Hormonas/uso terapéutico , Octreótido/uso terapéutico , Péptidos Cíclicos/uso terapéutico , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Acromegalia/sangre , Acromegalia/radioterapia , Adolescente , Adulto , Anciano , Preparaciones de Acción Retardada , Esquema de Medicación , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Irradiación Hipofisaria , Distribución Aleatoria , Resultado del TratamientoRESUMEN
BACKGROUND: Abnormal visceral mechanosensory and vagal function may play a role in the development of functional gastrointestinal disorders. AIMS: To assess whether vagal efferent and afferent function is linked with small intestinal mechanosensory function. METHODS: In seven patients with functional dyspepsia, six patients with a history of Billroth I gastrectomy and/or vagotomy, and seven healthy controls, intestinal perception thresholds were tested by a randomised ramp distension procedure performed with a barostat device. On a separate day, an insulin hypoglycaemia test was performed to assess the plasma levels of pancreatic polypeptide (PP) in response to hypoglycaemia, as a test of efferent vagal function. RESULTS: First perception of intestinal balloon distension occurred at significantly lower pressures in patients with functional dyspepsia (median 19.3, range 14.7-25.3 mm Hg) compared with healthy controls (median 26.0, range 21.7-43.7 mm Hg, p < 0.01). Sensory thresholds were significantly lower in patients after gastrectomy (median 12.2, range 8.0-14.7 mm Hg, p < 0.05 versus all others). In healthy controls and patients with functional dyspepsia, insulin hypoglycaemia significantly (p < 0.001) increased plasma PP levels. However, only two out of seven patients with functional dyspepsia had a more than twofold increase in PP values whereas all healthy controls had a more than twofold increase in PP levels after insulin hypoglycaemia (p < 0.05). In contrast, there was no significant PP response in the gastrectomised patients (median 2%, range -10 to +23%). PP responses and visceral sensory thresholds were significantly correlated (r = 0.65, p < 0.002). CONCLUSIONS: The diminished PP response after insulin hypoglycaemia indicates disturbed efferent vagal function in a subgroup of patients with functional dyspepsia. The data also suggest that the intact vagal nerve may exert an antinociceptive visceral effect.