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SummaryObjective To evaluate the efficacy, safety and tolerability of octreotide LAR ® (long-acting repeatable octreotide) in the primary therapy of acromegaly. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10 -30 mg every 4 weeks, and constituted the population used for this analysis.Measurements and results A clinically relevant reduction (i.e. to ≤ 5 µ g/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value ( ≤ 2·5 µ g/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µ g/l and ≤ 5 µ g/l) and 44% had reached a GH level ≤ 2·5 µ g/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm 3 to 139 ± 94 mm 3 after 24 weeks and to 99 ± 70 mm 3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm 3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm 3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant ( > 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.

The term primary empty sella (PES) makes reference to the herniation of the subarachnoid space within the sella turcica in patients with no history of pituitary tumor, surgery or radiotherapy. To retrospectively assess clinical features, radiological findings and the biochemical endocrine function from the records of 175 patients with a diagnosis of PES. One hundred seventy-five patients (150 females) were studied. The mean age at diagnosis was 48.2 ± 14 year. Most diagnoses were made by magnetic resonance imaging (n = 172). In most patients, the pituitary function was assessed by basal pituitary hormones measurements. Pituitary scans were ordered for different reasons: headache (33.1 %), endocrine disorders (30.6 %), neurological symptoms (12.5 %), visual disturbances (8.75 %), abnormalities on sella turcica radiograph (8.75 %) and others (6.25 %). Multiple pregnancies were observed in 58.3 % of women; headaches, obesity, and hypertension were found in 59.4, 49.5, and 27.3 % of the studied population, respectively. Mild hyperprolactinemia (<50 ng/ml) was present in 11.6 % of women and 17.3 % of men. Twenty-eight percent of our patients had some degree of hypopituitarism. In the male population, hypopituitarism represented 64 % of cases, whereas it accounted for 22 % of all females. PES seems to be more commonly found in middle-aged women, with a history of multiple pregnancies. In most patients, PES was discovered as an incidental finding on imaging studies, while in almost a quarter of patients PES was found during the diagnostic evaluation of anterior pituitary deficiency, which was more common in men.

The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.