ABSTRACT
BACKGROUND: Pheochromocytoma and paraganglioma are rare tumours of neuroectodermal origin. Pheochromocytoma occurs in 0.1-2% of people with hypertension, while the incidence rises to 4-5% in patients with incidental adrenal mass. AIM: To analyse the presentation, diagnosis and localization, pathology, molecular genetic aspects, surgical management and long-term outcome of a large series of patients with pheochromocytoma referred to a single centre. METHODS: From 1992 to 2008, we observed 91 patients with pheochromocytoma, 70 (77%) with the sporadic form and 21 (23%) with the hereditary form. In the group with the hereditary form, the mean age at diagnosis was significantly lower than the mean age of the group with the sporadic form (38 vs 48 years; p < 0.001). RESULTS: Eighty (88%) patients with pheochromocytoma were symptomatic and the classical triad of palpitations, headache and diaphoresis was present in 30% of patients. In 12% of patients, the pheochromocytoma was discovered during radiological images (adrenal incidentaloma). The unilateral adrenal localization was observed in 78% of patients, bilateral in 15% and extra-adrenal in 7% of patients. All pheochromocytoma patients underwent surgical procedure and the laparotomic approach was used in 49 (53%) patients, while the laparoscopic approach was performed in 42 (47%) patients. Pheochromocytoma was benign in 86 patients (93%) [mean size was 4.3 cm] and the malignant form was found in five patients (7%) [mean size was 10 cm]. CONCLUSIONS: These data from a large cohort of patients are consistent with those reported in the literature and show that pheochromocytoma is an in important challenge for clinicians.
ABSTRACT
OBJECTIVE: Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. SETTING AND PATIENTS: Twenty-five patients with PAH (idiopathic n=16, CTD n=9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1<18.7 pg/ml, Gr.2>18.7 pg/ml). RESULTS: Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435+/-85) m to 467+/-77 m, p>0.001) and an improvement in WHO class (from 2.4+/-0.5 to 2+/-0.6 p>0.01), with a significant decrease in BNP (from 87+/-33 pg/ml to 67+/-41 pg/ml, p=0.006) and a trend towards lower ET-1 plasma levels (from 17.7+/-5 pg/ml to 16+/-6 pg/ml, p=ns). Improvement in effort tolerance (Delta distance) was not correlated to modification in ET-1 (DeltaET-1) and BNP (DeltaBNP) plasma levels, while we found a significant correlation between DeltaET-1 and DeltaBNP (r=0.63, p=0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41+/-10 years vs Gr.2: 50+/-9 years, p=0.04), had less effort capacity (6MWT distance, Gr.1: 469+/-76 m, vs Gr.2: 398+/-82 m, p=0.03), and showed a trend towards higher BNP values (Gr.1: 82+/-41 pg/ml vs Gr.2: 92+/-23 pg/ml, p=0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: +32+/-24 m, Gr.2: +32+/-21 m p=0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: -0.5+/-0.5, Gr.2: -0.3+/-0.4 p=0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: -6+/-41 pg/ml, Gr.2: -34+/-19 pg/ml p=0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2+/-4.6 pg/ml, Gr.2: -3.8+/-6.6 pg/ml p=0.09). CONCLUSIONS: Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy.
