LUIZ ROBERTO SALGADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- High variability in baseline urinary free cortisol values in patients with Cushing's disease(2014) PETERSENN, S.; NEWELL-PRICE, J.; FINDLING, J. W.; GU, F.; MALDONADO, M.; SEN, K.; SALGADO, L. R.; COLAO, A.; BILLER, B. M. K.ObjectiveTwenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data. DesignObservational study (enrolment phase of Phase III study). MethodsPatients (n=152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) 15xULN (normal: 30-145nmol/24h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2weeks. ResultsOver 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000nmol/24h (SD 1872) and 940nmol/24h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism. ConclusionsThere is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.
- Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study(2014) PIVONELLO, Rosario; PETERSENN, Stephan; NEWELL-PRICE, John; FINDLING, James W.; GU, Feng; MALDONADO, Mario; TROVATO, Andrew; HUGHES, Gareth; SALGADO, Luiz R.; LACROIX, Andre; SCHOPOHL, Jochen; BILLER, Beverly M. K.Objective Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Design Phase III study with double-blind randomization of two pasireotide doses. Methods Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels >= 1.5 x upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 mu g bid). At month 3, patients with UFC <= 2 x ULN and not exceeding the baseline value continued their randomized dose; all others received 300 mu g bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 mu g bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Results Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72.8% of patients. Conclusions In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased.