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.
- A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease(2012) COLAO, Annamaria; PETERSENN, Stephan; NEWELL-PRICE, John; FINDLING, James W.; GU, Feng; MALDONADO, Mario; SCHOENHERR, Ulrike; MILLS, David; SALGADO, Luiz Roberto; BILLER, Beverly M. K.BACKGROUND Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients. CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.)