Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing's disease.

The expression of dopamine receptor subtypes has been reported in corticotroph adenomas, and this finding support the possibility for medical treatment of Cushing's disease (CD) with dopamine agonists when conventional treatment has failed. The aim of this study was to evaluate the effectiveness of cabergoline (at doses of up 3 mg/week), alone or combined with relatively low doses of ketoconazole (up to 400 mg/day), in 12 patients with CD unsuccessfully treated by transsphenoidal surgery. After 6 months of cabergoline therapy, normalization of 24 h urinary free cortisol (UFC) levels occurred in three patients (25%) at doses ranging from 2-3 mg/week, whereas reductions ranging from 15.0 to 48.4% were found in the remaining. The addition of ketonocazole to the nine patients without an adequate response to cabergoline was able to normalize UFC excretion in six patients (66.7%) at doses of 200 mg/day (three patients), 300 mg/day (two patients) and 400 mg/day (one patient). In the remaining patients UFC levels did not normalize but a significant reduction ranging from to 44.4 to 51.7% was achieved. In two of the six responsive patients to combination therapy, the weekly dose of cabergoline could be later reduced from 3 to 2 mg. Our findings demonstrated that cabergoline monotherapy was able to reverse hypercortisolism in 25% of patients with CD unsuccessfully treated by surgery. Moreover, the addition of relatively low doses of ketoconazole led to normalization of UFC in about two-thirds of patients not achieving a full response to cabergoline.

Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS: Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-alpha and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS: NAFLD was observed in 42% of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, TNF-alpha, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION: Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, gamma-GT, uric acid, TNF-alpha, insulin and HOMA-IR than subjects without NAFLD.

Comparison of metformin, gliclazide MR and rosiglitazone in monotherapy and in combination for type 2 diabetes.

OBJECTIVE: To compare the efficacy and tolerability of metformin, rosiglitazone and gliclazide MR as monotherapy and in combination in the treatment of type 2 diabetes. SUBJECTS AND METHODS: 250 patients treated with oral antidiabetic agents for at least 24 weeks in monotherapy or in combination therapy were included in this retrospective study. RESULTS: As monotherapy the reduction of fasting plasma glucose (FPG), postprandial glycemia (PPG) and HbA1c was similar with the three drugs after 24 weeks. Among patients on combination therapy, the reduction in HbA1c, FPG and PPG was significantly lower with rosiglitazone plus metformin, as compared to metformin plus gliclazide MR or gliclazide MR plus rosiglitazone. Patients treated with rosiglitazone achieved less favorable changes in lipid profile. CONCLUSION: In monotherapy all drugs were equally effective in improving glycemic control, whereas the combination of metformin plus gliclazide MR provided the best results concerning the improvement of both, glycemic control and lipid profile.

Adrenal incidentalomas: diagnostic evaluation and long-term follow-up.

OBJECTIVE: To evaluate the cause and the clinical and laboratory features of adrenal incidentalomas (AI) in 52 patients and to assess the evolution of nonsurgically treated lesions during long-term follow-up. METHODS: We retrospectively analyzed the medical records of 52 patients with AI undergoing routine follow-up in 2 Brazilian endocrine centers. RESULTS: In our study group, nonfunctioning adenomas were the most frequent cause of AI (42%), followed by cortisol-secreting adenomas (15%), metastatic disease (10%), pheochromocytomas (8%), myelolipomas (6%), cysts (6%), carcinomas (4%), lymphomas (4%), tuberculosis (4%), and aldosteronoma (2%). Only 13 lesions (25%) were functioning (8 cortisol-secreting adenomas, 4 pheochromocytomas, and 1 aldosteronoma). Carcinomas were the largest adrenal masses (mean diameter, 11.7 +/- 1.3 cm). With the exception of 1 pheochromocytoma, 1 cyst, and 1 myelolipoma, all AI larger than 6 cm were carcinomas. During follow-up of 21 patients with nonsurgically treated AI for 6 to 36 months (mean, 24.8 +/- 8.9), no patient had tumor reduction or disappearance. After 12 months of follow-up, however, a 45-year-old woman had adrenal mass enlargement from 3.2 cm to 4.4 cm; the excised lesion proved to be an adenoma. Moreover, evidence of cortisol hypersecretion developed after 24 months of follow-up in a 30-year-old man with a 3.5-cm adenoma in the left adrenal gland. CONCLUSION: Our findings demonstrate that most AI are nonfunctioning benign lesions and emphasize the need for long-term follow-up of patients with conservatively managed lesions, in light of the potential for evolution to hormonal hypersecretion or tumor growth.

Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus / Frequência e fatores de risco associados à doença hepática gordurosa não alcoólica em pacientes com diabetes melito tipo 2

OBJECTIVE: To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS: Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-α and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS: NAFLD was observed in 42 percent of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, TNF-α, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION: Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, γ-GT, uric acid, TNF-α, insulin and HOMA-IR than subjects without NAFLD.

OBJETIVO: Avaliar a frequência de doença hepática gordurosa não alcoólica (DHGNA) em pacientes com diabetes mellitus tipo 2 (DM2) e descrever seus fatores de risco. SUJEITOS E MÉTODOS: Amostras de sangue foram coletadas de 78 pacientes para avaliação dos perfis glicídico e lipídico, enzimas hepáticas, TNF-α e HOMA-IR. O diagnóstico de DHGNA foi estabelecido por ultrassonografia. RESULTADOS: NAFLD foi observada em 42 por cento dos pacientes que apresentaram maior IMC (p < 0,001). Hipertensão arterial sistêmica (p < 0,001) e síndrome metabólica foram mais frequentes naqueles com DHGNA (p = 0,019). Os níveis de aspartato aminotransferase, alanina aminotransferase, γ-glutamil transpeptidase, ácido úrico, TNF-α, insulina e HOMA-IR foram significativamente maiores nos pacientes com do que naqueles sem DHGNA. CONCLUSÃO: Quase metade dos pacientes com DM2 apresentaram DHGNA, os quais tiveram IMC mais elevado, bem como maiores níveis de aminotransferases, γ-GT, ácido úrico, TNF-α, insulina e HOMA-IR do que os indivíduos sem DHGNA.

Comparison of metformin, gliclazide MR and rosiglitazone in monotherapy and in combination for type 2 diabetes / Comparação de metformina, gliclazida MR e rosiglitazona em monoterapia e em combinação para o diabetes tipo 2

OBJECTIVE: To compare the efficacy and tolerability of metformin, rosiglitazone and gliclazide MR as monotherapy and in combination in the treatment of type 2 diabetes. SUBJECTS AND METHODS: 250 patients treated with oral antidiabetic agents for at least 24 weeks in monotherapy or in combination therapy were included in this retrospective study. RESULTS: As monotherapy the reduction of fasting plasma glucose (FPG), postprandial glycemia (PPG) and HbA1c was similar with the three drugs after 24 weeks. Among patients on combination therapy, the reduction in HbA1c, FPG and PPG was significantly lower with rosiglitazone plus metformin, as compared to metformin plus gliclazide MR or gliclazide MR plus rosiglitazone. Patients treated with rosiglitazone achieved less favorable changes in lipid profile. CONCLUSION: In monotherapy all drugs were equally effective in improving glycemic control, whereas the combination of metformin plus gliclazide MR provided the best results concerning the improvement of both, glycemic control and lipid profile.

OBJETIVO: Comparar a eficácia e a tolerabilidade da metformina, rosiglitazona e gliclazida MR em monoterapia ou em combinação no tratamento do diabetes tipo 2. SUJEITOS E MÉTODOS: 250 pacientes tratados com antidiabéticos orais por pelo menos 24 semanas, em monoterapia ou em terapia combinada, foram incluídos neste estudo retrospectivo. RESULTADOS: Como monoterapia, a redução da glicemia de jejum (GJ), glicemia pós-prandial (GPP) e HbA1c foi similar com as três drogas, após 24 semanas. Entre os pacientes em terapia combinada, a redução da HbA1c, GJ e GPP foi significativamente menor com rosiglitazona e metformina, em comparação com metformina e gliclazida MR ou gliclazida MR mais rosiglitazona. Os pacientes tratados com rosiglitazona obtiveram mudanças menos favoráveis no perfil lipídico. CONCLUSÃO: Em monoterapia todos os medicamentos foram igualmente eficazes na melhora do controle glicêmico, enquanto a combinação de metformina e gliclazida MR proporcionou os melhores resultados relativos à melhoria de ambos, controle glicêmico e perfil lipídico.