Effectiveness of adding vildagliptin to the treatment of diabetic patients nonresponsive to the combination of metformin and a sulphonylurea.

OBJECTIVE: To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS: 37 T2DM patients with HbA1c ranging from 7.7% to 12.4% (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS: During triple oral therapy (TOT) HbA1c levels < 7% were achieved in 11 patients (29.7%), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4%). Both findings were observed in 10 patients (27.0%). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONCLUSION: Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.

Effectiveness of adding vildagliptin to the treatment of diabetic patients nonresponsive to the combination of metformin and a sulphonylurea / Eficácia da adição de vildagliptina ao tratamento de pacientes diabéticos não responsivos à combinação de metformina e uma sulfonilureia

OBJECTIVE: To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS: 37 T2DM patients with HbA1c ranging from 7.7 percent to 12.4 percent (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS: During triple oral therapy (TOT) HbA1c levels < 7 percent were achieved in 11 patients (29.7 percent), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4 percent). Both findings were observed in 10 patients (27.0 percent). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONLUSION: Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.

OBJETIVO: Avaliar a eficácia da adição de vildagliptina ao tratamento de pacientes com diabetes melito tipo 2 (DM2) inadequadamente controlados com a terapia de combinação com metformina e sulfonilureia. SUJEITOS E MÉTODOS: 37 pacientes com DM2 e HbA1c variando entre 7,7 por cento e 12,4 por cento (média, 9,30 ± 1,38), apesar do uso de metformina associada a uma sulfonilureia, foram adicionalmente tratados com vildagliptina (100 mg/dia) durante, pelo menos, 6 meses. RESULTADOS: Durante a terapia oral tripla TOT), níveis de HbA1c < 7 por cento foram alcançados em 11 pacientes (27,9 por cento), enquanto a glicemia de jejum (GJ) < 120 mg/dL foi observada em 12 pacientes (32,4.1 por cento). Ambos os resultados foram descritos em 10 pacientes (27,0 por cento). Em comparação com indivíduos não responsivos, os pacientes responsivos tinham níveis basais mais baixos de HbA1c e GJ, mas a diferença foi estatisticamente significativa somente para glicemia de jejum. Além disso, houve grande sobre-posição entre os dois grupos. CONSLUSÃO: Nossos resultados preliminares sugerem que a TOT com metformina, uma sulfonilureia e vildagliptina pode ser útil para alguns pacientes com DM2 não responsivos à combinação com metformina e uma sulfonilureia.

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.

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.

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.

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.

[Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves' disease]. / Avaliação da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doença de Graves.

The treatment options for the hyperthyroidism of Graves disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of (131)I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of (131)I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs.

Avaliação da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doença de graves / Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with graves’ disease

As opções terapêuticas para a hipertireoidismo da doença de Graves são as drogas antitireoidianas, a cirurgia e o radioiodo, porém nenhuma delas é considerada ideal pois não atuam diretamente na etiopatogênese da doença. O radioiodo vem sendo cada vez mais utilizado como primeira escolha, sendo um tratamento definitivo, seguro e de fácil administração. Há autores que preferem doses mais altas para induzir deliberadamente o hipotireoidismo, enquanto outros recomendam doses mais baixas que, a curto prazo, implicam menor incidência de hipotireoidismo e maior de eutireoidismo. Não há consenso sobre o melhor esquema de doses fixas a ser utilizado, sendo esse o principal enfoque deste estudo, no qual comparamos doses de 10 e 15 mCi. Dos 164 pacientes analisados, 61 (37,2 por cento) foram submetidos a 10 mCi e 103 (62,8 por cento), a 15 mCi de 131I. Na análise longitudinal, observou-se que a remissão do hipertireoidismo foi estatisticamente diferente no sexto mês (p < 0,001), sendo maior no grupo em que foi empregada a dose de 15 mCi. Contudo, foi semelhante nos dois grupos após 12 e 24 meses. É possível concluir que doses fixas de 10 e 15 mCi promovem semelhante remissão do hipertireoidismo após 12 meses de tratamento. A remissão do hipertireoidismo não teve associação com idade, sexo ou uso prévio de drogas antitireoidianas.

The treatment options for the hyperthyroidism of Graves’ disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of 131I were compared. Among the 164 patients analyzed, 61 (37.2 percent) were submitted to 10 mCi and 103 (62.8 percent) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of 131I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs.

[Endogenous Cushing's syndrome: clinical and laboratorial features in 73 cases]. / Síndrome de Cushing endógena: características clínico-laboratoriais em 73 casos.

We studied clinical and laboratorial features of 73 patients with endogenous Cushing's syndrome, subdivided as follows: 46 (63%) with Cushing's disease (CD), 21 (28.7%) with an adrenal tumor and 6 (8.2%) with ectopic ACTH secretion (EAS). The rate of typical manifestations of hypercortisolism was similar regardless its etiology. In 100% of cases of Cushing's syndrome we observed serum cortisol levels greater than 1.8 microg/dL in low-dose dexamethasone (DMS) suppression tests, as well as elevation of serum or salivary midnight cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and always high in EAS. In the 8-mg overnight DMS suppression test, serum cortisol suppression > 50% was observed in 78.2% of cases of CD and in 33.3% of subjects with EAS, while an 80% suppression was only seen in CD. After stimulation with CRH or DDAVP an ACTH increase > 35% occurred in 81% of individuals with CD and 16.6% of those with EAS, while an ACTH increase > 50 achieved 100% specificity. Moreover, the combination of serum cortisol suppression > 50% and an ACTH increase > 35% in both tests only occurred in Cushing's disease. Pituitary magnetic resonance imaging identified 100% of macroadenomas and 59.4% of microadenomas in patients with CD. Among 10 patients that underwent bilateral inferior petrosal sinus sampling, a central-to-peripheral ACTH gradient > 3 after CRH or DDAVP had 90% sensitivity and 100% specificity for Cushing's disease.

Síndrome de cushing endógena: características clínico-laboratoriais em 73 casos / Endogenous cushings syndrome: clinical and laboratorial features in 73 cases

Avaliamos as características clínico-laboratoriais de 73 pacientes com síndrome de Cushing (SC) endógena, assim distribuídos: 46 (63 por cento) com doença de Cushing (DC), 21 (28,7 por cento) com tumores adrenais (TA) e 6 (8,2 por cento) com a síndrome do ACTH ectópico (SAE). A freqüência de manifestações clássicas do hipercortisolismo foi similar, independentemente da etiologia da SC. Em 100 por cento dos casos de SC, observaram-se níveis do cortisol sérico (CS) > 1,8 µg/dL após supressão com doses baixas de dexametasona (DMS), além de elevação do cortisol à meia-noite (sérico ou salivar). Contudo, o cortisol livre urinário foi normal em 11,5 por cento dos pacientes. Os níveis de ACTH mostraram-se suprimidos nos pacientes com TA, normais ou elevados na DC e sempre elevados na SAE. No teste de supressão noturna com 8 mg de DMS, supressão do CS > 50 por cento foi observada em 78,2 por cento dos casos de DC e 33,3 por cento dos casos de SAE, enquanto uma supressão > 80 por cento foi exclusiva da DC. Após estímulo com CRH ou DDAVP, um incremento do ACTH > 35 por cento aconteceu em 81 por cento dos indivíduos com DC e em 16,6 por cento daqueles com SAE, ao passo que um incremento do ACTH > 50 por cento restringiu-se à DC. A combinação de incremento do ACTH > 35 e supressão do CS > 50 por cento foi também exclusiva da DC. A ressonância magnética visualizou 100 por cento dos macroadenomas e 59,4 por cento dos microadenomas hipofisários nos casos de DC. Em 10 pacientes submetidos ao cateterismo bilateral do seio petroso inferior, um gradiente centro-periferia de ACTH > 3 pós-CRH ou DDAVP teve sensibilidade de 90 por cento e especificidade de 100 por cento para a doença de Cushing.

We studied clinical and laboratorial features of 73 patients with endogenous Cushings syndrome, subdivided as follows: 46 (63 percent) with Cushings disease (CD), 21 (28.7 percent) with an adrenal tumor and 6 (8.2 percent) with ectopic ACTH secretion (EAS). The rate of typical manifestations of hypercortisolism was similar regardless its etiology. In 100 percent of cases of Cushings syndrome we observed serum cortisol levels greater than 1.8 µg/dL in low-dose dexamethasone (DMS) suppression tests, as well as elevation of serum or salivary midnight cortisol. However, urinary free cortisol was normal in 11.5 percent of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and always high in EAS. In the 8-mg overnight DMS suppression test, serum cortisol suppression > 50 percent was observed in 78.2 percent of cases of CD and in 33.3 percent of subjects with EAS, while an 80 percent suppression was only seen in CD. After stimulation with CRH or DDAVP an ACTH increase > 35 percent occurred in 81 percent of individuals with CD and 16.6 percent of those with EAS, while an ACTH increase > 50 achieved 100 percent specificity. Moreover, the combination of serum cortisol suppression > 50 percent and an ACTH increase > 35 percent in both tests only occurred in Cushings disease. Pituitary magnetic resonance imaging identified 100 percent of macroadenomas and 59.4 percent of microadenomas in patients with CD. Among 10 patients that underwent bilateral inferior petrosal sinus sampling, a central-to-peripheral ACTH gradient > 3 after CRH or DDAVP had 90 percent sensitivity and 100 percent specificity for Cushings disease.

[Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia]. / Prevalência da macroprolactinemia entre 115 pacientes com hiperprolactinemia.

Macroprolactinemia is characterized by the predominance in the serum of macroprolactin, a prolactin (PRL) with high molecular mass and low biological activity that does not need treatment. The prevalence of macroprolactinemia was evaluated in 115 consecutive patients with hyperprolactinemia. Among them, 19 (16.5%) had solely macroprolactinemia, 4 (3.5%) polycystic ovary syndrome, 7 (6.1%) acromegaly, 8 (6.9%) idiopathic hyperprolactinemia, 10 (8.6%) primary hypothyroidism, 14 (12.2%) clinically non-functioning pituitary adenomas, 20 (17.4%) drug-induced hyperprolactinemia and 33 (28.7%) prolactinomas. The diagnosis of macroprolactinemia was established by the demonstration of a PRL recovery < 30% after treatment of sera with polyethylene glycol. Among the 19 patients with isolated macroprolactinemia, 16 (84.2%) were female and 12 (63.2%) were asymptomatic, while 4 (21%) presented with oligomenorrhea and 3 (15.8%) with galactorrhea. In contrast, only 11.5% of individuals with other causes of hyperprolactinemia were asymptomatic (p< 0.001). Prolactin levels in cases of macroprolactin ranged from 45.1 to 404 ng/mL (mean 113.3 +/- 94.5) but in 15 (78.9%) were < 100 ng/mL. Our findings demonstrate that macroprolactinemia is a common condition and, therefore, we suggest that it should be routinely screened in patients with hyperprolactinemia.

Prevalência da macroprolactinemia entre 115 pacientes com hiperprolactinemia / Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia

Macroprolactinemia caracteriza-se pelo predomínio no soro de uma prolactina (PRL) de alto peso molecular e baixa atividade biológica que não requer tratamento. A prevalência de macroprolactinemia foi avaliada em 115 pacientes consecutivos com hiperprolactinemia. Entre eles, 19 (16,5 por cento) tinham exclusivamente macroprolactinemia, 4 (3,5 por cento) síndrome dos ovários policísticos, 7 (6,1 por cento) acromegalia, 8 (6,9 por cento) hiperprolactinemia idiopática, 10 (8,7 por cento) hipotiroidismo primário, 14 (12,2 por cento) adenomas clinicamente não-funcionantes, 20 (17,4 por cento) hiperprolactinemia farmacológica e 33 (28,7 por cento) prolactinomas. O diagnóstico de macroprolactinemia foi estabelecido pela obtenção de uma recuperação da PRL < 30 por cento após tratamento do soro com polietilenoglicol. Dentre os 19 pacientes com macroprolactinemia isolada, 16 (84,2 por cento) eram mulheres e 12 (63,2 por cento) eram assintomáticos, enquanto 4 (21 por cento) tinham oligomenorréia e 3 (15,8 por cento), galactorréia. Em contraste, apenas 11,5 por cento dos indivíduos com outras causas de hiperprolactinemia eram assintomáticos (p< 0,001). Os níveis de PRL nos casos de macroprolactinemia variaram de 45,1 a 404 ng/mL (média de 113,3 ± 94,5), mas em 15 (78,9 por cento) foram < 100 ng/mL. Nossos achados demonstram que macroprolactinemia é uma condição freqüente e, assim, sugerimos que seja rotineiramente pesquisada em pacientes com hiperprolactinemia.

Macroprolactinemia is characterized by the predominance in the serum of macroprolactin, a prolactin (PRL) with high molecular mass and low biological activity that does not need treatment. The prevalence of macroprolactinemia was evaluated in 115 consecutive patients with hyperprolactinemia. Among them, 19 (16.5 percent) had solely macroprolactinemia, 4 (3.5 percent) polycystic ovary syndrome, 7 (6.1 percent) acromegaly, 8 (6.9 percent) idiopathic hyperprolactinemia, 10 (8.6 percent) primary hypothyroidism, 14 (12.2 percent) clinically non-functioning pituitary adenomas, 20 (17.4 percent) drug-induced hyperprolactinemia and 33 (28.7 percent) prolactinomas. The diagnosis of macroprolactinemia was established by the demonstration of a PRL recovery < 30 percent after treatment of sera with polyethylene glycol. Among the 19 patients with isolated macroprolactinemia, 16 (84.2 percent) were female and 12 (63.2 percent) were asymptomatic, while 4 (21 percent) presented with oligomenorrhea and 3 (15.8 percent) with galactorrhea. In contrast, only 11.5 percent of individuals with other causes of hyperprolactinemia were asymptomatic (p< 0.001). Prolactin levels in cases of macroprolactin ranged from 45.1 to 404 ng/mL (mean 113.3 ± 94.5) but in 15 (78.9 percent) were < 100 ng/mL. Our findings demonstrate that macroprolactinemia is a common condition and, therefore, we suggest that it should be routinely screened in patients with hyperprolactinemia.

Síndrome de Cushing: Manifestações clínicas e avaliação diagnóstica / Cushing's syndrome: clinical manifestations and diagnostic evaluation

Resumo: Foram analisadas as manifestações clínicas e laboratoriais de 73 pacientes com síndrome de Cushing(SC) endógena, assim distribuidos: 46(63por cento) com doença de Cushing(DC), 21 (28,7por cento) com tumores adrenais (TA) e 6 (8,2por cento) com a síndrome do ACTH ectópico (SAE). Esta última resultou de 5 tumores carcinóides brônquicos e uma carcinóide tímico. A freqüência de manifestações clássicas do hipercortisolismo foi similar, independentemente da etiologia da SC. A DC e os TA (15 adenomas e 6 carcinomas) predominaram no sexo feminino e a SAE, no masculino. Em 100por cento dos casos de SC, observaram-se níveis do cortisol sérico (CS) >1,8mg/dL após supressão com doses baixas de dexametasona (DMS), além de elevação do cortisol à meia-noite (sérico ou salivar). Contudo o cortisol livre urinário foi normal em 11,5por cento dos pacientes. Os níveis de ACTH mostraram-se suprimidos nos pacientes com TA, normais ou elevados na DC e sempre elevados na SAE. No teste de supressão noturna com 8mg de DMS, supressão do CS>50 por cento foi observada em 78,2por cento dos casos de DC e 33,3por cento dos casos de SAE, enquanto uma supressão >80 por cento foi exclusiva da DC. Após estímulo com CRH ou DDAVP, um incremento do ACTH maior ou igual a 35 por cento aconteceu em 81 por cento dos indivíduos com DC e em 16,6 por cento daqueles com SAE, ao passo que um incremento do ACTH>50por cento restringiu-se à DC. A combinação de incremento do ACTH maior ou igual a35 e supressão do CS > 50por cento foi também exclusiva da DC. A ressonância magnética visualizou 100por cento dos macroadenomas e 59,4por cento dos microadenomas hipofisários nos casos de DC. Em 10 pacientes submetidos ao cateterismo bilateral do seio petroso inferior, um gradiente centroperiferia da ACTH maior ou igual a 3 pós-CRH ou DDAVP teve sensibilidade de 90por cento e especificidade de 100 por cento para a doença de Cushing

Avaliaçäo da associaçäo da terapêutica medicamentosa e a terapia cognitivo-comportamental no tratamento da obesidade / Assessment of pharmacotherapy association with cognitive-behavioral therapy in the treatment of obesity

A obesidade apresenta etiologia multifatorial, implicando em tratamento multidisciplinar. O objetivo do presente estudo é comparar a açäo da dietoterapia, estímulo de atividades físicas, a aplicaçäo da terapia cognitivo-comportamental (TCC) e a utilizaçäo do femproporex no tratamento da paciente obesa. Durante seis meses, 40 pacientes do sexo feminino com índice de massa corporal (IMC) maior que 30 foram orientadas quanto à dietoterapia com valor calórico total (VCT) de 1.200 kcal/dia, exercícios físicos e receberam femproporex, nas doses de 25 ou 50 mg diários. As pacientes foram divididas aleatoriamente em dois grupos: em um grupo foi aplicada a TCC (Grupo T) e no outro näo (Grupo M). Os dados antropométricos (peso, altura, índice de massa corporal e relaçäo cintura-quadril - RCQ) foram avaliados quinzenalmente, bem como a anamnese e o exame físico completo, sendo realizada avaliaçäo laboratorial no início e ao término do estudo. Ambos os grupos apresentavam valores basais semelhantes do peso corporal, IMC e RCQ. O grupo M apresentou apresentou reduçäo ponderal média do peso corporal de 13,1 (15,5 porcento) do peso inicial e reduçäo porcentual no IMC de 16,8 porcento. Ambos os grupos apresentaram reduçäo estatísticamente significante dos valores do colesterol total e triglicérides séricos. Os demais parâmetros laboratoriais näo apresentaram variaçäo nos dois grupos. O femproporex foi considerado pelas pacientes como eficaz em 100 porcento do grupo M e 92,7 porcento do grupo T, sendo a diminuíçäo do apetite o efeito positivo mais citados nos dois grupos. O femproporex demonstrou ser uma opçäo válida para o tratamento medicamentoso da obesidade, considerando sua boa tolerabilidade e seu baixo custo.(au)

Tratamento medicamentoso dos tumores hipofisários. Parte II: adenomas secretores de ACTH, TSH e adenomas clinicamente näo funcionantes / Drug therapy of hypophyseal tumors. Part II: ACTH and TSH secreting adenomas and functionless clinically adenomas

Este artigo revisa o potencial papel do tratamento medicamentoso para os adenomas hipofisários secretores de ACTH, TSH e aqueles clinicamente näo-funcionantes (ACNF). Metirapona, mitotano e cetoconazol (preferível por causar menos efeitos colaterais) säo as drogas mais eficazes no controle do hipercortisolismo, mas nenhuma delas supera a eficácia da cirurgia transesfeinodal (TSA). O tratamento medicamentoso da doença de Cushing está, portanto, melhor indicado para pacientes aguardando o efeito pleno da radioterapia ou, como alternativa para esta última, em casos de hipercortisolismo persistente após TSA, e para pacientes com rejeiçäo ou limitaçöes clínicaspara a cirurgia. Outra indicaçäo potencial seria em idosos com microadenomas ou pequenos macroadenomas, ou em casos associados a sela vazia. No que se refere aos adenomas secretores de TSH, os análogos somatostatínicos (SRIFa) proporcionam normalizaçäo dos hormônios tireoidianos em até 95 por cento dos casos. Assim, eles podem se mostrar úteis em casos de insucesso da cirurgia ou como terapia primária de casos selecionados. Ocasonalmente, agonistas dopaminérgicos (DA), sobretudo a cabergolina, também podem ser eficazes. Em contraste, DA e SRIFa raramente induzem uma significante reduçäo das dimensöes dos ACNFs. Por isso, em pacientes com tais tumores, essas drogas devem ser principlamente consideradas diante de contra-indicaçöes ou limitaçöes clínicas para a cirurgia ou quando a cirurgia e a radioterapia tenham sido mal-sucedidas.

Tratamento medicamentoso dos tumores hipofisários: parte I: prolactinomas e adenomas secretores de GH / Drug therapy of hypophyseal tumors: part I: prolactinomas and GH secretory adenomas

O recente desenvolvimento de novas drogas, particularmente os análogos da somatostatina (SRIFa), representou um grande processo na terapia dos tumores hipofisários. Os SRIFa mostram-se bastante eficazes na normalizaçäo dos níveis de GH e IGH- 1 em acromegálicos e podem ser uma alternativa para a cirurgia transesfeinodal, mas seu uso como terapia primária da acromegalia fica limitado pelo pequeno efeito dessas drogas na reduçäo das dimensöes do tumor. Os resultados preliminares com os antagonistas do receptor de GH, como o pegvisomant, säo bastante animadores. Tais drogas permitem a normalizaçäo do IGF-1 e melhora clínica em mais de 80 por cento dos casos; entretanto, nao causam reduçäo tumoral. Agonistas dopaminérgicos (DA) represemtam a terapia de escolha para microprolactinonas sintomáticos e macroprolactinomas, permitindo normalizaçäo dos níveis da prolactina e reduçäo do volume do adenoma na maioria dos pacientes . Podem também ser eventualmente eficazes em acromegálicos, sobretudo naqueles com adenomas co-secretores de prolactina e níveis näo muito elevados de GH e IGF-1. Devido a sua maior eficácia e maior tolerabilidade, a carbegolina representa o DA de escolha para o manuseio dos prolactinomas e da acromegalia.