Hypertension-related factors in patients with active and inactive acromegaly.

INTRODUCTION: There are several complications of the cardiovascular system caused by acromegaly, especially hypertension. OBJECTIVES: To evaluate hypertension characteristics in patients with cured/controlled acromegaly and with the active disease. PATIENTS AND METHODS: Cross-sectional study of the follow-up of forty-four patients with acromegaly submitted to clinical evaluation, laboratory tests and cardiac ultrasound. Patients with cured and controlled disease were evaluated as one group, and individuals with active disease as second one. RESULTS: Forty-seven percent of the patients had active acromegaly, and these patients were younger and had lower blood pressure levels than subjects with controlled/cured disease. Hypertension was detected in 50% of patients. Subjects with active disease showed a positive correlation between IGF-1 and systolic and diastolic blood pressure levels (r = 0.48, p = 0.03; and r = 0.42, p = 0.07, respectively), and a positive correlation between IGF-1 and urinary albumin excretion (UAE) rates. In patients with active disease, IGF-1 was a predictor of systolic blood pressure, although it was not independent of UAE rate. For individuals with cured/controlled disease, waist circumference and triglycerides were the predictors associated with systolic and diastolic blood pressure. CONCLUSIONS: Blood pressure (BP) levels in patients with active acromegaly dependent of the GH excess. However, once thedisease becomes controlled and IGF-1 levels decrease, their blood pressure levels are depend on the other cardiovascular riskfactors [corrected].

Diabetes mellitusin a cohort of patients with acromegaly / Diabetes melito em uma coorte de pacientes com acromegalia

OBJECTIVES: To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. METHODS: This was a cross sectional study. RESULTS: Fifty-eight acromegalic patients were assessed. Only 29 percent met the criteria for cure, and 27 percent had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2 percent. Most of the diabetic patients (18 out of 22, 82 percent) did not meet criteria for cure. They were more often hypertensive [16/22 (73 percent) vs. 17/36 (46 percent), p = 0.04], and used statins more frequently [14/22 (64 percent) vs. 8/36 (21 percent), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95 percent CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95 percent CI: 0.03 - 0.78), p = 0.02]. CONCLUSIONS: The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes.

OBJETIVOS: Avaliar a presença de diabetes melito (DM) em uma coorte de acromegálicos. MÉTODOS: Este é um estudo transversal. RESULTADOS: Cinquenta e oito pacientes acromegálicos foram analisados. Apenas 29 por cento preencheram critérios de cura e 27 por cento estavam com a doença controlada. Vinte e dois pacientes (38 por cento) apresentaram DM, HbA1c 7,34 ± 2,2 por cento. Destes, 18 não preencheram critérios de cura. Pacientes com DM foram mais frequentemente hipertensos [16/22 (73 por cento) vs. 17/36 (46 por cento), p = 0,04] e usavam mais estatina [14/22 (64 por cento) vs.8/36 (21 por cento), p = 0,004]. Após regressão múltipla, hipertensão foi associada a DM [razão de chances (RC): 9,28 (95 por cento CI: 1,59 - 54,00), p = 0,01], e acromegalia curada/controlada foi fator protetor para presença de diabetes [OR: 0,17 (95 por cento CI: 0,03-0,78), p = 0,02]. CONCLUSÕES: A presença de DM esteve associada com acromegalia ativa e com a presença de hipertensão. No entanto, os níveis absolutos de GH e IGF-1 não diferiram entre aqueles com e sem diabetes.

Hypertension-related factors in patients with active and inactive acromegaly / Fatores implicados com a hipertensão em pacientes com acromegalia ativa e inativa

INTRODUCTION: There are several complications of the cardiovascular system caused by acromegaly, especially hypertension. OBJECTIVES: To evaluate hypertension characteristics in patients with cured/controlled acromegaly and with the active disease. PATIENTS AND METHODS: Cross-sectional study of the follow-up of forty-four patients with acromegaly submitted to clinical evaluation, laboratory tests and cardiac ultrasound. Patients with cured and controlled disease were evaluated as one group, and individuals with active disease as second one. RESULTS: Forty-seven percent of the patients had active acromegaly, and these patients were younger and had lower blood pressure levels than subjects with controlled/cured disease. Hypertension was detected in 50 percent of patients. Subjects with active disease showed a positive correlation between IGF-1 and systolic and diastolic blood pressure levels (r = 0.48, p = 0.03; and r = 0.42, p = 0.07, respectively), and a positive correlation between IGF-1 and urinary albumin excretion (UAE) rates. In patients with active disease, IGF-1 was a predictor of systolic blood pressure, although it was not independent of UAE rate. For individuals with cured/controlled disease, waist circumference and triglycerides were the predictors associated with systolic and diastolic blood pressure. CONCLUSIONS: Our findings suggest that blood pressure levels in patients with active acromegaly are very similar, and depend on excess GH. However, once the disease becomes controlled and IGF-1 levels decrease, their blood pressure levels will depend on the other cardiovascular risk factors.

INTRODUÇÃO: Existem várias complicações no sistema cardiovascular causadas pela acromegalia, especialmente a hipertensão. OBJETIVOS: Avaliar as características da hipertensão em pacientes com acromegalia curada/controlada e com doença ativa. PACIENTES E MÉTODOS: Estudo transversal com 44 pacientes com acromegalia seguidos em nosso serviço. Eles foram submetidos a avaliação clínica, exames laboratoriais e ecocardiograma. Pacientes com doença curada/controlada foram avaliados como um grupo único e os indivíduos com doença ativa como outro grupo. RESULTADOS: Quarenta e sete por cento dos pacientes apresentaram acromegalia ativa. Esses indivíduos foram mais jovens e apresentaram níveis mais baixos de pressão arterial que os indivíduos com doença controlada/curada. A hipertensão foi detectada em 50 por cento da amostra. Indivíduos com doença ativa mostraram uma correlação positiva entre os níveis de IGF-1 e os níveis de pressão arterial sistólica e de pressão arterial diastólica (r = 0,48, p = 0,03; e r = 0,42, p = 0,07, respectivamente) e também apresentaram uma correlação positiva entre IGF-1 e excreção urinária de albumina (EUA). Em pacientes com doença ativa, o IGF-1 foi um preditor da pressão arterial sistólica, embora não tenha sido independente da taxa de EUA. Para indivíduos com doença curada/controlada, a circunferência da cintura e os triglicérides foram os preditores associados aos níveis de pressão arterial sistólica e diastólica. CONCLUSÕES: Nossos resultados sugerem que os níveis pressóricos em pacientes com acromegalia ativa dependem do excesso de GH. No entanto, uma vez que a doença torna-se controlada e os níveis de IGF-1 reduzem, os níveis de pressão arterial dependerão de outros fatores de risco cardiovasculares.

Diabetes mellitus in a cohort of patients with acromegaly.

OBJECTIVES: To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. METHODS: This was a cross sectional study. RESULTS: Fifty-eight acromegalic patients were assessed. Only 29% met the criteria for cure, and 27% had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2%. Most of the diabetic patients (18 out of 22, 82%) did not meet criteria for cure. They were more often hypertensive [16/22 (73%) vs. 17/36 (46%), p = 0.04], and used statins more frequently [14/22 (64%) vs. 8/36 (21%), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95% CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95% CI: 0.03 - 0.78), p = 0.02]. CONCLUSIONS: The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes.

Severe HDL-c reduction during rosiglitazone therapy in an obese woman with type 2 diabetes.

Treatment with rosiglitazone has been associated with severe paradoxical HDL-c reductions. To our knowledge, there are very few reports of this reaction occurring when patients are treated without the combination of a fibrate. A case of severe HDL-c lowering in a patient treated with rosiglitazone without a fibrate is presented. The patient has been treated at a private practice clinic in southern Brazil. A 64-year-old woman with a 2-year history of type 2 diabetes mellitus was referred to her endocrinologist in June 2008. Rosiglitazone 4 mg q.d. was prescribed. Nine months later, the patient experienced a 90.90% decrease of her HDL-c levels. Rosiglitazone was withdrawn and the HDL-c returned to baseline. This paradoxical HDL-c reduction is a potentially severe adverse event. Patients prescribed rosiglitazone should have their HDL-c levels measured before and during therapy.

Severe HDL-c reduction during rosiglitazone therapy in an obese woman with type 2 diabetes / Redução severa de HDL-colesterol durante terapia com rosiglitazona em uma mulher obesa com diabetes tipo 2

Treatment with rosiglitazone has been associated with severe paradoxical HDL-c reductions. To our knowledge, there are very few reports of this reaction occurring when patients are treated without the combination of a fibrate. A case of severe HDL-c lowering in a patient treated with rosiglitazone without a fibrate is presented. The patient has been treated at a private practice clinic in southern Brazil. A 64-year-old woman with a 2-year history of type 2 diabetes mellitus was referred to her endocrinologist in June 2008. Rosiglitazone 4 mg q.d. was prescribed. Nine months later, the patient experienced a 90.90 percent decrease of her HDL-c levels. Rosiglitazone was withdrawn and the HDL-c returned to baseline. This paradoxical HDL-c reduction is a potentially severe adverse event. Patients prescribed rosiglitazone should have their HDL-c levels measured before and during therapy.

O tratamento com rosiglitazona tem sido associado a reduções paradoxais e severas no HDL-c. Há muito poucos relatos dessa reação ocorrendo em pacientes tratados com rosiglitazona sem a combinação com um fibrato. Apresentou-se um caso de diminuição severa no HDL-c em uma paciente tratada com rosiglitazona sem fibrato associado. A paciente foi tratada em uma clínica privada no Sul do Brasil. Uma mulher de 64 anos com história de diabetes melito tipo 2 há 2 anos foi encaminhada ao seu endocrinologista em junho de 2008. Prescreveu-se rosiglitazona 4 mg uma vez ao dia. Nove meses depois, a paciente teve redução de 90,90 por cento em seus níveis de HDL-c. A rosiglitazona foi retirada e o HDL-c retornou aos níveis prévios. Essa redução paradoxal do HDL-c é um evento adverso potencialmente severo. Pacientes aos quais se prescreve rosiglitazona devem ter seus níveis de HDL-c medidos antes e durante o tratamento.

Diabetes melito e acromegalia: interações entre hormônio de crescimento e insulina / Diabetes mellitus and acromegaly: interactions between growth hormone and insulin

Introdução: o hormônio de crescimento humano (GH) possui um importante papel na fisiologia do metabolismo glicêmico, lipídico e protéico. O excesso deste hormônio, como encontrado na acromegalia, induz a um estado de resistência insulínica que pode estar associado à presença de diabetes melito (DM). Objetivo: descrever a frequência de DM e as características dos indivíduos com acromegalia e DM em acompanhamento no Hospital de Clínicas de Porto Alegre (HCPA). Métodos: estudo transversal avaliando o perfil clínico e laboratorial de uma coorte de pacientes com acromegalia. Os critérios utilizados para cura da doença foram os sugeridos pelo consenso de 2000 e, para considerar-se sob remissão, a presença de IGF-1 normal para sexo e idade em uso de medicação para controle da acromegalia. As dosagens de IGF-1 foram realizadas pelo método imunoradiométrico e as de GH por quimioluminescência. Resultados: cinquenta e nove pacientes com acromegalia foram analisados. Desses, 24% preencheram critérios de cura e 25% estavam em remissão da doença, os restantes apresentavam doença ativa. Trinta e sete por cento dos pacientes apresentavam DM, com HbA1c média de 7,3±2,2%. Entre os pacientes com DM, 86% não preencheram critérios de cura e mais frequentemente eram hipertensos [16/22 (73%) vs. 17/37 (46%), P=0,04] e faziam mais uso de estatina [14/22 (64%) vs. 8/37 (21%), P=0,004] em relação aos pacientes sem DM. Após análise de regressão logística múltipla, a presença de DM foi associada à presença de acromegalia ativa [razão de chances: 17,4 (IC 95%: 1,08-28,0), P=0,04] e essa associação foi independente do ajuste para idade, níveis de IGF-1 ou GH, hipertensão arterial e níveis séricos de triglicerídeos. Conclusões: O DM foi frequente entre os pacientes com acromegalia e significativamente relacionado ao controle da doença.

Background: human growth hormone (GH) plays an important role in the physiology of glucose, lipid and protein metabolism. The excess of this hormone, such as in cases of acromegaly, leads to a state of insulin resistance that can be associated with diabetes. Aim: to describe the frequency of diabetes in the sample of patients with acromegaly followed up at Hospital de Clínicas de Porto Alegre (HCPA). Methods: cross-sectional study assessing the metabolic profile of a cohort of acromegalic patients. The criteria used for cure of the disease were those suggested in the 2000 consensus, and the remission criteria were presence of normal IGF-1 levels for age and gender. IGF-1 was measured using the immunoradiometric assay and GH levels were measured using chemiluminescence. Results: fifty-nine acromegalic patients were analyzed. Only 24% met criteria for cure and 25% were in remission, the remaining had active disease. Thirty-seven percent of patients had diabetes, with a mean HbA1c of 7.3±2.2%. Among patients with diabetes, 86% did not meet criteria for cure and they were more often hypertensive [16/22 (73%) vs. 17/37 (46%), P=0.04] and were on statins [14/22 (64%) vs. 8/37 (21%), P=0.004] compared with patients without diabetes. After the multiple regression analysis, the presence of diabetes was associated with the presence of active acromegaly [odds ratio: 17.4 (95% CI: 1.08-28.0), P=0.04], and this association was independent from adjustment for age, IGF-1 levels or GH levels, hypertension, and triglycerides levels. Conclusions: diabetes was frequent among patients with acromegaly and it was closely related to the control of the underlying disease.

Distúrbios cardiovasculares na acromegalia: [revisão] / Cardiovascular disturbances in acromegaly: [review]

A acromegalia acarreta uma série de distúrbios ao sistema cardiovascular, decorrentes da exposição crônica a níveis elevados de GH e IGF-1. Estes distúrbios são os principais responsáveis pelo aumento da mortalidade de acromegálicos. Entre as várias formas de acometimento cardiovascular, destaca-se a miocardiopatia acromegálica, entidade caracterizada, inicialmente, pelo estado hiperdinâmico, seguido de hipertrofia ventricular esquerda concêntrica e disfunção diastólica por déficit de relaxamento, culminando com disfunção sistólica e, por vezes, insuficiência cardíaca franca. Além disso, são também relevantes as arritmias, as valvulopatias, sobretudo mitral e aórtica, a cardiopatia isquêmica, a hipertensão e os distúrbios dos metabolismos glicêmico e lipídico. Nesta revisão são abordados os principais aspectos clínicos e prognósticos destas entidades, os efeitos do tratamento da acromegalia sobre elas e as repercussões correspondentes sobre a sobrevida dos pacientes.

Acromegaly causes a number of disorders in the cardiovascular system, resulting from chronic exposure to high levels of GH and IGF-1. Such disorders are the main responsible for increased mortality rates among acromegalic patients. Among several forms of cardiovascular impairment is acromegalic cardiomyopathy, an entity that is initially characterized by a hyperdynamic state, followed by concentric left ventricular hypertrophy and diastolic dysfunction due to relaxation deficit, culminating in systolic dysfunction and sometimes heart failure. In addition, arrhythmias and heart valve diseases are also relevant, especially mitral and aortic, ischemic heart disease, hypertension, and glucose and lipid metabolism disorders. This review approaches the main clinical and prognostic aspects of these entities, the effects of acromegaly treatment on them, and the respective consequences on patient survival.

[Cardiovascular disturbances in acromegaly]. / Distúrbios cardiovasculares na acromegalia.

Acromegaly causes a number of disorders in the cardiovascular system, resulting from chronic exposure to high levels of GH and IGF-1. Such disorders are the main responsible for increased mortality rates among acromegalic patients. Among several forms of cardiovascular impairment is acromegalic cardiomyopathy, an entity that is initially characterized by a hyperdynamic state, followed by concentric left ventricular hypertrophy and diastolic dysfunction due to relaxation deficit, culminating in systolic dysfunction and sometimes heart failure. In addition, arrhythmias and heart valve diseases are also relevant, especially mitral and aortic, ischemic heart disease, hypertension, and glucose and lipid metabolism disorders. This review approaches the main clinical and prognostic aspects of these entities, the effects of acromegaly treatment on them, and the respective consequences on patient survival.