RESUMO
Acromegaly is a systemic disease caused by excessive inappropriate secretion of GH and IGF-I levels, resulting in many systemic complications, including cardiovascular, respiratory, metabolic diseases, and a possible increased risk of some neoplasias. Although many studies on acromegaly and cancer remain uncertain, most data indicate that colorectal cancer (CRC) incidence is increased in this population. The exact mechanism involved in the role of GH-IGF-I axis in CRC has not been fully explained, yet it is associated with local and circulating effects of GH and IGF-I on the colon, promoting angiogenesis, cell proliferation, risk of mutation, inhibition of tumor-suppressor genes and apoptosis, thus facilitating a tumor microenvironment. Nevertheless, population-based studies present controversial findings on CRC incidence and mortality. All worldwide guidelines and expert consensuses agree with the need for colonoscopic screening and surveillance in acromegaly, although there is no consensus regarding the best period to do this. This review aims to analyze the existing data on CRC and acromegaly, exploring its pathophysiology, epidemiological studies and their limitations, colonic polyp characteristics, overall cancer and CRC incidences and mortality, risk factors for colon cancer pathophysiology, and recommendation guideline aspects.
Assuntos
Acromegalia , Neoplasias Colorretais , Acromegalia/complicações , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Humanos , Fator de Crescimento Insulin-Like I , Microambiente TumoralRESUMO
Acromegaly is a rare disease, mainly caused by a pituitary tumor secreting growth hormone. It is characterized by slow progression and is associated with a multisystemic involvement, being the cardiovascular system, one of the most involved, even reaching, more than 10 years ago, to represent the main cause of death. Cardiovascular complications develop as a result of elevated blood concentrations of growth hormone and insulin-like growth factor 1, which exert direct and indirect effects on the endothelium, large vessels, kidney and cardiomyocytes; causing arterial hypertension, valve disease, cardiac arrhythmia and a specific heart disease called acromegalic cardiomyopathy. After the literature overview related to the pathophysiology, clinical manifestations, diagnosis and treatment of cardiovascular involvement, we found that from a cardiovascular point of view, patients with acromegaly can range from an asymptomatic state to severe cardiac dysfunction, being the biochemical markers and imaging studies diagnostic tools that allow assessment the degree of cardiovascular disease in order to provide individualized treatment. The normalization of growth hormone and insulin-like growth factor 1 levels improves cardiovascular parameters, and therefore its prognosis.
La acromegalia es una enfermedad rara, causada principalmente por un tumor hipofisiario secretor de hormona de crecimiento (GH), se caracteriza por tener progresión lenta y asociarse a un compromiso multisistémico, siendo el aparato cardiovascular uno de los más comprometidos, llegando, incluso, desde hace más de 10 años a representar la principal causa de muerte. Las complicaciones cardiovasculares se desarrollan como resultado de las concentraciones sanguíneas elevadas de la GH y del factor de crecimiento similar a la insulina tipo 1 (IGF-1), los cuales ejercen efectos directos e indirectos sobre el endotelio, grandes vasos, riñón y los cardiomiocitos; produciendo hipertensión arterial, enfermedad valvular, arritmia cardiaca y una cardiopatía propia de la acromegalia denominada miocardiopatía acromegálica. Luego de la revisión bibliográfica actualizada relacionada con la fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento del compromiso cardiovascular, encontramos que desde el punto de vista cardiovascular los pacientes con acromegalia pueden variar desde un estado asintomático hasta presentar disfunción cardiaca severa, siendo los marcadores bioquímicos y exámenes de imagen herramientas diagnósticas que permiten evaluar el grado de afección cardiovascular para poder brindar un tratamiento individualizado. La normalización de los valores de la GH y del IGF-1 mejora los parámetros cardiovasculares y, por tanto, su pronóstico.
Assuntos
Acromegalia , Cardiopatias , Hormônio do Crescimento Humano , Humanos , Acromegalia/complicações , Fator de Crescimento Insulin-Like I , Cardiopatias/complicações , Hormônio do CrescimentoRESUMO
Acromegaly is a rare disease characterized by changes in the bone and soft tissue systems, induced by excess growth hormone and insulin-like growth factor type 1. Among the skin lesions associated with acromegaly is cutis verticis gyrata, an hypertrophic, and coarse folding of the skin of the scalp, an association of uncommon incidence and unknown prevalence. This case report describes the case of a patient diagnosed with acromegaly at age 60 with previously unidentified cutis verticis gyrata. This report aims to review the literature on cutis verticis gyrata and its unusual association with acromegaly.
Assuntos
Acromegalia , Doenças do Tecido Conjuntivo , Dermatoses do Couro Cabeludo , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/patologia , Doenças do Tecido Conjuntivo/patologia , Humanos , Pessoa de Meia-Idade , Doenças Raras/patologia , Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/complicações , Dermatoses do Couro Cabeludo/diagnóstico , Pele/patologiaRESUMO
Resumo Fundamento Embora se saiba que a fração de ejeção (FE) do ventrículo esquerdo (VE) medida por eletrocardiograma seja preservada em pacientes com acromegalia, não há informação suficiente sobre deformação longitudinal global e deformação do átrio esquerdo (SLG-VE e SAE). Objetivo O objetivo deste estudo foi avaliar as funções do ventrículo esquerdo (VE) e do átrio esquerdo (AE) por ecocardiograma strain (ES) em pacientes com acromegalia. Métodos Este estudo incluiu 50 pacientes com acromegalia na forma ativa da doença e 50 controles saudáveis com idade, sexo e área de superfície corporal similares. Além dos ecocardiogramas de rotina, medições de SLG-VE e SAE foram realizadas com o ES. Resultados Os valores dos SAE e SLG-VE foram significativamente mais baixos em pacientes com acromegalia (p<0,05 para todos). Na análise bivariada, a pressão arterial sistólica, o pró-hormônio N-terminal do peptídeo natriurético cerebral, o fator de crescimento semelhante à insulina tipo 1, e detectou-se que os níveis de IMVE tinham correlação positiva com SAE e SLG-VE (p<0,05). O nível de IGF-1 tinha forte correlação com SAE e SLG-VE (p<0,001 e β=0,5 vs. p<0,001 e β=0,626, respectivamente); 48% dos pacientes com acromegalia têm SLG-VE reduzido (<20%). O índice de massa do ventrículo esquerdo (IMVE) determina independentemente a presença de SLG-VE reduzido, e cada 1g/m2 de aumento no nível de IMVE aumenta a probabilidade de redução de SLG-VE em 6%. Conclusão Embora a fração de ejeção de VE seja normal em pacientes com acromegalia, os valores de SAE e SLG-VE são significativamente mais baixos. Além do aumento em IMVE, outro achado do envolvimento cardíaco pode ser a redução de SAE e SLG-VE. Portanto, além do ecocardiograma de rotina, SAE e SLG-VE podem ser úteis para avaliar os sinais iniciais de envolvimento cardíaco antes da ocorrência de alterações cardíacas irreversíveis.
Abstract Background Although it is known that the left ventricular (LV) ejection fraction (EF) measured by echocardiography is preserved in patients with acromegaly, there is not enough information about the LV and left atrial strain (LV-GLS and LAS). Objective This study aimed to evaluate the left ventricular (LV) and left atrial (LA) functions with strain echocardiography (SE) in patients with acromegaly. Methods This study included 50 acromegaly patients with active disease and 50 healthy controls with similar age, gender, and body surface area. In addition to routine echocardiography examinations, LV-GLS and LAS measurements were performed with SE. Results LAS and LV-GLS values were significantly lower in patients with acromegaly (p<0.05 for all). In bivariate analysis, systolic blood pressure, N-terminal prohormone of brain natriuretic peptide, Insulin-like growth factor-1, LA diastolic diameter, and LVMI levels were found to be positively correlated with both LAS and LV-GLS (p <0.05). IGF-1 level was strongly correlated with LAS and LV-GLS (p<0.001 and β=0.5 vs. p<0.001 and β=0.626, respectively); 48% of patients with acromegaly have reduced LV-GLS (<20%). Left ventricular mass-index (LVMI) independently determines the presence of reduced LV-GLS and each 1g/m2increase in LVMI level increases the likelihood of reduced LV-GLS by 6%. Conclusion Although LV ejection fraction is normal in patients with acromegaly, LAS and LV-GLS values were significantly reduced. Apart from LVMI increase, another finding of cardiac involvement may be LAS and LV-GLS decrease. Therefore, in addition to routine echocardiography, LAS and LV-GLS may be useful to evaluate early signs of cardiac involvement before the occurrence of irreversible cardiac changes.
Assuntos
Humanos , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Volume Sistólico/fisiologia , Ecocardiografia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Although it is known that the left ventricular (LV) ejection fraction (EF) measured by echocardiography is preserved in patients with acromegaly, there is not enough information about the LV and left atrial strain (LV-GLS and LAS). OBJECTIVE: This study aimed to evaluate the left ventricular (LV) and left atrial (LA) functions with strain echocardiography (SE) in patients with acromegaly. METHODS: This study included 50 acromegaly patients with active disease and 50 healthy controls with similar age, gender, and body surface area. In addition to routine echocardiography examinations, LV-GLS and LAS measurements were performed with SE. RESULTS: LAS and LV-GLS values were significantly lower in patients with acromegaly (p<0.05 for all). In bivariate analysis, systolic blood pressure, N-terminal prohormone of brain natriuretic peptide, Insulin-like growth factor-1, LA diastolic diameter, and LVMI levels were found to be positively correlated with both LAS and LV-GLS (p <0.05). IGF-1 level was strongly correlated with LAS and LV-GLS (p<0.001 and ß=0.5 vs. p<0.001 and ß=0.626, respectively); 48% of patients with acromegaly have reduced LV-GLS (<20%). Left ventricular mass-index (LVMI) independently determines the presence of reduced LV-GLS and each 1g/m2increase in LVMI level increases the likelihood of reduced LV-GLS by 6%. CONCLUSION: Although LV ejection fraction is normal in patients with acromegaly, LAS and LV-GLS values were significantly reduced. Apart from LVMI increase, another finding of cardiac involvement may be LAS and LV-GLS decrease. Therefore, in addition to routine echocardiography, LAS and LV-GLS may be useful to evaluate early signs of cardiac involvement before the occurrence of irreversible cardiac changes.
FUNDAMENTO: Embora se saiba que a fração de ejeção (FE) do ventrículo esquerdo (VE) medida por eletrocardiograma seja preservada em pacientes com acromegalia, não há informação suficiente sobre deformação longitudinal global e deformação do átrio esquerdo (SLG-VE e SAE). OBJETIVO: O objetivo deste estudo foi avaliar as funções do ventrículo esquerdo (VE) e do átrio esquerdo (AE) por ecocardiograma strain (ES) em pacientes com acromegalia. MÉTODOS: Este estudo incluiu 50 pacientes com acromegalia na forma ativa da doença e 50 controles saudáveis com idade, sexo e área de superfície corporal similares. Além dos ecocardiogramas de rotina, medições de SLG-VE e SAE foram realizadas com o ES. RESULTADOS: Os valores dos SAE e SLG-VE foram significativamente mais baixos em pacientes com acromegalia (p<0,05 para todos). Na análise bivariada, a pressão arterial sistólica, o pró-hormônio N-terminal do peptídeo natriurético cerebral, o fator de crescimento semelhante à insulina tipo 1, e detectou-se que os níveis de IMVE tinham correlação positiva com SAE e SLG-VE (p<0,05). O nível de IGF-1 tinha forte correlação com SAE e SLG-VE (p<0,001 e ß=0,5 vs. p<0,001 e ß=0,626, respectivamente); 48% dos pacientes com acromegalia têm SLG-VE reduzido (<20%). O índice de massa do ventrículo esquerdo (IMVE) determina independentemente a presença de SLG-VE reduzido, e cada 1g/m2 de aumento no nível de IMVE aumenta a probabilidade de redução de SLG-VE em 6%. CONCLUSÃO: Embora a fração de ejeção de VE seja normal em pacientes com acromegalia, os valores de SAE e SLG-VE são significativamente mais baixos. Além do aumento em IMVE, outro achado do envolvimento cardíaco pode ser a redução de SAE e SLG-VE. Portanto, além do ecocardiograma de rotina, SAE e SLG-VE podem ser úteis para avaliar os sinais iniciais de envolvimento cardíaco antes da ocorrência de alterações cardíacas irreversíveis.
Assuntos
Acromegalia , Disfunção Ventricular Esquerda , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Ecocardiografia , Humanos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologiaRESUMO
Introduction: Symptomatic heart disease may be present in patients with advanced-stage acromegaly. However, earlier assessment of subclinical ventricular systolic dysfunction can be accomplished through speckle-tracking echocardiography (STE) for the study of myocardial strain. The few such studies in this population to date have produced conflicting results. This study was performed to evaluate the parameters of ventricular strain in patients with acromegaly with no cardiac symptoms. Methods: In this prospective observational study, STE was performed in patients with active acromegaly with no detectable heart disease and in a control group to assess ventricular dysfunction through global longitudinal strain (GLS), radial strain, circumferential strain, and twist. The left ventricular (LV) ejection fraction, LV mass index, and relative wall thickness were also compared between the groups. Results: Twenty-five patients with active acromegaly (median age, 49 years; median disease duration, 11 years) and 44 controls were included. LV hypertrophy was more prevalent in the acromegaly group (40% vs. 19%, p < 0.01). The LV ejection fraction was similar between the groups (65.2% ± 5.99% vs. 62.9% ± 7.41%). The mean GLS (-18.8 ± 2.49 vs. -19.7 ± 3.29, p = 0.24), circumferential strain (-16.7 ± 3.18 vs. -16.6 ± 3.42, p = 0.90), and twist (14.6 ± 5.02 vs. 15.1 ± 3.94, p = 0.60) were not significantly different between the groups. Conclusion: Despite showing higher rates of LV hypertrophy, patients with long-term acromegaly had no impairment of ventricular contractility as assessed by strain echocardiography when compared with a control group.
Assuntos
Acromegalia , Disfunção Ventricular Esquerda , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Ecocardiografia/métodos , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
INTRODUCTION: Goiter is very common in patients with acromegaly; its development is correlated to the duration of the disease. Thyroid cells express the IGF-1 receptor and the TSH/IGF-1 interaction has been demonstrated to have a synergistic effect in thyroid cell growth. There is a correlation between IGF-1 levels and the thyroid volume of patients with acromegaly. The aim of this study was to evaluate, in a retrospective case-cohort study of patients with acromegaly, the associated risk factors for thyroid nodules disease in this population. METHODS: This was a case-cohort study matched by age, gender, and growth hormone at diagnosis. Cases consisted of acromegalic patients that developed thyroid nodules during the follow up, and controls consisted in acromegalic patients without thyroid nodules. A Cox proportional hazard estimation was carried out for measure the associated risk factors for thyroid nodules disease in acromegalic patients. A nodular thyroid disease-free survival analysis was estimated using the Kaplan-Meier analysis. RESULTS: We recruited 49 cases and 56 controls. In a multivariate Cox proportional hazard analysis age and IGF-1â¯≥â¯2.2 x ULN were significantly related with the presence of thyroid nodules [HR of 2.21 (95% CI; 1.15-4.25, pâ¯=â¯0.01)]. Nodularity-free survival rates in patients who had an IGF-1 X ULNâ¯≥â¯2.2 was found to be lower in comparison to those who had IGF-1 X ULNâ¯<â¯2.2, according to a Kaplan-Meier survival analysis. CONCLUSIONS: Our findings support that exist more probability to develop thyroid nodular disease in patients with acromegaly that present IGF-1 X ULNâ¯≥â¯2.2, suggesting a possible direct effect between the time of exposure to the IGF-1 axis hyperactivity and the genesis of thyroid nodules.
Assuntos
Acromegalia/complicações , Biomarcadores/sangue , Fator de Crescimento Insulin-Like I/análise , Centros de Atenção Terciária/estatística & dados numéricos , Nódulo da Glândula Tireoide/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Nódulo da Glândula Tireoide/etiologia , Nódulo da Glândula Tireoide/metabolismoRESUMO
Objective: To study the impact of secondary mental disorders in patients affected with acromegaly and correlate them with quality of life (QoL) and disease status. Design: An observational transversal descriptive and comparative study that evaluates QoL's impact due to secondary mental disorders in affected Mexicans with acromegaly using AcroQoL and SF-36 instruments. Correlation of the results with the disease's biochemical status was performed. According to Beck's scales, anxiety and depression analyses evaluate QoL's impact, and its gender variability is described. Results: Eighty-five patients with diagnoses of acromegaly were included. The mean age was 43.18 years, 47 being women (55.29%). The mean age at diagnosis was 37.95 years, with no difference between men and women. AcroQoL and SF-36 global and sub-domain scores differed significantly between men and women, the latter having lower global and individual sub-domain scores. The mean score of QoL, according to AcroQoL, is 59.40. In women, the mean values are less (55.13) than men (64.68), p = 0.021. The sub-domain analyses' scores in physical, appearance and social relationships were less in women (53.21; 47.34; 62.32) than men (62.68; 56.76; 73.87) p = 0.044, 0.069 and 0.013, respectively. Higher Beck's Depression Inventory (BDI) and Beck's Anxiety Inventory (BAI) scores correlated with lower QoL as assessed by global and individual sub-domain scores. Women presented significantly higher BDI and BAI mean scores when compared to men regardless of their biochemical status. Anxiety (p = 0.027) and depression (p < 0.001) severity were higher in women compared to men. Conclusion: Correlations between female gender, depression/anxiety scores and QoL require further validation. There is much to be routinely done to improve secondary psychopathology in patients affected by this disease. The need for mental status screening at diagnosis should be emphasized to identify secondary mental illnesses to improve QoL with its treatment.
Assuntos
Acromegalia/complicações , Transtornos Mentais/etiologia , Qualidade de Vida , Adulto , Ansiedade , Depressão , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Fatores SexuaisRESUMO
Acromegaly is a chronic and slowly progressive disease that results from the hypersecretion of growth hormone (GH) and consequently insulin-like growth factor type 1 (IGF-1), due to a GH-secreting pituitary adenoma in 95-98% of cases. There are several complications or co-morbidities associated with acromegaly, the most frequent being cardiovascular, metabolic and neoplastic. The cardiovascular complications of acromegaly go from arterial hypertension to a peculiar form of cardiomyopathy and are the result of the long-standing exposure to high GH and IGF-1 levels. The pathophysiology of these complications is complex and includes an increased tubular reabsorption of sodium and the direct effects of GH and IGF-1 on the endothelium and the cardiac tissue itself. Frequently, the cardiovascular comorbidities of acromegaly occur concomitantly with metabolic complications such as diabetes and respiratory abnormalities such as the sleep apnea syndrome. In this brief review we analyze the pathophysiology, the clinical manifestations and the management of the cardiovascular complications of acromegaly.
La acromegalia es una enfermedad crónica lentamente progresiva causada por la hipersecreción de hormona de crecimiento (GH) y consecuentemente de factor de crecimiento insulinoide tipo 1 (IGF-1), originada en el 95-98% de las ocasiones por un adenoma hipofisario secretor de GH. Existen diversas complicaciones o comorbilidad asociadas a la acromegalia, de las cuales destacan las enfermedades cardiovasculares, metabólicas y neoplásicas. Las complicaciones cardiovasculares van desde la hipertensión arterial hasta la cardiomiopatía acromegálica, y resultan de la exposición crónica a valores elevados de GH y de IGF-1. La fisiopatología de estas complicaciones es compleja e incluye tanto un aumento en la reabsorción tubular de sodio como efectos directos de la GH y del IGF-1 sobre el endotelio vascular y las células cardiacas. Con frecuencia estas alteraciones cardiovasculares ocurren simultáneamente con trastornos metabólicos como la diabetes y trastornos respiratorios como la apnea del sueño, y son agravadas por ellos. En esta breve revisión se analizan la fisiopatología, las manifestaciones clínicas y el manejo de las complicaciones cardiovasculares de la acromegalia.
Assuntos
Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/complicações , Acromegalia/diagnóstico , HumanosRESUMO
OBJECTIVE: To evaluate the prevalence of differentiated thyroid cancer (DTC) in patients with non-GH secreting pituitary adenomas [NGHPA group: non-functioning (NFPA), prolactin (PRL) and corticotropin (ACTH)-secreting adenomas] compared to patients with acromegaly, a pituitary disease that has been associated with increased risk for thyroid cancer. PATIENTS AND METHODS: Prospective, cross-sectional study involving consecutive outpatients followed in our institution with diagnosis of acromegaly (n = 71; 43 women, median age 57 yrs) and NGHPA (n = 57; 38 women, median age 48 yrs.; PRL (n = 35), ACTH (n = 7), NFPA (n = 15). All participants were subjected to thyroid ultrasound (US) by the same examiner, and US-guided fine needle aspiration (FNA) biopsy when indicated. RESULTS: Thyroid volume was higher in acromegaly than in NGHPA (median 12.5 ml vs 6.3 ml; p < 0.0001), and thyroid nodules were present in 27/71 (38.0%) of acromegaly patients and in 14/57 (24.6%) of NGHPA group. FNA was indicated in 15/27 (55.5%) of acromegaly patients [Bethesda I (n = 1); II (n = 11), III (n = 1), two patients refused FNA], and in 8/14 (57.1%) of the NGHPA group [Bethesda I (n = 2); II (n = 4); V (n = 1); VI (n = 1)]. The two patients of NGHPA group with Bethesda V and VI were operated and papillary carcinoma was confirmed histologically. CONCLUSION: DTC was not detected in our acromegaly patients and its presence in patients with NGHPA suggests that DTC predisposition is not related to GH excess.