Disfunção Ventricular e do Átrio Esquerdo Subclínica em Pacientes com Acromegalia: Um Estudo de Ecocardiograma de Rastreamento de Manchas / Subclinical Left Atrial and Ventricular Dysfunction in Acromegaly Patients: A Speckle Tracking Echocardiography Study

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.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Determinants of morbidities and mortality in acromegaly

ABSTRACT Acromegaly is a systemic disease associated with increased morbidity, presenting cardiovascular, metabolic, respiratory, neoplastic, endocrine, articular and bone complications. Most of these comorbidities can be prevented or delayed with adequate disease treatment and, more recent studies with the use of modern treatments of acromegaly, have shown a change in the severity and prevalence of these complications. In addition, acromegaly is associated with increased mortality, but recent studies (especially those published in the last decade) have shown a different scenario than older studies, with mortality no longer being increased in adequately controlled patients and a change in the main cause of death from cardiovascular disease to malignancy. In this review, we discuss this changing face of acromegaly summarizing current knowledge and evidence on morbimortality of the disease. Arch Endocrinol Metab. 2019;63(6):630-7

Acromegalia y silla turca vacía: una asociación infrecuente: presentación de un caso / Acromegaly and empty sella syndrome: an infrequent association: presentation of a case

La acromegalia, originada por un exceso de producción de Hormona de crecimiento (Gh), se caracteriza por crecimiento somático exagerado, alto riesgo cardio-metabólico, así como reducción de la expectativa de vida. Tiene una incidencia de 3-4 casos por millón de habitantes. El diagnóstico se retrasa hasta 10 años aumentando la morbi-mortalidad. Las alternativas terapéuticas incluyen medicamentos y cirugía, que van encaminados a reducir los efectos de masa tumoral, normalizar los parámetros bioquímicos y resolver las manifestaciones clínicas. En casos muy infrecuentes, el tumor hipofisario que la origina se asocia a silla turca vacía.

Acromegaly, caused by an excess production of growth hormone (Gh), it is characterized by exaggerated somatic growth, high cardio-metabolic risk, as well as reduction of life expectancy. It has an incidence of 3-4 cases per million population. The diagnosis is delayed up to 10 years increasing morbidity and mortality. The therapeutic alternatives include medications and surgery, which are aimed at reduce the effects of tumor mass, normalize biochemical parameters and resolve clinical manifestations. In very infrequent cases, the pituitary tumor that originates it is associated with empty sella syndrome. Key words: Acromegaly, Empty sella syndrome, Pituitary tumor.

Clinical and functional variables can predict general fatigue in patients with acromegaly: an explanatory model approach

ABSTRACT Objective To evaluate whether hormonal profile, arterial function, and physical capacity are predictors of fatigue in patients with acromegaly. Subjects and methods: This is a cross-sectional study including 23 patients. The subjects underwent a Modified Fatigue Impact Scale (MFIS) assessment; serum growth hormones (GH) and IGF-1 measurements; pulse wave analysis comprising pulse wave velocity (PWV), arterial compliance (AC), and the reflection index (IR1,2); dominant upper limb dynamometry (DYN); and the six-minute walking distance test (6MWT). Multiple linear regression models were used to identify predictors for MFIS. The coefficient of determination R2 was used to assess the quality of the models' fit. The best model was further analyzed using a calibration plot and a limits of agreement (LOA) plot. Results The mean ± SD values for the participants' age, MFIS, PWV, AC, IR1,2, DYN, and the distance in the 6MWT were 49.4 ± 11.2 years, 31.2 ± 18.9 score, 10.19 ± 2.34 m/s, 1.08 ± 0.46 x106 cm5/din, 85.3 ± 29.7%, 33.9 ± 9.3 kgf, and 603.0 ± 106.1 m, respectively. The best predictive model (R2 = 0.378, R2 adjusted = 0.280, standard error = 16.1, and P = 0.026) comprised the following regression equation: MFIS = 48.85 - (7.913 × IGF-I) + (1.483 × AC) - (23.281 × DYN). Conclusion Hormonal, vascular, and functional variables can predict general fatigue in patients with acromegaly.

Hearing Loss in Acromegaly - A Review

Abstract Introduction Acromegaly is a chronic disease caused by growth hormone (GH) excess due to a GH-secreting pituitary adenoma in most cases. There is reasonable data to presume the possible influence of chronic GH and insulin-like growth factor I (IGF-I) hyperproduction on the anatomical structures involved in normal sound perception, and on its conductive and/or sensorineural part. Objectives To review the literature about acromegaly and hearing loss. Data Synthesis A systematic literature search was performed using the MEDLINE database, including hand-searching reference lists from original articles. The search was performed using the terms hearing loss and acromegaly, and only 5 studies were found. Conclusion The results are not consistent, but led to different conclusions. Therefore, more studies with greater numbers of patients with acromegaly are needed.

Asociación entre cetoacidosis diabética y acromegalia / Association between diabetic ketoacidosis and acromegaly

La diabetes mellitus ocurre en cerca del 10% de los pacientes con acromegalia y es secundaria a la insulino resistencia causada por altos niveles de hormona de crecimiento. La cetoacidosis diabética ha sido descripta como una rara complicación de la acromegalia, resultado de una relativa deficiencia de insulina causada por exceso de hormona de crecimiento. Describimos el caso de un hombre de 38 años de edad que se presentó en el servicio de emergencias con historia de polifagia, polidispsia y poliuria con pérdida de peso de 6 semanas de evolución. Agregó en las últimas 48 horas náuseas, vómitos y dolor abdominal. A su ingreso, la glucosa plasmática fue 880 mg/dl, osmolaridad plasmática 368 mOsm/l, pH arterial 7.06 y bicarbonato plasmático 8.6 mEq/l. No tenía antecedentes personales ni familiares de diabetes. No se encontraron causas precipitantes de cetoacidosis. En el examen clínico presentaba características compatibles con acromegalia. La resonancia magnética nuclear mostró un macroadenoma pituitario y los dosajes de hormona de crecimiento fueron elevados. Luego de la resección del tumor, los niveles de glucosa plasmáticos resultaron normales. Este caso mostró la rara asociación de acromegalia con cetoacidosis diabética. La cirugía fue la modalidad definitiva de tratamiento.

Diabetes mellitus occurs in nearly 10% of patients with acromegaly and is secondary to insulin resistance caused by high levels of growth hormone. Diabetes ketoacidosis has been described as a rare complication of acromegaly, resulting from a relative insulin deficiency caused by growth hormone excess. We described the case of a 38 year-old man who presented to the emergency room with a 6-week history of polydipsia, polyuria, polyphagia and weight loss. He also had nausea, vomiting and abdominal pain from two days before admission. His plasma glucose level was 880 mg/dl, plasma osmolarity 368 mOsm/l, arterial pH 7.06 and serum bicarbonate 8.6 mEq/l. At the clinical examination, he had features of acromegaly. Magnetic resonance imaging showed a pituitary macro adenoma and growth hormone dosages were abnormally high. After tumor removal, plasma glucose levels became normal. This case shows the rare association between diabetic ketoacidosis and acromegaly. Surgery, in this case, was the definite modality of treatment.

Riesgo aumentado de lesiones colónicas preneoplásicas en acromegalia: estudio multicéntrico caso control. Resultados preliminares / Increased risk of pre-cancerous bowel lesions in acromegaly: Multicentre case-control study. Preliminary results

Introducción: El riesgo de desarrollar neoplasias colónicas en pacientes acromegálicos y su relación directa con los niveles elevados de GH/IGF-1 no están bien establecidos y continúan siendo motivo de controversia en la literatura mundial. El objetivo de este trabajo fue evaluar el riesgo de desarrollar lesiones neoplásicas avanzadas (LNA) (adenomas mayores a 1 cm, componente velloso mayor del 75% y/o displasia de alto grado), en pacientes con acromegalia, comparado con un grupo control. Materiales y métodos: Estudio multicéntrico caso-control retrospectivo. Ciento treinta y siete pacientes con acromegalia que realizaron videocolonoscopia (VCC) fueron incluidos inicialmente, aunque solo 69 cumplieron criterios de inclusión. Sesenta y dos controles fueron obtenidos: por cada caso (paciente con acromegalia) 2 «controles¼ fueron seleccionados aleatorizadamente e igualados por edad y sexo. El riesgo se expresó en odds ratio (OR) y su correspondiente intervalo de confianza (IC) del 95%. La significación estadística fue considerada una p < 0,05. Resultados: De los 69 pacientes con VCC completa y datos adecuados para su análisis, 28 presentaron VCC positiva con hallazgos de pólipos (40%) y 41 VCC negativa o normal (60%). Dentro del grupo con VCC positiva, 14 presentaron LNA (20%) y solo un paciente presentó diagnóstico de cáncer colorrectal. Para el análisis caso-control se incluyó a 31 pacientes frente al grupo control (n = 62) que cumplieron con los criterios de inclusión. La presencia de pólipos colónicos, adenomas y LNA en los pacientes con acromegalia fue de 19/31 (61,9%), 14/31 (45,16%) y 10/31 (32,25%), y en el grupo control de 18/62 (29,03%), 11/62 (17,74%) y 4/62 (6,45%), respectivamente. El riesgo de adenomas y LNA fue mayor en el grupo de acromegalia en comparación con el grupo control, siendo ambos resultados estadísticamente significativos: adenomas OR 2,54 (IC 1,22-5,25) p = 0,005, LNA OR: 7,3 (2,4-25), p = 0,00. Conclusión: La acromegalia se asocia a un mayor riesgo de lesiones colónicas preneoplásicas. Este hallazgo justifica el cribado con VCC al diagnóstico en pacientes con acromegalia.

Background: The risk of developing cancerous lesions in the colon of acromegaly patients and their direct relationship with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels is not well established, and is still controversial in the international literature. The objective of this study was to evaluate the risk of developing advanced neoplastic lesions (ALN: greater than 1 cm adenomas, villous component greater than 75% and/or high grade dysplasia) in patients with acromegaly compared to a control group. Materials and methods: A multicentre, retrospective case-control study was conducted initially on 137 patients with acromegaly (cases) who underwent videocolonoscopy (VCC), although only 69 met inclusion criteria. Sixty-two controls were obtained, and for each case two "controls" were randomly selected and matched by age and gender. Risk was expressed as odds ratio (OR) and its corresponding 95% con"dence interval (CI). P values < .05 were considered statistical significantly. Results: Of the 69 acromegaly patients with a completed VCC and adequate data for their analysis, 28 had a positive VCC with findings of polyps (40%), and 41 VCC negative with no lesions (60%). Within the group with positive VCC, 14 were ALN (20%) and one a colorectal cancer. In the case-control analysis, 31 cases were to be analysed against the control group (n = 62). The presence of colonic polyps, adenomas, and ALN in patients with acromegaly was 19/31 (61.9%), 14/31 (45.16%), and 10/31 (32.25%), respectively, and in the control group, it was 18/62 (29.03%), 11/62 (17.74%), and 4/62 (6.45%), respectively. The risk of adenomas and ALN was higher in the acromegaly group compared to the control group: adenomas OR: 2.54 (95% CI 1.22-5.25) P=.005, ALN OR: 7.3 (2.4-25) P=.00. Conclusion: This preliminary case control study showed an increased risk of pre-cancerous colprectal lesions in patients with acromegaly, supporting the VCC screening at diagnosis.

Síndrome de apneas del sueño: revisión de 25 años de experiencia / Sleep apnea syndrome: review of 25 years of experience / Síndrome da apnéia do sono: revisão de 25 anos de experiência

El conocimiento científico y clínico sobre los trastornos respiratorios del sueño se ha desarrollado de manera acelerada en las últimas décadas. El objetivo de este estudio es presentar la experiencia adquirida en nuestro país, en el diagnóstico y tratamiento del síndrome de apneas del sueño de tipo obstructivo, durante el desarrollo de una nueva disciplina en el ámbito de la neumología. Se revisaron los registros de 3109 pacientes; 447 con historias clínicas electrónicas y cuestionarios para cuantificación de síntomas y 1779 polisomnografías de pacientes con apneas de tipo obstructivo. Se presenta la evolución de la referencia de pacientes, las características demográficas (en especial el aumento de la prevalencia en jóvenes) y los hallazgos clínicos más frecuentes. Se destacan los factores de riesgo relevantes: obesidad y su relación con la severidad, enfermedades endocrinas y desplazamiento cefálico de fluidos. Se destaca el modo de acceso y la adherencia al tratamiento. La implementación de unidades clínicas de sueño permitió la referencia de pacientes para el diagnóstico y el tratamiento, dando lugar a una nueva disciplina de la neumología. La prevalencia de las apneas obstructivas del sueño es muy elevada, con progresivo y sostenido incremento. El tratamiento con aplicación de presión nasal no invasiva es factible. Aunque con distintos grados de accesibilidad y adherencia, ha permitido la corrección del trastorno respiratorio del sueño más relevante.

Scientific and clinical knowledge on sleep-disordered breathing has developed at an accelerated pace in the last decades. The objective of this study is to present the experience gained in our country in the diagnosis and treatment of obstructive sleep apnea syndrome during the development of a new discipline in the field of pneumology. Clinical records of 3109 patients were reviewed; 447 with electronic medical records and questionnaires for quantification of symptoms and 1779 polysomnographies of patients with obstructive apneas. The time evolution of the patient referral, the demographic characteristics (especially the increase in the prevalence in young people) and the most frequent clinical findings are presented. We highlight the relevant risk factors: obesity and its relationship with severity, endocrine diseases and cephalic fluid displacement. Access mode and adherence to treatment are highlighted. The implementation of sleep clinics allowed the referral of patients for diagnosis and treatment, giving rise to a new discipline of pneumology. The prevalence of obstructive sleep apnea is high, with progressive and sustained increase. Treatment with non-invasive nasal pressure application is feasible. Although with different degrees of accessibility and adherence, it has allowed the correction of the most relevant respiratory sleep disorder

O conhecimento científico e clínico sobre os transtornos respiratórios do sono desenvolveu-se rapidamente nas últimas décadas. O objetivo deste estudo é apresentar a experiência adquirida em nosso país no diagnóstico e tratamento da síndrome da apneia obstrutiva do sono durante o desenvolvimento de uma nova disciplina no campo da pneumologia. Os registros de 3109 pacientes foram revisados; 447 com registros médicos eletrônicos e questionários para quantificação de sintomas e 1779 polissonografias de pacientes com apnéia obstrutiva. Apresentamos a evolução da referência do paciente, as características demográficas (especialmente o aumento da prevalência em jovens) e os achados clínicos mais freqüentes. Destacamos os fatores de risco relevantes: obesidade e sua relação com severidade, doenças endócrinas e deslocamento do cefálico de fluídos. O modo de acesso e a adesão ao tratamento são destacados. A implementação de unidades de sono clínicas permitiu a referência de pacientes para diagnóstico e tratamento, dando origem a uma nova disciplina de pneumologia. A prevalência da apneia obstrutiva do sono é muito alta, com aumento progressivo e sustentado. O tratamento com pressão nasal não invasiva é viável. Embora com diferentes graus de acessibilidade e adesão, permitiu a correção do transtorno do sono respiratório mais relevante.

Malignant ventricular tachycardia in acromegaly: a case report / Taquicardia ventricular maligna na acromegalia: relato de caso

CONTEXT: In patients with acromegaly, cardiovascular complications are the main cause of death; sudden death has been associated with ventricular tachyarrhythmias. In other patients with life-threatening malignant ventricular tachyarrhythmias, surgical placement of an implantable cardioverter-defibrillator (ICD) has proved highly effective in reducing sudden death rates. CASE REPORT: The present article reports the case of a 50-year-old male acromegalic patient who presented symptoms of syncope induced by ventricular tachycardia. An ICD was surgically implanted and a pituitary adenoma, which was responsible for the acromegaly, was completely removed in the same procedure. The surgery was successful and the ventricular arrhythmias were effectively terminated. During six months of follow-up, no documented arrhythmic episodes occurred. CONCLUSION: In patients with acromegaly, malignant ventricular tachyarrhythmia might be effectively controlled by implantation of an ICD and surgical removal of the pituitary adenoma. .

CONTEXTO: As complicações cardiovasculares são a principal causa de morte em pacientes com acromegalia, e a morte súbita tem sido associada a taquiarritmias ventriculares. Em outros pacientes com risco de vida por taquiarritmias ventriculares malignas, a aplicação cirúrgica de um cardioversor-desfibrilador implantável (CDI) provou ser altamente eficaz na redução das taxas de morte súbita. RELATO DE CASO: O presente artigo relata o caso de um paciente acromegálico de 50 anos de idade e do sexo masculino, que apresentava sintomas de síncope induzida por taquicardia ventricular. Foi implantado cirurgicamente nesse paciente um CDI e na mesma intervenção cirúrgica foi completamente removido um adenoma hipofisário responsável pela acromegalia. A cirurgia foi bem-sucedida e o paciente deixou de sofrer de arritmias ventriculares. Durante seis meses de acompanhamento, não se documentaram, nesse paciente, episódios arrítmicos. CONCLUSÃO: A taquiarritmia ventricular maligna pode ser efetivamente controlada em pacientes com acromegalia pela implantação de um CDI combinado com a remoção cirúrgica do adenoma hipofisário. .

Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center / Prevalência das doenças tireoidianas em pacientes com acromegalia: experiência de um centro brasileiro

OBJECTIVES: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS: We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS: Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS: Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.

OBJETIVOS: Acromegalia está frequentemente associada a doenças tireoidianas. Neste estudo, avaliamos a presença de tireoidopatias em uma série de pacientes acromegálicos. SUJEITOS E MÉTODOS: Foram avaliados 106 pacientes por ultrassonografia (US) e dosagens de GH, IGF-1, T4 livre, TSH e anticorpo antitireoperoxidase. O IGF-I foi expresso em unidades de massa e desvio-padrão (DP-IGF-I). Punção aspirativa por agulha fina (PAAF) foi realizada quando os nódulos eram maiores que um centímetro ou tinham características suspeitas. RESULTADOS: Alterações tireoidianas foram encontradas em 75 pacientes. Onze apresentavam bócio difuso, 42, bócio nodular e 22, alterações morfológicas inespecíficas. Houve quatro casos (3,8%) de câncer diferenciado de tireoide. Considerando os pacientes com bócio difuso ou nodular, o volume tireoidiano foi maior naqueles com acromegalia em atividade e correlacionou-se positivamente com os níveis de GH, IGF-1 e DP-IGF-1. CONCLUSÕES: Nosso estudo confirmou que as doenças tireoidianas benignas são frequentes nos pacientes acromegálicos. A prevalência de câncer diferenciado de tireoide foi maior que na população geral. Sugerimos que US de tireoide seja realizado rotineiramente nos pacientes com acromegalia.

Frequency of various types of neoplasia in a group of acromegalic patients / Frequência de neoplasia de diversos tipos em um grupo de pacientes acromegálicos

OBJECTIVE: To determine the frequency of colon cancer, primary hyperparathyroidism, thyroid tumor, and skin cancer in all acromegalic patients in follow-up at the Clinics Hospital - Botucatu Medical School, from 2005 to 2011. SUBJECTS AND METHODS: These patients were evaluated retrospectively for colon cancer, primary hyperparathyroidism, dermatological, and thyroid tumors. RESULTS: Of 29 patients included at the beginning of the study, two were excluded. Among 19 patients submitted to colonoscopy, one presented colon adenocarcinoma (5%). Thyroid nodules were present in 63% of patients, and papilliferous carcinoma was confirmed in two patients (7,7%). Four patients were confirmed as having primary hyperparathyroidism (15%). The most common dermatologic lesions were thickened skin (100%), acrochordons (64%), epidermal cysts (50%), and pseudo-acanthosis nigricans (50%). Only one patient presented basal cell carcinoma. CONCLUSION: Although a small number of acromegalic patients was studied, our findings confirm the high frequency of thyroid neoplasias and primary hyperparathyroidism in this group of patients.

OBJETIVO: Determinar a frequência de câncer de cólon, hiperparatireoidismo primário, tumores de tireoide e pele em todos os acromegálicos em seguimento no Hospital de Clínicas da Faculdade de Medicina de Botucatu de 2005 a 2011. SUJEITOS E MÉTODOS: Esses pacientes foram avaliados retrospectivamente quanto a presença de câncer de cólon, hiperparatiroidismo primário, tumores da tiroide e pele. RESULTADOS: Dos 29 pacientes incluídos no início do estudo, dois foram excluídos. Dentre os 19 pacientes submetidos à colonoscopia, um apresentou adenocarcinoma de cólon (5%). Nódulos de tireoide estiveram presentes em 65% dos pacientes e carcinoma papilífero, em dois deles (7,7%). Quatro pacientes apresentaram hiperparatireoidismo primário (15%). A maioria das lesões de pele foram: espessamento (100%), acrochordons (64%), cistos epidérmicos (50%), pseudoacantose nigricans (50%) e apenas um paciente apresentou carcinoma basocelular. CONCLUSÃO: O tamanho da amostra é pequeno, mas nossos achados confirmam a alta frequência da neoplasia da tireoide e hiperparatireroidismo neste grupo de pacientes.

Genetic studies in a coexistence of acromegaly, pheochromocytoma, gastrointestinal stromal tumor (GIST) and thyroid follicular adenoma / Estudos genéticos na coexistência de acromegalia, feocromocitoma, tumor do estroma gastrointestinal (GIST) e adenoma folicular de tireoide

We report on an adult woman with rare coexistence of acromegaly, pheochromocytoma (PHEO), gastrointestinal stromal tumor (GIST), intestinal polyposis, and thyroid follicular adenoma. At the age of 56, she was diagnosed with acromegaly caused by a pituitary macroadenoma, treated by transsphenoidal surgery, radiotherapy, and octreotide. During routine colonoscopy, multiple polyps were identified as tubular adenomas with high-grade dysplasia on histology. Years later, an abdominal mass of 8.0 x 6.2 cm was detected by routine ultrasound. Surgical exploration revealed an adrenal mass and another tumor adhered to the lesser gastric curvature, which were removed. Pathology confirmed the diagnosis of PHEO and GIST. PHEO immunohistochemistry was negative for GHRH. During follow-up, nodular goiter was found with normal levels of calcitonin and inconclusive cytology. Near-total thyroidectomy was performed, revealing a follicular adenoma. Her family history was negative for all of these tumor types. Genetic analysis for PHEO/paraganglioma genes (SDH A-D, SDHAF2, RET, VHL, TMEM127, and MAX), and pituitary-related genes (AIP, MEN1, and p27) were negative. Though the finding of PHEO and acromegaly with multiple other tumors could be a fortuitous coexistence, we suggest that this case may represent a new variant of MEN syndrome with a de novo germline mutation in a not yet identified gene. Arq Bras Endocrinol Metab. 2012;56(8):507-12.

Relatamos o caso de uma mulher com rara coexistência de acromegalia, feocromocitoma (FEO), tumor do estroma gastrointestinal (GIST), polipose intestinal e adenoma folicular de tireoide. Aos 56 anos, ela foi diagnosticada com acromegalia por um macroadenoma hipofisário, tratado com cirurgia transesfenoidal, radioterapia e octreotide. Uma colonoscopia de rotina detectou múltiplos pólipos, que à histologia eram adenomas tubulares com alto grau de displasia. Anos mais tarde, uma ecografia detectou uma massa abdominal de 8.0 x 6.2 cm, que na exploração cirúrgica era uma lesão adrenal e outro tumor aderido à pequena curvatura gástrica. A patologia confirmou os diagnósticos de FEO e GIST. A imuno-histoquímica do FEO foi negativa para GHRH. No seguimento, encontrou-se um bócio nodular com níveis normais de calcitonina e citologia inconclusiva. Após tireoidectomia total o diagnóstico histológico foi de adenoma folicular. A história familiar era negativa para todos esses tumores. As análises genéticas para genes de síndromes de FEO/paragangliomas (SDH A-D, SDHAF2, RET, VHL, TMEM127 e MAX) e para hipofisárias (AIP, MEN1 e p27) foram todas negativas. Embora a presença de FEO e acromegalia com múltiplos outros tumores possa ser uma coexistência fortuita, acreditamos na possibilidade de uma nova variante de NEM com uma mutação germinativa de novo em um gene ainda não identificado Arq Bras Endocrinol Metab. 2012;56(8):507-12.

Perda auditiva sensorioneural em pacientes com acromegalia em tratamento / Sensorineural hearing loss in acromegalic patients under treatment

Acromegalia é uma doença endócrina rara. Poucos estudos avaliaram sua associação com deficiência auditiva (DA) e os resultados são conflitantes. OBJETIVOS: Avaliar a prevalência e características da DA em um grupo de pacientes com acromegalia em tratamento. Analisar a transmissão auditiva central e periférica. MATERIAL E MÉTODOS: Estudo transversal. Um grupo de 34 pacientes com acromegalia submeteu-se à avaliação metabólica, audiometria tonal e potenciais evocados auditivos de tronco encefálico (PEATE). Considerou-se DA quando a média dos tons puros foi > 25 DBNA para baixas frequências (250, 500, 1000 e 2000 Hz) ou altas frequências (3000, 4000, 6000 e 8000 Hz). Os pacientes foram divididos em grupo A (com DA) e B (sem DA). RESULTADOS: Doze pacientes (35,3%) mostraram DA sensorioneural (grupo A), sendo oito bilateral e quatro unilateral. Nenhum apresentou DA mista ou condutiva. A prevalência de diabetes/intolerância à glicose de jejum foi similar entre os grupos. As frequências de 3000, 4000, 6000 e 8000 Hz foram as mais afetadas e com padrão similar em ambos os lados. CONCLUSÃO: DA sensorioneural esteve presente em 35,3% dos casos. Não foram notadas diferenças clínicas ou metabólicas significativas entre os grupos, bem como na transmissão neural auditiva periférica e central.

Acromegaly is a rare endocrine disease. Few studies have evaluated its association with hearing loss (HL) and the results are conflicting. AIM: To evaluate the prevalence and features of HL in a group of patients being treated for acromegaly. To analyze peripheral and central auditory transmission. METHODS: Cross-sectional study. A group of 34 patients with acromegaly were submitted to metabolic evaluation, tonal audiometry and brainstem auditory evoked potentials. HL was considered when pure tone average was > 25 DBHL for low frequencies (250, 500, 1000 and 2000 Hz) or high frequencies (3000, 4000, 6000 and 8000 Hz). The patients were divided in group A (with HL) and B (without HL). RESULTS: Twelve patients (35.3%) had sensorineural HL (Group A), being 8 bilateral and 4 unilateral. No one had mixed or conductive HL. The prevalence of diabetes/impaired glucose tolerance was similar between the groups. The frequencies 3000, 4000, 6000 and 8000 Hz were the most affected and with a similar pattern in both ears. CONCLUSION: sensorineural HL was found in 38.9% of cases. Neither clinical nor metabolic differences were noted between the groups, as well as in regards to peripheral and central auditory transmission.

Thyroid nodules in acromegaly / Nódulos tiroideanos na acromegalia

OBJECTIVE: We made a prospective study evaluating the prevalence of thyroid nodular disease in acromegalic patients. SUBJECTS AND METHODS: Thyroid ultrasound and ultrasound-guided fine needle aspiration biopsy were performed when nodules were detected. Nodules were characterized by cytology and histopathology. RESULTS: We found high prevalence of nodular thyroid disorder, 23/34 (67%) in acromegalic patients. High risk and malignant cytology were significantly higher in acromegalic patients than in our non-acromegalic population (25% vs. 9%). Differentiated thyroid carcinoma was present in 11% of the acromegalic patients. CONCLUSIONS: We strongly recommend periodic thyroid evaluation by ultrasound in patients with acromegaly. Fine needle aspiration biopsy should be performed in nodules larger than 10 mm, and in all suspicious nodules, regardless of the size.

OBJETIVO: Realizamos um estudo prospectivo avaliando a prevalência de patologia nodular tireói­dea em 34 pacientes acromegálicos. SUJEITOS E MÉTODOS: Avaliamos os pacientes com ecografia tireóidea e punção biópsia com agulha fina quando se detectavam nódulos. RESULTADOS: Encontramos uma alta prevalência de patologia nodular tireóidea 23/34 (67%) em acromegálicos. A citologia tireóidea de alto risco e maligna foi significativamente mais elevada em pacientes acromegálicos que em uma população não acromegálica (25% vs. 9%). O grupo acromegálico apresentou carcinoma diferenciado de tireoides em 11%. CONCLUSÕES: Recomendamos fortemente a ecografia periódica tireóidea em pacientes acromegálicos. Uma punção biópsia aspirativa com agulha fina deve ser realizada em presença de nódulos tireóideos maiores que 10 mm e daqueles com critérios ecográficos suspeitos de malignidade, independentemente do tamanho deles.

The use of nasal dilator strips as a placebo for trials evaluating continuous positive airway pressure

OBJECTIVES: The aim of the current study was to compare the objective and subjective effects of continuous positive airway pressure to the use of nasal dilator strips in patients with acromegaly and moderate to severe obstructive sleep apnea. METHODS: We studied 12 patients with acromegaly and moderate to severe obstructive sleep apnea (male/ females = 8/4, age = 52±8 ys, body mass index = 33.5±4.6 Kg/m², apnea-hypopnea index = 38±14 events/h) who had been included in a randomized, crossover study to receive three months of treatment with continuous positive airway pressure and nasal dilator strips. All patients were evaluated at study entry and at the end of each treatment by polysomnography, and Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and treatment satisfaction questionnaires. ClinicalTrials.gov: NCT01265121 RESULTS: The apnea-hypopnea index values decreased significantly with continuous positive airway pressure treatment but did not change with the use of nasal dilator strips. All of the subjective symptoms improved with both treatments, but these improvements were significantly greater with continuous positive airway pressure than with the nasal dilator strips CONCLUSION: The use of nasal dilator strips had a much smaller effect on the severity of obstructive sleep apnea in patients with acromegaly and moderate to severe obstructive sleep apnea in comparison to the use of continuous positive airway pressure. Moreover, the improvement in several subjective parameters without any significant objective improvement in obstructive sleep apnea resulting from the use of nasal dilator strips is compatible with a placebo effect.

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.

Guía para la evaluación y preparación preoperatoria de los pacientes neuroquirúrgicos de coordinación / Guidelines for the preoperative evaluation and preparation of coordination neurosurgical patients

En neurocirugía, la valoración pre anestésica habitual debe complementarse de acuerdo a la patología quirúrgica, debido a que algunos casos se asocian con problemas anestésicos específicos como dificultad de intubación, enfermedad cardíaca y alteraciones endócrinas. La presente revisión expone dichos casos organizándolos de acuerdo al siguiente esquema: lesiones de la región selar (tumores de hipófisis y cráneofaringioma), deformidades cráneofaciales (cráneosinostosis) y disrafias espinales. Dicho esquema no incluye las patologías neuroquirúrgicas que no requieren per se de valoración pre anestésica diferente al común de los pacientes. Para cada patología se presenta el esquema diagnóstico de las alteraciones anatómicas y fisiológicas que podrán originar problemas anestésicos, así como su enfoque terapéutico perioperatorio de modo de facilitar la tarea del anestesiólogo actuante.

Manejo multidisciplinario de la acromegalia / Multidisciplinary management of acromegaly

Acromegaly is a chronic disease caused in most cases by hypophysiary adenoma. It is of complex management due to the high variability of the causing lesion and its clinical repercussion. Surgical outcomes are poor with remission rates of 80 percent for microadenomas and 50 percent for macroadenomas. The author's experience in treating 38 patients with this pathology as well as the remission results of the illness and the complications are presented herein. Handling alternatives and associated complications are discussed and a clinical case is presented to show the therapeutical options in more complex cases.

La acromegalia es una enfermedad crónica causada en la mayoría de los casos por un adenoma hipofisario. Su manejo es complejo por la gran variabilidad de la lesión causante y su repercusión clínica. Los resultados quirúrgicos son pobres, con tasas de remisión de la enfermedad en promedio de un 80 por ciento en microadenomas y 50 por ciento en macroadenomas. Se presenta la experiencia del autor en el manejo de esta patología en 38 pacientes, los resultados de remisión de la enfermedad. Se discute las alternativas de manejo, complicaciones asociadas y se ilustra con un caso clínico para demostrar las opciones terapéuticas en los casos más complejos.