Brazilian multicenter study on pegvisomant treatment in acromegaly

ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.

A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors’ experience. Arch Endocrinol Metab. 2016;60(4):374-90.

Recommendations of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism for the diagnosis of Cushing's disease in Brazil

ABSTRACT Although it is a rare condition, the accurate diagnosis and treatment of Cushing’s disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing’s syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushing’s syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing’s disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86.

Prevalence of lung structure abnormalities in patients with acromegaly and their relationship with gas exchange: cross-sectional analytical study with a control group / Prevalência de alterações na estrutura pulmonar em pacientes com acromegalia e sua relação com a troca gasosa: estudo transversal analítico com grupo controle

CONTEXT AND OBJECTIVE: Different functional respiratory alterations have been described in acromegaly, but their relationship with pulmonary tissue abnormalities is unknown. The objective of this study was to observe possible changes in lung structure and explain their relationship with gas exchange abnormalities. DESIGN AND SETTING: Cross-sectional analytical study with a control group, conducted at a university hospital. METHODS: The study included 36 patients with acromegaly and 24 controls who were all assessed through high-resolution computed tomography of the thorax (CT). Arterial blood gas, effort oximetry and serum growth hormone (GH) and insulin-like growth factor I (IGF-1) were also assessed in the patients with acromegaly. RESULTS: The abnormalities found in the CT scan were not statistically different between the acromegaly and control groups: mild cylindrical bronchiectasis (P = 0.59), linear opacity (P = 0.29), nodular opacity (P = 0.28), increased attenuation (frosted glass; P = 0.48) and decreased attenuation (emphysema; P = 0.32). Radiographic abnormalities were not associated with serum GH and IGF-1. Hypoxemia was present in seven patients; however, in six of them, the hypoxemia could be explained by underlying clinical conditions other than acromegaly: chronic obstructive pulmonary disease in two, obesity in two, bronchial infection in one and asthma in one. CONCLUSION: No changes in lung structure were detected through thorax tomography in comparison with the control subjects. The functional respiratory alterations found were largely explained by alternative diagnoses or had subclinical manifestations, without any plausible relationship with lung structural factors.

CONTEXTO E OBJETIVO: Diferentes alterações funcionais respiratórias são descritas na acromegalia. Sua relação com anormalidades do tecido pulmonar é desconhecida. O objetivo foi observar possíveis alterações da estrutura pulmonar e explicar sua relação com anormalidades da troca gasosa. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, com grupo de controle, realizado em um hospital universitário. MÉTODOS: Incluíram-se 36 pacientes com acromegalia e 24 controles que foram avaliados com tomografia computadorizada de alta resolução de tórax (TC); os acromegálicos também foram avaliados com gasometria arterial, oximetria de esforço e dosagens de hormônio de crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). RESULTADOS: As alterações encontradas na TC não foram estatisticamente diferentes entre os grupos acromegálico e de controle: bronquiectasia cilíndrica leve (P = 0,59), opacidades lineares (P = 0,29), opacidades nodulares (P = 0,28), aumento da atenuação (vidro fosco) (P = 0,48) e redução da atenuação (enfisema; P = 0,32). As alterações radiológicas não se relacionaram com as dosagens de GH e IGF-1. Hipoxemia estava presente em sete pacientes; contudo, em seis deles a hipoxemia poderia ser explicada por condição clínica subjacente diversa da acromegalia: doença pulmonar obstrutiva crônica em dois, obesidade em dois, infecção brônquica em um e asma em um. CONCLUSÕES: Não foram observadas alterações da estrutura pulmonar por tomografia de tórax, quando comparadas ao grupo de controle; as alterações funcionais respiratórias encontradas são explicáveis em grande parte por diagnósticos alternativos, ou se manifestam de forma subclínica, não apresentando relação plausível com o aspecto da estrutura pulmonar.

Increasing levels of phytase in diets formulated with reduced available phosphorus content supplied to male and female broilers / Níveis crescentes de fitase em dietas formuladas com reduzido teor de fósforo disponível, fornecidas a frangos de corte machos e fêmeas

The reduction of the available phosphorus (avP) content in the broiler diet must be followed by the supplementation of adequate phytase. One experiment was conducted with broilers from 15 to 28 days of age to determine the level of necessary phytase when the mashed diet is formulated with 0.213% of avP to enable the results of performance, tibia ash content, and calcium (Ca) utilization similar to those determined for birds fed with diet formulated to meet their nutritional requirements. Thus, 120 broilers were distributed in (4+1) x2 factorial arrangement corresponding to four deficient diets in avP (0.213%) supplemented with phytase (0; 750; 1,500 or 2,250FTU kg-1) plus one positive control diet without phytase (0.426% of avP), supplied to male and female broilers. Males showed better performance and higher totalP retention. Decrease in the avP content of the diet without phytase use worsened the performance, tibia ash content, and Ca retention; however, these parameters were improved gradually with the increase of the phytase level in the diet. Regardless of sex, using 2,250FTU kg-1, it is possible to reduce the avP to 0.213% without impairing performance, tibia ash content, and Ca retention; in addition to reducing the totalP excretion in 56.75% and improving its utilization in 38.58%.

A redução do teor de fósforo disponível (Pdisp) na dieta de frangos deve ser acompanhada de adequada suplementação da fitase. Um experimento foi conduzido com frangos de corte, no período de 15 a 28 dias de idade, para determinar o nível de fitase necessário quando a ração farelada é formulada com 0,213% de Pdisp para permitir resultados de desempenho, teor de cinzas na tíbia e aproveitamento do cálcio (Ca) semelhantes ao determinado para aves alimentadas com uma dieta formulada para atender suas exigências nutricionais. Desse modo, 120 frangos foram distribuídos em esquema fatorial (4+1) x2, correspondendo a quatro rações deficientes em Pdisp (0,213%) suplementadas com fitase (0; 750; 1.500 ou 2.250FTU kg-1) mais uma ração controle positivo sem fitase (0,426% de Pdisp), fornecidas a frangos machos e fêmeas. Os machos apresentaram melhor desempenho e maior retenção de Ptotal. A redução do teor de Pdisp da dieta sem o uso de fitase piorou o desempenho, o teor de cinzas ósseas e a retenção do Ca, todavia, esses parâmetros foram gradativamente melhorados com o aumento do nível de fitase na ração. Independente do sexo, ao utilizar 2.250FTU kg-1, é possível reduzir o teor de Pdisp para 0,213% sem prejudicar o desempenho, teor de cinzas na tíbia e a retenção do Ca, além de reduzir a excreção do Ptotal em 56,75% e melhorar seu aproveitamento em 38,58%.

Níveis da bacitracina de zinco como melhorador do desempenho de frangos de corte / Levels of zinc bacitracin used to improve the performance of broilers

A utilização de antimicrobianos melhoradores de desempenho na criação de frangos de corte é uma prática comum na indústria avícola e, no Brasil, seu uso deve ser feito de acordo com os limites determinados pelo Ministério da Agricultura Pecuária e Abastecimento (MAPA).Objetivou-se com o presente trabalho determinar o efeito da utilização da bacitracina de zinco, dentro dos níveis recomendados pelo Ministério da Agricultura Pecuária e Abastecimento (MAPA), em dietas para frangos de corte sobre o desempenho de aves e criadas de 1 a 42 dias de idade. Utilizou-se o delineamento inteiramente casualizado, com 5 tratamentos, distribuídos em 10 repetições de 25 pintos machos de corte da linhagem Cobb 500®, totalizando 1250 aves. Os tratamentos experimentais foram constituídos de cinco níveis de inclusão de bacitracina de zinco (0, 10, 25, 40 e 55ppm). As variáveis analisadas foram consumo de ração, ganho de peso, conversão alimentar e avaliação econômica das dietas. Para o período total de criação, avaliou-se também a viabilidade dos frangos de corte. A bacitracina de zinco foi eficiente como beneficiador do desempenho de frangos de corte criados no período de 1 a 21, 1 a 35 e 1 a 42 dias. Para o período de 1 a 21 dias, o uso de 55 e 29,3ppm de bacitracina de zinco resultou em menor consumo de ração e maior ganho de peso, respectivamente. No geral, a melhor conversão alimentar foi obtida quando se adicionou 55ppm de bacitracina de zinco na ração de frangos de corte.

The use of growth promoters in the broilers production is a common practice in the poultry industry and its use must be made accordance with limits in Brazil set by the Ministry of Agriculture, Livestock and Supply (MAPA).The main objective of this study was to verify the effect of the use of zinc bacitracin, within the levels recommended by the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA), in broiler diets for the performance of birds from 1 to 42 days old. We used a randomized design with five treatments in 10 replications of 25 male chicks from Cobb cut 500®, totaling 1250 birds. The treatments consisted of five inclusion levels of zinc bacitracin (0, 10, 25, 40 and 55ppm). The variables studied were feed intake, weight gain, feed conversion and economic evaluation of feed. For the breeding period as a whole, this study also evaluated the viability of broilers. Zinc bacitracin was effective as growth promoter of broilers reared during 1 to 21, 1 to 35 and 1 to 42 days. For the period 1-21 days, using 55 and 29.3ppm of zinc bacitracin resulted in a lower feed intake and increased weight gain, respectively. In general, the best feed conversion was obtained when 55ppm of zinc bacitracin was added to the feed of broilers.

Physical activities in daily life and functional capacity compared to disease activity control in acromegalic patients: impact in self-reported quality of life / Avaliação da atividade física na prática de vida diária comparada com o nível de atividade da doença em pacientes acromegálicos: impacto na percepção da qualidade de vida

OBJECTIVE: To evaluate the quality of life and its association with daily physical activity and disease control in acromegalic patients. SUBJECTS AND METHODS: A cross-sectional, case series study, composed of 42 patients recruited from the Neuroendocrinology Unit of the University Hospital of Brasilia. Level of physical activity was accessed by the International Physical Activity Questionnaire (IPAQ 6-short-form), which evaluates the weekly time spent on physical activity of moderate to vigorous intensity in different contexts of life. Quality of life was evaluated by The Medical Outcome Study Questionnaire Short Form (SF-36). Data was compared to growth hormone (GH) and insulin-like growth factor (IGF-1) levels. Students' t test and Fisher test were used, p < 0.05, SPSS 17.0. RESULTS: Twenty-two women, aged 51.33 ± 14.33 and 20 men, aged 46.2 ± 13.18 were evaluated. Arthralgia was present in 83% of cases. In men, the most common sites of pain were the knees (73%), spine (47% lumbar, and 53% thoracic and cervical segments), hands and wrists (40%). Higher scores on SF-36 were observed in patients with intermediate or high levels of physical activity, in the domains social functioning (75 CI 57.3-92.6), general health (75.5 CI 60.4-90.5), mental health (70 CI 57.8-82.1). CONCLUSIONS: In this study, the presence and severity of physical disability and pain were not associated with initial GH and IGF-1 levels or time of exposure to GH excess. However, the patients considered controlled, with normal a normal age-adjusted IGF-1, presented higher scores in SF-36, in physical and emotional domains, compared with patients with persistent hypersomatotrophism. These findings suggest benefits of metabolic control in self-reported quality of life.

OBJETIVO: Avaliar a qualidade de vida e sua associação com a prática de vida diária e controle metabólico em pacientes portadores de acromegalia. SUJEITOS E MÉTODOS: Estudo seccional de série de casos, composto por 42 pacientes recrutados na Unidade de Neuroendocrinologia do Hospital Universitário de Brasília. O nível de atividade física foi estimado pelo Questionário Internacional de Atividade Física (IPAQ-6), que avalia o tempo gasto semanalmente em atividades físicas que variam de intensidade em diferentes contextos de vida. A qualidade de vida foi avaliada pelo questionário SF-36. Os dados obtidos foram comparados aos níveis de hormônio do crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). Os testes t Students e Fisher foram aplicados e p < 0,05 foram considerados significativos, SPSS 17.0. RESULTADOS: Avaliaram-se 22 mulheres com idades de 51,33 ± 14,33 e 20 homens com idades de 46,2 ±13,18. Artralgia foi relatada em 83% dos pacientes. Em homens, os sítios de dor mais comuns foram os joelhos (73%), coluna vertebral (47% lombar, 53% segmentos torácico e cervical), mãos e quadris (40%). Os maiores escores no SF-36 foram observados em pacientes com níveis intermediário ou alto de atividade física, sobretudo nos domínios social (75 CI 57,3-92,6), saúde geral (75,5 CI 60,4-90,5), saúde mental (70 CI 57,8-82,1). CONCLUSÕES: A presença e a severidade do prejuízo no desempenho físico e dor não se associaram com Gh e IGF-1 no diagnóstico, tempo de exposição prévio à doença. Todavia, pacientes considerados controlados apresentaram melhores escores nos domínios físico e emocional, comparados com pacientes com hipersomatotrofismo persistente. Tais achados sugerem benefícios do controle metabólico na qualidade de vida.

Clinical and laboratorial characterization and post-surgical follow-up of 87 patients with non-functioning pituitary macroadenomas / Caracterização clínica e laboratorial e seguimento pós-cirúrgico de 87 portadores de macroadenomas hipofisários não funcionantes

Objective: It was to assess the main characteristics of patients undergoing pituitary tumor surgery. Method: Eighty-seven patients (44 men; 44.8±13 years old) were included. Results: The main symptoms were visual alterations (87.3%), headache (70.1%), diminished libido (34.4%), galactorrhea (22.9%) and hair loss (19.5%). The axes affected were gonadotropic (72.6%), thyrotropic (48.4%) and corticotropic (38.7%), without significant changes after surgery. The average largest tumor diameter was 3.1 cm before surgery and 1.56 cm after surgery. The most frequent postoperative complications were hydro-electrolyte and acid-base disorders (12%), diabetes insipidus (9%), visual field alterations (9%), liquoric fistula (8%) and nasal obstruction (7%). The patients were affected by more than one complication. Conclusion: Although a decrease in tumor volume was achieved through surgery, hormonal deficiencies persisted in most of the patients and new surgical approaches were necessary for dealing with tumor recurrence or persistence. .

Objetivo: Avaliar as principais características de pacientes operados de tumor de hipófise. Método: Foram incluídos 87 pacientes (44 homens; 44,8±13 anos). Resultados: Os principais sintomas foram alterações visuais (87,3%), cefaleia (70,1%), diminuição da libido (34,4%), galactorreia (22,9%) e queda de pelos (19,5%). Os eixos afetados foram gonadotrófico (72,6%), tireotrófico (48,4%) e corticotrófico (38,7%). Não houve mudanças significativas após a cirurgia. A média do maior diâmetro do tumor foi 3,1 cm antes da cirurgia e 1,56 cm após a cirurgia. As complicações pós-cirúrgicas mais frequentes foram distúrbios hidroeletrolíticos e ácido-básicos (12%), diabetes insipidus (9%), alterações do campo visual (9%), fístula liquórica (8%) e obstrução nasal (7%). Ocorreu mais de uma complicação no mesmo paciente. Conclusão: Embora tenha obtido diminuição da massa tumoral com a cirurgia, as deficiências hormonais persistiram na maioria dos pacientes e ocorreu necessidade de novas abordagens por recidiva ou persistência do tumor. .

Activity of fungal phytases stored in two ways in response to the period of storage at room temperature / Atividade de fitases fúngicas armazenadas de duas maneiras em resposta ao período de armazenamento à temperatura ambiente

Two distinct experiments were conducted simultaneously with phytases of Aspergillus oryzae and A. niger for determining enzyme activity in response to storage period (up to 180 days at room temperature - RT). In the first experiment, enzymes were stored as they were acquired (pure form) and the activity was measured periodically during 180 days of storage at RT. In the second experiment, the phytases were incorporated to a supplement containing vitamins, minerals, and amino acids; and then this supplement was stored at RT up to 180 days, so that every 30 days of storage was collected one aliquot from each replicate for determining enzymatic activity. In conclusion, the phytase activity is affected by storage duration. To ensure 80 percent of the initial activity, the phytases of A. oryzae and A. niger can be stored in the pure forms for up to 53 and 135 days at RT, respectively. However, if the phytases of A. oryzae and A. niger are incorporated to a supplement containing vitamins, minerals, and amino acids then the storage period at RT should not exceed 67 and 77 days, respectively.

Dois experimentos distintos foram realizados simultaneamente com fitases de Aspergillus oryzae e A. niger para a determinação da atividade enzimática em resposta ao período de armazenamento (por até 180 dias em temperatura ambiente - TA). No primeiro experimento, as enzimas foram armazenadas como adquiridas (forma pura) e a atividade foi determinada periodicamente durante 180 dias de armazenamento em TA. No segundo experimento, as fitases foram incorporadas a um suplemento contendo vitaminas, minerais e aminoácidos. Então este suplemento foi armazenado em TA por até 180 dias, de modo que, a cada 30 dias de armazenamento, uma alíquota de cada repetição foi coletada para a determinação da atividade enzimática. Conclui-se que a atividade da fitase é afetada pela duração do armazenamento. Para assegurar 80 por cento da atividade inicial, as fitases de A. oryzae e A. niger podem ser armazenadas nas formas pura por até 53 e 135 dias em TA, respectivamente. Entretanto, se as fitases de A. oryzae e A. niger são incorporadas a um suplemento contendo vitaminas, minerais e aminoácidos, o período de armazenamento em TA não deve exceder 67 e 77 dias, respectivamente.

Clinical and genetic aspects of familial isolated pituitary adenomas

Pituitary adenomas represent a group of functionally diverse neoplasms with relatively high prevalence in the general population. Most occur sporadically, but inherited genetic predisposing factors are increasingly recognized. Familial isolated pituitary adenoma is a recently defined clinical entity, and is characterized by hereditary presentation of pituitary adenomas in the absence of clinical and genetic features of syndromic disease such as multiple endocrine neoplasia type 1 and Carney complex. Familial isolated pituitary adenoma is inherited in an autosomal dominant manner and accounted for approximately 2-3% of pituitary tumors in some series. Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. Pituitary adenomas with mutations of the aryl-hydrocarbon interacting protein gene are predominantly somatotropinomas and prolactinomas, but non-functioning adenomas, Cushing disease, and thyrotropinoma may also occur. These tumors may present as macroadenomas in young patients and are often relatively difficult to control. Furthermore, recent evidence indicates that aryl-hydrocarbon interacting protein gene mutations occur in >10% of patients with sporadic macroadenomas that occur before 30 years of age, and in >20% of children with macroadenomas. Genetic screening for aryl-hydrocarbon interacting protein gene mutations is warranted in selected high-risk patients who may benefit from early recognition and follow-up.

Recomendações do Departamento de Neuroendocrinologia da Sociedade Brasileira de Endocrinologia e Metabologia para o diagnóstico e tratamento da acromegalia no Brasil / Recommendations of Neuroendocrinology Department from Brazilian Society of Endocrinology and Metabolism for diagnosis and treatment of acromegaly in Brazil

A acromegalia é uma doença associada à elevada morbidade e à redução da expectativa de vida. Em virtude do seu caráter insidioso e do seu não reconhecimento, o diagnóstico é frequentemente realizado com atraso, o que, associado às complicações relacionadas ao excesso do GH/IGF-I, determina elevada morbimortalidade. No entanto, um diagnóstico precoce e um tratamento efetivo minimizam a morbidade e normalizam a taxa de mortalidade. Nesta publicação, o objetivo do Departamento de Neuroendocrinologia da Sociedade Brasileira de Endocrinologia e Metabologia é divulgar quando suspeitar clinicamente da acromegalia e como diagnosticá-la. Além disso, discute-se a maneira mais eficaz e segura de realizar o tratamento da acromegalia, enfatizando que este deve ser realizado em centros de referência. Assim, com base em dados publicados em periódicos de nível científico reconhecido e na experiência dos autores, são apresentadas as recomendações para o diagnóstico e tratamento da doença.

Acromegaly is a disease associated with increased morbidity and reduced life expectancy. Because of its insidious character and its non-recognition, the diagnosis is often made with delay, which, along with the complications related to GH/IGF-I excess, determines high morbidity and mortality. However, an early diagnosis and an effective treatment reduce the morbidity and normalize the mortality rate. In this publication, the goal of Neuroendocrinology Department from Brazilian Society of Endocrinology and Metabolism is to disclose which clinical set should arouse the suspicious of acromegaly and how to diagnose it. Furthermore, we discuss the most effective and safe approach to perform the treatment of acromegaly, emphasizing that it must be carried out in reference centers. Therefore, based on data published in journals with recognized scientific level and authors' experience, recommendations are presented for diagnosis and treatment of the disease.

Predição da síndrome metabólica em crianças por indicadores antropométricos / Prediction of metabolic syndrome in children through anthropometric indicators / Predicción del síndrome metabólico en niños por indicadores antropométricos

FUNDAMENTO: Devido à necessidade de mensurar as variáveis antropométricas, bioquímicas e hemodinâmicas para o diagnóstico da síndrome metabólica, percebe-se a dificuldade da avaliação de grandes populações, principalmente em crianças, provocada pelo difícil acesso e pelo caráter invasivo. É premente a necessidade de desenvolverem-se formas diagnósticas de fácil aplicação, boa precisão e baixo custo, com a finalidade de predizer a síndrome metabólica já nas idades iniciais. OBJETIVO: Verificar a prevalência da síndrome metabólica em crianças e testar os indicadores antropométricos com capacidade preditiva. MÉTODOS: Estudo transversal realizado com 109 crianças, de 7 a 11 anos. Utilizou-se o critério National Cholesterol Education Program para o diagnóstico da síndrome metabólica, adaptado à idade. Como possíveis preditores, foram testados: índice de massa corporal (IMC), circunferência da cintura (CC), relação cintura/quadril (RCQ), índice de conicidade (índice C) e o percentual de gordura corporal. RESULTADOS: A prevalência da síndrome metabólica foi de 13,3 por cento e 36 por cento para meninos e meninas, respectivamente. Os principais indicadores antropométricos foram: IMC = 0,81 (0,69 - 0,94), CC = 0,79 (0,64 - 0,94), gordura corporal = 0,79 (0,66 - 0,92) e RCQ = 0,37 (0,21 - 0,54). CONCLUSÃO: Foram considerados fatores preditores da síndrome metabólica a CC superior a 78 cm, a gordura corporal superior a 41 por cento e o IMC superior a 24,5 kg/m². O índice C e a RCQ não foram considerados preditores.

BACKGROUND: Because of the need to measure anthropometric, biochemical and hemodynamic variables for the diagnosis of metabolic syndrome, we realize how difficult it is to analyze large populations, especially children, due to the poor accessibility and the invasive character. There is an urgent need to develop easy-to-use, accurate and low-cost diagnostic tools in order to predict metabolic syndrome at early ages. OBJECTIVE: To verify the prevalence of metabolic syndrome in children and to test predictive anthropometric indicators. METHODS: Cross-sectional study conducted among 109 children aged 7 to 11 years. The age-adjusted National Cholesterol Education Program definition was used for the diagnosis of metabolic syndrome. The following parameters were tested as possible predictors: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), conicity index (C index), and body fat percentage. RESULTS: The prevalence of metabolic syndrome was 13.3 percent and 36 percent for boys and girls, respectively. The main anthropometric indicators were: BMI = 0.81 (0.69 - 0.94), WC = 0.79 (0.64 - 0.94), body fat = 0.79 (0.66 - 0.92) and WHR = 0.37 (0.21 - 0.54). CONCLUSION: WC higher than 78 cm, body fat higher than 41 percent, and BMI higher than 24.5 kg/m² were considered predictors of metabolic syndrome. The C index and WHR were not considered predictors.

FUNDAMENTO: Debido a la necesidad de medir las variables antropométricas, bioquímicas y hemodinámicas para el diagnóstico del síndrome metabólico, se percibe la dificultad de la evaluación de grandes poblaciones, principalmente en niños, provocada por el difícil acceso y por el carácter invasivo. Es urgente la necesidad de desarrollar formas diagnósticas de fácil aplicación, buena precisión y bajo costo, con la finalidad de predecir el síndrome metabólico ya en las edades iniciales. OBJETIVO: Verificar la prevalencia del síndrome metabólico en niños y probar los indicadores antropométricos con capacidad predictiva. MÉTODOS: Estudio transversal realizado con 109 niños, de 7 a 11 años. Se utilizó el criterio National Cholesterol Education Program para el diagnóstico del síndrome metabólico, adaptado a la edad. Como posibles predictores, fueron probados: índice de masa corporal (IMC), circunferencia de la cintura (CC), relación cintura/cadera (RCC), índice de conicidad (índice C) y el porcentual de grasa corporal. RESULTADOS: La prevalencia del síndrome metabólico fue de 13,3 por ciento y 36 por ciento para niños y niñas, respectivamente. Los principales indicadores antropométricos fueron: IMC = 0,81 (0,69 - 0,94), CC = 0,79 (0,64 - 0,94), grasa corporal = 0,79 (0,66 - 0,92) y RCC = 0,37 (0,21 - 0,54). CONCLUSIÓN: Fueron considerados factores predictores del síndrome metabólico la CC superior a 78 cm, la grasa corporal superior a 41 por ciento y el IMC superior a 24,5 kg/m². El índice C y la RCC no fueron considerados predictores.

The brazilian version of the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA): Four-stage translation and validation / Versão brasileira do questionário "Quality of Life - Assessment of Growth Hormone Deficiency in Adults" (QoL-AGHDA): Tradução e validação em quatro estágios

OBJECTIVE: This study reports on the Brazilian Portuguese adaptation of the QoL-AGHDA (Quality of Life Assessment of Growth Hormone Deficiency in Adults) for use in adult growth hormone deficient (GHD) patients. MATERIALS AND METHODS: The translation process adopted the dual panel methodology. The questionnaire was tested through field-test interviews (16 GHD patients). In the final stage, data from 120 GHD patients (81 included in a test-retest analysis) were analyzed for internal consistency, test-retest reliability, convergent validity and validity among known groups. RESULTS: The translation panels were successful and the draft version was amended to improve the wording as a result of the field-test interviews. Cronbach's alpha was 0.90 and test-retest reliability 0.88. QoL-AGHDA scores had the expected pattern of association with NHP scale scores and QoL-AGHDA was able to differentiate significantly between patients based on patient-reported general health (p < 0.01) and QoL (p < 0.01). CONCLUSIONS: The adaptation of the QoL-AGHDA for a Brazilian population was successful and the adapted questionnaire was shown to be reliable and valid.

OBJETIVO: Este estudo relata o processo de adaptação da versão brasileira do questionário QoL-AGHDA (Quality of Life - Assessment of Growth Hormone Deficiency in Adults) para pacientes com deficiência do hormônio de crescimento (DGH). MATERIAIS E MÉTODOS: A tradução adotou a metodologia de duplo painel. O questionário foi testado por intermédio de entrevistas direcionadas com 16 pacientes com DGH. No estágio final, dados de 120 pacientes com DGH (81 com teste/reteste) foram analisados para consistência interna, confiabilidade teste/reteste, validade convergente e validade entre grupos conhecidos. RESULTADOS: Os grupos de tradução foram bem-sucedidos e a versão final foi adaptada seguindo sugestões obtidas das entrevistas com os 16 pacientes. O coeficiente alfa de Cronbach foi 0,90, confiabilidade teste/reteste 0,88, escores QoL-AGHDA se correlacionaram com o NHP (p < 0,01) e também com a saúde geral relatada pelos pacientes (p < 0,01). CONCLUSÕES: A adaptação do QoL-AGHDA para a população brasileira foi bem-sucedida, e a nova versão demonstrou ser válida e confiável.

Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene / Prolactinoma agressivo na infância relacionado à mutação no gene da proteína Aryl hidrocarbono (AIP)

The objective of this study was to describe a familial screening for AIP mutations in the context of aggressive prolactinoma in childhood. A 12-year-old boy, presented headaches and bilateral hemianopsia. He had adequate height and weight for his age (50th percentile), Tanner stage G1 P1. His bone age was 10 years. Prolactin was 10.560 ng/mL (3-25), FSH and LH were undetectable, IGF-1, TSH, Free T4, ACTH, and cortisol were within normal ranges. MRI showed a pituitary macroadenoma, 5.3 X 4.0 X 3.5 cm with compression of the optic chiasm, bilateral cavernous sinus invasion, encasement of carotids, and extension to clivus. Surgical debulking was performed. Resistance to cabergoline was characterized and he was submitted to two surgeries and radiotherapy. Immunohistochemical evaluation included prolactin, ACTH, GH, FSH, LH,AIP, c-erb B2, Ki-67, and p53. Genomic DNA was isolated from the index case and 48 relatives, PCR and sequencing were performed.A germline A195V mutation in AIP was identified in the index case and in five asymptomatic relatives. Germline mutations in the AIP gene may be involved in the predisposition to pituitary adenoma formation, as cause or co-factor in pathogenesis of aggressive tumors in young patients.

O objetivo deste estudo foi descrever o rastreamento familiar para mutações AIP em paciente portador de prolactinoma agressivo e resistente na infância. Um menino de 12 anos foi avaliado com queixa de cefaleia e hemianopsia bitemporal. Apresentava peso e altura adequados para a idade (percentil 50), estádio puberal Tanner G1 P1 e idade óssea de 10 anos. Prolactina 10.560 ng/mL (3-25), FSH e LH indetectáveis, IGF-1, TSH, T4 livre, ACTH, e cortisol normais. A ressonância magnética de sela evidenciou macroadenoma hipofisário, 53 X 40 X 35 mm com compressão de quiasma ótico, invasão de seios cavernosos, envolvimento de carótidas internas e extensão para o clivus. Foi realizada descompressão cirúrgica por via transesfenoidal e caracterizada resistência a doses máximas de cabergolina, sendo o paciente operado por mais duas vezes e submetido à radioterapia. Realizou-se imuno-histoquímica para prolactina, ACTH, GH, FSH, LH, AIP, c-erb B2, Ki-67 e p53. O DNA genômico foi extraído do caso índice e de 48 familiares, e PCR e sequenciamento. Uma mutação A195V na AIP foi detectada no paciente e em cinco parentes assintomáticos. As mutações no gene da AIP podem estar envolvidas na predisposição à formação de adenomas, como causa ou cofator na patogênese de tumores agressivos em jovens.

Mean intrasellar pressure, visual field, headache intensity and quality of life of patients with pituitary adenoma / Pressão intra-selar média, campo visual, intensidade de cefaléia e qualidade de vida em portadores de adenoma hipofisário

Intrasellar pressure (ISP) measurement technique has recently opened a new line of research in neuroendocrinology. The absolute and mean ISP values were investigated in 25 patients consecutively operated at the Brasilia University Hospital (DF). These data were correlated with serum prolactin levels, number of visual quadrant affected, tumor size, quality of life (measured through the SF-36 scale) and graded headache (measured through the HIT-6 scale). No correlation was observed. The p values were 0.887; 0.137; 0.892; 0.812 and 0.884; respectively. The HIT-6 values were inversely and moderately correlated with total RAND SF-36 and its mental and physical dimensions.

A técnica da medida da pressão intra-selar (PIS) abriu, recentemente, uma nova linha de pesquisa em neuroendocrinologia. O objetivo deste estudo foi aferir os valores absolutos da PIS e calcular a pressão intra-selar média (PIM) em uma população de 25 pacientes operados consecutivamente no Hospital Universitário de Brasília (DF). Não se observou correlação significativa entre a PIM e o número de quadrantes visuais comprometidos (p=0,137), área do tumor (p=0,892), nível de qualidade de vida mensurado pela escala SF-36 (p=0,812) e a presença e a intensidade da cefaléia mensurada pela escala HIT-6 (p=0,884). Contudo, o HIT-6 correlacionou-se de forma inversa e intensidade moderada com os valores de HIT-6 e suas dimensões mental e física.