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.

ABSTRACT Objective: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. Subjects and methods: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. Results: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). Conclusion: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

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

OBJETIVO: Avaliar a acurácia da dosagem sérica de IGF-1 no diagnóstico da deficiência de hormônio de crescimento isolada (DGHI) ou combinada (DGHC) na fase de transição. SUJEITOS E MÉTODOS: Quarenta e nove pacientes com DGH na infância [16 DGHI (10 homens) e 33 DGHC (24 homens); idade 23,2 ± 3,5 anos] realizaram teste de tolerância à insulina (TTI), com pico de GH < 5 µg/L considerado diagnóstico de DGH na transição. Função hipofisária e níveis de IGF-1 foram determinados na amostra basal do TTI e os pacientes foram reclassificados em GH suficientes (SGH; n = 12), DGHI (n = 7) ou DGHC (n = 30). RESULTADOS: Cinco (31%) pacientes com DGHI e 32 (97%) com DGHC na infância persistiram com DGH no reteste. Um paciente com DGHI foi reclassificado como DGHC e três com DGHC como DGHI. Os picos médios de GH foram 0,2 ± 0,3 µg/L (DGHC), 1,3 ± 1,5 µg/L (DGHI) e 18,1 ± 13,1 µg/L (SGH). O nível médio de IGF-1 foi maior no grupo SGH (272 ± 107 ng/mL) comparado com DGHI (100,2 ± 110) e DGHC (48,7 ± 32,8) (p < 0,01). IGF-1 baixo foi observado em todos os pacientes reclassificados como DGHC, 86% dos DGHI e 8,3% dos SGH, resultando em sensibilidade de 97,3% e especificidade de 91,6% para detecção de DGH na transição; valor de corte de 110 ng/mL mostrou 94,5% sensibilidade e 100% especificidade. O nível médio de IGF-1 foi similar nos pacientes com DGHI ou DGHC com uma, duas, três ou quatro deficiências hipofisárias associadas. CONCLUSÃO: A dosagem sérica de IGF-1 mostrou-se acurada para substituir o TTI na detecção tanto de DGHI como DGHC na transição.

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

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.

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - seja no tratamento das epilepsias como para outros fins - freqüentemente por longo tempo. Por estas razões, os médicos que utilizam DAE no seu arsenal terapêutico, devem estar atentos para os potenciais efeitos adversos do uso prolongado destes medicamentos. O objetivo desta revisão é analisar a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, função gonadal e tireoideana e suas aplicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AEDs) have been widely used for treatment of epilepsy and other diseases. Continuous and prolonged use of AEDs might be associated with potential adverse effects in different systems, including endocrine and metabolic abnormalities. The purpose of this review was to examine the relationship of AEDs with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism, as well as their implications in the treatment of diabetic neuropathy.

OBJETIVO: Avaliar a eficácia, a segurança e a aderência de quatro anos de tratamento com GH em 18 adultos [12 mulheres, 6 homens, com idade média de 50,5 anos (25-66 anos)] com deficiência grave de GH (DGH). MÉTODOS: Avaliações clínica, laboratorial e de composição corporal (DXA) realizadas antes e anualmente após o início do GH, e ecocardiografia realizada antes e após quatro anos de tratamento. Dose de 0,2 mg GH/dia mantida fixa no primeiro ano, com posteriores ajustes para normalizar IGF-1. RESULTADOS: Redução significativa da gordura corporal total (média 2,8 kg) e da gordura truncal (média 1,9 kg), associadas com aumento da massa magra (média 0,8 kg) e aumento da densidade mineral óssea (DMO) em coluna lombar e fêmur, particularmente nos sítios com T-escore menor que 1,0 na avaliação basal. Houve piora dos níveis de insulina e HOMA no primeiro ano de terapia, mas ao final do quarto ano os valores de glicose, insulina, HOMA e hemoglobina glicosilada não eram diferentes dos basais. Desenvolveram diabetes tipo 2 no seguimento dois pacientes com intolerância à glicose pré-tratamento. O colesterol total e o LDL colesterol reduziram significativamente, e as mudanças foram proporcionais aos valores basais. Os parâmetros ecocardiográficos não se alteraram. Os efeitos colaterais foram leves e bem tolerados. Não foi observada recorrência tumoral. Baixa adesão ao tratamento (estimada por níveis baixos de IGF-1) ocorreu em quatro (22%), dois (11%) e seis (30%) pacientes ao final do segundo, terceiro e quarto ano, respectivamente. CONCLUSÕES: Quatro anos de tratamento com GH em adultos com DGH teve impacto positivo sobre a composição corporal, a DMO e o perfil lipídico, e nenhum efeito sobre sensibilidade insulínica e o coração. A intolerância à glicose deve ser cuidadosamente monitorada no tratamento de longo prazo.

AIM: To study efficacy, safety and compliance of GH therapy for 4 years in 18 GH deficient (GHD) adults [12 women; mean age 50.5 yrs (25-66 yrs)]. METHODS: Clinical, biochemical and body composition (DXA) measurements were performed before and every year after GH therapy. Ecocardiography was performed at baseline and after 4 years. Dose of GH was 0.2 mg/day during the first year with subsequent titration to attain normal IGF-1 levels. RESULTS: There was a significant reduction of total body fat (mean 2.8 kg), truncal fat (mean 1.9 kg) and an increase of lean body mass (mean 0.8 kg) and bone mineral density (BMD) on lumbar spine and femur, particularly in sites with T-score < -1,0 at baseline. Insulin levels and HOMA index worsened in the first year, but at the end no changes were noted on glucose, insulin, HOMA index and glycosylated hemoglobin. Two patients with altered glucose tolerance at baseline developed type 2 diabetes during follow-up. Total and LDL-cholesterol were significantly lower after therapy, with changes directly associated with baseline values. Cardiac parameters did not change. Side effects were mild and disappeared spontaneously. Tumor recurrence was not observed. Low compliance (estimated by low IGF-1 levels) was observed in 4 (22%), 2 (11%) and 6 (33%) patients at the end of second, third and fourth year, respectively. CONCLUSIONS: Four years of GH therapy in GHD adults had a positive impact on body composition, BMD and lipid profile, with no effects on insulin sensitivity and heart. Glucose tolerance should be monitored carefully during long-term GH therapy.

Relatamos o caso de uma mulher de 53 anos com episódios de hipoglicemia espontânea com um ano de evolução. A paciente referia fraqueza, sudorese e tremores, especialmente após as refeições. A avaliação laboratorial confirmou hipoglicemia com altos níveis de insulina e peptídeo C. A tomografia axial computadorizada (TAC) de abdome evidenciou uma grande massa com calcificações na cauda do pâncreas. Após ressecção cirúrgica o exame histológico revelou insulinoma maligno. Após 12 meses de acompanhamento a paciente permanecia assintomática e normoglicêmica.

We report on a case of a 53-year-old woman with episodes of spontaneous hypoglycemia in the last year, before her first visit in our outpatient clinic. She complained of weakness, sweating and trembling specially after meals. Blood tests confirmed low plasma glucose values and elevated insulin and C-peptide levels. An abdominal computed tomography (CT) scan showed a large mass with calcifications in the pancreas tail. Surgery was performed and histological evaluation revealed a malignant insulinoma. Since then, she has been followed for twelve months with no symptoms of hypoglycemia and no evidence of relapse.