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Orphan diseases are of medical and social importance as they are difficult to diagnose and treat. Moreover, they have poor prognosis and are frequently the cause of patients’ disability. The adoption of National strategy for prevention, diagnosis and treatment of orphan diseases in Ukraine is the evidence of the recognition of this problem on the country level and makes it possible to resolve the issues of timely detection of rare diseases, treatment of patients and providing them with the necessary medications., Медико-социальное значение орфанных заболеваний обусловлено трудностями в диагностике и лечении, а также неблагоприятным прогнозом и высокой частотой инвалидизации пациентов. Принятие Национальной стратегии по профилактике, диагностике и лечению орфанных заболеваний в Украине свидетельствует о признании проблемы на государственном уровне и дает возможность решения вопросов своевременного выявления редких заболеваний, лечения и обеспечения пациентов жизненно необходимыми лекарственными средствами., Медико-соціальне значення орфанних захворювань обумовлене труднощами в діагностиці й лікуванні, а також несприятливим прогнозом і високою частотою інвалідизації пацієнтів. Ухвалення Національної стратегії з профілактики, діагностики й лікування орфанних захворювань в Україні свідчить про визнання проблеми на державному рівні та дає можливість вирішення питань своєчасного виявлення рідкісних захворювань, лікування й забезпечення пацієнтів життєво необхідними лікарськими засобами.

Introduction and Objective: Acromegaly is a rare, chronic and slowly developing endocrine disorder caused by hypersecretion of human growth hormone and consequently of insulin-like growth factor-1 during adulthood. The present study was conducted to assess mitral annular (MA) size and function between acromegalic patients and age- and gender-matched healthy controls by three-dimensional speckle-tracking echocardiography (3D-STE). It also aimed to examine whether activity of the disease has any effect on MA parameters. Methods: This study included 27 patients with acromegaly, three of whom were excluded due to inferior image quality. The mean age of the remaining 24 patients was 55.7±14.0 years and seven were male. Complete two-dimensional Doppler echocardiography and 3D-STE were performed in all cases. Results: Significantly increased end-diastolic and end-systolic MA diameter (2.81±0.36 cm vs. 2.44±0.34 cm and 2.00±0.32 cm vs. 1.65±0.37 cm, respectively), area (9.67±2.33 cm2 vs. 7.38±1.93 cm2 and 5.14±1.62 cm2 vs. 3.74±1.19 cm2, respectively) and perimeter (11.76±1.42 cm vs. 10.27±1.33 cm and 8.61±1.23 cm vs. 7.36±1.10 cm, respectively) were demonstrated in acromegalic patients compared with control subjects. MA functional parameters were not significantly altered compared to those of healthy individuals. Conclusions: MA dilation could be seen in acromegaly regardless of its activity. Acromegaly is not associated with MA functional impairment. Resumo: Introdução e Objectivo: A acromegalia é uma doença endócrina rara, crónica e de desenvolvimento lento, causada pela hipersecreção da hormona do crescimento humano e, consequentemente, do fator de crescimento semelhante à insulina-1 durante a idade adulta. O presente estudo foi conduzido para avaliar o tamanho e a função do anel mitral (MA) nos doentes com acromegalia e controles saudáveis emparelhados por idade e sexo, por meio de ecocardiografia tridimensional com speckle-tracking (3DSTE). O objetivo foi também examinar se a atividade da doença tem algum efeito nos parâmetros da MA. Métodos: Este estudo incluiu 27 pacientes com acromegalia, três dos quais tiveram de ser excluídos devido à qualidade inferior de imagem. A média de idade dos 24 pacientes restantes foi de 55,7 ± 14,0 anos (7 homens). Foram realizados em todos os casos uma ecocardiografia Doppler bidimensional completa e um 3DSTE. Resultados: Quando comparados com os controlos, os doentes acromegálicos apresentaram diâmetros diastólico e sistólico finais significativamente dilatados (2,81 ± 0,36 cm versus 2,44 ± 0,34 cm e 2,00 ± 0,32 cm versus 1,65 ± 0,37 cm, respetivamente), assim como a área valvular (9,67 ± 2,33 cm2 versus 7,38 ± 1,93 cm2 e 5,14 ± 1,62 cm2 versus 3,74 ± 1,19 cm2, respetivamente) e o perímetro (11,76 ± 1,42 cm versus 10,27 ± 1,33 cm e 8,61 ± 1,23 cm versus 7,36 ± 1,10 cm, respetivamente) Os parâmetros funcionais da MA não estavam significativamente alterados em comparação com indivíduos saudáveis. Conclusões: A dilatação do MA pode ser observada na acromegalia, independentemente de sua atividade. A acromegalia não está associada ao comprometimento funcional da MA.

Introduction: Acromegaly is a relatively rare chronic hormonal disease resulting in disfigurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone-secreting tumor. The aim of the present study was to determine the presence of left ventricular (LV) deformation abnormalities using three-dimensional speckle-tracking echocardiography in a group of acromegalic patients. Methods: Thirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age: 52.7±4.9 years, 15 male). Results: Global and mean segmental LV radial strain (RS) (33.2±13.4% vs. 25.2±10.8%, p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be significantly higher in acromegaly compared to controls. Active acromegalic patients had significantly higher global and mean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%, p=0.03 and 37.9±13.3% vs. 28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegaly groups, only basal LV circumferential strain (-30.2±4.8% vs. -26.7±4.1%, p=0.02) was found to be significantly different. Conclusion: The presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegaly is associated with enhanced LV RS as compared to healthy controls and those with inactive acromegaly. Resumo: Introdução: A acromegalia é uma doença hormonal crónica relativamente rara, associada a dismorfismos somáticos. Em 90% dos casos, ela é causada por um tumor benigno monoclonal da hipófise, secretor de hormona do crescimento. O objetivo do presente estudo foi detetar a presença de alterações da deformação miocárdica do ventrículo esquerdo (VE) através de ecocardiografia tridimensional por speckle tracking num grupo de doentes portadores de acromegalia. Métodos: Foram incluídos 38 doentes portadores de acromegalia. Treze foram excluídos devido à má qualidade de imagem. A idade média dos restantes foi de 57,2±13,6 anos (7 homens). Os seus dados foram comparados com uma população controlo emparelhada por idade e género, que compreendeu 34 voluntários saudáveis (idade média: 52,7±4,9 anos, sendo 15 indivíduos do sexo masculino). Resultados: O strain radial (SR) global e segmentar VE (respetivamente 33,2±13,4% versus 25,2±10,8%, p=0,01 e 36,0±12,1% versus 28,2±10,0%, p=0,009) foi significativamente superior nos casos de acromegalia em relação aos casos controlo. Os doentes portadores de acromegalia ativa tiveram um SR global e segmentar significativamente superior (35,5±14,4% versus 25,2±10,8%, p=0,03 e 37,9±13,3% versus 28,2±10,0%, p=0,03, respetivamente), quando comparados com os grupos controlo. Entre os grupos portadores de acromegalia ativos e inativos, só foi considerado significativamente diferente o strain circunferencial basal VE (-30,2±4,8% versus -26,7±4,1%, p=0,02). Conclusões: Com base nas características clínicas, demográficas, terapêuticas e ecocardiográficas apresentadas, a acromegalia ativa apresenta SR-VE aumentado em relação à população saudável e ao grupo de portadores de acromegalia inativa.

The skeleton is regulated by and responds to pituitary hormones, especially when the circulating levels are perturbed in disease. This study aims to analyse the between-group differences in 3D dual-energy X-ray absorptiometry (DXA) parameters at the hip site among patients with acromegaly or adult growth hormone deficiency (AGHD) and a healthy control group. The current cross-sectional study includes data for 67 adults, 20 with acromegaly, 14 with AGHD and 33 healthy controls. We obtained the areal bone mineral density (aBMD) outcomes using DXA and cortical and trabecular parameters using 3D-DXA software (3D-SHAPER). The mean-adjusted 3D-DXA parameters did not differ between acromegaly patients and the controls (p &gt, 0.05), however, we found cortical bone impairment (−7.3% to −8.4%, effect size (ES) = 0.78) in AGHD patients (p &lt, 0.05). Differences in the cortical bone parameters were more evident when comparing AGHD patients (−8.5% to −16.2%, ES = 1.22 to 1.24) with acromegaly patients (p &lt, 0.05). In brief, the 3D mapping highlighted the trochanter as the site with greater cortical bone differences between acromegaly patients and the controls. Overall, AGHD patients displayed lower cortical parameters at the trochanter, femoral neck and intertrochanter compared to the controls and acromegaly patients. To sum up, 3D-DXA provided useful information about the characteristics of bone involvement in growth hormone (GH)-related disorders. Patients with AGHD showed distinct involvement of the cortical structure.

SommarioUn aumento del numero di pazienti acromegalici anziani è atteso nei prossimi anni grazie ai miglioramenti apportati in campo diagnostico e terapeutico. La diagnosi di acromegalia nell’anziano può risultare insidiosa a causa di quadri clinici sfumati che possono sovrapporsi alle manifestazioni tipiche dell’invecchiamento. Non esistono criteri diagnostici specifici per l’anziano. La chirurgia si è dimostrata efficace e relativamente sicura anche nel paziente anziano che, tuttavia, presenta una buona risposta agli analoghi della somatostatina.

Background Biochemical control of GH/IGF-I excess in acromegaly (ACRO) is associated with persistent impairment of trabecular microstructure leading to increased risk of vertebral fractures. Circulating miRNAs modulate the activity of osteoblasts and osteoclasts, and may be potential biomarkers of osteoporosis. Aims Identify differentially expressed miRNAs in the serum of patients with controlled ACRO vs controls and correlate miRNA levels with both biochemical and structural bone parameters. Patients and methods Twenty-seven patients with controlled ACRO (11 males, 16 females; mean age, 48 ± 5 years; BMI, 28 ± 4 kg/m2) and 27 age-, gender- and BMI-matched controls were recruited. Areal BMD at lumbar spine and femur, and trabecular bone score were assessed; volumetric BMD was measured by quantitative computed tomography QCT-Pro (Mindways). Twenty miRNAs, chosen by their putative role in bone, were quantified in serum using real-time qPCR. Results In ACRO patients, miR-103a-3p and miR-191-5p were found overexpressed, whereas miR-660-5p was underexpressed (P P P P P P P Conclusions Circulating miR-103a-3p and miR-660-5p are differentially expressed in controlled ACRO patients and associated with bone structural parameters. miRNAs may be one of the mechanisms involved in the pathogenesis of bone disease and could be used as biomarkers in ACRO patients.

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.

Purpose: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. Methods: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥3months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. Results: High IGF-I levels (ULN 1.01–1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was&nbsp

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.

Introduction: The quality of life of acromegalics is compromised. Treatment with the "Think healthy and feel the difference" technique has been described as effective in the improvement of the quality of life of these patients in the short term. However, its effectiveness in the long term needs to be evaluated. Objective: The purpose of this study was to evaluate whether the good results obtained from the "Think healthy and feel the difference" technique in the short term persists in the long term, after the end of the treatment. Method: This is a non-randomized longitudinal study with 23 acromegalic divided into two groups: an intervention group with 10 patients and a control group with 13 patients. The intervention itself covered nine group sessions, organized weekly, using a technique called "Think healthy and feel the difference." The control group did not receive the aforementioned treatment. The Short Form 36 Question Health Survey (SF-36) and the Beck Depression Inventory were administered before the sessions began, at the end of the nine therapy sessions and at the 9-month follow-up. Results: At the end of the treatment, the results of the SF-36 showed improvement in the mental health of the intervention group compared to the control group. The effects of therapy were maintained at the 9 month follow-up. Conclusion: Cognitive-behavioral therapy, applied in a group format, can improve the quality of life of acromegalic patients in the short- and long-term.

[Abstract] PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p

Resumen: La acromegalia es una enfermedad caracterizada por una desfiguración somática de progresión lenta causada por la sobreproducción de hormona de crecimiento (GH) y factor de crecimiento insulinoide tipo 1 (IGF-1), predominantemente asociada con un adenoma hipofisario. La manifestación más evidente a nivel facial es un prognatismo mandibular por exceso de crecimiento de la mandíbula. El propósito del presente trabajo fue realizar una comparación morfológica craneofacial mediante análisis cefalométrico y superposición cefalométrica entre un paciente con diagnóstico de acromegalia y su hermano gemelo que no presenta la enfermedad. Nuestros resultados mostraron que en el hermano con acromegalia existe un significativo aumento del tamaño de la silla turca, un desplazamiento hacia anterior del maxilar y mandíbula, siendo más marcado el desplazamiento mandibular. El cambio morfológico que experimenta la mandíbula en la acromegalia es atribuido principalmente al crecimiento de la rama mandibular por aumento de la unidad condilar.

Background Acromegaly is produced by excess growth hormone secreted by a pituitary adenoma of somatotroph cells (ACRO). First-line therapy, surgery and adjuvant therapy with somatostatin analogs, fails in 25% of patients. There is no predictive factor of resistance to therapy. New therapies are investigated using few dispersed tumor cells in acute primary cultures in standard conditions where the cells do not grow, or using rat pituitary cell lines that do not maintain the full somatotroph phenotype. The RET/PIT1/p14ARF/p53 pathway regulates apoptosis in normal pituitary somatotrophs whereas the RET/GDNF pathway regulates survival, controlling PIT1 levels and blocking p14ARF (ARF) and p53 expression. Methods We investigated these two RET pathways in a prospective series of 32 ACRO and 63 non-functioning pituitary adenomas (NFPA), studying quantitative RNA and protein gene expression for molecular-clinical correlations and how the RET pathway might be implicated in therapeutic success. Clinical data was collected during post-surgical follow-up. We also established new'humanized’ pituitary cultures, allowing 20 repeated passages and maintaining the pituitary secretory phenotype, and tested five multikinase inhibitors (TKI: Vandetanib, Lenvatinib, Sunitinib, Cabozantinib and Sorafenib) potentially able to act on the GDNF-induced RET dimerization/survival pathway. Antibody arrays investigated intracellular molecular pathways. Findings In ACRO, there was specific enrichment of all genes in both RET pathways, especially GDNF. ARF and GFRA4 gene expression were found to be opposing predictors of response to first-line therapy. ARF cut-off levels, calculated categorizing by GNAS mutation, were predictive of good response (above) or resistance (below) to therapy months later. Sorafenib, through AMPK, blocked the GDNF/AKT survival action without altering the RET apoptotic pathway. Interpretation Tumor ARF mRNA expression measured at the time of the surgery is a prognosis factor in acromegaly. The RET inhibitor, Sorafenib, is proposed as a potential treatment for resistant ACRO. Fund This project was supported by national grants from Agencia Estatal de Investigacion (AEI) and Instituto Investigacion Carlos III, with participation of European FEDER funds, to IB (PI150056) and CVA (BFU2016-76973-R). It was also supported initially by a grant from the Investigator Initiated Research (IIR) Program (WI177773) and by a non-restricted Research Grant from Pfizer Foundation to IB. Some of the pituitary acromegaly samples were collected in the framework of the Spanish National Registry of Acromegaly (REMAH), partially supported by an unrestricted grant from Novartis to the Spanish Endocrine Association (SEEN). CVA is also supported from a grant of Medical Research Council UK MR/M018539/1.

[EN] [Objectives]: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). [Methods]: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels, [ES]: [Objetivos]: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline® Autogel®) utilizados en la práctica clínica. [Métodos]: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH, This study was funded by Ipsen Pharma S.A., Spain.

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels are the main targets for monitoring acromegaly activity, but they are not in close relationship with the clinical course of the disease and the associated comorbidities. The present study was aimed at identifying metabolites that could be used as biomarkers for a better disease phenotyping. For this purpose, metabolic fingerprint using an untargeted metabolomic approach was examined in serum from 30 patients with acromegaly and 30 age-matched controls. Patients with acromegaly presented fewer branched-chain amino acids (BCAAs) compared to the control group (valine: 4.75 &plusmn, 0.87 vs. 5.20 &plusmn, 1.06 arbitrary units (AUs), p &lt, 0.05, isoleucine: 2.54 &plusmn, 0.41 vs. 2.80 &plusmn, 0.51 AUs, p &lt, 0.05). BCAAs were also lower in patients with active disease compared to patients with normal levels of IGF-1 with or without medical treatment. GH, but not IGF-1, serum levels were inversely correlated with both valine and isoleucine. These findings indicate that low levels of BCAAs represent the main metabolic fingerprint of acromegaly and that GH, rather than IGF-1, might be the primary mediator. In addition, our results suggest that the assessment of BCAAs could help to identify active disease and to monitor the response to therapeutic strategies.

The objective of this study was to report a rare fatal complication in the postoperative period of transsphenoidal surgery of the pituitary gland (adenoma), with a brief review of the subject. The patient was a 54-year-old white man with acromegaly and severe heart failure, who after microsurgery developed blood pressure instability within 32 hours after the procedure and died. The autopsy revealed: hypertrophy and ventricular dilation with myocarditis, pericarditis and myocardial fibrosis; mesenteric ischemia with transmural coagulation necrosis of the intestinal loops; acute tubular necrosis; and hepatic steatosis. The findings are consistent with cardiogenic shock and abdominal sepsis due to necrosis of the intestinal loops.

Objective: The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. Methods: A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. Results: The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease controlThe mos . t common complication was diabetes insipidus and the most severe was an ischemic stroke .Conclusion: The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.Keywords: acromegaly; growth hormone-secreting pituitary adenoma; endoscopy

ResumoA síndrome de neoplasia endócrina múltipla tipo 1 (MEN1) é transmitida de forma autossómica dominante e caracteriza‐se pela presença de tumores das glândulas paratiroideias, pâncreas endócrino e hipófise. Outros tumores encontram‐se menos frequentemente associados: adenomas da suprarrenal, tumores carcinoides, feocromocitomas, angiofibromas, lipomas, colagenomas e meningiomas. A presença de 2 ou mais tumores permite o diagnóstico clínico.Apresenta‐se o caso de um homem de 56 anos, referenciado à consulta de endocrinologia para investigação de patologia nodular da tiroideia, assintomática, com aspetos benignos na ecografia e citologia aspirativa. Ao exame físico eram evidentes traços faciais grosseiros e mãos grandes. O doente tinha diagnóstico prévio de hipertensão arterial, litíase renal, síndrome de apneia obstrutiva do sono e tinha sido submetido recentemente a excisão de pólipo do cólon (benigno). A história familiar era negativa para patologia endócrina. A avaliação endócrina revelou aumento da hormona de crescimento e IGF‐1 e a prova de tolerância à glicose oral confirmou o diagnóstico de acromegalia. Os níveis séricos das restantes hormonas adeno‐hipofisárias eram normais. A ressonância magnética craniana e selar revelou macroadenoma hipofisário esquerdo e ainda uma volumosa massa extra‐axial frontal esquerda, sugestiva de meningioma. Dada a coexistência de acromegalia e meningioma, foi equacionada a hipótese de síndrome MEN1 e averiguada a presença de endocrinopatias associadas. Os níveis séricos de cálcio e paratormona encontravam‐se aumentados, com função renal e níveis de vitamina D normais, sugerindo hiperparatiroidismo primário. A insulinemia e gastrinemia eram normais. O estudo genético não identificou mutações no gene MEN1.As manifestações fenotípicas e comorbilidades associadas sugeriram o diagnóstico de acromegalia, confirmado laboratorialmente. A associação pouco habitual de acromegalia, meningioma e hiperparatiroidismo primário sugere etiologia genética comum e permite o diagnóstico clínico de síndrome MEN1, com implicações na monitorização clínica do doente e familiares.AbstractMultiple Endocrine Neoplasia type 1 (MEN1) syndrome is inherited as an autosomal dominant trait and is characterized by the presence of tumors in the parathyroid glands, endocrine pancreas and pituitary. Other tumors are more rarely associated: adrenal adenomas, carcinoid tumors, pheochromocytomas, angiofibromas, lipomas, collagenomas and meningiomas. The presence of two or more tumors is diagnostic of the syndrome.We present the case of a 56 year old man referred to the Endocrine consultation for investigation of asymptomatic nodular thyroid disease, with benign features in the neck sonogram and fine needle aspiration cytology. At physical examination, coarse facial features and enlarged hands were apparent. The patient had previous diagnosis of primary hypertension, kidney stones, obstructive sleep apnea syndrome and had recent excision of a colonic polyp (benign). Family history was negative for endocrine disease. The endocrine evaluation revealed increased growth hormone and IGF‐1 and the oral glucose tolerance test confirmed the diagnosis of acromegaly. Seric levels of the remaining anterior pituitary hormones were normal. The cranial and sellar magnetic resonance revealed a left pituitary macroadenoma, and also a voluminous extra‐axial left frontal tumor, suggestive of a meningioma. Due to the coexistence of acromegaly and meningioma, the possibility of MEN1 syndrome was considered and associated endocrinopathies were investigated. Serum levels of calcium and parathormone were increased, with normal renal function and vitamin D levels, suggesting primary hyperparathyroidism. Insulinemia and gastrinemia were normal. Genetic testing did not identify mutations in MEN 1 gene.The phenotypic manifestations of acromegaly and associated co‐morbidities were suggestive of acromegaly, which was biochemically confirmed. The unsual association of acromegaly, primary hyperparathyroidism and meningioma is suggestive of a common genetic background and is clinically diagnostic of MEN1 syndrome, which has implications in future monitoring of the patient and his relatives.

ResumoIntroduçãoA literatura sugere que a acromegalia está associada a risco de pólipos e cancro colorectal (CCR), não existindo dados consensuais quanto aos fatores associados ao seu desenvolvimento.ObjetivosCalcular a prevalência de pólipos adenomatosos (PA), pólipos hiperplásicos (PH), CCR e divertículos do cólon (DC) em doentes com acromegalia; comparar com as respetivas prevalências na população em geral; estudar relação entre os achados endoscópicos e os níveis de hormona de crescimento e fator de crescimento semelhante à insulina 1, a duração da doença e a presença de fibromas cutâneos.MétodosEstudo retrospetivo com análise dos processos clínicos dos doentes, seguidos no Hospital Garcia de Orta entre 1992‐2012.ResultadosIdentificados 33 indivíduos com acromegalia, 28 dos quais submetidos a pelo menos uma colonoscopia. A prevalência de alterações encontradas neste estudo versus dados na população em geral foi: PA 14,3 versus 38% (p=0,0098), PH 14,3 versus 9% (p=0,33), CCR 7,1 versus 1% (p=0,0012) e DC 21,4 versus 19% (p=0,75). Nos doentes com acromegalia e CCR a mediana da duração da doença (anos) foi de 30, comparativamente a 11 no grupo sem alteração na colonoscopia (p=0,028). Não houve diferenças significativas nos valores hormonais nem na presença de fibromas cutâneos.ConclusõesNos doentes com acromegalia foram encontrados significativamente menos PA e mais CCR que na população em geral. A duração da doença foi significativamente maior nos doentes com acromegalia e CCR, comparativamente ao grupo sem alteração na colonoscopia. Não se obteve relação entre os achados endoscópicos e os doseamentos laboratoriais ou os fibromas cutâneos. Este estudo realça o risco de CCR na acromegalia e sugere a duração da doença como um dos possíveis fatores associados ao desenvolvimento de neoplasia do cólon. No entanto, o número limitado de doentes não permite obter conclusões válidas e incentiva a realização de estudos a nível nacional.AbstractIntroductionSeveral studies suggest that acromegaly is associated with an increased risk of colon polyps and colorectal cancer (CRC). There is no consensus on the factors associated with its development.ObjectivesTo assess the prevalence of colon adenomas (CA), hyperplastic polyps (HP), CRC and colon diverticula (CD) in patients with acromegaly; to compare with the prevalence in the general population; to determine the relationship between colonoscopic lesions and growth hormone and insulin‐like growth factor 1 levels, the duration of the disease and the presence of skin tags.MethodsRetrospective study with analysis of medical records of the patients, followed in Garcia de Orta hospital, between 1992 and 2012.ResultsThirty three patients with acromegaly were identified and 28 underwent at least one endoscopic examination. The prevalence of abnormalities found in this study versus data in the general population was: CA 14.3 versus 38% (p=0.0098), HP 14.3 versus 9% (p=0.33), CRC 7.1 versus 1% (p=0.0012) and CD 21.4 versus 19% (p=0.75). In patients with acromegaly and CRC the median disease duration (years) was 30 compared to 11 in the group without any colonoscopic lesion (p=0.028). There were no significant differences in hormone levels or in the presence of skin tags.ConclusionsPatients with acromegaly had significantly less CA and more CRC than the general population. Disease duration was significantly higher in patients with acromegaly and CRC, compared to those with no colonoscopic abnormalities. There was no relationship between endoscopic findings and laboratory results or skin tags. This study highlights the risk of CRC in acromegaly and suggests the duration of the disease as one of the possible factors associated with the development of cancer. However, the limited number of patients prevents reaching valid conclusions and encourages the performance of studies at a national level.

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.

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.

ObjectiveTo evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40–120 mg/week) in acromegaly.DesignThis is a 28-week, multicenter, open-label, single-arm sequential study.MethodsPatients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40–80 mg once weekly or 40 or 60 mg twice weekly).ResultsIn total, 33 (57.9%) patients had normalized IGF1 following coadministration (PP5×upper limit of normal with normalization after withdrawal).ConclusionsIn patients partially controlled by SSAs, LA (120 mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.

Se l’acromegalia sia associata, o meno, ad un aumentato rischio di neoplasia rimane un problema assai dibattuto. La mancanza di univocita della letteratura e riconducibile a diversi motivi, tra i quali il piu importante e verosimilmente l’effetto della mortalita competitiva per cause cardiovascolari che puo aver portato ad una sottostima del rischio di neoplasia in molti studi. E verosimile che l’allungamento della vita media dei pazienti acromegalici possa produrre un netto aumento nell’incidenza di neoplasie cosi come accade nella popolazione generale. La neoplasia del colon e quella maggiormente studiata ed e la neoplasia per la quale esistono le piu convincenti evidenze di un’aumentata frequenza nell’acromegalia. Gli studi che hanno impiegato come metodica di screening la colonscopia su casistiche numerose dimostrano che l’acromegalia si associa ad un moderato, ma significativo, aumento di rischio di neoplasia del colon. Pertanto, e indicato procedere a screening colonscopico in tutti i pazienti acromegalicici che non presentino controindicazioni alla procedura. E anche indicato procedere alla ripetizione della colonscopia nei pazienti con neoplasia benigna o maligna al primo esame, soprattutto se la malattia rimane attiva.

The authors review the most important contributions of Pierre Marie to the elucidation and description of several neurological diseases, such as Charcot-Marie-Tooth’s disease and hereditary cerebellar ataxia, as well as his contributions to Internal Medicine, including his pioneering studies on acromegaly, ankylosing spondylitis, and hypertrophic pulmonary osteoarthropathy. His works led to incontestable advances in the medical sciences that transcended his time. Os autores revisaram as mais importantes contribuições de Pierre Marie para a elucidação e a descrição de várias doenças neurológicas, tais como a doença de Charcot-Marie-Tooth e a ataxia cerebelar hereditária, bem como na medicina interna, incluindo os seus estudos pioneiros na acromegalia, espondilite anquilosante e osteo-artropatia hipertrófica pulmonar. Os seus trabalhos promoveram uma crescimento incontestável das ciências médicas que transcenderam o seu tempo.

A acromegalia é uma doença de alta mortalidade, especialmente em razão de complicações cardiovasculares. Com o objetivo de avaliar os fatores determinantes da hipertrofia ventricular esquerda (HVE) e as alterações cardíacas na acromegalia, analisamos 40 acromegálicos submetidos a exames clínico-laboratoriais e ao ecocardiograma. As variáveis analisadas foram idade, sexo, duração de doença, hipertensão arterial (HA), intolerância à glicose/DM, uso ou não de octreotide, GH e %IGF-I. Na análise univariada, pacientes com HVE foram mais idosos (p= 0,031), apresentaram maior prevalência de HA (p= 0,009) e maiores valores da %IGF-I (p= 0,002), comparados aos sem HVE. Na análise multivariada, HA e %IGF-I foram determinantes de HVE (p= 0,035 e p= 0,016). Após a dicotomização da %IGF-I, foi criado um escore e a freqüência de HVE foi 9%, 65%, 92% x 0, 1, 2; p< 0,0001. Encontramos uma prevalência de ectasia de aorta maior e de doença valvar menor do que a da literatura. Concluímos que HA e %IGF-I foram determinantes de HVE.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:02:35Z No. of bitstreams: 1 S0365-05962012000100031.pdf: 81859 bytes, checksum: 8f9412e5418dfca8839ece67b4fdb572 (MD5) Made available in DSpace on 2013-08-22T19:02:35Z (GMT). No. of bitstreams: 1 S0365-05962012000100031.pdf: 81859 bytes, checksum: 8f9412e5418dfca8839ece67b4fdb572 (MD5) Previous issue date: 2012-02-01 Made available in DSpace on 2013-09-30T20:03:37Z (GMT). No. of bitstreams: 2 S0365-05962012000100031.pdf: 81859 bytes, checksum: 8f9412e5418dfca8839ece67b4fdb572 (MD5) S0365-05962012000100031.pdf.txt: 11996 bytes, checksum: 4896632a62ab593fe3b90ec977e7d484 (MD5) Previous issue date: 2012-02-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:33:56Z No. of bitstreams: 2 S0365-05962012000100031.pdf: 81859 bytes, checksum: 8f9412e5418dfca8839ece67b4fdb572 (MD5) S0365-05962012000100031.pdf.txt: 11996 bytes, checksum: 4896632a62ab593fe3b90ec977e7d484 (MD5) Made available in DSpace on 2014-05-20T13:33:56Z (GMT). No. of bitstreams: 2 S0365-05962012000100031.pdf: 81859 bytes, checksum: 8f9412e5418dfca8839ece67b4fdb572 (MD5) S0365-05962012000100031.pdf.txt: 11996 bytes, checksum: 4896632a62ab593fe3b90ec977e7d484 (MD5) Previous issue date: 2012-02-01 Acromegalia é doença crônica rara, insidiosa, decorrente da hipersecreção de hormônio do crescimento, cujos efeitos tróficos e metabólicos frequentemente incorrem em manifestações cutâneas, que podem ser precoces. Os autores avaliaram 15 pacientes portadores de acromegalia e evidenciaram alterações dermatológicas em todos, principalmente espessamento da pele, acrocórdons, cistos epidérmicos, pseudoacantose nigricante, queratoses seborreicas, nevos melanocíticos e manchas lentiginosas. Acromegaly is a chronic, insidious and rare disease, caused by hyper secretion of the growth hormone, which metabolic and trophic effects commonly result in cutaneous manifestations, sometimes preceding other clinical symptoms. The authors have assessed 15 patients with acromegaly and found dermatologic lesions in all of them, mainly skin thickening, acrochordons, epidermoid cysts, pseudoacanthosis nigricans, seborrheic keratosis, melanocytic naevi and lentiginous spots. Universidade Estadual Paulista Julio de Mesquita Filho Dermatology and Radiology Department Universidade Estadual Paulista Julio de Mesquita Filho Internal Medicine Department Universidade Estadual Paulista Julio de Mesquita Filho Dermatology and Radiology Department Universidade Estadual Paulista Julio de Mesquita Filho Internal Medicine Department

Os adenomas produtores de GH podem ser mono, bi ou pluri-hormonais. A associação mais frequente do GH é com a sub unidade alfa ou com a prolactina. Apresentam-se com as alterações clássicas de acromegalia, mas quando produzem mais que um hormônio podem apresentar sintomas visuais. Os mono-hormonais são geralmente microadenomas e os outros dois grupos tendem a ser macroadenomas. Analisamos nossa experiência com 20 casos deste tipo de adenomas e mostramos o resultado cirúrgico, que foi bastante satisfatório para o grupo mono-hormonal. A radioterapia deve ser considerada quando a ressecção não foi total. The growth hormone secreting pituitary adenomas can be mono, bi or pluri-hormonals. The most frequent association of GH is with the sub unit alpha or with the prolactin. This type of adenoma comes with the classic alterations of acromegaly, but when they produce more than one hormone, visual symptoms can be present. The adenoma producing just GH hormone is generally microadenoma and the other two groups tend to be macroadenoma. We analyze 20 cases of these adenomas and we have found quite satisfactory surgical result for the mono-hormonal type group. Radiotherapy should be considered in cases of partial resection.

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.

Os autores fizeram estudo retrospectivo de 18 pacientes com acromegalia, que foram diagnosticados, tratados e acompanhados pelos Serviços de Endocrinologia e Neurocirurgia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, no período de 1979 a 1985. A média de idade dos pacientes foi 43,2 anos (variação entre 15 e 63), as queixas clínicas iniciais se deveram principalmente às alterações somáticas (83,33%), em 50% dos casos tivemos manifestações secundárias à compressão tumoral e em 53,33% havia alterações neuro-oftalmológicas. A comprovação de hipersecreção de hormônio de crescimento foi feita por dosagens hormonais basais e por testes dinâmicos. A avaliação neuro-radiológica evidenciou expansão suprasselar em 61,11% dos casos e em 100% dos casos o acesso cirúrgico foi por via transesfenoidal. O objetivo principal deste estudo foi o de estabelecer critérios para o diagnóstico, discutir a conduta terapêutica e avaliar os resultados obtidos, comparando-os com outras séries da literatura.

The present case reports an acromegalic 38-yearold female patient who developed fatal congestive heart failure after surgery with an infarct-like ECG pattern. No pre-existing cardiovascular disease was present. Autopsy diagnosis revealed eosinophilic myocarditis. Ranitidine and cephalosporin-antibiotics are considered as potential causal agents. Despite high dose of glucocorticoids before surgery, the eosinophilic myocarditis was fatal for the patient.

Consensus document [Abstract] Acromegaly and gigantism are due to excess GH secretion, usually by a pituitary adenoma. It is an uncommon disease. Diagnosis is made by showing elevated GH and IGF-I levels in patients with a clinical picture suggesting the condition. Once excess GH is confirmed by biochemical tests, MRI of the hypothalamic–pituitary area should be performed to ascertain the source of excess GH. Transsphenoidal surgery of the pituitary adenoma is the treatment of choice. However, introduction of new drugs has changed the treatment sequence in recent years. Medical treatment with somatostatin analogs may be indicated as primary treatment in patients in whom surgery is not expected to be curative or is contraindicated. The GH receptor antagonist should be used in patients not controlled after surgery who do not adequately respond to somatostatin analogs. Radiotherapy would be indicated in patients not controlled after surgery and medical treatment or with large tumor remnants after surgery. [Resumen] La acromegalia y el gigantismo se deben a la producción excesiva de GH, generalmente por un adenoma hipofisario. Es una enfermedad poco frecuente. El diagnóstico se realiza ante un paciente con un cuadro clínico sugerente con la demostración de concentraciones de GH e IGF-I elevadas. Tras la confirmación bioquímica del exceso de GH debe realizarse una RM del área hipotálamo-hipofisaria a fin de confirmar el origen del exceso de GH. El tratamiento de elección es el quirúrgico del adenoma hipofisario mediante cirugía transesfenoidal, si bien en los últimos años los avances en cuanto a la aparición de nuevos fármacos han modificado la secuencia terapéutica. El tratamiento médico con análogos de somatostatina puede estar indicado como procedimiento primario en pacientes no subsidiarios de curación tras cirugía, o en aquellos casos en que esta esté contraindicada. El antagonista del receptor de GH debe utilizarse en pacientes no controlados tras cirugía que no responden de forma adecuada a análogos de somatostatina. La radioterapia estaría indicada en aquellos casos no controlados tras tratamiento quirúrgico y médico o en aquellos pacientes con grandes restos tumorales tras el tratamiento quirúrgico.

[Abstract] Context. Transsphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA) treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences. Objective. The aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly. Data Sources. All studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. Study Selection: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49%) fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model. Data Extraction. Data were extracted from published reports by two independent observers. Data Synthesis: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR) for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93–2.82). In the analysis of the three prospective controlled trials, a statistically significant effect was idenfified OR: 3.62 (95% CI, 1.88–6.96). Conclusions. Preoperative treatment with SSA og GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment. Instituto de Salud Carlos III PI070413 Instituto de Salud Carlos III; PI10/00088 Xunta de Galicia; PS07/12 Xunta de Galicia; INCITE08ENA916110ES Xunta de Galicia; INCITE09E1R91634ES Xunta de Galicia; IN845B-2010/187 Xunta de Galicia; 10CSA916014PR

Made available in DSpace on 2014-10-01T13:08:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-11-01Bitstream added on 2014-10-01T14:03:06Z : No. of bitstreams: 1 S0004-27302013000800005.pdf: 102494 bytes, checksum: 2c511f7d3e1797e3be6b52b308fc240a (MD5) 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. 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. Universidade Estadual Paulista Departamento de Clínica Médica Serviço de Endocrinologia e Metabologia Universidade Estadual Paulista Departamento de Dermatologia e Radioterapia Serviço de Dermatologia Universidade Estadual Paulista Departamento de Clínica Médica Serviço de Gastroenterologia Clínica Universidade Estadual Paulista Departamento de Clínica Médica Serviço de Endocrinologia e Metabologia Universidade Estadual Paulista Departamento de Dermatologia e Radioterapia Serviço de Dermatologia Universidade Estadual Paulista Departamento de Clínica Médica Serviço de Gastroenterologia Clínica

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% 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. Introduction: There are several complications of the cardiovascular system caused by acromegaly, especially hypertension. Objectives: To evaluate hypertension characteristics in patients with cured/controlled acromegaly and with the active disease. Patients and methods: Cross-sectional study of the follow-up of forty-four patients with acromegaly submitted to clinical evaluation, laboratory tests and cardiac ultrasound. Patients with cured and controlled disease were evaluated as one group, and individuals with active disease as second one. Results: Forty-seven percent of the patients had active acromegaly, and these patients were younger and had lower blood pressure levels than subjects with controlled/cured disease. Hypertension was detected in 50% of patients. Subjects with active disease showed a positive correlation between IGF-1 and systolic and diastolic blood pressure levels (r = 0.48, p = 0.03; and r = 0.42, p = 0.07, respectively), and a positive correlation between IGF-1 and urinary albumin excretion (UAE) rates. In patients with active disease, IGF-1 was a predictor of systolic blood pressure, although it was not independent of UAE rate. For individuals with cured/controlled disease, waist circumference and triglycerides were the predictors associated with systolic and diastolic blood pressure. Conclusions: 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.

OBJECTIVES: To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. METHODS: This was a cross sectional study. RESULTS: Fifty-eight acromegalic patients were assessed. Only 29% met the criteria for cure, and 27% had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2%. Most of the diabetic patients (18 out of 22, 82%) did not meet criteria for cure. They were more often hypertensive [16/22 (73%) vs. 17/36 (46%), p = 0.04], and used statins more frequently [14/22 (64%) vs. 8/36 (21%), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95% CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95% CI: 0.03 - 0.78), p = 0.02]. CONCLUSIONS: The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes. 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% preencheram critérios de cura e 27% estavam com a doença controlada. Vinte e dois pacientes (38%) apresentaram DM, HbA1c 7,34 ± 2,2%. Destes, 18 não preencheram critérios de cura. Pacientes com DM foram mais frequentemente hipertensos [16/22 (73%) vs. 17/36 (46%), p = 0,04] e usavam mais estatina [14/22 (64%) vs.8/36 (21%), p = 0,004]. Após regressão múltipla, hipertensão foi associada a DM [razão de chances (RC): 9,28 (95% CI: 1,59 - 54,00), p = 0,01], e acromegalia curada/controlada foi fator protetor para presença de diabetes [OR: 0,17 (95% 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.

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.

OBJETIVO: Avaliar os resultados iniciais de uma equipe cirúrgica no controle hormonal dos adenomas hipofisários secretores. MATERIAIS E MÉTODOS: Em cinco anos, foram operados 51 adenomas secretores (31 GH, 14 ACTH, 5 prolactina, 1 TSH). O controle hormonal foi GH basal < 2,5 ng/dL, cortisol livre urinário normal, redução dos níveis de prolactina, e T3 e T4 livre normais. RESULTADOS: As taxas de controle foram 36% na acromegalia e 57% no Cushing. Dois prolactinomas (40%) normalizaram a prolactina. Os hormônios tiroidianos normalizaram no adenoma secretor de TSH. O controle do hipercortisolismo correlacionou-se com o tempo de experiência da equipe (p = 0,01). CONCLUSÃO: Nossos resultados, limitados aos primeiros anos de experiência cirúrgica, situam-se abaixo da variação reportada em grandes casuísticas com maior tempo de experiência. Ao longo do tempo, observou-se melhora progressiva nos níveis de cortisol urinário no pós-operatório inicial da doença de Cushing em função da experiência cirúrgica.

ObjectiveIn this study, the effect of high-dose octreotide LAR on glucose metabolism in patients with acromegaly was investigated.DesignA post-hoc analysis of a clinical trial enrolling 26 patients with acromegaly not controlled by standard maximal somatostatin analog (SSAs) dose and randomized to receive high-dose (60 mg/28 days) or high-frequency (30 mg/21 days) octreotide i.m. injection (octreotide LAR) for 6 months.MethodsGlucose metabolic status was defined as worsened when a progression from normoglycemia to impaired fasting glucose (IFG) or from IFG to diabetes occurred or when an increase of HbAlc by at least 0.5% was demonstrated. An improvement of glucose metabolism was defined in the presence of a regression from IFG to normoglycemia and/or when HbAlc decreased by at least 0.5%.ResultsGlucose metabolic status remained unchanged in a majority of patients (16/26 patients, 65.3%), worsened in six patients, and improved in four patients. Pre-existing metabolic status did not predict worsening of glucose metabolism, which, conversely, was significantly related to persistent biochemical activity of the disease. In fact, patients with worsened glucose metabolism exhibited a less frequent decrease in serum GH and IGF1 levels, compared with patients with improved or unchanged glucose metabolism (2/6 vs 18/20; P=0.01).ConclusionAn increase in octreotide LAR dose or frequency did not impact on glucose metabolism in most patients. Worsening of glucose metabolic status occurred in close relation with persistently uncontrolled acromegaly.

ContextMammographic density is a strong independent risk factor for breast cancer, whose prevalence in acromegaly is still controversial.ObjectiveTo compare breast density in premenopausal acromegalic patients and controls and to determine whether density correlated with disease duration, GH, and IGF1 levels.Design, setting and participantsA prospective study involving 30 patients and 60 controls matched for age and body mass index.InterventionsA quantitative computer-aided mammographic density estimation (MDEST) and a qualitative blind evaluation by two experienced radiologists using the breast imaging reporting and data system (BI-RADS) was performed. Totally, 60 (acromegaly) and 120 (controls) craniocaudal and mediolateral oblique mammograms were evaluated in both patients and controls.Main outcome measuresBreast density.ResultsPatients showed a significantly (Pk=0.63 and k=0.85). In patients grouped according to disease activity (17 controlled and 13 uncontrolled) and medical therapy (15 treated and 15 untreated), no differences were found. All these groups had significantly increased mammographic breast density compared with controls (PA positive correlation was found between mammographic breast density, IGF1 values and disease duration (r=0.29 and r=0.39), whereas it was not found with GH (r=−0.02).ConclusionsMammographic breast density in premenopausal acromegalic patients is significantly higher than controls and positively correlated with IGF1 and disease duration.

OBJECTIVE: To evaluate the frequency of subclinical acromegaly (in the absence of clinical phenotype but biochemically uncontrolled) in patients with prolactinoma during treatment with dopaminergic agonists. SUBJECTS AND METHODS: One hundred twenty one patients without a phenotype suggestive of acromegaly were studied. RESULTS: Initially, the laboratory diagnosis of acromegaly was unequivocal (elevated IGF-1 for gender and age with nadir GH > 1 μg/L) in two patients, and likely (elevated IGF-1 with nadir GH > cut-off but < 1 μg/L) in another patient. In two other patients, this diagnosis was possible (normal IGF-1 with nadir GH > 1 μg/L). Repetition of the tests 6 months after withdrawal of the dopaminergic agonist confirmed the diagnosis of subclinical acromegaly (elevated IGF-1 for gender and age with nadir GH > 1 μg/L) in these 5 patients. False-positive results were excluded in all cases. CONCLUSION: In patients with prolactinomas, acromegaly should be investigated not only in cases with a clinical phenotype. OBJETIVO: Avaliar a frequência de acromegalia subclínica (na ausência de fenótipo clínico, mas bioquimicamente não controlada) em pacientes com prolactinoma em tratamento com agonistas dopaminérgicos. SUJEITOS E MÉTODOS: Cento e vinte e um pacientes sem fenótipo de acromegalia foram estudados. RESULTADOS: Inicialmente, o diagnóstico laboratorial de acromegalia foi inequívoco (IGF-1 elevado para sexo e idade com nadir do GH > 1 μg/L) em dois pacientes, e provável (IGF-1 elevado com nadir do GH > valor de corte ensaio-específico mas < 1 μg/L) em outro paciente. Em outros dois, esse diagnóstico foi possível (IGF-1 normal com nadir do GH > 1 μg/L). A repetição dos testes seis meses após a suspensão dos agonistas dopaminérgicos confirmou o diagnóstico de acromegalia subclínica (IGF-1 elevado para sexo e idade com nadir do GH > 1 μg/L) em cinco desses pacientes. Os resultados falso-positivos foram excluídos em todos os casos. CONCLUSÃO: Em pacientes com prolactinomas, a acromegalia deveria ser investigada não apenas nos casos com fenótipo clínico.

OBJETIVOS: Investigar a influência do IGF-I e testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos. MÉTODOS: Foram avaliados 15 homens acromegálicos. RESULTADOS: Os pacientes hipogonádicos apresentaram HDL-c mais baixo e triglicérides, LDL-c, glicemia, GH e IGF-I mais elevados. Os valores de IGF-I correlacionaram-se inversamente com HDL-c (r = - 0,57, p = 0,04) e diretamente com triglicerídeos (r = 0,62, p = 0,01) e glicemia (r = 0,66, p = 0,008), enquanto a testosterona correlacionou-se diretamente com HDL-c (r = 0,52, p = 0,05) e inversamente com triglicerídeos (r = - 0,57, p = 0,02); LDL (r = - 0,53, p = 0,04) e glicemia (r = - 0,54, p = 0,03). O IGF-I e a testosterona correlacionaram-se inversamente (r = - 0,585, p = 0,028). CONCLUSÃO: Estes resultados sugerem que a intervenção mais importante na redução do risco cardiovascular nesses pacientes é o controle da atividade da doença. OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

Contexto - Pacientes com acromegalia apresentam maiores chances de desenvolver pólipo e câncer colorretal e, sendo considerados integrantes do grupo de risco, necessitam serem submetidos aos exames de rastreamento. Por sua vez, na acromegalia, o maior comprimento do cólon e a formação de alças intestinais complexas podem prever maiores dificuldades técnicas e aumentar o risco em potencial de complicações durante o exame de colonoscopia convencional. A colonografia tomográfica computadorizada, também denominada colonoscopia virtual, é uma tecnologia inovadora e segura, que está revolucionando o diagnóstico das neoplasias do cólon e do reto. Objetivo - Analisar o desempenho da colonografia tomográfica computadorizada no rastreamento de pólipos colorretais em pacientes com acromegalia. Métodos - Estudo prospectivo com 21 pacientes acromegálicos, 12 do sexo masculino e 9 do sexo feminino, idade média de 49 anos, assintomáticos, submetidos a colonografia tomográfica computadorizada e colonoscopia convencional. A colonografia tomográfica computadorizada foi realizada com aparelho de tomografia computadorizada helicoidal multislice da marca GE. A colonoscopia convencional foi realizada, no mesmo dia, sem prévio conhecimento do diagnóstico da colonografia tomográfica computadorizada. O estudo avaliou a capacidade da colonografia tomográfica computadorizada para detectar pacientes acromegálicos com pólipos colorretais e a identificação de cada lesão colorretal descrita pela colonoscopia. Resultados - Em dois pacientes (2/21) a colonoscopia convencional foi incompleta. Entretanto, em todos os pacientes a colonografia tomográfica computadorizada foi completa na avaliação colorretal. Na primeira fase (“por paciente”), a colonografia tomográfica computadorizada diagnosticou oito de nove pacientes com pólipos colorretais e mostrou 88% de sensibilidade, 75% de especificidade e 81% de precisão. Na segunda fase (“por pólipo”), dos 21 pacientes acromegálicos incluídos no estudo, 12 apresentaram colonoscopia convencional normal. Um total de 19 pólipos foram identificados em 9 pacientes. Dez dos 19 pólipos eram menores que 10 mm e 9 foram iguais ou maiores que 10 mm. A colonografia tomográfica computadorizada identificou 7 dos 9 pólipos ≥10 mm descritos pela colonoscopia convencional e somente 6 dos 10 pólipos pequenos detectados pela colonoscopia convencional. A análise histológica das lesões ressecadas revelaram 12 adenomas tubulares, 6 pólipos hiperplásicos e 1 adenoma túbulo-viloso com um foco de adenocarcinoma. Conclusão - São apresentados os primeiros relatos da realização de colonografia tomográfica computadorizada no rastreamento de pólipos colorretais em doentes com de acromegalia. Neste estudo, a colonografia tomográfica computadorizada realizou avaliação colorretal completa e sem complicações em todos os pacientes acromegálicos. A colonografia tomográfica computadorizada apresentou boa sensibilidade, especificidade e precisão para identificar pacientes acromegálicos com presença de pólipos colorretais de qualquer diâmetro e melhores resultados no diagnóstico de pólipos grandes quando comparados com pequenas lesões polipóides. Context - Acromegalic patients have better chances to develop colorectal polyps and cancer and, considered a high-risk group, need to undergo frequent screening examinations. Moreover, in acromegalia, the increased bowel length and the intestinal loop complexity can lead to higher levels of technical difficulties and increase the risks of complications at conventional colonoscopy. Computed tomographic colonography, also known as virtual colonoscopy, is an innovative and secure technology which is revolutionizing the diagnosis of colon and rectum neoplasias. Objective - To analyze computed tomographic colonography performance for the screening of colorectal polyps in acromegalic patients. Methods - A prospective study of 21 asymptomatic acromegalic patients, 12 male and 9 female, average age 49, who underwent computed tomographic colonography and conventional colonoscopy. Computed tomographic colonography was performed with a GE Helical Multislice Computed Tomography Apparatus. Conventional colonoscopy was performed in the same day, without previous knowledge of the computed tomographic colonography diagnostics. The study evaluated the capacity of computed tomographic colonography to detect patients with colorectal polyps and identify each colorectal lesion described by the colonoscopy. Results - In two patients (2/21), conventional colonoscopy was incomplete. However, in all patients computed tomographic colonography was complete. In Phase I (“per patient”), computed tomographic colonography diagnosed eight of the nine patients with colorectal polyps and showed 88% sensitivity, 75% specificity and 81% accuracy. In Phase II (“per polyp”), out of the 21 acromegalic patients included in this study, 12 presented normal findings at conventional colonoscopy. A total of 19 polyps were identified in 9 patients. Ten of the 19 polyps were smaller than 10 mm, and 9 were equal to or larger than 10 mm. Computed tomographic colonography identified 7 of the 9 polyps ≥10 mm described by conventional colonoscopy and only 6 of the 10 small polyps identified at conventional colonoscopy were detected by computed tomographic colonography. The histological analysis of resected lesions revealed 12 tubular adenomas, 6 hyperplastic polyps and 1 colonic tubulo-villous adenoma with an adenocarcinoma focus. Conclusion - The authors present the first reports of computed tomographic colonography in the screening of colorectal polyps in acromegalic patients. In this study, computed tomographic colonography was performed without complications and a complete and safe colorectal evaluation was possible in all acromegalic patients. Moreover, computed tomographic colonography presented good sensitivity, specificity and accuracy for the identification of acromegalic patients with polyps of any size and better results in the diagnosis of large polyps, when they were compared to small polypoid lesions.

To evaluate GH and IGF-I control and tumour shrinkage in newly diagnosed patients with acromegaly treated first-line with lanreotide-Autogel (ATG) 120 mg. Design Open, prospective.Twenty-six patients (17 women, aged 31-70 years): eight enclosed and 12 extrasellar (eight invasive) macroadenomas and six microadenomas (one invasive). ATG 120 mg initially given every 4 weeks for 12 weeks; then intervals between injections increased to every 6 or 8 weeks if GH levels wereor= 2.5 or1 microg/l (equal to 6.5 and 2.6 mU/l), respectively.Final dosage was ATG 120 mg every 4 weeks in nine patients (34.6%), every 6 weeks in eight patients (30.8%) and every 8 weeks in the remaining nine patients (34.6%). After 12 months, both GH and IGF-I were controlled in 14 patients (53.8%). The mean tumour volume decreased from 1405 +/- 1827 mm(3) at study entry to 960 +/- 1381 mm(3) after 6 months, and 799 +/- 1161 mm(3) after 12 months (P0.0001). Overall tumour shrinkage was 35.8 +/- 28.1% after 6 months and 48.4 +/- 27.6% after 12 months. After 12 months, 20 patients (76.9%) achieved25% tumour shrinkage: 12 of 14 with controlled disease (85.7%) and 8 of 12 with noncontrolled disease (66.7%; P = 0.49). Hyperhydrosis, paresthesiae and arthralgias significantly reduced after treatment. No patient withdrew from the study because of adverse events.ATG 120 mg in newly diagnosed patients with acromegaly controls GH and IGF-I secretion in 53.8% and inducesor= 25% tumour shrinkage in 76.9% during a 12-month period. The treatment was associated with improvement of clinical symptoms and with a good safety profile.

O objetivo deste estudo é comparar o impacto econômico e o impacto nos pacientes com acromegalia do tratamento com dois diferentes análogos de somatostatina (octreotida LAR e lanreotide SR) no Brasil. Um estudo de custoefetividade foi realizado a partir da perspectiva do Sistema Único de Saúde (SUS). Foi desenvolvido um modelo analítico de decisão baseado no Protocolo Clínico e Diretrizes Terapêuticas de Acromegalia do SUS. Uma coorte hipotética de 276 pacientes foi seguida por dois anos. Dados foram obtidos da literatura e bases de dados oficiais do SUS. Baseado no modelo analítico, o tratamento com octreotida LAR evitaria 12 e 17 casos com níveis elevados de GH e IGF-I, respectivamente. Octreotida LAR foi uma estratégia econômica, gerando economia de R$10.448.324 (US$4.465.096) para o SUS. A economia anual por paciente foi de R$18.928 (US$8.089). O tratamento de acromegalia com octreotida LAR é estratégia dominante quando comparado com o tratamento com lanreotida SR no Brasil. A análise de sensibilidade não alterou seu status de econômica. This study aims to compare economic and patient impacts of the treatment of acromegaly with two different somatostatin analogues (octreotide LAR and lanreotide SR) in Brazil. A cost-effectiveness analysis was carried out under the Brazilian Public Health Care System (SUS) perspective. A decision analytical model was developed based on the Brazilian Public Health Care System Clinical Guideline for Acromegaly. A hypothetical cohort of 276 patients was followed for two years. Data were extracted from literature and administrative databases. Based on the analytical model, treatment with octreotide LAR would avoid 12 and 17 cases of GH and IGF-I elevated serum levels, respectively. Octreotide LAR was a cost-saving strategy, with net savings of R$10,448,324 (US$4,465,096) to SUS. Annual net savings per patient were R$ 18,928 (US$8,089). Treatment of acromegaly with octreotide LAR is a dominant strategy when compared to the treatment with lanreotide SR in Brazil. Sensitivity analysis did not alter the cost-saving status. Universidade de São Paulo Faculdade de Medicina Departamento de Medicina Preventiva Novartis Pharmaceuticals Universidade Federal de São Paulo (UNIFESP) Clínica Médica Novartis Biociências S.A. UNIFESP, Clínica Médica SciELO

A acromegalia acarreta uma série de distúrbios ao sistema cardiovascular, decorrentes da exposição crônica a níveis elevados de GH e IGF-1. Estes distúrbios são os principais responsáveis pelo aumento da mortalidade de acromegálicos. Entre as várias formas de acometimento cardiovascular, destaca-se a miocardiopatia acromegálica, entidade caracterizada, inicialmente, pelo estado hiperdinâmico, seguido de hipertrofi a ventricular esquerda concêntrica e disfunção diastólica por défi cit de relaxamento, culminando com disfunção sistólica e, por vezes, insufi ciência cardíaca franca. Além disso, são também relevantes as arritmias, as valvulopatias, sobretudo mitral e aórtica, a cardiopatia isquêmica, a hipertensão e os distúrbios dos metabolismos glicêmico e lipídico. Nesta revisão são abordados os principais aspectos clínicos e prognósticos destas entidades, os efeitos do tratamento da acromegalia sobre elas e as repercussões correspondentes sobre a sobrevida dos pacientes. Acromegaly causes a number of disorders in the cardiovascular system, resulting from chronic exposure to high levels of GH and IGF-1. Such disorders are the main responsible for increased mortality rates among acromegalic patients. Among several forms of cardiovascular impairment is acromegalic cardiomyopathy, an entity that is initially characterized by a hyperdynamic state, followed by concentric left ventricular hypertrophy and diastolic dysfunction due to relaxation defi cit, culminating in systolic dysfunction and sometimes heart failure. In addition, arrhythmias and heart valve diseases are also relevant, especially mitral and aortic, ischemic heart disease, hypertension, and glucose and lipid metabolism disorders. This review approaches the main clinical and prognostic aspects of these entities, the effects of acromegaly treatment on them, and the respective consequences on patient survival.

Neoplasias como câncer de próstata, mama e cólon estão relacionadas à acromegalia. Raras vezes foi mencionada a associação com melanoma. Descreve-se caso de paciente com acromegalia no qual foi identificada lesão melanocítica suspeita, com posterior confirmação de melanoma. A excisão cirúrgica da lesão levou à cura da neoplasia. Chama-se a atenção para a necessidade de exame cuidadoso da pele de pacientes com acromegalia. Neoplasias such as prostate, breast, and colon cancer are commonly associated with acromegaly. However, the association of the latter with melanoma has been rarely mentioned. We describe the case of a patient with acromegaly in whom a suspicious melanocytic lesion was detected, and later confirmed to be melanoma by means of biopsy. Surgical excision of the lesion led to the cure of the neoplasia. More attention should be drawn to the need for careful skin examination of patients with acromegaly.

OBJETIVO: Avaliar o metabolismo da glicose em pacientes acromegálicos antes e após o tratamento com octreotide LAR. PACIENTES E MÉTODOS: Este foi um estudo longitudinal e prospectivo com 30 pacientes do ambulatório de pesquisa em acromegalia do Serviço de Endocrinologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (HUCFF/UFRJ). Eles foram submetidos à avaliação clínica e laboratorial com dosagens de hormônio do crescimento (GH), fator de crescimento semelhante à insulina tipo I (IGF-I), insulina, pró-insulina, peptídeo C, hemoglobina glicosilada (HbA1c), proteína de ligação do IGF tipo 1 (IGFBP-1) e a um teste oral de tolerância à glicose (TOTG), antes e após seis meses de tratamento com octreotide LAR. Foi aplicado o teste dos postos sinalizados de Wilcoxon e o critério de determinação de significância adotado foi o nível de 5%. RESULTADOS: Encontraram-se 16 pacientes (54%) com tolerância normal à glicose, sete (23%) com intolerância à glicose e sete (23%) com diabetes melito (DM). Doze pacientes completaram os seis meses de tratamento, sendo que houve piora da tolerância à glicose em três e piora do controle glicêmico dos dois pacientes diabéticos. Houve aumento da circunferência abdominal (p = 0,03) e queda do GH (p = 0,04), % IGF-I acima do limite superior do valor de referência (%LSVR) (p = 0,001), insulina (p = 0,019), peptídeo C (p = 0,002) e do modelo de avaliação homeostática (HOMA-IR) (p = 0,039). CONCLUSÕES: Nesta série, o tratamento com octreotide LAR acarretou piora da tolerância à glicose em três pacientes não-diabéticos e piora do controle glicêmico em dois diabéticos, apesar da diminuição da resistência insulínica (RI). AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5% were considered statistically significant. RESULTS: We found 16 (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose tolerance and 7 (23%) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039]. CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.

I pazienti con acromegalia presentano cefalea la cui patogenesi è ancora sconosciuta. Le dimensioni del tumore non sono determinanti per la presenza nè per la gravità della cefalea. Il trattamento con analoghi della somatostatina migliora questo sintomo.

Hypoxemia secondary to sleep apnea is commonly seen in patients with acromegaly, and this alteration apparently leads to considerable morbidity and mortality among such patients. With the objective of identifying hypoxemia based on clinical data, we conducted a cross-sectional study of 34 patients with acromegaly, all of whom were submitted to nocturnal oximetry and evaluation of snoring, as well as to the determination of body mass index (BMI) and neck circumference. In addition, daytime sleepiness was evaluated using the Epworth sleepiness scale (ESS). In this study, sleep hypoxemia was defined as five or more episodes of desaturation per hour. The sensitivity and specificity of the various parameters in predicting such hypoxemia were, respectively, as follows: snoring (92.9% and 35%); BMI >28.5 kg/m² (71.4% and 60%); neck circumference >44 cm (28.6% and 95%); ESS score >10 (42.9% and 70%). For patients with a neck circumference of more than 44 cm, the probability of sleep hypoxemia was found to increase from 41% (pre-test) to 80% (post-test). For patients with a neck circumference of less than 44 cm, positivity for two or three of the other parameters (snoring, ESS score >10 and BMI >28.5 kg/m²) increased the post-test probability to 62%, whereas positivity for only one (or none) reduced post-test probability to 8%. We can conclude that the clinical parameters evaluated allowed us to predict, with considerable accuracy, whether or not sleep hypoxemia would occur in patients with acromegaly. A hipoxemia secundária a apnéia do sono é comumente encontrada na acromegalia e parece ser a alteração sobre a qual se estabelece considerável morbi-mortalidade. Com o objetivo de reconhecer sua presença a partir de dados clínicos foram estudados transversalmente 34 pacientes, os quais foram submetidos a oximetria noturna, medida do índice de massa corporal (IMC), circunferência do pescoço, sonolência pela escala de Epworth e avaliados quanto a presença de roncos. A sensibilidade e especificidade para predizer hipoxemia, mais de 5 episódios de dessaturação por hora, foram respectivamente: IMC >28,5 Kg/m² (71,4% e 60%); circunferência do pescoço >44 cm (28,6% e 95%); Epworth >10 pontos (42,9% e 70%); roncos (92,9% e 35%). Se presente circunferência do pescoço maior que 44 cm, a probabilidade de hipoxemia aumenta de 41% (pré-teste) para 80% (pós-teste). Se ausente este dado, a presença de dois ou três dos demais (ronco, Epworth >10, IMC >28,5 Kg/m²) eleva a probabilidade pós-teste para 62%, enquanto a presença de no máximo um deles é capaz de reduzir para 8%. Conclui-se que os achados clínicos avaliados permitem com alta probabilidade predizer ou não hipoxemia durante o sono na acromegalia.