ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Abstract Objective: Correlate serum magnesium (Mg) and Calcium (Ca) levels with body composition and metabolic parameters in women with fibromyalgia (FM). Patients and methods: Cross-sectional study compared with a control group paired by age and body mass index (BMI) of adult women diagnosed with fibromyalgia. All participants went through assessment of their body composition through dual-energy X-ray absorptiometry (DXA) and had blood samples collected for dosing of Mg, Ca, C-reactive Protein (CRP), lipidogram and glycemia. Results: 53 women with FM (average age 48.1 ±8.2 years, average BMI 26.6 ±4.5 kg/m2) and 50 control women (average age 47.1 ±9.9 years, average BMI 25.6 ± 3.6 kg/m2) participated in the study. Serum levels turned out to have inverse correlation with CRP in the FM group (r = −0.29, p = 0.03) and with BMI and glycemia in the control group (r = 0.31; p = 0.02 and r = 0.48; p = 0.0004 respectively). Serum levels of calcium correlated with triglycerides (r = 0.29; p = 0.03) in the FM group and with glycemia in the control group (r = 0.64; p = 0.0001). Conclusions: In patients with FM, magnesemia turned out to have inverse correlation with CRP and calcemia had positive association with triglycerides.

Abstract Objective: Determine food intake and levels of serum magnesium (Mg) and calcium (Ca) and correlate these minerals with pain, quality of life and depression risk in women with and without fibromyalgia (FM). Patients and methods: Fifty-three women diagnosed with FM and 50 healthy women participated in the study, where all of them had equivalent age and body mass index (BMI). All women underwent anthropometric assessment, physical exams of pain perception threshold and tender point (TP) count, blood sample collection, and filling out of FM impact questionnaire (FIQ), Patient Health Questionnaire-9 (PHQ-9), and 3-day dietary record (DR). Results: Dietary intake of Mg and Ca was substantially lower by women with FM. There were no differences in levels of serum Mg and Ca in the groups under analysis. For the FM group, dietary intake of Mg and Ca had inverse correlation with TP and direct relation with the pain threshold. Conclusions: Although women with FM had lower dietary intake of Mg and Ca, serum levels for these nutrients were not different between the groups. Low dietary intake of minerals correlated with worsened pain threshold parameters.

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

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

Objetivo: Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC. Métodos: Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição. Os pacientes realizaram absorciometria de dupla energia por raios X. O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso. A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD). O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE). Resultados: Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2. Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico. Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução). O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001). A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009). A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD. Conclusões: Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico.

Objective: To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD. Methods: A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index. Results: We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2. Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage. Conclusions: In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.

Background: Sub-optimal levels of vitamin D have been found to be highly prevalent in all age groups, with epidemiologic studies demonstrating a link between vitamin D deficiency and disease susceptibility, such as infection and cancer, and mortality rates. In adult transplant patients, it has been suggested that the immunomodulatory properties of vitamin D may have an important role in the prevention and treatment of graft-versus-host disease. Objective: The objective of this study was to assess serum 25-hydroxyvitamin D levels of children and adolescents submitted to allogeneic hematopoietic stem cell transplantation. Methods: Serum 25-hydroxyvitamin D levels of 66 patients, aged 4-20 years, were assessed at three stages: before hospitalization for hematopoietic stem cell transplantation and at 30 and 180 days after hematopoietic stem cell transplantation. The control group consisted of 25 healthy children. Results: At the pre-hematopoietic stem cell transplantation stage, patients had lower levels of 25-hydroxyvitamin D compared to controls (25.7 ± 12.3 ng/mL vs. 31.9 ± 9.9 ng/mL; p-value = 0.01), and a higher prevalence of 25-hydroxyvitamin D deficiency (32% vs. 8%; p-value = 0.01). Prevalence increased significantly after hematopoietic stem cell transplantation (p-value = 0.01) with half of the patients having vitamin D deficiency at 180 days after transplantation. At this stage, mean serum 25-hydroxyvitamin D levels were 20.9 ± 10.9 ng/mL, a significant decline in relation to baseline (p-value = 0.01). No correlation was found between 25-hydroxyvitamin D levels and vitamin D intake, graft-versus-host disease, corticoid use or survival rates. Conclusion: Low levels of 25-hydroxyvitamin D were detected even before hematopoietic stem cell transplantation and were significantly lower at 180 days after hematopoietic stem cell transplantation, thus recommending vitamin D supplementation for children and adolescents submitted to hematopoietic stem cell transplantation.

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

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

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

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

OBJETIVO: Comparar os níveis de androgênios e densidade mineral óssea (DMO) em mulheres ooforectomizadas (OOF) e não ooforectomizadas (NOOF) na pós-menopausa. Quarenta mulheres (53,9 ± 4 anos), 20 OOF e 20 NOOF foram selecionadas. MÉTODOS: Testosterona total (TT), testosterona livre (TL), androstenediona (AN), deidroepiandrosterona (DHEA) e sulfato de deidroepiandrosterona (DHEA-S) foram dosados. DMO foi avaliada em 16 NOOF e 14 OOF. RESULTADOS: Não houve diferença entre os grupos com relação à idade, ao índice de massa corporal (IMC) e ao tempo de menopausa. Concentração média de TT e TL foi duas vezes maior em mulheres NOOF (60,91 versus 30,17 ng/dL, p = 0,0001; 1,00 versus 0,48 pg/mL, p = 0,003). Não houve diferença na DMO. Houve correlação inversamente significativa entre IMC e TT, r = -0,3; p = 0,05, e do tempo de menopausa com AN (r = -0,35; p = 0,02), DHEA, (r = 0,3; p = 0,01). CONCLUSÃO: Ooforectomia bilateral resultou em deficiência androgênica mais severa que a menopausa natural, sem comprometimento da massa óssea.

OBJECTIVE: Compare levels of androgens and bone mineral density (BMD) of ovariectomized (OVX) and non-ovariectomized (NOVX) postmenopausal women. Forty women, 20 OVX and 20 NOVX, (53.9 ± 4 years) were selected. METHODS: Total testosterone (TT), free testosterone (FT), androstenedione (AN), dehidroepiandrostenedione (DHEA) and its sulfate (DHEA-S) were measured. BMD was measured in 14 OVX and 16 NOVX. RESULTS: No differences between groups with regard to age, body mass index (BMI) and time since menopause were found. Mean levels of TT and FT were two-fold higher in NOVX group (60.91 versus 30.17 ng/dL, p = 0.0001; 1.00 versus 0.48 pg/mL, p = 0.003). BMD was not different between groups. Inverse correlations were found between BMI and TT (r = -0.3; p = 0.05); time since menopause and AN (r = -0.35; p = 0.02) and time since menopause and DHEA (r = -0.3; p = 0.01). CONCLUSION: Bilateral ovariectomy leads to a more severe androgen deficiency than natural menopause in postmenopausal women and did not compromise bone mass.

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.

Aproximadamente 10% das crianças nascidas pequenas para a idade gestacional (PIG) não apresentam recuperação pós-natal do crescimento e permanecem com baixa estatura na infância e na vida adulta. Em alguns casos é possível identificar alterações no eixo GH/IGF-1. Em outros, a avaliação com os recursos diagnósticos disponíveis até o momento é normal. O tratamento com GH tem mostrado resultados promissores com recuperação do crescimento e da altura adulta dentro do esperado para a população. Nesta revisão são apresentados resultados do tratamento com GH em crianças com baixa estatura nascidas PIG ressaltando a necessidade do tratamento precoce.

Approximately 10% of all children born small for gestational age (SGA) fail to achieve sufficient catch-up growth and remain with short stature throughout childhood and adult life. Abnormalities of the GH/IGF-1 axis are not always identified. Several studies have demonstrated that GH is an effective and well-tolerated therapy and most children will reach a normal adult height. In this review, it can be seen the encouraging results of GH treatment in growth-retarded children born SGA highlighting the benefits of early treatment.

Avaliamos retrospectivamente os resultados da cirurgia transesfenoidal num grupo de acromegálicos operados por um único neurocirurgião, comparando-os com uma meta-análise cumulativa de 10 séries (1.632 pacientes) publicadas entre 1992-2005. Estudamos 28 pacientes (17M/11F; 44,1 ± 12,7 anos; 27 com macroadenomas, sendo 86% invasivos), acompanhados por 21,4 ± 17,6 meses após a cirurgia; eles foram classificados de acordo com a atividade da acromegalia em: 1) doença controlada (DC): GH basal ou médio < 2,5 ng/ml ou GH nadir no TTOG < 1ng/ml e IGF-1 normal; 2) não controlada (DNC): GH basal ou médio > 2,5 ng/ml ou nadir no TTOG > 1 ng/ml e IGF-1 elevado; 3) inadequadamente controlada (DIC): GH normal e IGF-1 elevado ou GH elevado e IGF-1 normal. Após a cirurgia, os níveis de GH reduziram de 61,7 ± 101,1 ng/ml para 7,2 ± 13,7 ng/ml (p< 0,001), e os de IGF-1 de 673,1 ± 257,7 ng/ml para 471,2 ± 285 ng/ml (p= 0,01). A taxa de remissão bioquímica foi de 57% [10 pacientes (35,5%) com DC e 6 (21,5%) com DIC], similar àquela obtida na meta-análise de cirurgias de macroadenomas. Sete dos 28 pacientes foram submetidos à re-intervenção (4 operados em outro hospital e 3 pelo nosso neurocirurgião), sendo 5 (71,5%) classificados como DC no pós-operatório. Invasão de seio cavernoso foi mais prevalente nos DNC e DIC, e desvio de haste hipofisária no grupo DNC. A taxa de remissão foi maior nas séries em que apenas um único cirurgião realizou os procedimentos (66% vs. 49%; p< 0,05). Em conclusão, esses dados comprovam que a experiência do neurocirurgião pode aumentar significativamente as taxas de remissão do tratamento cirúrgico da acromegalia, especialmente em tumores maiores e mais invasivos, e que a re-intervenção realizada por cirurgião experiente deve ser considerada nos algoritmos de abordagem terapêutica desta doença.

The aim of this retrospective study was to evaluate the results of transsphenoidal surgery in a group of patients with acromegaly who were operated by the same neurosurgeon. Our results were compared to those from a cumulative meta-analysis of 10 series (1,632 patients) published between 19922005. We followed 28 patients (17M/11F; 44.1 ± 12.7 yr; 27 with macroadenomas; 86% being invasive) during 21.4 ± 17.6 months after treatment. Patients were classified according to disease activity as follows: 1) controlled (CD): basal or mean GH < 2.5 ng/ml or nadir GH (OGTT) < 1 ng/ml and normal IGF-1; 2) uncontrolled (UCD): basal or mean GH > 2.5 ng/ml or nadir GH > 1 ng/ml and elevated IGF-1; 3) inadequately controlled (ICD): normal GH and elevated IGF-1 or elevated GH and normal IGF-1. After surgery, GH levels decreased from 61.7 ± 101.1 ng/ml to 7.2 ± 13.7 ng/ml (p< 0.001) and mean IGF-1 from 673.1 ± 257.7 ng/ml to 471.2 ± 285 ng/ml (p= 0.01). Biochemical remission rate was 57% [10 (35.5%) patients with CD and 6 (21.5%) with ICD], similar to the mean remission rate observed in the meta-analysis of surgical outcome of macroadenomas. Seven of 28 patients were submitted to surgical re-intervention (4 had been previously operated elsewhere and 3 by our neurosurgeon), with CD observed in 5 (71.5%) on follow-up. Cavernous sinuses invasion was more prevalent in UCD and ICD, whereas infundibular stalk deviation occurred only in patients with UCD. Remission rate was significantly higher in series where all surgical procedures were performed by the same surgeon (66% vs. 49%; p< 0.05). Thus, the surgeon's experience significantly improves the surgical outcome in acromegaly, especially in patients harboring large and invasive tumors, and re-intervention performed by an experienced surgeon should be considered in the algorithms for clinical management of this disease.

Acromegalia é uma síndrome clínica característica, que na maior parte das vezes resulta de um macroadenoma hipofisário produtor de hormônio de crescimento (GH, growth hormone). A hipersecreção tumoral crônica de GH provoca deformidades esqueléticas, distúrbios metabólicos, complicações em vários órgãos e sistemas, e acaba reduzindo a expectativa de vida do paciente. O diagnóstico presuntivo baseia-se nos achados clínicos característicos da doença, com a confirmação vindo através de exames laboratoriais e da avaliação radiológica. Do ponto de vista laboratorial, a abordagem diagnóstica inclui dosagens basais e testes endócrinos que comprovem o excesso de GH, através de dosagens diretas do GH e/ou de fatores circulantes GH-dependentes, cujo melhor exemplo é o fator de crescimento insulina-símile-1 (IGF-1, insulin-like growth factor-1). A adenomectomia transesfenoidal permanece como o tratamento inicial de escolha na acromegalia, mas infelizmente a cura cirúrgica ocorre em menos da metade dos pacientes portadores de macroadenomas. Conseqüentemente, os exames laboratoriais têm um papel muito importante no seguimento dos pacientes após a cirurgia, para definir os critérios de cura e monitorar a atividade da doença durante tratamento complementar com radioterapia ou medicamentos. Neste artigo, revisaremos os exames laboratoriais mais freqüentemente utilizados no diagnóstico da acromegalia e alguns métodos experimentais que vêm sendo testados na sua abordagem. Na parte final, apresentaremos as principais recomendações de dois workshops internacionais realizados nos últimos anos com o objetivo de padronizar a avaliação diagnóstica e a conduta terapêutica na acromegalia.

Acromegaly is a characteristic clinical syndrome caused in most cases by a GH-producing pituitary macroadenoma. Tumoral GH hypersecretion results in skeletal changes, metabolic abnormalities, multi-systemic complications and a significant increase in the overall mortality. The diagnosis is suspected on clinical grounds, and it is normally confirmed by biochemical and radiological examinations. From the biochemical standpoint, the diagnostic approach for demonstration of GH excess involves either basal hormone measurements, mainly GH and insulin-like growth factor-1 (IGF-1), and endocrine tests, such as the oral glucose load. Transphenoidal adenomectomy remains the primary therapy of choice for most patients but, unfortunately, post-surgical remission is observed in less than half of the patients with macroadenomas. Consequently, hormone measurements have an important role in the follow-up of acromegalic patients, not only to define criteria for remission ("cure"), both also to evaluate the outcome of other therapeutic approaches such as radiotherapy and medical treatment. In this article, the most common biochemical measurements used in the management of acromegaly and some novel experimental assays are reviewed. In addition, a summary of a recently published consensus statement with guidelines for the diagnosis and therapeutic approach of acromegaly is presented.