Impaired Bone Microarchitecture in Premenopausal Women With Acromegaly: The Possible Role of Wnt Signaling.

CONTEXT: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs). OBJECTIVE: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC). DESIGN, SETTING, AND PATIENTS: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, ß-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously. MAIN OUTCOME AND RESULTS: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R = 0.45, P = 0.044). Mild VFs were present in approximately 30% of patients. CONCLUSIONS: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (P = 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.

Effect of sulpiride on menopausal hot flashes: a randomized, double-blind, placebo-controlled clinical trial.

Low doses of sulpiride have been used off-label to treat menopausal hot slashes in Southern Brazil despite limited scientific evidence. This randomized controlled trial aimed at assessing the effects of sulpiride as compared to placebo on the frequency and severity of hot flashes. Postmenopausal women, aged 47-62, were recruited from the Menopause Clinic at Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, between March 2016 and January 2017. After a baseline assessment of 4 weeks, women were included if they had at least a mean of five moderate to severe hot flashes per day and then randomized to receive for 8 weeks either placebo (n= 14) or sulpiride 50 mg/d (n= 14). The number and severity of hot flashes were evaluated after the 8-week intervention. A generalized estimating equations (GEE) model with Bonferroni correction was used to simultaneously assess the frequency and severity of hot flashes. Baseline frequency and severity of hot flashes/day were similar in both groups. Sulpiride significantly reduced the total weekly mean of hot flash frequency (GEE, pinteraction=.019) and the total weekly mean of severity scores (GEE, pinteraction=.09, pgroup=.006, ptime≤.0001) after 4 and 8 weeks of treatment. Treatment with sulpiride 50 mg/d significantly reduced the frequency and severity of hot flashes. Further studies are needed to confirm its benefits and related mechanisms of action.

CLAUDINS 1, 3, 4, 7 AND 10-YEAR SURVIVAL IN TRIPLE-NEGATIVE BREAST TUMORS / Claudinas 1, 3, 4, 7 e sobrevida de 10 anos em tumores de mama triplo-negativos

Purpose: Breast cancer is a major cause of morbidity and mortality and is known to be a heterogeneous disease. The clinical and molecular characterization of its subtypes is critical to guide its prognosis and treatment. The study of the expression of Claudins (CLDN) might help in the characterization of these tumors. This study investigated the association of expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 with 10-year survival in a series of triple-negative breast cancers. Methods: Eighty triple negative tumors were analyzed by automated immunohistochemistry for CLDN-1, CLDN-3, CLDN-4 and CLDN-7. The immunohistochemical expression was assessed by the H-Score (intensity multiplied by the percentage of staining on membrane). The associations between the expression of CLDN and 10-year survival were evaluated by Kaplan-Meier curves and Cox regressions. Results: Positive expression (H-score ≥50) of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 were observed in 41.3, 77.5, 67.5 and 18.8% of the cohort, respectively. Patients with positive CLDN-1 expression had a significant lower survival than their counterparts [HR=2.37 (95%CI 1.19­4.72)]. Further, CLDN-3 was inversely associated with overall survival. Patients with positive expression of CLDN-1 and negative expression of CLDN-3 had a HR 10.4 (95%CI 3.40­31.8) higher than patients with negative expression of CLDN-1 and positive expression of CLDN-3. Neither CLDN-4 nor CLDN-7 expression was associated with 10-year survival. Conclusions: Differential expression of CLDN can help in clinicopathological characterization of triple-negative tumors. Moreover, CLDN-1 and CLDN-3 appear to be important prognostic factors for these tumors.

Objetivo: O câncer de mama é uma das principais causas de morbidade e mortalidade, conhecido por ser uma doença heterogênea. A caracterização clínica e molecular de seus subtipos é fundamental para orientar seu prognóstico e tratamento. O estudo da expressão de claudinas (CLDN) pode auxiliar na caracterização desses tumores. Este estudo investigou a associação da expressão de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 com 10 anos de sobrevida em uma série de cânceres de mama triplo-negativos. Métodos: Oitenta tumores triplo-negativos foram analisados por imuno-histoquímica automatizada para CLDN-1, CLDN-3, CLDN-4 e CLDN-7. A expressão imuno-histoquímica foi avaliada pelo escore H (intensidade multiplicada pela porcentagem de coloração na membrana). As associações entre a expressão de CLDN e a sobrevida em 10 anos foram avaliadas pelas curvas de Kaplan-Meier e regressões de Cox. Resultados: Foi observada expressão positiva (escore H ≥ 50) de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 em 41,3, 77,5, 67,5 e 18,8% da coorte, respectivamente. Pacientes com expressão positiva de CLDN-1 tiveram uma sobrevida significativamente menor do que suas contrapartes [HR = 2,37 (IC 95% 1,19-4,72)]. Além disso, o CLDN-3 foi inversamente associado à sobrevida global. Pacientes com expressão positiva de CLDN-1 e expressão negativa de CLDN-3 tiveram uma FC 10,4 (IC 95% 3,40­31,8) vezes maior do que pacientes com expressão negativa de CLDN-1 e expressão positiva de CLDN-3. Nem a expressão de CLDN-4 nem de CLDN-7 foi associada a uma sobrevida de 10 anos. Conclusões: A expressão diferencial de CLDN pode ajudar na caracterização clinico-patológica de tumores triplo-negativos. Além disso, CLDN-1 e CLDN-3 parecem ser importantes fatores prognósticos para esses tumores.

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing's Disease to Pituitary Carcinoma.

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing's disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Thickened pituitary stalk associated with a mass in the sphenoidal sinus: an alarm to suspect hypophysitis by immunoglobulin g4?

Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormonesecreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed.

Thickened Pituitary Stalk Associated with a Mass in the Sphenoidal Sinus: An Alarm to Suspect Hypophysitis by Immunoglobulin G4?

Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormone-secreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed.

Efeitos do fumo materno durante a gestação e complicações perinatais / Effects of maternal smoking during pregnancy and perinatal complications

Objetivos: Avaliar o perfil de puérperas tabagistas no Hospital de Clínicas de Porto Alegre (HCPA), determinar a prevalência do tabagismo nestas pacientes e avaliar efeitos do fumo sobre a gestação e os recém-nascidos (RNs). Métodos: Estudo prospectivo, transversal, com dados coletados a partir de um questionário estruturado. Foram incluídas pacientes hígidas, com gestação a termo. Foram excluídas puérperas que tiveram gestações múltiplas, RNs com crescimento intrauterino restrito, anormalidades cromossômicas, malformações ou infecção intrauterina, e puérperas com dados incompletos no prontuário. As pacientes foram divididas em dois grupos: gestantes fumantes e não-fumantes. Foram avaliadas variáveis demográficas, clínicas e relacionadas à gestação, e variáveis relacionadas ao recém-nascido. Resultados: Foram incluídas no estudo 718 puérperas, sendo que 23% eram fumantes ativas durante a gestação. Não houve diferença estatística com relação à idade materna, número de cesarianas ou abortos e idade gestacional no momento do parto. Foram fatores de risco para o tabagismo na gravidez o maior número de gestações prévias, ser solteira ou separada, não branca, com menor escolaridade e não realizar pré-natal. O peso dos RNs foi estatisticamente menor no grupo das gestantes tabagistas, com uma variação média de 143g a menos nesse grupo. O número de RNs pequenos para idade gestacional foi significativamente maior no grupo de gestantes fumantes. A evolução clínica do RN, o peso da placenta e o índice de Apgar não foram diferentes entre os grupos. Conclusão: Este estudo foi relevante para o melhor conhecimento do perfil das puérperas fumantes do HCPA e aponta para a importância da realização de pré-natal e a busca de estratégias de tratamento para estas pacientes como forma de prevenção de complicações gestacionais e perinatais.

Aims: To evaluate the clinical profile of smoker post-pregnant women at Hospital de Clínicas de Porto Alegre (HCPA), to determine the prevalence of smoking in these patients and to evaluate the effects of smoking on pregnancy and on the newborns. Methods: This is a cross-sectional prospective study, with data collected through a structured questionnaire. Healthy patients with term pregnancies were included. Exclusion criteria were multiple pregnancies, newborns with intrauterine growth restriction, chromosomal abnormalities, malformations or intrauterine infection, and incomplete data on medical records. Patients were divided in two groups: smokers and non-smokers. Demographic and clinical variables were evaluated, as well as data related to the pregnancy and to the newborn. Results: Seven hundred and eighteen post-pregnant women were included in the study, of whom 23% were current smokers during pregnancy. There was no statistic difference regarding maternal age, number of cesarean sections or abortions, and gestational age at childbirth. Higher number of previous pregnancies, being single/separated, non-white, less education and no prenatal follow up visits were risk factors for smoking in pregnancy. The weight of the newborns was statistically lower in the smoking pregnant group, with a negative variation of 143 grams in average in this group. The number of newborns small for gestational age was significantly higher in the smoking pregnant group. Clinical evolution of the newborn, placenta weight and the Apgar score were not different between the groups. Conclusion: This study was relevant to improve the knowledge about the profile of post pregnant smokers at HCPA, underscores the importance of prenatal follow up visits and the need for treatment strategies to these patients as preventive measures to avoid perinatal and gestational complications.