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4.
J Am Coll Cardiol ; 77(22): 2777-2791, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082907

RESUMO

BACKGROUND: The metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale). OBJECTIVES: The purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs). METHODS: A cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography. RESULTS: After adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335). Relative risk estimations using Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease predictors confirmed that inclusion of HbA1c modified the risk of multiterritorial SA in most risk categories. CONCLUSIONS: Routine use of HbA1c can identify asymptomatic individuals at higher risk of SA on top of traditional CVRFs. Lifestyle interventions and novel antidiabetic medications might be considered to reduce both HbA1c levels and SA in individuals without diabetes.


Assuntos
Doenças Assintomáticas , Aterosclerose/sangue , Fatores de Risco Cardiometabólico , Hemoglobinas Glicadas/metabolismo , Placa Aterosclerótica/sangue , Adulto , Artérias/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Glicemia , Técnicas de Imagem Cardíaca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos , Medição de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia
5.
Clin Res Cardiol ; 110(10): 1612-1624, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33929598

RESUMO

BACKGROUND: Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE). METHODS: Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling. RESULTS: The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04-1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87-1.22 for women; HR = 1.14; 95% CI 0.96-1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13-2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07-1.66) and nominally so in women (HR = 1.23; 95% CI 0.99-1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex. CONCLUSIONS: Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.


Assuntos
Síndrome Coronariana Aguda/terapia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Fatores Etários , Idoso , Método Duplo-Cego , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , Grupos Raciais/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia
6.
Obes Surg ; 31(2): 517-522, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32915359

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of bariatric surgery in metabolically healthy obese (MHO) patients. METHODS: In this retrospective, observational study, we reviewed the medical records of patients who underwent bariatric surgery at a tertiary care hospital between January 2007 and March 2015. Patients who underwent revisional surgery and patients with type 1 diabetes were excluded from the analysis. MHO patients were defined as those without a previous diagnosis of diabetes or atherogenic dyslipidemia and absence of hypoglycemic treatment or treatment with fibrates. RESULTS: A total of 188 patients were included (mean age 48.97 ± 10.32 years, 68.6% of women). Sleeve gastrectomy was performed in 121 patients (64%) and a gastric bypass in 67 patients (36%). Prior to surgery, 36 patients (19%) were MHO. In the second- and third-year post-surgery, MHO patients presented a higher percentage of total weight loss (%TWL) (35.16% vs. 30.34%; p = 0.02 and 33.97% vs. 27.78%; p = 0.013 respectively). Multiple regression analysis showed that MHO was associated with a higher weight loss irrespective of age, sex, baseline BMI, and type of surgery. We did not detect any differences in acute complications between patients with and without MHO after bariatric surgery. CONCLUSIONS: Bariatric surgery in MHO patients in our study was associated with higher weight loss than that in MUHO patients. There were no differences between the two groups in respect to acute complications following surgery.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade , Obesidade Mórbida/cirurgia , Fenótipo , Estudos Retrospectivos
7.
Neurology ; 95(3): e268-e279, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32606227

RESUMO

OBJECTIVE: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions) is a paraneoplastic disorder resulting in severe neurologic disability. Understanding the clinical, laboratory, neurophysiologic, and histopathologic features as well as treatment responses of POEMS will assist in more accurate and timely diagnosis, risk stratification, and effective management. METHODS: This was a retrospective longitudinal cohort study from 1998 to March 2019, with 7,184 person-months of follow-up time. Hospital databases were used to collate presenting features, investigations, therapies, and response. RESULTS: One hundred patients were included with a median follow-up time of 59 months (range, 1-252). Mean symptom onset to diagnosis was 15 months (range, 1-77), with 54% of patients initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy. Median number of multisystem features at diagnosis was 7. Ninety-six (96%) presented with neuropathy, which was length-dependent in 93 (93%) and painful in 75 (75%). At diagnosis, 35% of patients were wheelchair or bedbound, with median Overall Neuropathy Limitation Score of 6, improving to 3 following treatment (p < 0.05). Five-year survival was 90% and 82% at 10 years, with 5- and 10-year progression-free survival of 65% and 53%. Nontreatment with autologous stem cell transplantation, nonhematologic response, and non-vascular endothelial growth factor response are significant risk factors in multivariate analysis to predict progression or death. Risk factors are incorporated to develop a risk score enabling stratification of high- and low-risk cases. CONCLUSIONS: POEMS syndrome is a rare multisystem condition with delayed diagnosis and poor neurologic function at presentation. Therapy has favorable outcomes. Patients at high risk of death or progression can be identified, which may allow for more active monitoring and influence management.


Assuntos
Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
Obes Surg ; 30(5): 1793-1798, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31942689

RESUMO

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDLc) are independent predictive factors of coronary heart disease. Bariatric surgery increases HDLc concentration, but the chronology and predictors of this improvement in HDLc levels are not well-established. The aim of the present study was to analyse the changes over time in HDLc concentrations after bariatric surgery and to determine the predictors of their increase. SUBJECTS AND METHODS: This was a retrospective, observational study. The medical records of patients who had undergone bariatric surgery at a tertiary care hospital between January 2007 and March 2015 were reviewed. Patients who underwent revisional surgery or were treated with fibrates were excluded from the analysis. RESULTS: A total of 185 patients were included in the study. Follow-up rates were as follows: 87% (year 2) and 28% (year 5). At postoperative month 3, HDLc levels decreased significantly versus baseline (- 11.1%; p = 0.000), at which point they began to rise, reaching their maximum level 2 years after bariatric surgery (26.2% increase from baseline; p = 0.000). The increase in HDLc concentration 2 years after surgery correlated with the preoperative HDLc level (r = - 0.292, p = 0.001), and it was greater in patients who underwent sleeve gastrectomy versus gastric bypass (0.36 ± 0.4 vs. 0.18 ± 0.4 mmol/L, respectively; p = 0.018). CONCLUSION: Bariatric surgery has a beneficial effect on HDLc levels. The maximum increase in postoperative HDLc concentrations is observed 2 years after surgery. Preoperative HDLc and the type of surgery are both significant predictors of the maximum increase in HDLc levels.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , HDL-Colesterol , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos
9.
J Clin Endocrinol Metab ; 105(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996917

RESUMO

CONTEXT: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). OBJECTIVE: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. DESIGN: 12-year prospective, observational study. PARTICIPANTS & SETTING: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. INTERVENTIONS & OUTCOME: AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). RESULTS: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). CONCLUSIONS: Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.


Assuntos
Biomarcadores/análise , Testes Genéticos/métodos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Programas de Rastreamento/métodos , Mutação , Neoplasias Hipofisárias/diagnóstico , Adolescente , Adulto , Idade de Início , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Humanos , Masculino , Neoplasias Hipofisárias/genética , Prognóstico , Estudos Prospectivos , Adulto Jovem
10.
Eur J Intern Med ; 65: 69-77, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076345

RESUMO

BACKGROUND: Little is known about the prevalence and impact of risk of malnutrition on short-term mortality among seniors presenting with acute heart failure (AHF) in emergency setting. The objective was to determine the impact of risk of malnutrition on 30-day mortality risk among older patients who attended in Emergency Departments (EDs) for AHF. MATERIAL AND METHODS: We performed a secondary analysis of the OAK-3 Registry including all consecutive patients ≥65 years attending in 16 Spanish EDs for AHF. Risk of malnutrition was defined by the Mini Nutritional Assessment Short Form (MNA-SF) < 12 points. Unadjusted and adjusted logistic regression models were used to assess the association between risk of malnutrition and 30-day mortality. RESULTS: We included 749 patients (mean age: 85 (SD 6); 55.8% females). Risk of malnutrition was observed in 594 (79.3%) patients. The rate of 30-day mortality was 8.8%. After adjusting for MEESSI-AHF risk score clinical categories (model 1) and after adding all variables showing a significantly different distribution among groups (model 2), the risk of malnutrition was an independent factor associated with 30-day mortality (adjusted OR by model 1 = 3.4; 95%CI 1.2-9.7; p = .020 and adjusted OR by model 2 = 3.1; 95%CI 1.1-9.0; p = .033) compared to normal nutritional status. CONCLUSIONS: The risk of malnutrition assessed by the MNA-SF is associated with 30-day mortality in older patients with AHF who were attended in EDs. Routine screening of risk of malnutrition may help emergency physicians in decision-making and establishing a care plan.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Insuficiência Cardíaca/mortalidade , Desnutrição/epidemiologia , Avaliação Nutricional , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Desnutrição/diagnóstico , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Espanha/epidemiologia
11.
Oncogene ; 38(27): 5381-5395, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30867568

RESUMO

The molecular mechanisms leading to aryl hydrocarbon receptor interacting protein (AIP) mutation-induced aggressive, young-onset growth hormone-secreting pituitary tumors are not fully understood. In this study, we have identified that AIP-mutation-positive tumors are infiltrated by a large number of macrophages compared to sporadic tumors. Tissue from pituitary-specific Aip-knockout (AipFlox/Flox;Hesx1Cre/+) mice recapitulated this phenotype. Our human pituitary tumor transcriptome data revealed the "epithelial-to-mesenchymal transition (EMT) pathway" as one of the most significantly altered pathways in AIPpos tumors. Our in vitro data suggest that bone marrow-derived macrophage-conditioned media induces more prominent EMT-like phenotype and enhanced migratory and invasive properties in Aip-knockdown somatomammotroph cells compared to non-targeting controls. We identified that tumor-derived cytokine CCL5 is upregulated in AIP-mutation-positive human adenomas. Aip-knockdown GH3 cell-conditioned media increases macrophage migration, which is inhibited by the CCL5/CCR5 antagonist maraviroc. Our results suggest that a crosstalk between the tumor and its microenvironment plays a key role in the invasive nature of AIP-mutation-positive tumors and the CCL5/CCR5 pathway is a novel potential therapeutic target.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Invasividade Neoplásica , Neoplasias Hipofisárias/genética , Microambiente Tumoral , Animais , Biomarcadores Tumorais/metabolismo , Quimiocina CCL5/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Camundongos Knockout , Receptores CCR5/metabolismo
12.
J Clin Endocrinol Metab ; 104(6): 2140-2146, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239770

RESUMO

CONTEXT: POEMS syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, and skin changes, among other features. OBJECTIVE: To describe the prevalence and course of endocrine dysfunction in POEMS. DESIGN: Cohort study with systematic review of the endocrinopathy in POEMS. SETTING: Seventy-five patients with POEMS were evaluated by the multidisciplinary team at our tertiary specialist center. PATIENTS: Endocrine data were available for 59 patients who attended the clinic from June 1999 to May 2018. INTERVENTIONS: All patients had regular endocrine screening, including testing for diabetes, pituitary and thyroid dysfunction and assessment of bone metabolism. MAIN OUTCOME MEASURE: Prevalence and survival time to develop endocrinopathy in POEMS. RESULTS: Thirty-four (63%) patients presented with an endocrinopathy at POEMS diagnosis and 54 (92%) had at least one endocrine abnormality at follow-up. The median follow-up was 4.4 (interquartile range, 1.5, 7.9) years. The most common endocrine abnormality was hypogonadism in 68%, followed by hyperprolactinemia (56%), hypothyroidism (54%), abnormal glucose metabolism (24%), adrenal insufficiency (17%), and high IGF-1 levels (15%). Spontaneous resolution of endocrine abnormalities at the end of follow-up was observed: 14% of patients with hypogonadism; 42%, hyperprolactinemia; 34%, hypothyroidism; and 38%, high IGF-1 levels. CONCLUSIONS: Endocrinopathy was found in 63% of patients at diagnosis and in 92% of patients during follow-up in our cohort. Therefore, patients with POEMS should be systematically assessed for endocrinopathy. The most common deficiencies were hypogonadism and hypothyroidism; however, but endocrinopathy can normalize, so ongoing treatment should remain under review.


Assuntos
Doenças do Sistema Endócrino/epidemiologia , Síndrome POEMS/complicações , Adulto , Feminino , Humanos , Hiperprolactinemia/epidemiologia , Hipogonadismo/epidemiologia , Hipotireoidismo/epidemiologia , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Prevalência
14.
Minerva Endocrinol ; 43(4): 435-445, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29442480

RESUMO

Pregnancy in women with a diagnosis of Cushing' syndrome (CS) is an extremely rare event and its diagnosis and treatment are a real medical challenge. During pregnancy, the hypothalamus-pituitary-adrenal axis undergoes major changes leading to a significant increase in plasma cortisol levels throughout gestation. The difficulties in diagnosis are related to the resemblance of symptoms of CS and those of pregnancy, and to the complex interpretation of the screening tests. Moreover, the diagnostic work up in the postnatal period may be difficult in the first weeks postpartum. Importantly, the etiology of CS in pregnancy differs from non-pregnant status. In pregnancy, the adrenal origin is the most frequent in up to 60% of the cases, in contrast to ACTH-secreting corticotroph adenomas of the pituitary gland, which account for 70% of the cases outside pregnancy. Nevertheless, maternal and fetal outcomes are severely affected in the context of CS whichever the etiology is, with high rates of maternal and fetal morbimortality, and with a rate of overall fetal loss of about 25% of the pregnancies. There is no consensus as to the most effective treatment in these circumstances in terms of improving maternal and fetal outcomes, as there are no studies comparing the different modalities of treatment for CS in pregnancy. However, evidence suggests that patients receiving treatment during pregnancy achieve better fetal outcomes than those who do not receive treatment. We aim to summarize in this review the major diagnostic and management difficulties during pregnancy.


Assuntos
Hipersecreção Hipofisária de ACTH/terapia , Complicações na Gravidez/terapia , Adulto , Feminino , Humanos , Hipersecreção Hipofisária de ACTH/diagnóstico , Gravidez , Complicações na Gravidez/diagnóstico
15.
J Med Genet ; 55(4): 254-260, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29440248

RESUMO

BACKGROUND: Predictive tools to identify patients at risk for gene mutations related to pituitary adenomas are very helpful in clinical practice. We therefore aimed to develop and validate a reliable risk category system for aryl hydrocarbon receptor-interacting protein (AIP) mutations in patients with pituitary adenomas. METHODS: An international cohort of 2227 subjects were consecutively recruited between 2007 and 2016, including patients with pituitary adenomas (familial and sporadic) and their relatives. All probands (n=1429) were screened for AIP mutations, and those diagnosed with a pituitary adenoma prospectively, as part of their clinical screening (n=24), were excluded from the analysis. Univariate analysis was performed comparing patients with and without AIP mutations. Based on a multivariate logistic regression model, six potential factors were identified for the development of a risk category system, classifying the individual risk into low-risk, moderate-risk and high-risk categories. An internal cross-validation test was used to validate the system. RESULTS: 1405 patients had a pituitary tumour, of which 43% had a positive family history, 55.5% had somatotrophinomas and 81.5% presented with macroadenoma. Overall, 134 patients had an AIP mutation (9.5%). We identified four independent predictors for the presence of an AIP mutation: age of onset providing an odds ratio (OR) of 14.34 for age 0-18 years, family history (OR 10.85), growth hormone excess (OR 9.74) and large tumour size (OR 4.49). In our cohort, 71% of patients were identified as low risk (<5% risk of AIP mutation), 9.2% as moderate risk and 20% as high risk (≥20% risk). Excellent discrimination (c-statistic=0.87) and internal validation were achieved. CONCLUSION: We propose a user-friendly risk categorisation system that can reliably group patients into high-risk, moderate-risk and low-risk groups for the presence of AIP mutations, thus providing guidance in identifying patients at high risk of carrying an AIP mutation. This risk score is based on a cohort with high prevalence of AIP mutations and should be applied cautiously in other populations.


Assuntos
Adenoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hipofisárias/genética , Medição de Risco/métodos , Adenoma/epidemiologia , Adenoma/patologia , Adulto , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia
16.
Endocrine ; 55(2): 555-563, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27704478

RESUMO

Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.


Assuntos
Adenoma/complicações , Neoplasias do Córtex Suprarrenal/complicações , Síndrome de Cushing/etiologia , Complicações na Gravidez/etiologia , Resultado da Gravidez , Feminino , Humanos , Gravidez
17.
Clin Cancer Res ; 22(20): 5030-5042, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27742789

RESUMO

Recently, a number of novel genetic alterations have been identified that predispose individuals to pituitary adenomas. Clinically relevant pituitary adenomas are relatively common, present in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior lobe of the pituitary gland, and cause disease due to hormonal alterations and local space-occupying effects. The pathomechanism of pituitary adenomas includes alterations in cell-cycle regulation and growth factor signaling, which are mostly due to epigenetic changes; somatic and especially germline mutations occur more rarely. A significant proportion of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and McCune-Albright syndrome. Pituitary tumors have also been described in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx mutations. Pituitary adenomas with no other associated tumors have been described as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations often present with pituitary gigantism either in a familial or simplex setting. GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic mosaicism involving the pituitary gland and resulting in growth hormone excess. Senescence has been suggested as the key mechanism protecting pituitary adenomas turning malignant in the overwhelming majority of cases. Here we briefly summarize the genetic background of pituitary adenomas, with an emphasis on the recent developments in this field. Clin Cancer Res; 22(20); 5030-42. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING PARADIGMS".


Assuntos
Adenoma/genética , Adenoma/patologia , Adeno-Hipófise/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Cromograninas/genética , Endopeptidases/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação em Linhagem Germinativa/genética , Humanos , Proteínas Proto-Oncogênicas/genética , Ubiquitina Tiolesterase/genética
18.
Acta Neuropathol Commun ; 4(1): 56, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27245663

RESUMO

Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.


Assuntos
Duplicação Gênica , Gigantismo/genética , Receptores Acoplados a Proteínas G/genética , Acromegalia/complicações , Acromegalia/genética , Acromegalia/patologia , Adenoma/complicações , Adenoma/genética , Adenoma/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Mutação em Linhagem Germinativa , Gigantismo/complicações , Gigantismo/patologia , Gigantismo/terapia , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Resultado do Tratamento , Adulto Jovem
19.
Cir Esp ; 94(7): 392-8, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25882331

RESUMO

BACKGROUND: The aim of this study was to evaluate the strategy and efficacy of a hyperglycemia treatment program supervised by Endocrinology. METHODS: All patients with type 2 diabetes hospitalized at the vascular surgery department over a 12 month period were retrospectively reviewed. Clinical characteristics and hyperglycemia treatment during hospitalization, at discharge and 2-6 month after discharge were collected. Glycemic control was assessed using capillary blood glucose profiles and HbA1c at admission and 2-6 months post-discharge. RESULTS: A total of 140 hospitalizations of 123 patients were included. The protocol to choose the insulin regimen was applied in 96.4% of patients (22.8% correction dose, 23.6% basal-correction dose and 50% basal-bolus-correction dose [BBC]). Patients with BBC had higher HbA1c (7.7±1.5% vs. 6.7 ±0.8%; P<.001) and mean glycemia on the first day of hospitalization (184.4±59.2 vs. 140.5±31.4mg/dl; P<.001). Mean blood glucose was reduced to 162.1±41.8mg/dl in the middle and 160.8±43.3mg/dl in the last 24h of hospitalization in patients with BBC (P=.007), but did not change in the remaining patients. In 22.1% patients with treatment changes performed at discharge, HbA1c decreased from 8.2±1.6 to 6.8±1.6% at 2-6 months post-discharge (P=.019). CONCLUSIONS: The hyperglycemia treatment protocol applied by an endocrinologist in the hospital, allows the identification of the appropriate therapy and the improvement of the glycemic control during hospitalization and discharge, supporting its efficacy in clinical practice.


Assuntos
Hiperglicemia/terapia , Idoso , Protocolos Clínicos , Diabetes Mellitus Tipo 2/complicações , Endocrinologia , Feminino , Departamentos Hospitalares , Hospitalização , Humanos , Hiperglicemia/etiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares
20.
Diabetes Metab Res Rev ; 31(7): 680-90, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25663190

RESUMO

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies.


Assuntos
Complicações do Diabetes , Diabetes Gestacional , Resultado da Gravidez , Gravidez em Diabéticas , Progressão da Doença , Feminino , Humanos , Recém-Nascido , Gravidez , Terminologia como Assunto
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