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1.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(1): 36-42, ene. 2020. tab
Artigo em Inglês | IBECS-Express | ID: ibc-ET2-3640

RESUMO

Introduction: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. Study design: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. Results: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p = 0.007) and had more frequently high TSH levels (>2.5 μIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p < 0.001). Conclusions: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain


Introducción: Los procedimientos a seguir para el diagnóstico y tratamiento de la disfunción tiroidea en la gestación no están del todo consensuados. Aún se discute el rango de normalidad de los valores de la hormona estimulante del tiroides (TSH) y el uso de screening para detectar hipotiroidismo gestacional (HG). El objetivo de este estudio es evaluar la forma de diagnóstico y tratamiento de la disfunción tiroidea durante la gestación en un grupo de hospitales de España. Diseño del estudio: Estudio retrospectivo, multicéntrico en mujeres embarazadas con HG atendidas en instituciones sanitarias españolas entre marzo de 2013 y julio de 2014. Las variables analizadas incluyeron criterios diagnósticos de HG (disponibilidad de screening universal para trastornos tiroideos gestacionales y valores de referencia de TSH según el trimestre gestacional); factores de riesgo de HG, ingesta de yodo mediante alimentos o suplementos, edad gestacional (al diagnóstico/tratamiento) y tratamiento con L-tiroxina. Resultados: Participaron un total de 14 centros. Únicamente la mitad de los centros empleaba el screening universal, y solo el 14% tenía valores de referencia de TSH propios. Se incluyeron un total de 257 embarazadas, 53,7% con diagnóstico de hipotiroidismo previo al embarazo (pre-HG) y 46,3% con hipotiroidismo diagnosticado durante el embarazo (intra-HG). Comparando los casos de pre-HG e intra-HG, las mujeres con intra-HG realizaban la primera visita más tarde (antes de la semana 12; 59,7% vs. 75,4% respectivamente, p = 0,007) y tenían más frecuentemente valores elevados de TSH (> 2,5 μUI/ml) durante el primer trimestre (94,4% vs. 67,0% respectivamente, p < 0,001). Conclusiones: Nuestros resultados sugieren que el HG puede estar infradiagnosticado o diagnosticado indebidamente en la mayoría de los centros sanitarios. Estos hallazgos sugieren la necesidad de mejorar la práctica actual en España

2.
Endocrinol Diabetes Nutr ; 67(1): 36-42, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31109823

RESUMO

INTRODUCTION: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. STUDY DESIGN: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. RESULTS: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5µIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). CONCLUSIONS: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

3.
Sci Total Environ ; 706: 136041, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855644

RESUMO

We addressed the efficiency of a nanoremediation strategy using zero-valent iron nanoparticles (nZVI), in a case of co-mingled heavy metals (HM) pollution (Pb, Cd and Zn). We applied a combined set of physical-chemical, toxicological and molecular analyses to assess the effectiveness and ecosafety of nZVI (5% w/w) for environmental restoration. After 120 days, nZVI showed immobilization capacity for Pb (20%), it was scarcely effective for Zn (8%) and negligibly effective for Cd. The HMs immobilization in the nZVI treated soils (compared to control soil), reaches its maximum after 15 days (T3) as reflected in the decrease of HM toxicity towards V. fischeri. The overall abundance of the microbial community was similar in both sets of samples during all experiment, although an increase in the number of metabolically active bacteria was recorded 15 days post treatment. We studied the induced impact of nanoremediation on the soil microbial community structure by Next Generation Sequencing (NGS). Even when higher HM immobilization was recorded, no significant recovery of the microbial community structure was found in nZVI-treated soil. The most marked nZVI-induced structural shifts were observed at T3 (increase in the Firmicutes population with a decrease in Gram-negative bacteria). Predictive metagenomic analysis using PICRUSt showed differences among the predicted metagenomes of nZVI-treated and control soils. At T3 we found decrease in detoxification-related proteins or over-representation of germination-related proteins; after 120 days of nZVI exposure, higher abundance of proteins involved in regulation of cellular processes or sporulation-related proteins was detected. This study highlights the partial effectiveness of nanoremediation in multiple-metal contaminated soil in the short term. The apparent lack of recovery of biodiversity after application of nZVI and the decreased effectiveness of nanoremediation over time must be carefully considered to validate this technology when assurance of medium- to long-term immobilization of HMs is required.

4.
Pituitary ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823249

RESUMO

AIM: The ACROPRAXIS program aims to describe the management of acromegaly in Spain and provide guidance. METHODS: Ninety-three endocrinologists were organized into 13 panels to discuss the practical issues in managing acromegaly. Based on the key learnings, an online Delphi survey with 62 statements was performed, so those statements achieving consensus could be used as guidance. Statements were rated on a 9-point scale (9, full agreement; consensus > 66.6% of response in the same tertile). RESULTS: Ninety-two endocrinologists (98.8%) answered two rounds of the survey (mean age 47.6 years; 59.8% women; median 18.5 years of experience). Consensus was achieved for 49 (79%) statements. DIAGNOSIS: The levels of insulin-like growth factor I (IGFI) is the preferred screening test. If IGFI levels 1-1.3 ULN, the test is repeated and growth hormone (GH) after oral glucose tolerance test (OGTT) is assessed. A pituitary magnetic resonance is performed after biochemical diagnosis. TREATMENT: Surgery is the first treatment choice for patients with microadenoma or macroadenoma with/without optical pathway compression. Pre-surgical somatostatin analogues (SSA) are indicated when surgery is delayed and/or to reduce anaesthesia-associated risks. After unsuccessful surgery, reintervention is performed if the residual tumor is resectable, while if non-resectable, SSA are administered. Follow-up First biochemical and clinical controls are performed 1-3 months after surgery. Disease remission is considered if random GH levels are < 1 µg/L or OGTT is < 1 or ≤ 0.4 µg/L, depending on the assay's sensitivity. CONCLUSION: Current clinical management for acromegaly is homogeneous across Spain and generally follows clinical guidelines.

5.
Cancers (Basel) ; 11(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835737

RESUMO

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

6.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(10): 654-662, dic. 2019.
Artigo em Espanhol | IBECS | ID: ibc-184793

RESUMO

Las enfermedades endocrinas están experimentando un importante incremento de su prevalencia, debido a causas de diversa índole, entre ellas la epidemia de obesidad y de desnutrición, el envejecimiento de la población, pero también el efecto de los disruptores endocrinos, entre otros. Por otra parte, las nuevas tecnologías, tanto a nivel de analítica molecular y genética, de imagen y de nuevos dispositivos terapéuticos, obligan a que la comunidad profesional endocrina en España tenga que estar en constante formación. La conexión con los pacientes a través de sus asociaciones, cada vez más activas, y con la sociedad civil en general, el compromiso profesional y la demanda de diversos colectivos sociales de una atención moderna y equitativa, y a llevar a cabo investigación que facilite la consecución de avances para los pacientes, obligan al especialista en Endocrinología y Nutrición, y a la Sociedad Española de Endocrinología y Nutrición (SEEN), a posicionarse y dar respuesta a todos estos retos. En el presente documento, la SEEN expone sus propuestas y su estrategia hasta el 2022


Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022


Assuntos
Endocrinologia/organização & administração , Sociedades Médicas/organização & administração , Sociedades Médicas/tendências , Estratégias , Endocrinologia/tendências , Sistemas Nacionais de Saúde , Medicina/organização & administração , Promoção da Saúde , Espanha
7.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 30(5): 215-221, sept.-oct. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-183874

RESUMO

Introducción: El tratamiento de elección para la mayor parte de los adenomas hipofisarios es su resección quirúrgica por vía transesfenoidal. Las fístulas posquirúrgicas de líquido cefalorraquídeo (LCR) constituyen una de las complicaciones más características y potencialmente graves de este tratamiento. Su incidencia es variable para las principales series publicadas en la literatura, con un rango del 0,5 al 15%. Objetivos: El objetivo principal de nuestro trabajo fue establecer la incidencia de fístulas de LCR tras cirugía transesfenoidal en una muestra de 302 intervenciones realizadas en pacientes afectos de adenomas hipofisarios en el Hospital Universitario de la Ribera y por un mismo equipo quirúrgico. Como objetivos secundarios se plantearon: conocer las características diferenciales entre pacientes con y sin fístulas posquirúrgicas de LCR, detectar factores de riesgo para su desarrollo, valorar la relación entre la técnica de cierre de la silla turca y la aparición de fístulas posquirúrgicas de LCR y valorar las diferentes pautas de tratamiento de la complicación. Métodos: Se realizó un estudio descriptivo retrospectivo basado en una revisión sistemática de 302 casos de adenomas hipofisarios intervenidos en nuestro centro a través de una vía de abordaje transesfenoidal entre los años 1999 y 2017. Resultados y conclusiones: La incidencia de fístulas posquirúrgicas de LCR en nuestra serie fue del 2,3% (concordante con la descrita en series amplias previamente publicadas). La aparición de una fístula intraoperatoria de LCR se correlacionó con dos variables del estudio: macroadenomas y tumores con extensión supraselar (p<0,005). Esta correlación no existió para fístulas posquirúrgicas. Sí fue posible establecer una relación estadísticamente significativa entre la aparición de fístulas intraoperatorias y posquirúrgicas de LCR (p<0,005). La baja incidencia de fístulas posquirúrgicas de LCR tras cirugía transesfenoidal de adenomas hipofisarios en nuestra casuística no permitió identificar factores de riesgo para su desarrollo


Introduction: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series. Objectives: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. Methods: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. Results and conclusions: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development


Assuntos
Humanos , Fístula/cirurgia , Líquido Cefalorraquidiano , Adenoma/complicações , Adenoma/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Fatores de Risco , Estudos Retrospectivos , Procedimentos Neurocirúrgicos , Osso Esfenoide/cirurgia
8.
Endocr Connect ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394502

RESUMO

OBJECTIVES: To analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48 hours prior to discharge). DESIGN: A prospective study was made of 65 patients with CD operated upon between 2005-2016. METHODS: Postsurgery plasma ACTH and cortisol were measured every 6 hours, in the absence of corticosteroid coverage. Hydrocortisone was started in the presence of adrenal insufficiency or cortisol <2 µg/dL. Plasma ACTH was again determined before discharge. MAIN OUTCOME MEASURE: Usefulness of plasma ACTH in predicting CD remission. RESULTS: Late remission of CD was achieved in 86.2% of the cases, with late recurrence in 31%. Following resection, the ACTH nadir was significantly lower referred to late remission (12.8 vs 29.5 pg/mL; p=0.031) and non-recurrence (9.5 vs 21.8 pg/mL; p<0.001), and identical results were obtained for the ACTH values before discharge. In the analysis of the ROC curves, both ACTH values (nadir and before discharge) <11.9 pg/mL were indicative of early remission (AUC 0.828; p<0.001); <15.3 pg/mL of late remission (AUC 0.848; p=0.001); and <14.6 pg/mL of non-recurrence (AUC 0.811; p<0.001). A time to ACTH nadir <46 hours was indicative of early remission (AUC 0.751; p=0.001), while a time <39 hours was indicative of non-recurrence (AUC 0.773; p=0.001). We propose an ACTH value <15 pg/mL as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate.

9.
Eur J Intern Med ; 69: 14-19, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31431315

RESUMO

BACKGROUND: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. METHODS AND RESULTS: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 ±â€¯18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. CONCLUSION: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.

10.
Endocrinol Diabetes Nutr ; 66(10): 654-662, 2019 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31272927

RESUMO

Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022.

11.
Neurocirugia (Astur) ; 30(5): 215-221, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31130305

RESUMO

INTRODUCTION: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series. OBJECTIVES: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. METHODS: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. RESULTS AND CONCLUSIONS: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development.

12.
J Clin Endocrinol Metab ; 104(4): 1272-1282, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423170

RESUMO

CONTEXT: Epigenetic alterations may play a role in the development and behavior of pituitary neuroendocrine tumors (PitNETs). OBJECTIVE: To evaluate the effect of methylation of tumor suppressor genes (TSGs) on their gene expression and on the behavior of PitNETs. MATERIAL AND METHODS: We used methylation-specific multiplex ligation-dependent probe amplification and quantitative real-time PCR techniques to analyze the DNA-promoter hypermethylation and gene expression of 35 TSGs in 105 PitNETs. We defined functionality, size, and invasiveness of tumors according to their clinical manifestations, Hardy's classification, and MRI invasiveness of the cavernous sinus, respectively. RESULTS: We observed different methylation patterns among PitNET subtypes. The methylation status of TP73 correlated negatively with its gene expression in the overall series (P = 0.013) and in some subtypes. MSH6 and CADM1 showed higher methylation frequency in macroadenomas than in microadenomas in the overall series and in corticotroph PitNETs (all P ≤ 0.053). ESR1 and RASSF1 were more highly methylated in noninvasive than in invasive tumors in the overall series (P = 0.054 and P = 0.031, respectively) and in the gonadotroph subtype (P = 0.055 and P = 0.050, respectively). ESR1 and CASP8 appeared more hypermethylated in functioning than in silent corticotroph tumors (P = 0.034 and P = 0.034, respectively). CONCLUSIONS: DNA methylation of TSGs has a selective effect on their gene expression and on the growth and invasiveness of PitNETs. Its involvement in their functionality is biased because all silent operated tumors are macroadenomas, whereas all operated microadenomas are functioning ones. Therefore, the subtypes of PitNETs should be considered different entities.


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Tumores Neuroendócrinos/genética , Neoplasias Hipofisárias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Regulação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Tumores Neuroendócrinos/patologia , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Regiões Promotoras Genéticas/genética , Carga Tumoral/genética , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-30588856

RESUMO

Nanoscale zero-valent iron (nZVI) is a strong reducing agent used for in situ remediation of soil. The impacts of nZVI (5-10% w/w) on the soil microbial biodiversity and functionality of two soils (Lufa 2.2 and 2.4) were assessed. Illumina MiSeq technology was used to evaluate the structure of soil microbiomes after 21 days of exposure. Proteobacteria, Verrucomicrobia, Firmicutes and Actinobacteria were the most abundant phyla in both soils. However, the dynamics of bacterial community composition following nZVI addition differed. nZVI exposure induced pronounced shifts in the microbial composition of soil 2.4, but not in soil 2.2; an increase in Verrucomicrobia abundance was the unique common taxonomic pattern observed in both soils. The PICRUSt approach was applied to predict the functional composition of each metagenome. Environmental information processing function (membrane transport) was decreased in both nZVI-spiked soils, although soil 2.4 samples were enriched in functions involved in cellular processes and metabolism. The effects of nZVI on autochthonous bacterial communities clearly varied with the soil type assessed; changes at the phylogenetic level appeared to be more abundant than those observed at the functional level, and thus, the overall effort of the soil ecosystem might involve the maintenance of functionality following nZVI exposure.


Assuntos
Ferro/toxicidade , Microbiota/efeitos dos fármacos , Nanopartículas/química , Microbiologia do Solo/normas , Poluentes do Solo/toxicidade , Solo/química , Actinobacteria/isolamento & purificação , Biodiversidade , Firmicutes/isolamento & purificação , Ferro/química , Metagenoma/efeitos dos fármacos , Microbiota/genética , Filogenia , Proteobactérias/isolamento & purificação , Poluentes do Solo/química
14.
PLoS One ; 13(7): e0198877, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979686

RESUMO

The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.


Assuntos
Tumores Neuroendócrinos/diagnóstico , Hormônios Hipofisários/genética , Neoplasias Hipofisárias/diagnóstico , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Vasopressinas/genética , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Hipófise/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia
15.
Eur J Endocrinol ; 179(2): 97-108, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29789410

RESUMO

OBJECTIVE: ATL1103 is a second-generation antisense oligomer targeting the human growth hormone (GH) receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. DESIGN: Twenty-six patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once or twice weekly for 13 weeks and monitored for a further 8-week washout period. METHODS: The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, acid labile subunit (ALS), GH, growth hormone-binding protein (GHBP)), comparison was between baseline and week 14. Safety was assessed by reported adverse events. RESULTS AND CONCLUSIONS: Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups respectively. Compared to baseline, at week 14, twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (P = 0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (P = 0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and remained lower at week 21 than at baseline by a median of 18.7% (P = 0.0005). Compared to baseline, by week 14, IGFBP3 and ALS had declined by a median of 8.9% (P = 0.027) and 16.7% (P = 0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (P = 0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (P = 0.027 and P = 0.005) respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild-to-moderate injection-site reactions. This study provides proof of concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.


Assuntos
Oligonucleotídeos Antissenso , Oligonucleotídeos/uso terapêutico , Receptores da Somatotropina/genética , Acromegalia/tratamento farmacológico , Adulto , Idoso , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , RNA Mensageiro/antagonistas & inibidores , Receptores da Somatotropina/antagonistas & inibidores , Resultado do Tratamento
16.
Eur J Endocrinol ; 178(4): 399-409, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29440375

RESUMO

BACKGROUND: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/cirurgia , Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Síndrome de Cushing/fisiopatologia , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Cetoconazol/uso terapêutico , Masculino , Metirapona/uso terapêutico , Pessoa de Meia-Idade , Síndromes Endócrinas Paraneoplásicas , Hipófise/fisiopatologia , Cuidados Pós-Operatórios , Período Pós-Operatório , Qualidade de Vida , Resultado do Tratamento
17.
PLoS One ; 12(9): e0183539, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28898247

RESUMO

Acromegaly is a rare disease with nonspecific symptoms with acral enlargement being almost universally present at diagnosis. The estimated prevalence is 40-125 cases/million but targeted universal screening studies have found a higher prevalence (about 10 fold). The aim of the ACROSAHS study was to investigate the prevalence of acromegaly and acromegaly comorbidities in patients with sleep apnea symptoms and acral enlargement. ACROSAHS was a Spanish prospective non-interventional epidemiological study in 13 Hospital sleep referral units. Facial and acral enlargement symptoms including: ring size and shoe size increase, tongue, lips and jaws enlargement, paresthesia or carpal tunnel syndrome and widening of tooth spaces, as well as other typical acromegaly comorbidities were recorded with a self-administered questionnaire of patients who attended a first visit for sleep apnea symptoms between 09/2013 and 07/2014. Serum insulin-like growth factor type 1 (IGF1) was measured in patients with ≥1 acral symptom to determine the prevalence of acromegaly. Of the 1557 patients enrolled, 1477 with complete data (72% male) were analyzed. 530 patients (36%) reported at least 1 acral enlargement symptom and were tested for IGF-1, 41 were above range, persisted in 7, and among those, 2 cases of acromegaly were diagnosed (prevalence of at least 1.35 cases/1000). Overall, 1019 patients (69%) had ≥2 acromegaly symptoms and should have been screened according to guidelines; moreover 373 patients (25%) had ≥1 symptom of acral enlargement plus ≥3 other acromegaly symptoms. In conclusion, in patients with sleep apnea symptoms and acral enlargement, we found an acromegaly prevalence of at least 1.35 cases per 1000 and a high prevalence of typical acromegaly symptoms. It is important that sleep specialists are aware of acromegaly symptoms to aid with acromegaly diagnosis.


Assuntos
Acromegalia/epidemiologia , Acromegalia/etiologia , Síndromes da Apneia do Sono/complicações , Acromegalia/metabolismo , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Prevalência , Síndromes da Apneia do Sono/diagnóstico , Espanha/epidemiologia
18.
PLoS One ; 12(7): e0180039, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28692683

RESUMO

AIM: The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. METHODS: Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. CONCLUSIONS: According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.


Assuntos
Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hormônios/genética , Hormônios/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Prevalência , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Reprodutibilidade dos Testes
19.
Eur J Endocrinol ; 176(5): 613-624, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28377460

RESUMO

OBJECTIVE: To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. PATIENTS AND METHODS: We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). RESULTS: Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). CONCLUSIONS: Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.


Assuntos
Síndrome de Cushing/diagnóstico , Síndrome de Cushing/metabolismo , Testes Diagnósticos de Rotina/normas , Guias de Prática Clínica como Assunto/normas , Sistema de Registros , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Síndrome de Cushing/epidemiologia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Estatística como Assunto/métodos
20.
Endocrinol. nutr. (Ed. impr.) ; 63(8): 397-408, oct. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-156269

RESUMO

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<0.001 and 86% ULN (23–345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. Conclusion. In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated (AU)


Propósito. Describir el uso de lanreotida en combinación terapéutica en acromegalia en la práctica clínica. Pacientes y métodos. ACROCOMB es un estudio observacional, retrospectivo, de pacientes con acromegalia activa tratados en centros hospitalarios españoles con lanreotida en combinación con cabergolina o pegvisomant entre 2006 y 2011. Se revisaron los datos clínicos de 108 pacientes tratados en 44 departamentos de endocrinología: 61 pacientes recibieron lanreótido/cabergolina (cohorte cabergolina) y 47 lanreotida/pegvisomant (cohorte pegvisomant). Resultados. La edad mediana de los pacientes fue de 50,8 años en la cohorte de cabergolina y 42,7 años en la de pegvisomant. Los tratamientos médicos previos a la combinación con lanreótido fueron análogos de somatostatina (SSA) en monoterapia (40 [66%] pacientes) o agonistas de la dopamina (7 [11%] pacientes) en la cohorte de cabergolina y SSA (29 [62%] pacientes) y pegvisomant en monoterapia (16 [34%] pacientes) en la de pegvisomant. Doce pacientes no habían recibido tratamiento previo y en 4 pacientes se desconocía la terapia previa. La mediana de duración del tratamiento fue de 1,6 años (0,1-6) y 2,1 años (rango 0,4 a 6,3) en las cohortes de cabergolina y pegvisomant, respectivamente. Al inicio del estudio el valor mediano del factor de crecimiento de insulina-I era 149% el límite superior normal (LSN) (15-505%) en la cohorte de cabergolina y 156% LSN (15-534%) en la de pegvisomant. Al final del estudio se redujeron a 104% LSN (13-557%) p<0,001 y 86% LSN (23-345%) p<0,0001, respectivamente. Al final del estudio, se reportaron valores normales de factor de crecimiento de insulina-I ajustados por edad en el 48% de los pacientes tratados con lanreotida/cabergolina y 70% de los tratados con lanreotida/pegvisomant. No hubo cambios significativos en los parámetros hepáticos, cardíacos o glucémicos. Conclusión. En la práctica clínica las combinaciones con lanreotida son una opción útil en el tratamiento de pacientes con acromegalia que no está bien controlada en monoterapia, ya sea con SSA carbegolina o pegvisomant; particularmente, la combinación de lanreotida y pegvisomant tiene una alta eficacia y se tolera bien (AU)


Assuntos
Humanos , Acromegalia/tratamento farmacológico , Somatostatina/análogos & derivados , Agonistas de Dopamina/farmacocinética , Estudos Retrospectivos , Quimioterapia Combinada
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