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1.
Genes (Basel) ; 10(11)2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703244

RESUMO

Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3-9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred, with five cases of nonsyndromic FNMTC. Single Nucleotide Variants, and insertions and deletions that segregated with all the affected members, were analyzed by Sanger sequencing in 44 additional families with FNMTC (37 with two affected members, and seven with three or more affected members), as well as in an independent control group of 100 subjects. We identified the germline variant p. Asp31His in NOP53 gene (rs78530808, MAF 1.8%) present in all affected members in three families with nonsyndromic FNMTC, and not present in unaffected spouses. Our functional studies of NOP53 in thyroid cancer cell lines showed an oncogenic function. Immunohistochemistry exhibited increased NOP53 protein expression in tumor samples from affected family members, compared with normal adjacent thyroid tissue. Given the relatively high frequency of the variant in the general population, these findings suggest that instead of a causative gene, NOP53 is likely a low-penetrant gene implicated in FNMTC, possibly a modifier.

2.
Biomed Opt Express ; 10(8): 3899-3915, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31452983

RESUMO

Recently, multimodal imaging has gained an increasing interest in medical applications thanks to the inherent combination of strengths of the different techniques. For example, diffuse optics is used to probe both the composition and the microstructure of highly diffusive media down to a depth of few centimeters, but its spatial resolution is intrinsically low. On the other hand, ultrasound imaging exhibits the higher spatial resolution of morphological imaging, but without providing solid constitutional information. Thus, the combination of diffuse optical imaging and ultrasound may improve the effectiveness of medical examinations, e.g. for screening or diagnosis of tumors. However, the presence of an ultrasound coupling gel between probe and tissue can impair diffuse optical measurements like diffuse optical spectroscopy and diffuse correlation spectroscopy, since it may provide a direct path for photons between source and detector. A systematic study on the effect of different ultrasound coupling fluids was performed on tissue-mimicking phantoms, confirming that a water-clear gel can produce detrimental effects on optical measurements when recovering absorption/reduced scattering coefficients from time-domain spectroscopy acquisitions as well as particle Brownian diffusion coefficient from diffuse correlation spectroscopy ones. On the other hand, we show the suitability for optical measurements of other types of diffusive fluids, also compatible with ultrasound imaging.

3.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(6): 385-392, jun.-jul. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-182855

RESUMO

Purpose: Gender affirming hormone therapy (HT) in transgender men both improves and impairs several surrogate cardiovascular risk markers. However, few prospective works with long follow-up and control group are available. In this context, this work aimed to assess the changes in the metabolic and cardiovascular risk pattern after 12 months of HT in transgender men. Furthermore, we aimed to investigate early effects on target tissues that may reflect an initial vascular damage. Methods: Prospective observational study, including 20 transgender men, attended in the Gender Identity Unit (UIG) of the Hospital Clinic from July 2013 to November 2015. Anthropometric and body composition by dual-energy X-ray absorptiometry (DXA), hormonal, metabolic and coagulation parameters, endothelial dysfunction by flow-mediated dilation (FMD) and intima-media thickness (IMT) by carotid ultrasound, were assessed at baseline, at 6 and 12 months of HT. Results: We observed an impairment of lipid profile, and increase of homocysteine and leucocytes count, as well as changes in body composition with increased total lean mass together with decreased total fat mass. In addition, higher mean-maximum common IMT was observed after 12 months of HT. Conclusion: Our work shows changes in metabolic and inflammatory parameters after HT after short-medium follow-up, which could increase cardiovascular risk in this setting, together with initial evidence of vascular changes


Objetivo: En los transexuales masculinos (FtM) el tratamiento hormonal (TH) cruzado produce cambios tanto positivos como negativos en diversos marcadores subrogados de riesgo cardiovascular. Por otro lado, existen pocos estudios prospectivos con un grupo control y con un seguimiento prolongado que valoren los cambios en el perfil del riesgo cardiovascular. En este contexto, nuestro trabajo tiene como objetivo evaluar los cambios en el patrón de riesgo metabólico y cardiovascular tras 12 meses de TH en transexuales masculinos. Además, estudiamos los cambios tempranos en tejidos diana que puedan reflejar un daño vascular inicial. Metodología: Estudio observacional prospectivo en 20 transexuales masculinos atendidos en la unidad de identidad de género (UIG) del Hospital Clínic desde julio de 2013 a noviembre de 2015. Se valoraron los cambios antropométricos y de composición corporal mediante una absorciometría de rayos X de doble energía (DXA), así como las variaciones en los parámetros metabólicos y trombóticos. La disfunción endotelial fue evaluada mediante la dilatación mediada por flujo (FMD), y el grosor de íntima-media carotídea (IMT) a través de una ecografía carotídea, a los 6 y 12 meses del TH. Resultados: Observamos un deterioro en el perfil lipídico, y un aumento de los niveles de homocisteína y del recuento de leucocitos, así como cambios en la composición corporal con aumento de la masa magra y disminución de la masa grasa. Además, se observó un incremento en el grosor de la IMT tras 12 meses del TH. Conclusión: En un seguimiento a mediano-corto plazo tras TH, nuestro trabajo muestra cambios en los parámetros metabólicos inflamatorios que podrían incrementar el riesgo cardiovascular en los transexuales masculinos, sumado a la evidencia de cambios vasculares incipientes


Assuntos
Humanos , Masculino , Hormônios Esteroides Gonadais/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Pessoas Transgênero , Hormônios Esteroides Gonadais/efeitos adversos , Doenças Cardiovasculares/complicações , Estudos Prospectivos , Antropometria , Composição Corporal/efeitos dos fármacos , Absorciometria de Fóton
4.
Endocrinol Diabetes Nutr ; 66(6): 385-392, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30704917

RESUMO

PURPOSE: Gender affirming hormone therapy (HT) in transgender men both improves and impairs several surrogate cardiovascular risk markers. However, few prospective works with long follow-up and control group are available. In this context, this work aimed to assess the changes in the metabolic and cardiovascular risk pattern after 12 months of HT in transgender men. Furthermore, we aimed to investigate early effects on target tissues that may reflect an initial vascular damage. METHODS: Prospective observational study, including 20 transgender men, attended in the Gender Identity Unit (UIG) of the Hospital Clinic from July 2013 to November 2015. Anthropometric and body composition by dual-energy X-ray absorptiometry (DXA), hormonal, metabolic and coagulation parameters, endothelial dysfunction by flow-mediated dilation (FMD) and intima-media thickness (IMT) by carotid ultrasound, were assessed at baseline, at 6 and 12 months of HT. RESULTS: We observed an impairment of lipid profile, and increase of homocysteine and leucocytes count, as well as changes in body composition with increased total lean mass together with decreased total fat mass. In addition, higher mean-maximum common IMT was observed after 12 months of HT. CONCLUSION: Our work shows changes in metabolic and inflammatory parameters after HT after short-medium follow-up, which could increase cardiovascular risk in this setting, together with initial evidence of vascular changes.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Hormônios Esteroides Gonadais/efeitos adversos , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/epidemiologia , Procedimentos de Readequação Sexual/métodos , Adolescente , Adulto , Hormônios Esteroides Gonadais/uso terapêutico , Humanos , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Tempo , Adulto Jovem
5.
Psychoneuroendocrinology ; 98: 161-167, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30165284

RESUMO

BACKGROUND: Polymorphisms in sex steroid receptors have been associated with transsexualism. However, published replication studies have yielded inconsistent findings, possibly because of a limited sample size and/or the heterogeneity of the transsexual population with respect to the onset of dysphoria and sexual orientation. We assessed the role of androgen receptor (AR), estrogen receptors alpha (ERα) and beta (ERß), and aromatase (CYP19A1) in two large and homogeneous transsexual male-to-female (MtF) and female-to-male (FtM) populations. METHODS: The association of each polymorphism with transsexualism was studied with a twofold subject-control analysis: in a homogeneous population of 549 early onset androphilic MtF transsexuals versus 728 male controls, and 425 gynephilic FtMs versus 599 female controls. Associations and interactions were investigated using binary logistic regression. RESULTS: Our data show that specific allele and genotype combinations of ERß, ERα and AR are implicated in the genetic basis of transsexualism, and that MtF gender development requires AR, which must be accompanied by ERß. An inverse allele interaction between ERß and AR is characteristic of the MtF population: when either of these polymorphisms is short, the other is long. ERß and ERα are also associated with transsexualism in the FtM population although there was no interaction between the polymorphisms. Our data show that ERß plays a key role in the typical brain differentiation of humans. CONCLUSION: ERß plays a key role in human gender differentiation in males and females.


Assuntos
Receptor beta de Estrogênio/metabolismo , Disforia de Gênero/genética , Disforia de Gênero/metabolismo , Adulto , Alelos , Androgênios/metabolismo , Aromatase/metabolismo , Aromatase/fisiologia , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/fisiologia , Receptor beta de Estrogênio/fisiologia , Estrogênios/metabolismo , Feminino , Identidade de Gênero , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo Genético/genética , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Comportamento Sexual , Desenvolvimento Sexual/fisiologia , Transexualismo/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-29999291

RESUMO

BACKGROUND: The optimal surgical management of papillary thyroid cancer (PTC) for T1-T2 tumors without pre or intrasurgical evidence of lymph node metastasis (cN0) remains controversial, since approximately 40% of patients have lymph node involvement (pN1) which becomes evident when a prophylactic lymphadenectomy (PL) is performed. The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification with SPECT/CT lymphoscintigraphy imaging along with intraoperatory image techniques in early stages of PTC undergoing PL of central neck compartment (CNC). METHODS: A single-center, prospective consecutive study was designed for SLN mapping in patients with high suspicion of PTC (Bethesda V or VI) in early stage (cT1-2, cN0). Twenty-four patients underwent SLN identification with preoperative SPECT/CT and planar images (99mTc-nanocolloid albumin intratumoral injection). During surgery, SLN located in CNC was found by means of a gamma probe and portable gamma camera, and excised. Afterwards, CNC lymphadenectomy was performed in all cases without modifying the established protocol. RESULTS: SLNs were identified and accurately located in 23 (95.8%) patients. Nodal metastases (pN1) were confirmed in 9 (37.5%) patients, with one false negative case. The sensitivity was 88.9% and negative predictive value (NPV) was 93.3%, would have allowed to avoid PL in more than half of cases, a higher proportion than those found in other similar studies. No complications associated with the procedure were observed. CONCLUSIONS: Our results support that SLN biopsy by SPECT/CT along with intraoperatory image techniques is applicable in early stages of PTC (cT1-2, cN0), allowing to avoid unnecessary PL.

7.
Sci Rep ; 8(1): 10015, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968735

RESUMO

Thyroid plays an important role in the endocrine system of the human body. Its characterization by diffuse optics can open new path ways in the non-invasive diagnosis of thyroid pathologies. Yet, the absorption spectra of tyrosine and thyroglobulin-key tissue constituents specific to the thyroid organ-in the visible to near infrared range are not fully available. Here, we present the optical characterization of tyrosine (powder), thyroglobulin (granular form) and iodine (aqueous solution) using a time domain broadband diffuse optical spectrometer in the 550-1350 nm range. Various systematic errors caused by physics of photo migration and sample inherent properties were effectively suppressed by means of advanced time domain diffuse optical methods. A brief comparison with various other known tissue constituents is presented, which reveals key spectral regions for the quantification of the thyroid absorbers in an in vivo scenario.


Assuntos
Iodo/análise , Análise Espectral/métodos , Tireoglobulina/análise , Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Tirosina/análise , Humanos , Iodo/química , Fenômenos Ópticos , Tireoglobulina/química , Tirosina/química
8.
Amyloid ; 25(2): 75-78, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29446975

RESUMO

Several mutations in the gene encoding apolipoprotein AI (apoAI) have been described as a cause of familial amyloidosis. Individuals with apoAI-derived (AApoAI) amyloidosis frequently manifest with liver, kidney, laryngeal, skin and myocardial involvement. Although primary hypogonadism (PH) is considered almost pathognomonic of this disease, until now, primary adrenal insufficiency (PAI) has not been described as a common clinical feature. Here, we report the first kindred with AApoAI amyloidosis in which PAI is well-documented. All family members with the Leu60_Phe71delins60Val_61Thr heterozygous mutation who were regularly followed-up at our centre were considered. Nineteen individuals had the confirmed APOA1 deletion/insertion mutation, with detailed medical records available in 11 cases. Of these, 6 had PAI and 3 (all males) had PH. Among them, one 47-year-old man, not previously diagnosed with PAI, developed adrenal crisis after liver transplantation, precipitated by an opportunistic infection. Transplantation due to organ failure, which necessitates use of immunosuppressive medication such as corticosteroids, is frequently required during the course of hereditary amyloidosis. Consequently, PAI can remain masked, being discovered only when an adrenal crisis develops. Therefore, according to the present evidence, patients with AApoAI amyloidosis should be submitted to regular testing of corticotrophin and cortisol levels in order to avoid delaying corticosteroid replacement.


Assuntos
Insuficiência Adrenal/metabolismo , Amiloidose Familiar/metabolismo , Apolipoproteína A-I/metabolismo , Hipogonadismo/metabolismo , Transplante de Fígado , Corticosteroides/uso terapêutico , Insuficiência Adrenal/sangue , Insuficiência Adrenal/genética , Insuficiência Adrenal/cirurgia , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Amiloidose Familiar/sangue , Amiloidose Familiar/genética , Amiloidose Familiar/cirurgia , Apolipoproteína A-I/genética , Feminino , Humanos , Hidrocortisona/sangue , Hipogonadismo/sangue , Hipogonadismo/genética , Hipogonadismo/cirurgia , Masculino , Pessoa de Meia-Idade
9.
Cereb Cortex ; 28(8): 2846-2853, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29106544

RESUMO

Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thickness and the volume of subcortical structures. In order to understand the mechanism underlying these changes we have developed an adult female rat model of androgenization. Magnetic resonance imaging and spectroscopy were used to monitor brain volume changes, white matter microstructure and ex vivo metabolic profiles over 32 days in androgenized and control subjects. Supraphysiological doses of testosterone prevents aging decrease of fractional anisotropy values, decreased general cortical volume and the relative concentrations of glutamine (Gln) and myo-Inositol (mI). An increase in the N-acetylaspartate (NAA)/mI ratio was detected d. Since mI and Gln are astrocyte markers and osmolytes, we suspect that the anabolic effects of testosterone change astrocyte osmolarity so as to extrude Mi and Gln from these cells in order to maintain osmotic homeostasis. This mechanism could explain the brain changes observed in TM and other individuals receiving androgenic anabolic steroids.


Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Metaboloma/fisiologia , Virilismo/patologia , Animais , Anisotropia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Feminino , Lateralidade Funcional , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Inositol/metabolismo , Imagem por Ressonância Magnética , Ratos , Ratos Wistar , Testosterona/sangue , Propionato de Testosterona/farmacologia , Trítio/metabolismo , Virilismo/sangue , Virilismo/diagnóstico por imagem , Substância Branca/patologia
10.
Clin Endocrinol (Oxf) ; 88(3): 415-424, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29154455

RESUMO

OBJECTIVE: Sustained evidence from observational studies indicates that after remission of Cushing syndrome (CS) a cardiovascular risk phenotype persists. Here, we performed a translational study in active CS and CS in remission (RCS) to evaluate the subclinical cardiometabolic burden and to explore the direct pro-inflammatory and prothrombotic potential of their sera on the endothelium in an in vitro translational atherothrombotic cell model. PATIENTS: Cross sectional study. The groups were (n = 9/group): I. RCS; II. Active CS (ACS) and III. Controls (CTR), all matched for age, body mass index, sex, without other hormonal deficits. DESIGN: We evaluated in vivo: cardiometabolic profile; endothelial markers (sVCAM-1, NO); endothelial dysfunction (FMD); intima-media thickness and body composition (DEXA). In vitro endothelial cells (EC) were exposed to sera taken from the different subjects to evaluate inflammatory EC response (tisVCAM) and thrombogenicity of the generated extracellular matrix (ECM): von Willebrand factor (VWF) and platelet reactivity. RESULTS: Three of the 9 RCS subjects were on glucocorticoid replacement therapy (GC-RT). Patients on GC-RT had a shorter period of time in stable remission. In vivo analysis ACS showed typically metabolic features, while cardiometabolic markers reached statistical significance for RCS only for Hs-CRP (P < .01). In vitro:EC exposed to ACS and RCS sera displayed increased tisVCAM-1 (P < .01 for ACS and P < .05 for RCS vs CTR), VWF (P < .01 for ACS and P < .05 for RCS vs CTR) and platelet adhesion on ECM (P < .01 for ACC and P < .05 for RCS vs CTR). No statistically significant differences were observed between GC-RT RSC and RCS without GC-RT. CONCLUSIONS: The sera of premenopausal women with CS in remission, without atherothrombotic disease, contain circulatory endothelial deleterious factors with a direct thrombogenic and pro-inflammatory endothelial effect that could increase cardiovascular risk.


Assuntos
Doenças Cardiovasculares/etiologia , Síndrome de Cushing/sangue , Endotélio/lesões , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Síndrome de Cushing/complicações , Síndrome de Cushing/patologia , Endotélio/patologia , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Pós-Menopausa , Indução de Remissão , Trombose/etiologia , Pesquisa Médica Translacional , Adulto Jovem
11.
Int J Endocrinol ; 2017: 2912763, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29213284

RESUMO

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p < 0.05), WC (p < 0.001), WHR (p = 0.003), BMI (p < 0.001), and hs-CRP (p < 0.001). CD14++CD16+ (p = 0.047); CD14+CD16++ (p = 0.053) MN; CD15+ (p = 0.027); CD15+CD16+ (p = 0.008) N; and NK-Lym (p = 0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p = 0.039) and CD15+ N with hs-CRP (r = 0.446, p = 0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p = 0.021), WC (p = 0.002), and WHR (p = 0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p = 0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

12.
J Steroid Biochem Mol Biol ; 172: 20-28, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28539237

RESUMO

Cross-sex hormone therapy (CHT) is critical for phenotypical and physiological transition in adults with gender dysphoria (GD). However, the impact of the CHT onto the molecular level/epigenetic regulation has not been comprehensively addressed. We postulate that CHT in GD could drive changes at the androgen receptor (AR), estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2), affecting their DNA methylation pattern and mRNA expression that may influence in the phenotypical changes associated to CHT. We carried out a prospective observational study on individuals with a diagnosis of GD. 18 subjects (no previous CHT): 12 female to male (FtoM) and 6 male to female (MtoF). An Epityper Mass array TM method was used to study the DNA methylation and Real-time PCR quantitative reverse transcription PCR (qRT-PCR) was used to quantify the gene expression. The analysis of AR, ESR1 and ESR2 receptor was performed at baseline, 6 and 12 months after CHT. No differences in DNA methylation of ESR were found in MtoF, while DNA methylation was increased in FtoM at 6 and 12 months of CHT. The AR showed a significant increase of methylation in MtoF group after 12 months of estrogenic treatment. Regarding the expression analysis, AR expression was significantly decreased in FtoM upon CHT treatment. AR, ESR1 and ESR2 methylation were correlated with anthropometric, metabolic and hormonal parameters in FtoM and MtoF. Our results support that CHT is associated to epigenetic changes that might affect the response to treatment with sex steroids.


Assuntos
Acetato de Ciproterona/uso terapêutico , Estradiol/análogos & derivados , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Disforia de Gênero/tratamento farmacológico , Receptores Androgênicos/genética , Testosterona/análogos & derivados , Adolescente , Adulto , Antropometria , Metilação de DNA/efeitos dos fármacos , Esquema de Medicação , Epigênese Genética , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Disforia de Gênero/genética , Disforia de Gênero/metabolismo , Disforia de Gênero/patologia , Humanos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Masculino , Prolactina/genética , Prolactina/metabolismo , Regiões Promotoras Genéticas , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Globulina de Ligação a Hormônio Sexual , Transdução de Sinais , Testosterona/uso terapêutico
13.
Endocrinol Diabetes Nutr ; 64(1): 26-33, 2017 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28440767

RESUMO

INTRODUCTION: Cushing syndrome (CS), an endogenous hypercortisolemic condition with increased cardiometabolic morbidity, leads to development of abdominal obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated in regulation of adipose tissue metabolism and fat distribution. In vitro and animal studies suggest that glucocorticoids interact with ZAG secretion and action. To assess the relationship between ZAG and glucocorticoids in a human model of hypercortisolism, circulating ZAG levels were tested in patients with CS and its counterpart controls. METHODS: An observational, cross-sectional study on 39 women, 13 with active CS and 26 controls matched by age and body mass index. Plasma ZAG levels (µg/ml) were measured by ELISA and correlated with hypercortisolism, metabolic, and phenotypic parameters. RESULTS: Plasma ZAG levels were significantly higher in patients with CS compared to controls (64.3±16.6 vs. 44.0±16.1, p=0.002). In a univariate analysis, ZAG levels positively correlated to 24-h urinary free cortisol (p=0.001), body mass index (p=0.02), non-esterified fatty acids (p=0.05), glucose (p=0.003), LDL-C (p=0.028), and type 2 diabetes mellitus (p=0.016), and were inversely related to total adiponectin levels (p=0.035). In a multivariate analysis, after adjusting for CS, ZAG levels only correlated with body mass index (p=0.012), type 2 diabetes mellitus (p=0.004), and glucose (p<0.001). CONCLUSION: This study provides initial evidence that plasma ZAG levels are higher in patients with CS as compared to controls. The close relationship of ZAG with metabolic and phenotypic changes in CS suggests that ZAG may play a significant role in adipose tissue changes in hypercortisolism.


Assuntos
Proteínas de Transporte/sangue , Síndrome de Cushing/sangue , Glicoproteínas/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glucocorticoides/metabolismo , Glicoproteínas/metabolismo , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Lipólise , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Circunferência da Cintura
14.
Endocrinol. diabetes nutr. (Ed. impr.) ; 64(1): 26-33, ene. 2017. graf, tab
Artigo em Inglês | IBECS | ID: ibc-171235

RESUMO

Introduction: Cushing syndrome (CS), an endogenous hypercortisolemic condition with increased cardiometabolic morbidity, leads to development of abdominal obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated in regulation of adipose tissue metabolism and fat distribution. In vitro and animal studies suggest that glucocorticoids interact with ZAG secretion and action. To assess the relationship between ZAG and glucocorticoids in a human model of hypercortisolism, circulating ZAG levels were tested in patients with CS and its counterpart controls. Methods: An observational, cross-sectional study on 39 women, 13 with active CS and 26 controls matched by age and body mass index. Plasma ZAG levels (μg/ml) were measured by ELISA and correlated with hypercortisolism, metabolic, and phenotypic parameters. Results: Plasma ZAG levels were significantly higher in patients with CS compared to controls (64.3±16.6 vs. 44.0±16.1, p=0.002). In a univariate analysis, ZAG levels positively correlated to 24-h urinary free cortisol (p=0.001), body mass index (p=0.02), non-esterified fatty acids (p=0.05), glucose (p=0.003), LDL-C (p=0.028), and type 2 diabetes mellitus (p=0.016), and were inversely related to total adiponectin levels (p=0.035). In a multivariate analysis, after adjusting for CS, ZAG levels only correlated with body mass index (p=0.012), type 2 diabetes mellitus (p=0.004), and glucose (p<0.001). Conclusion: This study provides initial evidence that plasma ZAG levels are higher in patients with CS as compared to controls. The close relationship of ZAG with metabolic and phenotypic changes in CS suggests that ZAG may play a significant role in adipose tissue changes in hypercortisolism (AU)


Introducción: El síndrome de Cushing (SC) es un estado de hipercortisolismo endógeno en el que se observa un incremento del riesgo cardiovascular asociado al desarrollo de obesidad abdominal, insulinorresistencia, diabetes y dislipidemia aterogénica. La zinc alfa-2 glucoproteína (ZAG) es una adipocina lipolítica recientemente caracterizada que está implicada en la regulación del metabolismo del tejido adiposo y la distribución de la grasa. Estudios in vitro y en animales indican que los glucocorticoides interaccionan con la secreción y acción de ZAG. Para evaluar la relación entre ZAG y los glucocorticoides en un modelo humano de hipercortisolismo, se analizaron los niveles circulantes de ZAG en pacientes con SC y sus correspondientes controles. Métodos: Estudio observacional en 39 mujeres, 13 con SC activo y 26 controles pareadas por edad e índice de masa corporal. Los niveles plasmáticos de ZAG (μg/ml) se determinaron mediante ELISA y se correlacionaron con los parámetros de hipercortisolismo, metabólicos y fenotípicos. Resultados: Las concentraciones plasmáticas de ZAG fueron significativamente más elevadas en los pacientes con SC (64,3±16,6 vs. 44±16,1; p=0,002). En el análisis univariante los niveles de ZAG se correlacionaron positivamente con cortisol libre urinario (p=0,001), índice de masa corporal (p=0,02), ácidos grasos no esterificados (p=0,05), glucosa (p=0,003), c-LDL (p=0,028) y diabetes mellitus (p=0,016) e inversamente con adiponectina total (p=0,035). En el análisis multivariante, después de ajustar por el SC, los niveles de ZAG solo se correlacionaron con el índice de masa corporal (p=0,012), la diabetes mellitus tipo 2 (p=0,004) y la glucosa (p<0,001). Conclusión: Nuestro estudio proporciona la primera evidencia de las concentraciones plasmáticas de ZAG en el SC. Los pacientes con SC presentan concentraciones más elevadas de ZAG que los controles. La estrecha relación de ZAG con las alteraciones metabólicas y fenotípicas del SC indica que ZAG podría desempeñar un papel importante en las alteraciones del tejido adiposo en el hipercortisolismo (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , alfa-Macroglobulinas/análise , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Lipólise , Glucocorticoides/análise , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática/métodos , Tecido Adiposo , Estudos Transversais/métodos , Antropometria/métodos
15.
Neurocir.-Soc. Luso-Esp. Neurocir ; 27(5): 229-236, sept.-oct. 2016. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-155598

RESUMO

Introducción: Los tumores hipofisarios y de la región selar representan el 10-15% de los tumores benignos intracraneales, siendo los adenomas los más frecuentes. En el siguiente artículo exponemos la experiencia adquirida a lo largo de 9años en el tratamiento quirúrgico por vía endoscópica de lesiones selares. Explicaremos los aspectos característicos de nuestra técnica quirúrgica y los resultados en términos clínicos y hormonales. Material y métodos: Realizamos un estudio retrospectivo de 200 pacientes con lesiones selares intervenidos por un único neurocirujano (J.E.) mediante abordaje endoscópico endonasal transesfenoidal entre febrero de 2006 y febrero 2015. No se incluyen abordajes extendidos a la base craneal, craneofaringiomas, ni lesiones inflamatorias, metastásicas o malignas. Resultados: De 200 pacientes, 7 eran quistes de Rathke y 193 adenomas (26 microadenomas y 165 macroadenomas). Subclasificados estos, a su vez, según el grado de invasión del seno cavernoso (Knosp 0, 1 y 2: 129 casos; Knosp 3 y 4: 71 casos). Se consiguió una exéresis tumoral completa en 143 pacientes (71,5%), subtotal en 39 (19,5%) y parcial en 18 (9%). En el grupo de mayor ocupación del seno cavernoso (Knosp 3 y 4) se consiguió una resección completa en un 55,5% (40/71). Se logró una remisión hormonal en 34 pacientes (85%) con acromegalia, en 23 (76%) con prolactinomas y en 30 (86%) con enfermedad de Cushing. Conclusión: Los resultados obtenidos en nuestra serie, fruto de la centralización y la experiencia, son equiparables a los mejores resultados conseguidos en centros de referencia de cirugía hipofisaria. La exploración quirúrgica precoz de la fístula reduce la tasa de meningitis posquirúrgicas (AU)


Introduction: Pituitary and sellar region tumours account for 10-15% of intracranial benign tumours, with pituitary adenoma being the most common one. In this article, a review is presented on 9 years of experience in surgical treatment using an endoscopic approach of sellar region lesions. The main features of our surgical technique will be explained, as well as the results in clinical and hormonal terms. Material and methods: A retrospective analysis was conducted on 200 patients operated on due to sellar lesions by the same neurosurgeon (J.E.) using an endoscopic endonasal transsphenoidal approach between February 2006 and February 2015. The cases excluded were, those requiring extended approaches of the skull base, as well as craniopharyngiomas, inflammatory, metastatic, or malignant lesions. Results: Of the 200 patients treated (59.5% women, mean age of 51.7 years, range: 18-82 years old), there were: 7 Rathke cysts and 193 adenomas (26 micro-adenomas and 165 macro-adenomas). All of them sub-classified according to the degree of invasion of the cavernous sinus (Knosp 0, 1, and 2: 129 cases and Knosp 3 and 4: 71 cases). Total resection was achieved in 143 patients (71.5%), subtotal resection in 39 (19.5%), and partial resection in 18 (9%). In the group of higher occupancy of the cavernous sinus (Knosp 3 and 4) complete resection was achieved in 55.5% (40 of 71 patients). Hormonal remission was achieved in 34 patients with acromegaly (85%), 23 patients with prolactinomas (76%), and 30 patients with Cushing's disease (86%). Conclusion: The results obtained in our series, due to the centralisation of pathology and experience, are comparable to those achieved in pituitary surgery reference centres. Early surgical exploration of cerebrospinal fluid leaks reduces the risk of post-surgical meningitis (AU)


Assuntos
Humanos , Cirurgia Endoscópica Transanal/métodos , Neoplasias Hipofisárias/cirurgia , Hipersecreção Hipofisária de ACTH/cirurgia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Sela Túrcica/cirurgia , Acromegalia/cirurgia , Complicações Pós-Operatórias/epidemiologia
16.
Endocrinol. nutr. (Ed. impr.) ; 63(6): 274-284, jun.-jul. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-153139

RESUMO

Los adenomas hipofisarios son tumores infrecuentes de diagnóstico complejo, cuya heterogeneidad y baja incidencia dificultan estudios a gran escala. El Registro Molecular de Adenomas Hipofisarios (REMAH) nació en 2008 en el seno de la Sociedad Andaluza de Endocrinología y Nutrición (SAEN), como estrategia de cooperación clínico-básica y multicéntrica, para mejorar el diagnóstico y tratamiento de tumores hipofisarios mediante la combinación de información clínica, anatomopatológica y molecular. En 2010, la Sociedad Española de Endocrinología y Nutrición (SEEN) lo extendió a nivel nacional, estableciendo 6 nodos con protocolos y métodos comunes de recogida de muestras y datos clínicos, análisis molecular y anotación en un mismo registro (www.remahnacional.com). El registro combina datos clínicos con el fenotipado molecular del adenoma intervenido, mediante PCR cuantitativa en tiempo real de la expresión de 26 genes: hormonas hipofisarias (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptores (somatostatina, dopamina, GHRH, GnRH, CRH, arginina-vasopresina, ghrelina), otros marcadores (Ki67, PTTG1) y genes de control. Hasta 2015 se ha obtenido información molecular de 704 adenomas, de los 1.179 pacientes registrados. Esta estrategia permite abordar análisis comparativos y relacionales entre el perfil molecular de los distintos tipos de adenomas y el fenotipo clínico del paciente, lo que puede ofrecer un mejor conocimiento de la enfermedad y, potencialmente, ayudar en la selección del tratamiento. El REMAH constituye una red única, multicéntrica e interdisciplinar, cimentada en una base de datos compartida, que aporta un enfoque traslacional de gran proyección potencial para el manejo de los adenomas hipofisarios y abre el camino para estudios conjuntos clínico-básicos innovadores con un elevado número de pacientes (AU)


Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples (AU)


Assuntos
Humanos , Neoplasias Hipofisárias/patologia , Medicina de Precisão , Pesquisa Médica Translacional/métodos , Registros de Doenças/estatística & dados numéricos , Acromegalia/epidemiologia , Síndrome de Cushing/epidemiologia
17.
Endocrinol Nutr ; 63(6): 274-84, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27091627

RESUMO

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples.


Assuntos
Adenoma/epidemiologia , Endocrinologia/organização & administração , Neoplasias Hipofisárias/epidemiologia , Medicina de Precisão/tendências , Sistema de Registros , Pesquisa Médica Translacional/tendências , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Idoso , Criança , Bases de Dados Factuais , Endocrinologia/tendências , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Biologia Molecular , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Hormônios Hipofisários/análise , Hormônios Hipofisários/genética , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores do Hormônio Hipofisário/análise , Receptores do Hormônio Hipofisário/genética , Sociedades Médicas , Espanha/epidemiologia , Adulto Jovem
18.
Neurocirugia (Astur) ; 27(5): 229-36, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-27012678

RESUMO

INTRODUCTION: Pituitary and sellar region tumours account for 10-15% of intracranial benign tumours, with pituitary adenoma being the most common one. In this article, a review is presented on 9 years of experience in surgical treatment using an endoscopic approach of sellar region lesions. The main features of our surgical technique will be explained, as well as the results in clinical and hormonal terms. MATERIAL AND METHODS: A retrospective analysis was conducted on 200 patients operated on due to sellar lesions by the same neurosurgeon (J.E.) using an endoscopic endonasal transsphenoidal approach between February 2006 and February 2015. The cases excluded were, those requiring extended approaches of the skull base, as well as craniopharyngiomas, inflammatory, metastatic, or malignant lesions. RESULTS: Of the 200 patients treated (59.5% women, mean age of 51.7 years, range: 18-82 years old), there were: 7 Rathke cysts and 193 adenomas (26 micro-adenomas and 165 macro-adenomas). All of them sub-classified according to the degree of invasion of the cavernous sinus (Knosp 0, 1, and 2: 129 cases and Knosp 3 and 4: 71 cases). Total resection was achieved in 143 patients (71.5%), subtotal resection in 39 (19.5%), and partial resection in 18 (9%). In the group of higher occupancy of the cavernous sinus (Knosp 3 and 4) complete resection was achieved in 55.5% (40 of 71 patients). Hormonal remission was achieved in 34 patients with acromegaly (85%), 23 patients with prolactinomas (76%), and 30 patients with Cushing's disease (86%). CONCLUSION: The results obtained in our series, due to the centralisation of pathology and experience, are comparable to those achieved in pituitary surgery reference centres. Early surgical exploration of cerebrospinal fluid leaks reduces the risk of post-surgical meningitis.


Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nariz , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
PLoS One ; 11(1): e0147851, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26815533

RESUMO

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (µa, µs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 µM to 144.8 µM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 µM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.


Assuntos
Hemodinâmica , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/irrigação sanguínea , Nódulo da Glândula Tireoide/patologia , Adulto , Feminino , Humanos , Masculino , Análise Espectral
20.
PLoS One ; 10(9): e0136931, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26375586

RESUMO

BACKGROUND: The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. OBJECTIVES: We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. SUBJECTS AND METHODS: 824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. RESULTS: No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. CONCLUSION: Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects.


Assuntos
Grelina/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Caracteres Sexuais , Espanha
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