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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.

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.
Head Neck ; 41(1): 79-91, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30549360

RESUMO

BACKGROUND: Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1α (HIF-1α) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1α proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. METHODS: The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1α immunohistochemistry analysis was performed in 158 genetically defined patients. RESULTS: Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1α stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1α positive cells. CONCLUSION: As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1α stabilization in HNPGLs, this is not a clinically useful biomarker.

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.
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
8.
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
9.
Genet Med ; 20(8): 872-881, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29144511

RESUMO

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated. RESULTS: Of the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01). CONCLUSION: Pathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.


Assuntos
Síndrome CHARGE/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Hipogonadismo/genética , Síndrome CHARGE/diagnóstico , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Família , Feminino , Estudos de Associação Genética , Variação Genética/genética , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Análise de Sequência de DNA
10.
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.

11.
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
12.
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
13.
World Neurosurg ; 102: 102-110, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28254595

RESUMO

OBJECTIVE: To assess the contribution of low-field intraoperative magnetic resonance (iMRI) to endoscopic pituitary surgery. METHODS: We analyzed a prospective series of patients undergoing endoscopic endonasal surgery for pituitary macroadenomas assisted with a low-field iMRI (PoleStarN30, 0.15 T [Medtronic]). Clinical, radiologic, and surgical variables were analyzed and compared with our fully endoscopic historic cohort operated on without iMRI assistance. A bibliographic review of pituitary surgery assisted with iMRI was conducted. RESULTS: Thirty patients (57% female; mean age, 55 years) were prospectively analyzed. The most frequent tumor subtype was nonfunctioning macroadenoma (50%). The average Knosp grade was 2.3 and mean tumor size was 18 mm. Surgical and positioning time were 102 and 47 minutes, respectively. Hospital stay and complication rates were similar to our historical cohort for pituitary surgery. Mean follow-up was 10 months. Complete resection (CR) was achieved in 83% of patients. Seven patients (23%) benefited from iMRI assistance and achieved a CR in their surgeries. All patients except 1 experienced hormonal activity remission. iMRI sensitivity and specificity was 0.8 and 1, respectively. Although not statistically significant, CR rates were globally 11.5% superior in iMRI series compared with our historical cohort. This difference was independent of cavernous sinus invasiveness grade (CR rate increased 12.5% for Knosp grade 0-2 and 8.1% for Knosp grade 3-4). CONCLUSIONS: Low-field iMRI is a useful and safe assistance even in advanced surgical techniques such as endoscopy. Its contribution is limited by the intrinsic features of the tumor. Further randomized studies are required to confirm the cost-effectiveness of iMRI in pituitary surgery.


Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Imagem por Ressonância Magnética , Monitorização Intraoperatória , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Hormônios Hipofisários/metabolismo , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Transtornos das Sensações/etiologia , Transtornos das Sensações/cirurgia , Campos Visuais/fisiologia
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.
Thyroid ; 27(1): 59-66, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27796194

RESUMO

BACKGROUND: Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions. METHODS: This retrospective analysis is based on an assessment of the immunoexpression of 19 proteins on 81 benign thyroid lesions (FA) and 50 malignant tumors (FTC/FVPTC). The resulting expression profile allowed the design of a scoring system model to improve the differential diagnosis of benign and malignant thyroid lesions. The model was validated using an independent series of 69 FA and 40 FTC and an external series of 40 nodular hyperplasias, and was further tested in a series of 38 FNAB cell blocks. RESULTS: A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation groups, with specificities of 71.3% and 50.7%, respectively. For the nodular hyperplasia series, specificity reached 94.8%. Finally, in FNAB samples, the sensitivity was 100% and the specificity was 45% for discrimination between benign and malignant lesions. CONCLUSIONS: These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (FA) and malignant (FTC and FVPTC) tumors of the thyroid follicular epithelium.


Assuntos
Adenoma/diagnóstico , Precursor de Proteína beta-Amiloide/metabolismo , Carcinoma Papilar/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
16.
Clin Chem Lab Med ; 55(3): 441-446, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27754959

RESUMO

BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays the main tumor markers (TM) used in the diagnosis and follow-up of MTC patients are CT and carcinoembryonic antigen (CEA). Nonetheless, progastrin releasing peptide (proGRP) has been recently proposed as a TM useful in the MTC. Our aims were to investigate the release of proGRP in thyroid tumors, its role in the assessment of advanced MTC and its utility in the differential diagnosis between MTC and non-MTC thyroid tumors. METHODS: Serum samples from 22 patients with MTC and 16 with non-MTC were collected. Patients were classified into advanced cancer or no evidence of disease (NED). ProGRP was performed by Architect (Abbot Diagnostics), CT by Liaison (Diasorin) and CEA by Cobas E601(Roche Diagnostics). RESULTS: ProGRP median concentration in advanced MTC was significantly higher (1398.4 pg/mL) when compared with non-MTC, either in advanced disease (24.9 pg/mL) or NED (14.6 pg/mL). In non-MTC patients, proGRP median concentration was below its cutoff level (50 pg/mL). Similar to CT, proGRP was able to detect 88.9% of MTC patients, but with a slightly lower specificity of 76.9%. Using proGRP together with CT the sensitivity increased to 100%. CONCLUSIONS: The low prevalence of this malignancy strongly recommends further collaborative studies, mainly focused on monitoring proGRP during tyrosine kinase inhibitors treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and CEA.


Assuntos
Adenocarcinoma Folicular/secundário , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/secundário , Carcinoma/secundário , Fragmentos de Peptídeos/sangue , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitonina/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Papilar , Diagnóstico Diferencial , Feminino , Humanos , Imunoensaio , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/sangue , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/secundário , Adulto Jovem
17.
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
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.
Clin Endocrinol (Oxf) ; 84(4): 540-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26662620

RESUMO

BACKGROUND: Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established. OBJECTIVE: To re-evaluate the outcomes of long-term PEG in a series of previously published patients and analyse the escape phenomenon. METHODS: We reviewed all patients with acromegaly resistant to SSA in whom PEG was started as monotherapy, who had been included in a previous publication. We prospectively evaluated 64 (56·3% women) from six tertiary care referral hospitals in Spain, for whom data as of June 2014 were available. Escape to PEG was defined as confirmed loss of biochemical control (IGF-I >1·2xULN), after at least 6 months of previous control with a stable dose of PEG. RESULTS: Patients were followed up for 13·0 (5·9-34·8) years since diagnosis, and 9·0 (4·1-10·4) years since the first administration of PEG. Fifty-one (89·5%) patients had an adequate IGF-I control at the last follow-up visit, 9 of them without treatment. Tumour growth was reported in 6 of 64 cases (9·4%), none of whom had received prior radiotherapy (P = 0·011). Seven patients died during follow-up. We found 16 escapes in 10 patients (15·6%). We identified potential underlying causes in 9 cases (tumour regrowth, previous treatment modifications, concomitant menopause and change in testosterone administration). The reason was unknown in 7 escapes, which occurred in 6 patients (9·4%). All patients, except one, achieved subsequent biochemical control after treatment adjustment. CONCLUSIONS: We reassure the efficacy and safety of long-term PEG. An escape phenomenon may occur, but it can be overcome by adjusting therapy.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Acromegalia/metabolismo , Adulto , Idoso , Feminino , Seguimentos , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/metabolismo , Espanha , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
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