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1.
Autops Case Rep ; 13: e2023448, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034516

RESUMO

Internal watershed infarcts (IWIs) occur at the junction of the deep and superficial perforating arterial branches of the cerebrum. Despite documentation in the radiology literature, IWIs are rarely encountered at the time of autopsy. Here, we report the case of a 59-year-old incarcerated male who was brought to the emergency department after being found unresponsive on the floor of his jail cell. Initial examination and imaging demonstrated right-sided hemiplegia, aphasia, right facial droop, and severe stenosis of the left middle cerebral artery, respectively. Repeat imaging 4 days after admission and 26 days before death demonstrated advanced stenosis of the intracranial, communicating segment of the right internal carotid artery, a large acute infarct in the right posterior cerebral artery territory, and bilateral deep white matter ischemic changes with a right-sided "rosary-like" pattern of injury that is typical of IWIs. Postmortem gross examination showed that the right deep white matter lesion had progressed to a confluent, "cigar-shaped" subacute IWI involving the right corona radiata. This is the first well-documented case of an IWI with radiologic imaging and photographic gross pathology correlation. This case uniquely highlights a rarely encountered lesion at the time of autopsy and provides an excellent visual representation of internal watershed neuroanatomy.

2.
Autops. Case Rep ; 13: e2023448, 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520273

RESUMO

ABSTRACT Internal watershed infarcts (IWIs) occur at the junction of the deep and superficial perforating arterial branches of the cerebrum. Despite documentation in the radiology literature, IWIs are rarely encountered at the time of autopsy. Here, we report the case of a 59-year-old incarcerated male who was brought to the emergency department after being found unresponsive on the floor of his jail cell. Initial examination and imaging demonstrated right-sided hemiplegia, aphasia, right facial droop, and severe stenosis of the left middle cerebral artery, respectively. Repeat imaging 4 days after admission and 26 days before death demonstrated advanced stenosis of the intracranial, communicating segment of the right internal carotid artery, a large acute infarct in the right posterior cerebral artery territory, and bilateral deep white matter ischemic changes with a right-sided "rosary-like" pattern of injury that is typical of IWIs. Postmortem gross examination showed that the right deep white matter lesion had progressed to a confluent, "cigar-shaped" subacute IWI involving the right corona radiata. This is the first well-documented case of an IWI with radiologic imaging and photographic gross pathology correlation. This case uniquely highlights a rarely encountered lesion at the time of autopsy and provides an excellent visual representation of internal watershed neuroanatomy.

3.
Endocr Relat Cancer ; 27(1): R1-R20, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31645015

RESUMO

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement. Breast and lung cancers are the most common primaries metastasing to the pituitary, leading to pituitary dysfunction in approximately 30% of cases. The thyroid gland can be affected by renal, colorectal, lung and breast carcinomas, and melanomas, but has rarely been associated with thyroid dysfunction. Pancreatic metastasis can lead to exo-/endocrine insufficiency with renal carcinoma being the most common primary. Most parathyroid metastases originate from breast and lung carcinomas and melanoma. Breast and colorectal cancers are the most frequent ovarian metastases; prostate cancer commonly affects the testes. In the presence of endocrine deficiencies, glucocorticoid replacement for adrenal and pituitary involvement can be life saving. As most metastases to endocrine organs develop in the context of disseminated disease, surgical resection or other local therapies should only be considered to ameliorate symptoms and reduce tumour volume. Although few consensus statements can be made regarding the management of metastases to endocrine tissues because of the heterogeneity of the variable therapies, it is important that clinicians are aware of their presence in diagnosis.


Assuntos
Neoplasias das Glândulas Endócrinas/secundário , Neoplasias/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias das Glândulas Endócrinas/diagnóstico por imagem , Neoplasias das Glândulas Endócrinas/metabolismo , Humanos , Imagem Multimodal/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Prognóstico
4.
Clin Endocrinol (Oxf) ; 91(4): 534-543, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31254407

RESUMO

BACKGROUND: The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. METHODS: Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. RESULTS: We included 114 consecutive patients (74 women; age at baseline 54.5 ± 12.7 years [mean ± SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 ± 46 (mean ± SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. CONCLUSION: Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.


Assuntos
Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Gastrinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/mortalidade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/mortalidade , Curva ROC , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade
5.
Endocrine ; 64(3): 690-701, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30635793

RESUMO

PURPOSE: To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs). METHODS: Seventy-four patients were recruited from four NEN centers in this observational multicenter study. RESULTS: Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4-395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589-14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14-463) months. CONCLUSIONS: Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.


Assuntos
Neoplasias Ósseas/terapia , Difosfonatos/uso terapêutico , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Gerenciamento Clínico , Feminino , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Prognóstico , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
Endocrine ; 50(1): 146-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25690756

RESUMO

Biological anti-rheumatic agents (BAA) may induce autoimmune phenomena. Evidence on thyroid-specific effects of these agents is relatively limited. We studied prospectively, over 3 years, 36 rheumatic patients treated with BAA (18 Infliximab and 18 Rituximab) and no prior exposure to biological therapies (group-1), with respect to their thyroid function, thyroid antibody titers, and thyroid ultrasonographic parameters, such as left inferior thyroid artery peak systolic velocity (ITA PSV), left thyroid lobe vascularity index (TL VI), and echogenicity. Twenty-eight rheumatic patients treated with disease-modifying anti-rheumatic drugs and/or glucocorticoids (group-2), 21 rheumatic patients not receiving any treatment (group-3), and 49 healthy individuals (group-4) were used for comparison. Thyroid function and autoantibody titers were not significantly altered at any stage irrespectively of the administered BAA, previously unknown autoimmune thyroid disease (AITD) status, and/or concomitant treatment with glucocorticoids. Left ITA PSV was significantly increased in group-1 patients (mean ± SD start: 25.5 ± 14.1 cm/s vs. end: 29.8 ± 11.1 cm/s, p = 0.038 and p < 0.001, respectively). Six group-1, 7 group-2, and 3 group-3 patients developed reduced thyroid echogenicity during follow-up (start: p = 0.003 and end: p < 0.001). Left ITA PSV, left TL VI, and echogenicity changes were not related to alterations in thyroid volume, thyrotropin hormone levels, and/or underlying AITD. Infliximab and Rituximab do not cause any alterations in thyroid function and/or autoimmunity, even in patients with previously undiagnosed AITD. Elevated left ITA PSV and reduced thyroid echogenicity may be early features signaling progression to AITD in patients treated with BAA.


Assuntos
Antirreumáticos/efeitos adversos , Autoanticorpos/sangue , Terapia Biológica/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , Glândula Tireoide/efeitos dos fármacos , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacologia , Autoanticorpos/efeitos dos fármacos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Infliximab/farmacologia , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/farmacologia , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/diagnóstico por imagem , Hormônios Tireóideos/sangue , Tireoidite Autoimune/induzido quimicamente , Ultrassonografia
7.
Clin Endocrinol (Oxf) ; 81(2): 157-68, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24750249

RESUMO

The vast majority of gastrin-related gastrointestinal neuroendocrine neoplasms (GI-NENs) develop in the context of chronic atrophic gastritis (type 1), a condition closely related to autoimmune thyroid diseases. These neoplasms are defined as gastric NENs type 1 (GNEN1) and have recently been shown to constitute the commonest GI-NENs in a prospective study. GNEN1s are usually multiple and follow a relative indolent course, raising questions regarding the extent that such patients should be investigated and the appropriate therapeutic interventions needed. Recently, a number of consensus statements and guidelines have been published from various societies dealing with the diagnosis and management of GI-NENs. Endocrinologists are among the many different medical specialties involved in GNEN1s diagnosis and management. However, despite recent advances, few randomized trials are available, and thus existing evidence remains relatively weak compared to other malignancies. The purpose of this review is to provide recent evidence along with currently employed modalities addressing the diagnosis, management, long-term follow-up and potential comorbidities of GNEN1s.


Assuntos
Tumores Neuroendócrinos/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Humanos , Tumores Neuroendócrinos/epidemiologia , Estudos Prospectivos
8.
J Clin Endocrinol Metab ; 99(8): 2754-62, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24712565

RESUMO

CONTEXT: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. OBJECTIVE: Our objective was to investigate CVR in patients with NFAI. DESIGN AND SETTING: This case-control study was performed in a tertiary general hospital. SUBJECTS: SUBJECTS included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. MAIN OUTCOME MEASURES: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. RESULTS: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. CONCLUSIONS: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/metabolismo , Doenças Cardiovasculares/epidemiologia , Hidrocortisona/metabolismo , Neoplasias das Glândulas Suprarrenais/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Hidrocortisona/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Neuroendocrinology ; 99(2): 118-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24776735

RESUMO

AIM: Gastrin and chromogranin A (CgA) levels have been tested for the diagnosis of enterochromaffin-like cell hyperplasia (ECLH) in patients with type 1 diabetes and autoimmune atrophic gastritis but not for patients with Hashimoto's thyroiditis (HT). The aim of the study was to develop receiver operating characteristic (ROC) curves for gastrin and CgA levels and other clinical and biochemical parameters, as means for pretest probability of gastric ECLH in patients with HT. METHODS: A total of 115 patients with HT were prospectively studied for a median period of 4 (2-7) years. Gastrin, CgA, vitamin B12, anti-parietal cell antibodies, free thyroxine, thyrotropin, and neuron-specific enolase levels were measured. Their predictive values were calculated according to the histological findings for ECLH diagnosis from esophagogastroduodenoscopy-obtained biopsies. RESULTS: Thirteen patients (11.3%) had ECLH. The areas under the curve for gastrin and CgA level were 0.898 (p < 0.001) and 0.853 (p < 0.001), respectively. The product sensitivity × specificity was 0.803 and 0.653 for gastrin and CgA levels >89.5 and >89.1 ng/ml, respectively. Two and 4 patients with ECLH had normal gastrin and CgA levels, respectively. The most specific combined parameters predicting ECLH were gastrin >89.5 ng/ml with concomitant low B12 levels (96.1% specificity). CONCLUSION: Gastrin levels have high diagnostic accuracy for ECLH identification in patients with HT, and are highly specific when combined with low B12 levels. However, they should be interpreted with caution, as some patients may harbor gastric ECLH even if gastrin levels are not increased, necessitating further follow-up.


Assuntos
Cromogranina A/sangue , Celulas Tipo Enterocromafim/patologia , Gastrinas/sangue , Doença de Hashimoto/complicações , Gastropatias/diagnóstico , Gastropatias/patologia , Estômago/patologia , Adulto , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hiperplasia/sangue , Hiperplasia/diagnóstico , Hiperplasia/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Gastropatias/epidemiologia
10.
Clin Endocrinol (Oxf) ; 80(5): 685-90, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24118101

RESUMO

OBJECTIVE: The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease. DESIGN: Prospective observational study in a single institutional study. PATIENTS AND MEASUREMENTS: One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured. RESULTS: One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up. CONCLUSIONS: Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.


Assuntos
Doenças Autoimunes/diagnóstico , Gastrite/diagnóstico , Doença de Hashimoto/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Gástricas/genética , Doenças da Glândula Tireoide/diagnóstico , Idoso , Doenças Autoimunes/complicações , Cromogranina A/sangue , Endoscopia , Celulas Tipo Enterocromafim/citologia , Feminino , Gastrinas/sangue , Gastrite/complicações , Doença de Hashimoto/complicações , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Fenótipo , Prevalência , Estudos Prospectivos , Risco , Doenças da Glândula Tireoide/complicações
11.
J Ultrasound Med ; 32(11): 1969-78, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24154901

RESUMO

OBJECTIVES: The purpose of this study was to calculate a number of thyroid grayscale and Doppler sonographic parameters in healthy individuals and patients with Hashimoto thyroiditis or Graves disease and assess their sensitivity and specificity for the diagnosis of autoimmune thyroid disease using receiver operating characteristic curves. METHODS: A consecutive series of 153 patients (70 euthyroid and 54 hypothyroid patients with Hashimoto thyroiditis and 29 patients with Graves disease), all selected from an outpatient endocrine clinic, and 48 age- and sex-matched healthy control participants were evaluated with grayscale and power Doppler sonography. RESULTS: An irregular echo pattern in the thyroid parenchyma had 92.8% sensitivity for the diagnosis of autoimmune thyroid disease, and a left inferior thyroid artery peak systolic velocity (PSV) greater than 26.11 cm/s had 91.7% specificity. Of 8 patients with Hashimoto thyroiditis and normal grayscale sonographic characteristics, 6 had a left inferior thyroid artery PSV greater than 26.11 cm/s. A left inferior thyroid artery PSV greater than 61.65 cm/s had 82.8% sensitivity and 86.9% specificity for differentiating Hashimoto thyroiditis from Graves disease. CONCLUSIONS: The left inferior thyroid artery PSV was the most accurate sonographic parameter for the diagnosis of autoimmune thyroid disease. Measurement of the inferior thyroid artery PSV could be used in patients with a normal grayscale sonographic appearance and inconclusive clinical and biochemical parameters to substantiate the diagnosis of autoimmune thyroid disease. Further studies are needed to evaluate and expand the use of this index.


Assuntos
Ecocardiografia Doppler em Cores/estatística & dados numéricos , Doença de Graves/diagnóstico por imagem , Doença de Graves/fisiopatologia , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/fisiopatologia , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/diagnóstico por imagem , Adulto , Velocidade do Fluxo Sanguíneo , Diagnóstico Diferencial , Ecocardiografia Doppler em Cores/métodos , Doença de Graves/epidemiologia , Grécia/epidemiologia , Doença de Hashimoto/epidemiologia , Humanos , Masculino , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sístole
12.
Front Immunol ; 4: 238, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23966997

RESUMO

BACKGROUND: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM). METHODS: We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients. RESULTS: Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. CONCLUSION: Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity.

14.
Eur J Endocrinol ; 168(2): 185-93, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23132699

RESUMO

OBJECTIVE: To study the clinical presentation, diagnostic approach, response to treatment, and the presence of other pathologies in patients with gastric carcinoid type 1 (GC 1) tumors. DESIGN AND METHODS: Retrospective analysis of 111 patients from four institutions and a mean follow-up of 76 months. RESULTS: The main indications for gastroscopy were upper gastrointestinal tract symptoms. The mean number of lesions, maximum tumoral diameter, and percentage of cells expressing Ki-67 labeling index were 3.6±3.8, 8±12.1 mm and 1.9±2.4% respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in 100/101 and 85/90 patients respectively. Conventional imaging studies demonstrated pathology in 9/111 patients. Scintigraphy with radiolabeled octreotide was positive in 6/60 without revealing any additional lesions. From the 59 patients who had been followed-up without any intervention, five developed tumor progression. Thirty-two patients were treated with long-acting somatostatin analogs (SSAs), leading to a significant reduction of gastrin and CgA levels, number of visible tumors, and CgA immune-reactive tumor cells in 28, 19, 27, and 23 treated patients respectively. Antrectomy and/or gastrectomy were initially performed in 20 patients and a complete response was achieved in 13 patients. The most common comorbidities were vitamin B12 deficiency, thyroiditis, and parathyroid adenomas. CONCLUSIONS: Most GCs1 are grade 1 (82.7%) tumors presenting with stage I (73.9%) disease with no mortality after prolonged follow-up. Ocreoscan did not provide further information compared with conventional imaging techniques. Treatment with SSAs proved to be effective for the duration of administration.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Tumor Carcinoide/patologia , Octreotida/uso terapêutico , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/sangue , Tumor Carcinoide/sangue , Tumor Carcinoide/tratamento farmacológico , Cromogranina A/sangue , Feminino , Seguimentos , Gastrinas/sangue , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
15.
World J Gastroenterol ; 19(46): 8687-95, 2013 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-24379587

RESUMO

AIM: To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1 (GCA1). METHODS: Information on clinical, biochemical, radiological, histopathological findings, the extent of the disease, as well as the use of different therapeutic modalities and the long-term outcome were recorded. Patients' data were assessed at presentation, and thereafter at 6 to 12 monthly intervals both clinically and biochemically, but also endoscopically and histopathologically. Patients were evaluated for the presence of specific symptoms; the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded. The evaluation of response to treatment was defined using established WHO criteria. RESULTS: We studied twenty consecutive patients with a mean age of 55.1 years. The mean follow-up period was 83 mo. Twelve patients had regional lymph node metastases and 8 patients had liver metastases. The primary tumor mean diameter was 20.13 ± 10.83 mm (mean ± SD). The mean Ki-67 index was 6.8% ± 11.2%. All but one patient underwent endoscopic or surgical excision of the tumor. The disease was stable in all but 3 patients who had progressive liver disease. All patients remained alive during the follow-up period. CONCLUSION: Metastatic GCA1 carries a good overall prognosis, being related to a tumor size of ≥ 1 cm, an elevated Ki-67 index and high serum gastrin levels.


Assuntos
Tumor Carcinoide/secundário , Neoplasias Hepáticas/secundário , Neoplasias Gástricas/patologia , Adulto , Idoso , Tumor Carcinoide/sangue , Tumor Carcinoide/química , Tumor Carcinoide/classificação , Tumor Carcinoide/terapia , Quimioterapia Adjuvante , Progressão da Doença , Europa (Continente) , Feminino , Gastrectomia , Derivação Gástrica , Gastrinas/sangue , Gastroscopia , Humanos , Israel , Antígeno Ki-67/análise , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/terapia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/química , Neoplasias Gástricas/classificação , Neoplasias Gástricas/terapia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
17.
Neuroendocrinology ; 92(4): 252-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20924166

RESUMO

OBJECTIVE: Although a number of familiar syndromes are associated with primary hyperparathyroidism (PHP), there is no information regarding the prevalence of PHP in other sporadic neuroendocrine diseases. The aim of this study is to investigate the prevalence of PHP in our group of patients with gastric carcinoid (GC) type 1 tumors. METHODS: Twenty-six patients with biopsy-proven GC type 1 tumors were retrospectively studied. The diagnosis of PHP was suspected following elevated or high-normal serum calcium levels and elevated or inappropriate normal parathyroid hormone levels. Further tests for the localization of the hyperfunctioning parathyroid glands included neck ultrasound, (99m)Tc-SESTAMIBI scanning, and cervical or upper mediastinal MR imaging studies. Four control groups were also studied: two age- and sex-matched groups of individuals with (n = 49) and without (n = 34) thyroid autoimmunity and normal endoscopy of the stomach, a third group with nongastric neuroendocrine tumors (n = 68), and a fourth group with atrophic gastritis and hypergastrinemia, without gastric endocrine tumors (n = 30). RESULTS: PHP was diagnosed in 4 (15.38%) patients with GC type 1 tumors compared to none of the 4 control groups. Three of the 4 patients with PHP were operated and proved to have a parathyroid adenoma. No statistically significant differences were observed between patients with or without PHP in mean gastrin and chromogranin A levels, number of lesions, ki-67 labeling index expression, and maximum GC type 1 tumor diameter. CONCLUSION: PHP seems to be relatively common, approximately 15% in the present cohort, in patients with GC type 1 tumors. PHP should be actively looked for in such patients and treated accordingly.


Assuntos
Tumor Carcinoide/complicações , Hiperparatireoidismo Primário/complicações , Neoplasias Gástricas/complicações , Adenoma/complicações , Adenoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/epidemiologia , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Adulto Jovem
18.
J Pediatr Endocrinol Metab ; 22(4): 339-44, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19554808

RESUMO

BACKGROUND: Although thyroid ultrasound is a valuable tool for the diagnosis and follow-up of patients with Hashimoto's thyroiditis (HT), classical sonographic findings are not always present. AIM: To calculate the time needed for children with HT and normal ultrasound at diagnosis to develop characteristic sonographic findings. PATIENTS AND METHODS: 105 children (23 male and 82 female) with HT (mean age 9.4 +/- 2.9 years) were studied. Physical examination and measurements of TSH and fT4 levels were performed at diagnosis, at 3-month intervals for the first year, and twice yearly thereafter. Thyroid ultrasound was performed at diagnosis and twice yearly thereafter. The median follow-up duration was 18 months (range: 6-61 months). RESULTS: The time needed for 30%, 50%, and 70% of children to demonstrate an abnormal thyroid sonographic pattern was 4, 7, and 14 months, respectively. Important factors accelerating sonographic changes were goiter (p = 0.023), hypothyroidism (p = 0.0255), and seropositivity for both thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg) autoantibodies (p = 0.0005). CONCLUSION: Sonographic findings of HT are present in 37% of children at diagnosis. Fifty percent of children with normal initial thyroid US will develop changes within 7 months; however, characteristic findings may not develop for over 4 years.


Assuntos
Doença de Hashimoto/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Autoanticorpos/sangue , Criança , Feminino , Seguimentos , Humanos , Iodeto Peroxidase/imunologia , Masculino , Tireoglobulina/imunologia , Tireoidite Autoimune/diagnóstico por imagem , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Ultrassonografia
20.
Thyroid ; 18(9): 1015-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18788923

RESUMO

A 60-year-old female patient with a history of multifocal papillary thyroid carcinoma was referred to the endocrinology clinic for an exophytic and ulcerated lesion at the right base of the neck. Twelve years earlier she had undergone a total thyroidectomy for multinodular goiter. Four years after the total thyroidectomy she had a lymph node dissection of the neck and was then treated twice with 100 mCi 131I. Five years after the second dose of 131I she was lost to followup. Before she was lost to followup the serum thyroglobulin (Tg) after recombinant TSH administration was 84 ng/ml (normal values < 2 ng/ml) and there was no uptake on a radioiodine whole body scan. Neck ultrasonography and MRI revealed a 1.7 by 1.7 cm mass in the region where the right lobe of the thyroid gland is. Surgical removal of the lesion was not possible since the neoplasm infiltrated the adjacent vital structures. The disease was treated with external beam radiation therapy. Two years later the patient is still alive and local control of the disease is achieved. In selected patients where other therapeutic modalities such as surgery, levothyroxine suppression therapy or radioactive iodine are not an option or ineffective, external beam radiotherapy can likely prolong survival.


Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/radioterapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/radioterapia , Radioterapia/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/radioterapia , Feminino , Bócio/cirurgia , Humanos , Radioisótopos do Iodo/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Tireoglobulina/sangue , Tiroxina/uso terapêutico , Resultado do Tratamento , Úlcera/patologia , Ultrassonografia/métodos
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