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This retrospective study explores the utility of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in enhancing the intraoperative identification and guidance for the resection of abdominal paragangliomas. They can be challenging to detect during minimally invasive surgery, due to their anatomical location, varying size and similar appearance in regard to their surrounding tissue. Patients with suspected abdominal paragangliomas planned for a minimally-invasive resection were included. As part of standard of care they received single intravenous dose of 5 mg ICG after abdominal exploration. NIR fluorescence imaging of the anatomical region of the suspected lesion was performed immediately following intravenous administration, to assess fluorescence signals, intraoperative identification, and histopathological correlation. Out of five resected suspicious lesions, four were imaged with NIR fluorescence, pathology confirming four as paragangliomas, the latter turned out to be an adrenal adenoma. NIR fluorescence identified all four lesions, surpassing the limitations of white-light visualization. Homogeneous fluorescence signals appeared 30-60 s post-ICG administration, which lasted up to 30 min. The study demonstrates the feasibility and potential clinical value of fluorescence-guided minimally-invasive resections of abdominal paragangliomas using a single intravenous ICG dose. These findings support the scientific basis for routine use of ICG-fluorescence-guided surgery in challenging anatomical cases, providing valuable assistance in lesion detection and resection.
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Verde de Indocianina , Cirurgia Assistida por Computador , Humanos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Laparotomia , Imagem Óptica/métodosRESUMO
INTRODUCTION: In addition to catecholamines, pheochromocytomas and paragangliomas (PPGL) may secrete interleukin-6 (IL-6). IL-6 contributes to the development of unusual symptoms, which may hinder the diagnosis. PATIENTS AND METHODS: We report the clinical course and subsequent treatment of IL-6 producing PPGL in three patients from a single tertiary referral centre for PPGL patients in the Netherlands. CONCLUSION: PPGL combined with persistent elevated inflammatory markers, either in the presence or absence of pyrexia, raised suspicion of IL-6 overproduction in these three patients. Although surgical resection of the tumour is the only curative treatment option, our case series adds to the accumulating evidence that alpha-blockers might be effective in these patients.
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Neoplasias das Glândulas Suprarrenais/patologia , Interleucina-6/metabolismo , Paraganglioma/patologia , Feocromocitoma/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/metabolismo , Paraganglioma/cirurgia , Feocromocitoma/metabolismo , Feocromocitoma/cirurgia , Prognóstico , Adulto JovemRESUMO
Objective Gene alterations leading to activation of the MAPK pathway are of interest for targeted therapy in patients with advanced radioactive iodine refractory (RAI-R) thyroid carcinoma. Due to technical reasons gene fusion analysis in RNA isolated from formalin-fixed tumor tissues has till now been limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from formalin-fixed RAI-R thyroid carcinomas. Design Retrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hürthle cell- and 14 anaplastic thyroid carcinoma). Methods Total nucleic acid (undivided DNA and RNA) was isolated from formalin-fixed tissue. Extensive gene fusion analysis was performed in all samples that tested negative for pathogenic BRAF, NRAS, HRAS and KRAS variants. Results Seven targetable gene fusions were identified in the remaining 60 samples without known DNA variants. This includes frequently reported gene fusions such as CCDC6/RET (PTC1), PRKAR1A/RET (PTC2) and ETV6/NTRK3 , and gene fusions that are less common in thyroid cancer (TPM3/NTRK1, EML4/ALK and EML4/NTRK3). Of note, most gene fusions were detected in papillary thyroid carcinoma and MAPK-associated alterations in Hürthle cell carcinomas are rare (2/35). Conclusion Targetable gene fusions were found in 12% of RAI-R thyroid carcinoma without DNA variants and can be effectively identified in formalin-fixed tissue. These gene fusions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these patients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitality once progressive disease is seen.
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Fusão Gênica/genética , Marcação de Genes/métodos , Iodo , Neoplasias da Glândula Tireoide/genética , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
Introduction The association between type 1 diabetes (T1D) and other auto-immune diseases is well known. However, a quantitative overview of all associated auto-immune diseases and their prevalence in T1D is lacking. Methods We searched PubMed, Web of Science, EMBASE and Cochrane library in September 2018 to identify relevant articles about the prevalence of the following associated auto-immune diseases in T1D cohorts: auto-immune thyroid disease, celiac disease, gastric autoimmunity including pernicious anemia, vitiligo and adrenal gland insufficiency. A meta-analysis was performed to estimate pooled prevalence using a random-effects model. Furthermore, random-effects meta-regression analysis was performed to assess the association between prevalence and mean age or diabetes duration. Results One hundred eighty articles were eligible including a total of 293 889 type 1 diabetes patients. Hypothyroidism (65 studies) was prevalent in 9.8% (95% CI: 7.5-12.3) of patients. Meta-regression showed that for every 10-year age increase, hypothyroidism prevalence increased 4.6% (95% CI: 2.6-6.6, P < 0.000, 54 studies). Weighted prevalence of celiac disease was 4.5% (95% CI: 4.0-5.5, 87 studies). Gastric autoimmunity was found in 4.3% of patients (95% CI: 1.6-8.2, 8 studies) and vitiligo in 2.4% (95% CI: 1.2-3.9, 14 studies) of patients. The prevalence of adrenal insufficiency was 0.2% (95% CI: 0.0-0.4, 14 studies) and hyperthyroidism was found in 1.3 percent (95% CI: 0.9-1.8, 45 studies) of type 1 diabetes patients. For all analyses, statistical heterogeneity between studies was moderate to high. Conclusions The prevalence of antibody-mediated auto-immune disease is high among type 1 diabetes patients. Especially hypothyroidism and celiac disease are frequently found.
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Autoanticorpos/imunologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Doenças Autoimunes/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Humanos , Estudos Observacionais como AssuntoRESUMO
Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine (131I) therapy. Previous studies in adults showed that 131I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131I treatment. Median cumulative 131I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131I activity of the treatment.
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BACKGROUND: Germline mutations in the succinate dehydrogenase B (SDHB) gene predispose to hereditary paraganglioma (PGL) syndrome type 4. The aim of this study was to evaluate the clinical characteristics and outcome of treatment strategies for patients with head and neck paraganglioma (HNPGL) carrying SDHB germline mutations. METHODS: This was a retrospective evaluation of patients with HNPGL carrying SDHB germline mutations in the Netherlands. RESULTS: In a Dutch nationwide cohort study of SDHB germline mutation carriers, 54 patients with a total of 62 HNPGLs were identified. Forty-one of 54 patients (76 per cent) visited the outpatient clinic because of associated complaints. Eight patients (15 per cent) had multiple PGLs. One patient (2 per cent) developed a phaeochromocytoma and three (6 per cent) developed a malignant PGL. Twenty-seven patients (50 per cent) had an operation for their HNPGL and 15 (28 per cent) received radiotherapy. Three patients with HNPGL (6 per cent) were diagnosed with additional non-paraganglionic tumours. CONCLUSION: If an SDHB germline mutation is identified in a patient with HNPGL, the clinician should be aware of the variable manifestations of the SDHB-linked tumour syndrome, the risk of catecholamine excess, concurrent phaeochromocytoma, and association with non-paraganglionic tumours.
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Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers.
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Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa , Paraganglioma/genética , Feocromocitoma/genética , Succinato Desidrogenase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Penetrância , Fenótipo , Estudos RetrospectivosRESUMO
Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered. One hundred sixty patients were included in the analysis. Synchronous metastases were defined as diagnosis of metastasis ≤6 months after the initial diagnosis of ACC. Overall survival rate was calculated from the date of diagnosis of metastasis until death from any cause. At first presentation, 50 patients (31 %) had ACC with metastases (ENS@T stage IV). Another 67 (42 %) developed metastases during follow-up. Amongst the 117 patients with metastases, 84 (72 %) patients had synchronous metastases and 33 (28 %) developed metachronous metastases. Diagnosis of synchronous metastases (p = 0.046), more than one affected organ (p < 0.001) and four or more metastases (p < 0.001) were found to be associated with reduced overall survival. Limitations included retrospective design and limited details regarding pathological data. We conclude that synchronous metastases of ACC are associated with a poorer prognosis compared to metachronous metastases of ACC. The clinical characteristics associated with prognosis in this study support the view to refine the prognostic classification for patients with stage IV ACC.
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Neoplasias das Glândulas Suprarrenais/patologia , Carcinoma Adrenocortical/patologia , Neoplasias Primárias Múltiplas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias das Glândulas Suprarrenais/mortalidade , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/secundário , Segunda Neoplasia Primária/secundário , Países Baixos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to assess the reproducibility of different measurement methods and define the most workable technique for measuring head and neck paragangliomas, to determine the best method for evaluating tumour growth. The evaluation of tumour growth is vital for a 'wait-and-scan' policy, a management strategy that became increasingly important. STUDY DESIGN: Method comparison study. SETTING AND PARTICIPANTS: Thirty tumours, including carotid body, vagal body, jugulotympanic tumours and conglomerates of multiple tumours, were measured in duplicate, using linear dimensions, manual area tracing and an automated segmentation method. MAIN OUTCOME MEASURES: Reproducibility was assessed using the Bland-Altman method. RESULTS: The smallest detectable difference using the linear dimension method was 11% for carotid body and 27% for vagal body tumours, compared with 17% and 20% for the manual area tracing method. Due to the irregular shape of paragangliomas in the temporal bone and conglomerates, the manual area tracing method showed better results in these tumours (26% and 8% versus 54% and 47%). The linear dimension method was significantly faster (median 4.27 versus 18.46 minutes, P < 0.001). The automatic segmentation method yielded smallest detectable differences between 39% and 75%, and although fast (2.19 ± 1.49 minutes), it failed technically. CONCLUSIONS: Due to a relatively good reproducibility, fast and easy application, we found the linear dimension method to be the most pragmatic approach for evaluation of growth of carotid and vagal body paragangliomas. For jugulotympanic tumours, the preferred method is manual area tracing. However, volumetric changes of these tumours may be of less clinical importance than changes in relation to surrounding anatomical structures.
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Neoplasias de Cabeça e Pescoço/patologia , Paraganglioma/patologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Interpretação de Imagem Assistida por Computador , Angiografia por Ressonância Magnética , Masculino , Paraganglioma/diagnóstico por imagem , Reprodutibilidade dos Testes , Carga TumoralRESUMO
In the Netherlands, the majority of hereditary paragangliomas (PGL) is caused by SDHD, SDHB and SDHAF2 mutations. Founder mutations in SDHD are particularly prevalent, but several SDHB founder mutations have also been described. Here, we describe an extended PGL family with a Dutch founder mutation in SDHB, c.201-4429_287-933del. The proband presented with apparently sporadic head and neck paraganglioma at advanced age. Subsequently, evaluation of the family identified several unaffected mutation carriers, asymptomatic and symptomatic PGL patients, and patients presenting with early-onset malignant pheochromocytoma. The calculated penetrance of the SDHB mutation in this kindred is lower than the risk suggested for SDHB mutations in the literature. This may represent a characteristic of this particular SDHB mutation, but may also be a reflection of the inclusion of relatively large numbers of asymptomatic mutation carriers in this family and adequate statistical correction for ascertainment bias. The low penetrance of SDHB mutations may obscure the hereditary nature of SDHB-linked disease and is important in the counseling of SDHB-linked patients. Risk estimates should preferably be based on the specific mutation involved.
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Éxons , Mutação em Linhagem Germinativa , Paraganglioma/genética , Penetrância , Feocromocitoma/genética , Deleção de Sequência , Succinato Desidrogenase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Paraganglioma/mortalidade , Linhagem , Fenótipo , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidade , Adulto JovemRESUMO
Here we describe the role of laboratory assessment of autoantibodies against the thyroid antigens thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR) and thyroglobulin (TG) in the diagnosis of disorders of the thyroid. The practical use of these tests is illustrated by two case studies. This is followed by an in-depth discussion of the most recent literature, including national and international guidelines for thyroid disorders. The applicability of TPO antibodies in subclinical hypothyroidism, THSR antibodies in pregnant women with a history of Graves' hyperthyroidism, and TG antibodies in the follow-up of differentiated thyroid carcinoma, are highlighted.
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Autoanticorpos/sangue , Hipertireoidismo/diagnóstico , Hipotireoidismo/diagnóstico , Receptores da Tireotropina/imunologia , Doenças da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Autoanticorpos/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/imunologia , Hipotireoidismo/sangue , Hipotireoidismo/imunologia , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/imunologiaRESUMO
CONTEXT: Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients. METHODS: All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported. RESULTS: In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14-77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)% respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity. CONCLUSION: The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
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Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
BACKGROUND: Thyroid cancer is the most prevalent endocrine malignancy. Based on the increased understanding of thyroid tumourigenesis, novel therapeutic agents have been identified. However, given the low incidence, the good prognosis of the majority of these tumours and the limited evidence of different treatment modalities, a wide variety of treatment strategies are available. These are mostly based on small studies, data from retrospective analyses and the particular experiences of treating physicians. We discuss the recent developments in the treatment of advanced differentiated thyroid cancer. CASE DESCRIPTION: Three cases demonstrate the considerations involved in treatment decisions for patients with advanced thyroid cancer. The first patient achieved stable disease for over five years with different targeted therapies. The second patient shows the potential (severe) toxicity of these drugs and the third patient illustrates the indolent nature of this disease. CONCLUSION: The treatment of patients with extensively metastasised thyroid cancer is very complicated. The timing of initiation of therapy and the potential toxicity of targeted therapies are important in the clinical decision to treat or not to treat because of the slowly progressive course of differentiated thyroid cancer. When targeted therapy is considered, it remains of great importance to enrol patients in clinical studies in order to further determine the position of these therapies, to develop more effective (combination) treatment schemes, and above all, to identify those patients that truly benefit.
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Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adenocarcinoma Folicular/patologia , Idoso , Ensaios Clínicos Fase I como Assunto , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Niacinamida/farmacologia , Sorafenibe , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma. METHODS: A literature search was performed in October 2013 to identify potentially relevant studies. Main outcomes were the pooled percentages of complete response, partial response and stable disease after chemotherapy with CVD. A meta-analysis was performed with an exact likelihood approach using a logistic regression. Pooled percentages with 95% confidence intervals (CI) were reported. RESULTS: Four studies concerning a total of 50 patients with malignant paraganglioma/pheochromocytoma reported on treatment with a combination of CVD chemotherapy. A meta-analysis of the effect of chemotherapy on tumour volume showed pooled percentages of complete response, partial response and stable disease of, respectively, 4% (95% CI: 1%-15%), 37%(95% CI: 25%-51%) and 14% (95% CI: 7%-27%). Only two studies concerning a total of 35 patients assessed the response on catecholamine excess; pooled percentages for complete, partial and stable hormonal response were 14% (95% CI: 6%-30%), 40% (95% CI: 25%-57%) and 20% (95% CI: 10%-36%), respectively. Duration of response was also reported in only two studies with a median duration of response of 20 months and 40 months. CONCLUSIONS: Data on the effects of a combination of CVD chemotherapy on malignant paraganglioma/pheochromocytoma suggest that a partial response concerning tumour volume can be achieved in about 37% of patients and a partial response on catecholamine excess in about 40% of patients. However, in the included studies, the protocol when to initiate treatment was not well described. Therefore, it cannot be excluded that the reported effect of chemotherapy on tumour volume reflects the natural course of the disease, at least partially.
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Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paraganglioma/tratamento farmacológico , Feocromocitoma/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/patologia , Catecolaminas/metabolismo , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Humanos , Paraganglioma/epidemiologia , Paraganglioma/patologia , Feocromocitoma/epidemiologia , Feocromocitoma/patologia , Carga Tumoral , Vincristina/uso terapêuticoRESUMO
PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.
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Tumor do Corpo Carotídeo/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Tumor do Corpo Carotídeo/diagnóstico , Tumor do Corpo Carotídeo/fisiopatologia , Tumor do Corpo Carotídeo/cirurgia , Células Quimiorreceptoras/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/fisiopatologia , Neoplasias Primárias Múltiplas/cirurgia , Oxigênio/sangue , Polissonografia , Reflexo/fisiologia , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
Succinate dehydrogenase (SDH) mutation carriers are predisposed for developing paragangliomas. This study aimed to explore illness perceptions, risk perception and disease-related worry in these individuals. All consecutive SDHB and SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center (LUMC), a tertiary referral center, were eligible for inclusion. Illness perceptions were assessed using the validated Illness Perception Questionnaire-Revised and compared to reference populations. Risk perception and worry were measured by two items each and associations with illness perceptions explored. Twenty SDHB and 118 SDHD mutation carriers responded. Compared with various reference groups, SDH mutation carriers perceived less controllability of their condition. SDHB mutation carriers considered their condition to be less chronic in nature (p = 0.005) and perceived more personal (p = 0.018) and treatment control (p = 0.001) than SDHD mutation carriers. Mutation carriers with manifest disease reported more negative illness perceptions and a higher risk perception of developing subsequent tumors than asymptomatic mutation carriers. Illness perceptions, risk perception and disease-related worry were strongly correlated. Risk perception and disease-related worry may be assessed through illness perceptions. The development of interventions targeting illness perceptions may provide tools for genetic counseling.
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Predisposição Genética para Doença/psicologia , Heterozigoto , Succinato Desidrogenase/genética , Adulto , Fatores Etários , Ansiedade/genética , Ansiedade/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paraganglioma/genética , Percepção , Inquéritos e QuestionáriosRESUMO
BACKGROUND: (131)I-MIBG therapy can be used for palliative treatment of malignant paraganglioma and phaeochromocytoma. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of (131)I-MIBG therapy on tumour volume in patients with malignant paraganglioma/phaeochromocytoma. METHODS: A literature search was performed in December 2012 to identify potentially relevant studies. Main outcomes were the pooled proportions of complete response, partial response and stable disease after radionuclide therapy. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. RESULTS: Seventeen studies concerning a total of 243 patients with malignant paraganglioma/phaeochromocytoma were treated with (131)I-MIBG therapy. The mean follow-up ranged from 24 to 62 months. A meta-analysis of the effect of (131)I-MIBG therapy on tumour volume showed pooled proportions of complete response, partial response and stable disease of, respectively, 0·03 (95% CI: 0·06-0·15), 0·27 (95% CI: 0·19-0·37) and 0·52 (95% CI: 0·41-0·62) and for hormonal response 0·11 (95% CI: 0·05-0·22), 0·40 (95% CI: 0·28-0·53) and 0·21 (95% CI: 0·10-0·40), respectively. Separate analyses resulted in better results in hormonal response for patients with paraganglioma than for patients with phaeochromocytoma. CONCLUSIONS: Data on the effects of (131)I-MIBG therapy on malignant paraganglioma/phaeochromocytoma suggest that stable disease concerning tumour volume and a partial hormonal response can be achieved in over 50% and 40% of patients, respectively, treated with (131)I-MIBG therapy. It cannot be ruled out that stable disease reflects not only the effect of MIBG therapy, but also (partly) the natural course of the disease.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/radioterapia , Radioisótopos do Iodo/uso terapêutico , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Neoplasias das Glândulas Suprarrenais/patologia , Viés , Humanos , Paraganglioma/patologia , Feocromocitoma/patologia , Carga TumoralRESUMO
CONTEXT: Ig superfamily member 1 (IGSF1) deficiency was recently discovered as a novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism. However, clinical and biochemical data regarding growth, puberty, and metabolic outcome, as well as features of female carriers, are scarce. OBJECTIVE: Our objective was to investigate clinical and biochemical characteristics associated with IGSF1 deficiency in both sexes. METHODS: All patients (n = 42, 24 males) from 10 families examined in the university clinics of Leiden, Amsterdam, Cambridge, and Milan were included in this case series. Detailed clinical data were collected with an identical protocol, and biochemical measurements were performed in a central laboratory. RESULTS: Male patients (age 0-87 years, 17 index cases and 7 from family studies) showed CeH (100%), hypoprolactinemia (n = 16, 67%), and transient partial GH deficiency (n = 3, 13%). Pubertal testosterone production was delayed, as were the growth spurt and pubic hair development. However, testicular growth started at a normal age and attained macro-orchid size in all evaluable adults. Body mass index, percent fat, and waist circumference tended to be elevated. The metabolic syndrome was present in 4 of 5 patients over 55 years of age. Heterozygous female carriers (age 32-80 years) showed CeH in 6 of 18 cases (33%), hypoprolactinemia in 2 (11%), and GH deficiency in none. As in men, body mass index, percent fat, and waist circumference were relatively high, and the metabolic syndrome was present in 3 cases. CONCLUSION: In male patients, the X-linked IGSF1 deficiency syndrome is characterized by CeH, hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight. A subset of female carriers also exhibits CeH.
Assuntos
Envelhecimento , Hipotireoidismo Congênito/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Imunoglobulinas/deficiência , Proteínas de Membrana/deficiência , Doenças Testiculares/fisiopatologia , Adulto , Idoso de 80 Anos ou mais , Criança , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/imunologia , Hipotireoidismo Congênito/patologia , Saúde da Família , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Heterozigoto , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/deficiência , Humanos , Imunoglobulinas/genética , Lactente , Masculino , Proteínas de Membrana/genética , Síndrome Metabólica/etiologia , Tamanho do Órgão , Prolactina/sangue , Puberdade Tardia/etiologia , Doenças Testiculares/genética , Doenças Testiculares/imunologia , Doenças Testiculares/patologia , Inativação do Cromossomo XRESUMO
CONTEXT: Paraganglioma (PGL) patients and succinate dehydrogenase (SDH) gene mutation carriers at risk for PGLs have a decreased quality of life (QoL). QoL may be affected by the strategy an individual uses when dealing with a stressful situation, ie, specific coping styles. Understanding the various approaches to coping may allow the development of targeted interventions to improve patient QoL. OBJECTIVE: The objective of the study was to assess coping styles in PGL patients and SDH mutation carriers. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a tertiary referral center. PATIENTS AND METHODS: Coping styles were assessed using the Utrecht Coping List. The results from the study cohort were compared with a control group and data derived from the literature. Potential differences in coping styles between the various SDH mutation carriers and PGL patients without an SDH mutation were explored. RESULTS: Of the 174 patients who responded, 122 were SDHD, 25 SDHB, and 2 SDHC mutation carriers. An additional 25 patients lacked an SDH mutation. They recruited 100 peers as controls. Compared with the general population, the study cohort was more avoidant of problems (P < .001) and reported less expression of emotion (P < .01). Compared with patients with other conditions, they sought more social support (P < .001). There were no significant differences in coping styles between the various categories of mutation carriers or PGL patients lacking a mutation. CONCLUSIONS: Coping styles of PGL patients and SDH mutation carriers differ from those of control and reference groups and include an avoidant coping style and a lack of emotional expression.
Assuntos
Adaptação Psicológica , Predisposição Genética para Doença/psicologia , Paraganglioma/psicologia , Qualidade de Vida/psicologia , Succinato Desidrogenase/genética , Adulto , Idoso , Estudos Transversais , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paraganglioma/genética , Apoio Social , Inquéritos e QuestionáriosRESUMO
CONTEXT: A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensitive to detect biochemical activity in HNPGL patients than urinary excretion rates. OBJECTIVE: To compare plasma free levels vs urinary excretion rates of deconjugated 3MT and combined metanephrines (MNs) in patients with HNPGL. PATIENTS AND METHODS: We included 124 consecutive patients with HNPGL for screening of catecholamine excess by measurement of 24-h urinary excretion rates of deconjugated (nor)metanephrine, (nor)epinephrine, dopamine, vanillylmandelic acid, 3MT, and plasma free levels of (nor)metanephrine and 3MT. RESULTS: Plasma free 3MT levels were increased in 35 of the 124 patients (28%), whereas 24-h urinary excretion of deconjugated 3MT was increased in 30 patients (24%) (P=0.13). Plasma free MN levels were increased in seven patients (6%) and urinary deconjugated MN levels in six patients (5%) (P=1.00). Plasma free normetanephrine (NMN) levels were increased in seven patients (6%), and five patients had increased urinary excretion of deconjugated NMN (4%) (P=0.69). Plasma free combined MN levels (NMN, MN, and 3MT) were increased in 41 patients (33%), whereas 24-h urinary excretion rates of deconjugated combined MNs were increased in 33 patients (27%, P<0.05). CONCLUSIONS: The combined levels of free MNs and free 3MT in plasma indicate a higher number of biochemically active HNPGLs than the 24-h urinary excretion rates of these markers.