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Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.
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Fissura Palatina , Cisto Dermoide , Fatores de Transcrição Forkhead , Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Animais , Feminino , Humanos , Ratos , Fissura Palatina/genética , Cisto Dermoide/genética , Fatores de Transcrição Forkhead/genética , Neoplasias Ovarianas/metabolismo , Estruma Ovariano/genética , Estruma Ovariano/metabolismo , Estruma Ovariano/patologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
CONTEXT: Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long-term toxicities. OBJECTIVE: To characterize the endocrine disorders developed after HSCT. DESIGN AND PATIENTS: Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow-up at our endocrine late-effects clinics. RESULTS: Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z-score at diagnosis of -1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001). CONCLUSION: At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow-up of these patients.
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Doenças do Sistema Endócrino , Transplante de Células-Tronco Hematopoéticas , Nódulo da Glândula Tireoide , Criança , Humanos , Feminino , Pré-Escolar , Seguimentos , Estudos Retrospectivos , Doenças do Sistema Endócrino/etiologia , Nódulo da Glândula Tireoide/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodosRESUMO
OBJECTIVE: Insecure attachment is considered a general risk factor for eating disorders (ED). Emotion dysregulation has been proposed as one of the possible mechanisms by which attachment insecurity may affect ED psychopathology. Aim of the present study was to investigate whether difficulties in acceptance of emotions or emotional clarity may mediate the connection between insecure attachment and ED psychopathology. METHOD: One hundred and twenty patients participated and completed the Italian version of Eating Disorder Inventory-2, Experience in Close Relationship questionnaire and Difficulties in Emotion Regulation Scale. A mediator path model was performed, in which insecure attachment dimensions were set as independent variables, ED specific psychopathology measures as dependent variables, and non-acceptance of emotion and lack of emotional clarity as mediators. RESULTS: The association between both attachment avoidance and anxiety and ED specific symptoms was mediated by emotional non-acceptance, but not by emotional clarity. CONCLUSIONS: This study showed the importance to address emotion regulation in individuals with ED, focussing on improving emotional acceptance. Exploring early developmental processes which lead to non-acceptance of emotions could improve this psychological trait in people with ED.
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Transtornos da Alimentação e da Ingestão de Alimentos , Apego ao Objeto , Humanos , Feminino , Emoções , Ansiedade , Transtornos de Ansiedade/psicologiaRESUMO
INTRODUCTION: Cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, given the high radiosensitivity of this gland. The aim of this study is to assess the incidence and timeframe of thyroid complications in cancer patients, followed systematically since their radiation therapy, and to identify risk factors for the development of hypothyroidism and thyroid cancer. METHODS: We performed a retrospective study, including 282 subjects, who received neck, craniospinal, or total body irradiation (TBI). Patients were grouped into four primary diagnostic clusters: leukaemia, Hodgkin's disease, central nervous system, and head and neck tumours. RESULTS: Hypothyroidism was observed in 56.7% of patients, on average 6.8 ± 5.9 years after the treatment. Neck and craniospinal irradiation presented a 3.5-fold increased risk for the development of hypothyroidism compared to TBI. Papillary thyroid cancer was diagnosed in 8.5% of the patients, on average, 18.5 ± 4.9 years after radiotherapy (RT). Female gender, younger age, and lower irradiation doses were independently associated with thyroid cancer development. CONCLUSION: Our study provides useful information about the risk of hypothyroidism and thyroid cancer after RT, as it was performed in a cohort of patients closely followed since the oncological therapies, and, thus, may give new insights into the follow-up management of these patients.
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Neoplasias de Cabeça e Pescoço , Hipotireoidismo , Neoplasias da Glândula Tireoide , Feminino , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicaçõesRESUMO
OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.
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Hipercalcemia , Hiperparatireoidismo , Neoplasias das Paratireoides , Adulto , Idoso , Feminino , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo/genética , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
CONTEXT: Lymph node metastases (LNM) can be present in 35% of patients with differentiated thyroid cancer (DTC), and the management of persistent/recurrent nodal disease has been controversial. Watchful waiting may be a reasonable approach in selected patients, but uncertainty about clinical outcomes remains a concern. OBJECTIVE: To investigate the outcomes of patients with DTC with recurrent/persistent confirmed LNM under surveillance. METHODS: Patients with LNM from DTC were selected from databases of needle washout thyroglobulin measurements and fine-needle aspiration biopsies performed in our institution. Patients with confirmed metastases, in whom active surveillance was initially proposed, were selected. Main clinical outcomes were analysed. RESULTS: We found 89 patients with LNM under surveillance. Classic papillary was the most frequent variant (44%). During a median follow-up of 3 (0.5-17.2) years, different treatments were needed in 35 (39.3%) patients: radioactive iodine (RAI) in 23 (25.8%), surgery in 9 (10.1%) and radiotherapy (RT) in 3 (3.4%). From those submitted initially to RAI, progression of disease was observed in 8 patients, 4 requiring other treatment modalities: surgery (n = 2), RT (n = 1) and RAI (n = 1). The remaining 54 (60.7%) patients maintained surveillance. In this group, progression of disease was observed in 26 (48.1%), due to increase in the number and/or volume of metastases, but further treatments were not required. CONCLUSION: In a group of patients with cervical LNM under active surveillance, only 16.9% (n = 15) required invasive intervention (surgery or RT).
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Linfonodos , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Linfonodos/patologia , Metástase Linfática , Tireoglobulina , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
PURPOSE: Data regarding treatment options and their efficacy for metastatic paragangliomas (mPPGL) is limited. This study aims to report a single center experience in treating mPPGL, comparing the efficacy and safety of various treatment approaches. METHODS: Retrospective analysis of patients with mPPGL treated at an Endocrinology Department of a cancer institute between January 2000 and October 2022. RESULTS: We analyzed 25 patients with mPPGL, 8 pheochromocytomas and 20 paragangliomas (12% multifocal), followed for a median of 9 [4; 14] years. Surgical approach, aimed at the primary tumor or at debulking of metastases, was the only treatment achieving complete response: 87% in primary tumor and 87.5% with debulking of metastases. These were long-lasting results with a duration of 69 (23.8; 136.8) months in primary tumor removal and 35.1 (15.3; 41) months in metastases debulking. As for other therapeutic approaches, such as radioactive isotopes, tyrosine kinase inhibitors, chemotherapy and external beam radiotherapy, the main outcome was stable disease, with few partial responses. At the last follow-up, 66% of the patients were alive, 15.4% were in remission and 84.6% had stable disease. Median overall survival was 14 years. The 5-year and 10-year survival rates from primary tumor diagnosis were 77.9% and 66.9% respectively, and from metastasis diagnosis were 67.4% and 55.6%, respectively. CONCLUSION: This is the only European single center analysis addressing outcomes of different therapies in mPGL. The results support surgery as a first-line treatment, being the only approach that may achieve complete response with satisfactory and long-lasting results.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Paraganglioma/terapia , Paraganglioma/patologia , Adulto , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias das Glândulas Suprarrenais/mortalidade , Idoso , Resultado do Tratamento , Adulto Jovem , Metástase Neoplásica , Feocromocitoma/patologia , Feocromocitoma/terapia , Feocromocitoma/secundário , Feocromocitoma/mortalidadeRESUMO
BACKGROUND: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC. METHODS: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed. RESULTS: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported. CONCLUSIONS: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient´s performance status and comorbidities.
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Functioning metastases from differentiated thyroid carcinoma are rare and present a great therapeutic challenge. Here, we present an unusual case of a patient with metastatic thyroid carcinoma who developed a hyperthyroid state a few years after the diagnosis due to functioning metastases. Radioiodine treatment was effective in controlling the hyperthyroidism; however, it had no effect on tumor burden. By sharing our experience with this case, we hope to raise awareness for this rare condition and the ways to manage it.
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PURPOSE: The use of FDG-PET for cancer staging has led to the increasing incidence of adrenal lesions, which are usually a clinical challenge. We aimed to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center. METHODS: Retrospective analysis was conducted of all FDG-PET studies performed in our center in the last 10 years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized by the clinical, laboratory, imaging, and pathological findings. RESULTS: We identified 27,427 FDG-PET studies. Of those, 7.6% reported adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% of the patients were referred to the Endocrinology Department and 38% of the lesions were not studied. In 38.9% of the studied patients, malignant lesions were present, including metastases in 37.5%, carcinoma in 1.2%, and other malignant tumors in 0.4%. The median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p < 0.05). We also observed a higher median SUVmax in adrenal metastases than in adenomas (p < 0.05). There was a tendency for higher SUVmax of adrenal carcinomas when compared with other malignant lesions (p = 0.066). The median SUVmax was not different between pheochromocytomas and other tumors (p > 0.05). CONCLUSION: Occult adrenal lesions discovered during FDG-PET/CT are common in the cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats.
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Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Carcinoma Adrenocortical , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Tomografia por Emissão de Pósitrons , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologiaRESUMO
PURPOSE: Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. METHODS: A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. RESULTS: The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. CONCLUSION: Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.
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Neurofibromatose 1 , Glioma do Nervo Óptico , Neoplasias do Nervo Óptico , Puberdade Precoce , Humanos , Criança , Masculino , Feminino , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Seguimentos , Estudos Retrospectivos , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/diagnóstico , Glioma do Nervo Óptico/terapia , Neoplasias do Nervo Óptico/complicações , Puberdade Precoce/etiologia , Puberdade Precoce/complicações , Hormônio Liberador de GonadotropinaRESUMO
Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors. ATC is frequently diagnosed at advanced stages with unresectable disease and palliative care is often indicated. Recently, several patient-tailored therapies for ATC are emerging due to advances in molecular profiling of these tumors. Entrectinib is a potent oral selective inhibitor of neutrotrophic tropomyosin receptor kinase (NTRK), ROS1, and anaplastic lymphoma kinase fusions. The experience regarding ATC and other thyroid carcinomas, particularly in the neoadjuvant setting, is minimal. Case report: We present a case of a 51-year-old female patient presenting with a bulky mass of the left thyroid lobe measuring 100 × 108 × 80 mm that was considered surgically unresectable. While waiting for next-generation sequence (NGS) profiling, lenvatinib was initiated. There was an initial clinical and imagiologic response; however, progression occurred after 12 weeks, and at this time NGS identified an ETV6-NTRK3 fusion and entrectinib was started. After 12 weeks, tumor diameters reduced to a minimum of 68×60×49 mm, and the patient underwent total thyroidectomy plus central lymphadenectomy. Histological diagnosis confirmed an ATC (pT4a R2 N1a). Adjuvant radiotherapy (RT) (60 Grays) with weekly paclitaxel (45 mg/m2) was then administered followed by maintenance entrectinib 600 mg daily. Fluorodeoxyglucose positron emission tomography performed 3 months after completion of RT showed only non-specific uptake in the posterior wall of the hypopharynx and larynx, suggestive of inflammation. Conclusion: We report the first case of an ATC with a dramatic response to neoadjuvant therapy with entrectinib, which enabled surgical resection of an ab initio unresectable tumor.
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Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Anaplásico da Tireoide/genética , Terapia Neoadjuvante , Proteínas Tirosina Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagemRESUMO
Recurrence of Cushing's syndrome due to functional metastasis from adrenocortical carcinoma (ACC) after adrenalectomy is extremely rare. We describe a case of a 56-year-old woman who presented with Cushing's syndrome due to an ACC. Abdominal CT showed a heterogeneous left adrenal tumour of 8 cm as well as a right adrenal nodule with 3 cm. An 18F-fluorodeoxyglucose positron emission tomography-CT (18F-FDG/CT PET) revealed an increased uptake of both adrenal lesions (maximum standardised uptake values, 17.7 and 10.4 for left and right adrenal lesions, respectively). Patient underwent bilateral adrenalectomy with R0 resection. Pathological examination revealed a left ACC with a Weiss' score of 7, Ki67 10%, stage II European Network for the Study of Adrenal Tumours and a right adrenal adenoma. After surgery, clinical improvement was noted. Two months later, she noticed recurrence of hypercortisolism and multiple liver and lung metastasis were demonstrable, without evidence of local recurrence on the 18F-FDG/CT PET and abdominal MRI.
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Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Carcinoma Adrenocortical , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/cirurgia , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de PósitronsRESUMO
INTRODUCTION: Paragangliomas are usually benign slow-growing tumors, but they are locally invasive and can cause significant morbidity. The aim of this study was to characterize the presenting symptoms, secretory status, genetics, imaging features, treatment modalities, post-treatment complications and survival of patients with head and neck paragangliomas treated at a single institution. MATERIAL AND METHODS: We retrospectively reviewed the clinical records of patients managed at our center between 1997 and 2020. RESULTS: Seventy-three patients were included in the study, encompassing 89 head and neck paragangliomas. Forty-eight patients (65.8%) were female and 15 (20.5%) had multiple tumor sites (including 10 patients with multicentric benign paragangliomas and five with disseminated malignant disease). Regarding location, our series encompassed 40 temporal bone paragangliomas (44.9%), 24 carotid body paragangliomas (27%), 22 vagal paragangliomas (24.7%), two laryngeal paragangliomas (2.2%) and one sinonasal paraganglioma (1.1%). Excessive catecholamine secretion was detected in 11 patients (15.1%). Sixty-four patients (87.7%) underwent genetic testing. Of those, 24 (37.5%) exhibited pathogenic succinate dehydrogenase complex germline mutations. Regarding patients who presented with untreated disease, 45 patients (66.2%), encompassing 55 tumors, underwent surgery as primary treatment modality, 20 (29.4%; 23 tumors) were initially treated with radiotherapy and three patients (4.4%, encompassing three solitary tumors) were kept solely under watchful waiting. Five-year overall survival was 94.9% and disease-free survival was 31.9%. CONCLUSION: Head and neck paragangliomas are rare, slow-growing but locally aggressive tumors resulting in high morbidity but low mortality rates.
Introdução: Os paragangliomas apresentam frequentemente um comportamento benigno e um crescimento indolente. Apesar disso, são localmente invasivos, podendo causar morbilidade significativa. O objetivo deste trabalho foi descrever as manifestações clínicas, atividade secretora, estudos genéticos e imagiológicos, modalidades terapêuticas, complicações e sobrevivência dos doentes com paragangliomas da cabeça e pescoço. Material e Métodos: Estudo retrospetivo dos doentes com paragangliomas da cabeça e pescoço observados num centro hospitalar terciário entre 1997 e 2020. Resultados: Foram incluídos no estudo 73 doentes, englobando 89 paragangliomas. Quarenta e oito doentes (65,8%) eram do sexo feminino e 15 (20,5%) apresentavam múltiplos focos tumorais (10 por multicentricidade e cinco por doença maligna disseminada). Foram incluídos 40 paragangliomas do osso temporal (44,9%), 24 tumores do corpo carotídeo (27%), 22 vagais (24,7%), dois laríngeos (2,2%) e um nasossinusal (1,1%). A secreção excessiva de catecolaminas foi detetada em 11 doentes (15,1%). Sessenta e quatro doentes (87,7%) foram alvo de teste genético. Desses, 24 (37,5%) exibiram mutações patogénicas do complexo succinato desidrogenase. Dos doentes com doença primária, 45 (66,2%; 55 tumores) foram submetidos a tratamento cirúrgico, 20 (29,4%; 23 tumores) a radioterapia e três (4,4%) ficaram sob vigilância. Aos cinco anos, a sobrevida global foi de 94,9% e a sobrevida livre de doença foi de 31,9%. Conclusão: Os paragangliomas da cabeça e pescoço são tumores raros, de crescimento lento, mas localmente agressivos que resultam em elevadas taxas de morbilidade, mas baixas taxas de mortalidade.
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Tumor do Corpo Carotídeo , Neoplasias de Cabeça e Pescoço , Paraganglioma Extrassuprarrenal , Paraganglioma , Humanos , Feminino , Masculino , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/terapia , Paraganglioma/terapia , Paraganglioma Extrassuprarrenal/diagnóstico , Paraganglioma Extrassuprarrenal/genética , Paraganglioma Extrassuprarrenal/cirurgiaRESUMO
INTRODUCTION: Struma ovarii (SO) is a rare ovarian teratoma characterized by the presence of thyroid tissue in more than 50% of the tumor. Malignant transformation is rare and the most common associated malignancy is papillary thyroid carcinoma (PTC). Pregnancy may represent a stimulus to differentiated thyroid cancer (DTC) growth in patients with known structural or biochemical evidence of disease, but data about malignant SO evolution during pregnancy are rare. We present the first reported case of a pregnant patient with malignant SO and biochemical evidence of disease. CASE PRESENTATION: A previously healthy 35-year-old female diagnosed with a suspicious left pelvic mass on routine ultrasound was submitted to laparoscopic oophorectomy which revealed a malignant SO with areas of PTC. A 15-mm thyroid nodule (Bethesda V in the fine-needle aspiration cytology) was detected by palpation and total thyroidectomy was performed. Histology revealed a 15 mm follicular variant of PTC (T1bNxMx). Subsequently, she received 100 mCi of radioactive iodine therapy (RAIT) with the whole-body scan showing only moderate neck uptake. Her suppressed thyroglobulin (Tg) before RAI was 1.1 ng/mL. She maintained biochemical evidence of disease, with serum Tg levels of 7.6 ng/mL. She got pregnant 14 months after RAIT, and during pregnancy, Tg increased to 21.5 ng/mL. After delivery, Tg decreased to 14 ng/mL but, 6 months later, rose again and reached 31.9 ng/mL on the last follow-up visit. TSH was always suppressed during follow-up. At the time of SO diagnosis, a chest computed tomography scan showed 4 bilateral lung micronodules in the upper lobes which were nonspecific, and 9 months after diagnosis, a pelvic MRI revealed a suspicious cystic nodule located on the oophorectomy bed. These lung and pelvic nodules remained stable during follow-up. Neck ultrasonography, abdominal MRI, and fluorodeoxyglucose-positron emission tomography showed no suspicious lesions. DISCUSSION/CONCLUSION: As for DTC, pregnancy seems to represent a stimulus to malignant SO growth. This can be caused by the high levels of estrogen during pregnancy that may bind to receptors in malignant cells and/or by the high levels of hCG which is known to stimulate TSH receptors.
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Diabetes is a very common chronic disease in the Portuguese population, with an estimated prevalence of 13.6% in the adults. Doubts often arise regarding the best preparation and the risks associated with doing imaging tests in these patients. In this article we intend to review the main precautions in imaging tests in people with diabetes and to suggest a guideline to reduce the risks and optimize the sensitivity of these tests in this population. The main topics addressed in this article are the need to suspend metformin after the administration of endovascular iodinated contrast due to the risk of lactic acidosis, the precautions in insulin-treated patients or those taking medicines with a higher risk of hypoglycemia when performing imaging tests that require fasting, and the influence of hyperglycemia and of anti-diabetic therapy on the sensitivity of PET-FDG. With this review and the presentation of a guideline, we intend to demystify and simplify the management of individuals with diabetes who are undergoing imaging tests.
A diabetes é uma doença crónica muito frequente na população portuguesa, sendo a sua prevalência estimada de 13,6% nos adultos. A melhor preparação e os riscos associados à realização de exames de imagem em pessoas com diabetes são frequentemente objeto de dúvidas. Neste artigo, pretendemos rever as principais precauções e sugerir um protocolo de atuação, de forma a reduzir os riscos e otimizar a sensibilidade destes exames nesta população. Revemos também a necessidade de suspensão de metformina após a administração de contraste iodado endovascular, pelo risco de acidose láctica, as precauções em pessoas com diabetes insulinotratadas ou sob fármacos que apresentam maior risco de hipoglicemia na realização de exames de imagem que obriguem a jejum, e a influência da hiperglicemia e da terapêutica anti-diabética na sensibilidade da PET-FDG. Com a revisão deste tema e apresentação de um protocolo de atuação pretendemos desmistificar a orientação dos indivíduos com diabetes que vão ser submetidos a exames de imagem, tornando mais simples a sua gestão.
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Diabetes Mellitus , Guias como Assunto , Tomografia por Emissão de Pósitrons/métodos , Comportamento de Redução do Risco , Adulto , Diabetes Mellitus/tratamento farmacológico , Fluordesoxiglucose F18 , Humanos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Compostos RadiofarmacêuticosRESUMO
The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13-139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.
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Peso ao Nascer/genética , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/genética , Paladar/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , MasculinoRESUMO
INTRODUCTION: Current guidelines specify controversial areas in adrenocortical carcinomas (ACC), such as optimal follow-up time after remission and identification of prognostic markers. We aim to address these topics by analyzing four reference centers in our country. METHODS: Cross-sectional multicentric study of 69 patients (mean age: 51.7 ± 16.7 years-old; women, 72.5%). Kaplan-Meier survival curves and Cox regression analysis were used to calculate overall survival and its predictors. RESULTS: Thirty-eight individuals (55.0%) had hormonal autonomous production, and 40.6% of the patients presented with metastasis. Surgery was performed in 84.1% of them. Most of these patients (72.4%) were then assigned to adjuvant therapy, while 27.6% were actively surveilled. Among patients undergoing surgery, those who achieved transient remission presented a longer survival time (66 months) than those who never reached the disease-free status (21 months) (p = 0.021). One patient presented with recurrence more than 7 years after complete tumor resection. The lowest overall survival was observed in patients (n = 11) assigned to palliative care since diagnosis (9 months). Tumor stage was identified as the only independent predictor of survival in our cohort (p = 0.006). Five-year survival was 67% for tumors confined to the adrenal space (stage I/II), 56% for locally advanced disease (stage III), and 0% for metastatic disease (stage IV). CONCLUSION: This study reinforces the dismal prognosis of ACC, the need for long-term follow-up, and tumor stage as the most important survival predictor. Reviewing medical records in such rare conditions is an opportunity to identify insufficiencies and to improve medical care.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/terapia , Adulto , Assistência ao Convalescente , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Cuidados Paliativos , Prognóstico , Indução de Remissão , Análise de SobrevidaRESUMO
Merkel cell carcinoma is a rare and aggressive cutaneous tumor, and the use of checkpoint inhibitors immunotherapy is a recent indication in its metastatic setting, both first and second line. However, the widespread use of immunotherapy is associated with an increase of acute and late immune-mediated adverse events. We present a case of an elderly fit patient with metastatic Merkel cell carcinoma treated with pembrolizumab who developed diabetic ketoacidosis, a severe immune-mediated adverse event. A multidisciplinary approach was crucial to overcome the life-threatening event. Even with early treatment stop, the patient had a significant and durable response to the treatment for 15 months. Meanwhile, a progressive pan-cerebellar syndrome emerged, possible due to a paraneoplastic syndrome with a negative onco-neuronal antibody panel, although an autoimmune etiology associated with immunotherapy could not be excluded. Unfortunately, the situation was irreversible and refractory to immunomodulatory treatment. Despite the unpredictable toxicity, it is important to note the efficacy profile, with a progression-free survival of 15 months, which is higher than the one reported in reference clinical trials in this setting.
RESUMO
PURPOSE: Germline mutations in the four genes that encode the succinate dehydrogenase complex (SDHx) are a risk factor for developing pheochromocytomas and/or paragangliomas. The precise genotype-phenotype correlations are still uncertain and the most common SDHx genetic defects in the Portuguese population are poorly described. The objectives of our study were to characterize the genetic alterations, clinical features, and treatment outcomes of a cohort of SDHx-related pheochromocytomas and/or paragangliomas patients. METHODS: Single center, retrospective analysis based on the presence of a SDHx mutation in cases diagnosed from 1986 until October 2016. RESULTS: Thirty cases were included. The mean age at diagnosis was 36.8 years (±15.4 years) and 53.3% were females. Remission was observed in 33.3% and stable disease (including partial responses) in 53.0%. SDHC and SDHD patients were prone to develop single and multiple head and neck paragangliomas, respectively. SDHB patients carried an increased risk of malignancy. Deletions in SDHB exon-1 and in SDHD exon-4 were the most common genetic findings. SDHB patients and head and neck paragangliomas had the worse prognosis, the former related to malignancy, and the latter to cranial nerve deficits, unresectable disease, and multimodality interventions. Peptide receptor radionuclide therapy and radioactive iodine MIBG therapy proved to be ineffective. Radiotherapy represented a good alternative in unresectable head and neck paragangliomas and in bone metastases. CONCLUSION: This single center study is the most complete Portuguese cohort in the literature and helps to understand the behavior of tumors based on their genotype and anatomical location.