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1.
Ther Umsch ; 77(9): 457-465, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33146093

RESUMO

Surgical aspects of multiple endocrine neoplasia type 2 Abstract. The multiple endocrine neoplasia type 2 (MEN 2) is an autosomal-dominant hereditary tumor-syndrome. The subtypes show clinically specific disease manifestations. In MEN 2a, medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism occur, while in familial medullary thyroid carcinoma, the medullary thyroid carcinoma is the only clinical manifestation. In MEN 2b medullary thyroid carcinoma and pheochromocytoma are the clinically dominant manifestations. All MEN-2-specific disease is treated primarily surgically. It is of utmost importance to identify the individual gene carrier in order to enable timely intervention before malignancy develops (prophylactic surgery) or to reach surgical cure as well as to identify relatives that are MEN 2 gene-carriers. Typical MEN 2 manifestations and clinical signs important for surgery are outlined. In case MEN 2 is suspected, it may be vital to exclude underlying pheochromocytoma before diagnostic or surgical interventions are started to forego hyperadrenergic crisis unprepared.


Assuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma Medular , Neoplasia Endócrina Múltipla Tipo 2a , Neoplasia Endócrina Múltipla Tipo 2b , Neoplasias da Glândula Tireoide , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Humanos , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia
2.
Ther Umsch ; 77(9): 441-448, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33146097

RESUMO

Adrenal tumors Abstract. The term 'adrenal tumor' describes benign and malignant mass lesions of the adrenal gland, including primary adrenal tumors and metastases from extra-adrenal origin. With the widespread use of imaging technique, adrenal tumors have become increasingly detected as 'incidentalomas'. The detection of an adrenal tumor raises two questions: Is the mass malignant? Is the mass hormonally active? Whereas the evaluation for malignancy is based on specific imaging characteristics (imaging phenotype), a targeted clinical examination and specific biochemical tests are required to assess for hormonal secretion. An adrenal mass < 4 cm with clear benign features on imaging and with a normal hormonal workup does not require treatment. If malignancy is suspected further diagnostic procedures and / or adrenalectomy are indicated. For hormonally active tumors surgery is generally considered the treatment of choice; however, the decision for surgery has to be individualized for aldosterone-secreting tumors and for cortisol-secreting tumors with only mild cushing's syndrome. Also in patients with large tumors (> 4 cm), and in cases with non-conclusive evaluation for malignancy or hormonal activity, the decision for further management has to be made on an individual basis. A minimally invasive surgical approach may be considered in adrenal tumors < 6 cm and without local infiltration of adjacent structures. Both laparoscopic (transabdominal) and retroperitoneoscopic techniques are possible. The surgical outcome depends on the surgeon's experience. A close interdisciplinary collaboration is mandatory in the evaluation and treatment of adrenal tumors.


Assuntos
Neoplasias das Glândulas Suprarrenais , Síndrome de Cushing , Laparoscopia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Síndrome de Cushing/cirurgia , Síndrome de Cushing/terapia , Humanos
3.
Ther Umsch ; 77(8): 357-360, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-33054651

RESUMO

The adrenal incidentaloma Abstract. This article discusses the diagnostic workup of a patient with an incidentally discovered adrenal mass. Primarily, this situation raises two questions: Is the mass malignant? Is the mass hormonally active? The evaluation for malignancy is based on specific imaging characteristics ('imaging phenotype'). The evaluation for hormonal secretion is based on a targeted clinical examination and specific biochemical tests. In most cases, adrenal incidentalomas can be identified as benign, non-functioning adenomas. In unclear situations, patients should be referred for further evaluation.


Assuntos
Adenoma , Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Humanos , Achados Incidentais , Fenótipo
4.
Anticancer Res ; 40(10): 5933-5938, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988925

RESUMO

BACKGROUND/AIM: Primary small cell neuroendocrine carcinoma (SCNEC) of the adrenal gland is extremely rare with limited reports in the literature. There remain no definitive treatment guidelines, largely due to the rarity of the malignancy. CASE REPORT: We present the case of a 62-year-old Caucasian male who presented with low back pain and was found to have a large retroperitoneal mass arising from the left adrenal gland, measuring 18.3 × 12.2 centimeters (cm). Biopsy was consistent with small cell carcinoma/high grade neuroendocrine carcinoma. Staging workup including CT chest and bone scan was negative. The patient was treated with chemotherapy, radiation therapy, and surgery; complete pathological response of the left adrenal tumor was achieved. Surveillance imaging every three months continued to show no evidence of recurrent disease. CONCLUSION: Primary SCNEC of the adrenal gland is rare and lacks standard treatment guidelines. Our case represents a possible treatment approach that may provide better clinical outcomes, however, further investigations are necessary to help define ideal treatment guidelines.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma de Células Pequenas/diagnóstico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/radioterapia , Carcinoma Neuroendócrino/cirurgia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
5.
APMIS ; 128(11): 563-572, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32794589

RESUMO

Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs. We investigated the tissue microarray (TMA) of 86 primary tumors from 13 different organs and 9 metastatic NETs, including primary tumor-metastasis pairs, for PCSK2 expression with polymer-based IHC. PCSK2 was strongly positive in all small intestine and appendiceal NETs, the so-called midgut NETs, in most pheochromocytomas and paragangliomas, and in some of the typical and atypical pulmonary carcinoid tumors. NETs showing strong positivity were re-evaluated in larger tumor cohorts confirming the primary observation. In the metastases, the expression of PCSK2 mirrored that of the corresponding primary tumors. We found negative or weak staining in NETs from the thymus, gastric mucosa, pancreas, rectum, thyroid, and parathyroid. PCSK2 expression did not correlate with Ki-67 in well-differentiated NETs. Our data suggest that PCSK2 positivity can indicate the location of the primary tumor. Thus, PCSK2 could function in the IHC panel determined from screening metastatic NET biopsies of unknown primary origins.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Neuroendócrino/genética , Neoplasias Gastrointestinais/genética , Neoplasias Pulmonares/genética , Tumores Neuroendócrinos/genética , Paraganglioma/genética , Feocromocitoma/genética , Pró-Proteína Convertase 2/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Biomarcadores Tumorais/genética , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Cromogranina A/genética , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Paraganglioma/diagnóstico , Paraganglioma/patologia , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
6.
Eur J Endocrinol ; 183(4): 399-409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698132

RESUMO

Context: Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes. Objectives: To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure. Methods: In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. Results: Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure. Conclusions: In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/sangue , Aldosterona/sangue , Coleta de Amostras Sanguíneas/métodos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/epidemiologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Adrenalectomia/estatística & dados numéricos , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/epidemiologia , Adenoma Adrenocortical/cirurgia , Adulto , Aldosterona/análise , Canadá/epidemiologia , Estudos de Coortes , Técnicas de Diagnóstico Endócrino , Regulação para Baixo , Feminino , Humanos , Hidrocortisona , Hiperaldosteronismo/patologia , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
7.
Lancet Diabetes Endocrinol ; 8(9): 773-781, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711725

RESUMO

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/urina , Metabolômica/métodos , Esteroides/urina , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(6): 408-419, jun.-jul. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193366

RESUMO

La evaluación inicial de los incidentalomas adrenales se centra en dos objetivos: descartar malignidad y descartar funcionalidad. Para ello se debe realizar una historia clínica detallada, obtener una valoración radiológica adecuada y un estudio bioquímico-hormonal completo. La entidad que más dudas genera, por la falta de consenso en su definición, es la secreción autónoma de cortisol. Nuestra recomendación es que, salvo para valores de cortisol < 1,8 μg/dl en el test de supresión con dexametasona que descartan secreción autónoma de cortisol, y ≥ 5 μg/dl que establecen el diagnóstico; se debe emplear una definición combinada de test de supresión con dexametasona ≥ 3 μg/dl y al menos uno de los siguientes: cortisol libre urinario elevado, ACTH < 10 pg/ml o cortisol nocturno (sérico y/o salival) elevado para establecer el diagnóstico de secreción autónoma de cortisol. En el seguimiento se debe repetir el test de supresión con dexametasona, generalmente de forma anual, individualizando en función de los resultados de las pruebas previas y de la presencia de comorbilidades potencialmente relacionadas con el hipercortisolismo. La prueba radiológica inicial de elección para la caracterización de los incidentalomas adrenales es la tomografía axial computarizada sin contraste, pero no existe acuerdo unánime sobre el seguimiento posterior. Nuestra recomendación general es repetir la prueba de imagen a los 6-12 meses del diagnóstico (en función de las características radiológicas de la lesión). Si la lesión se mantiene estable y no existen características indeterminadas, no serían necesarios más estudios radiológicos. Consideramos que los pacientes con secreción autónoma de cortisol con comorbilidades potencialmente relacionadas con el hipercortisolismo, especialmente si existe un control deficiente y se trata de pacientes jóvenes, se pueden beneficiar de una suprarrenalectomía unilateral. La indicación de suprarrenalectomía unilateral es clara en pacientes con síndromes hormonales manifiestos o sospecha de malignidad. Como conclusión, los incidentalomas adrenales deben ser valorados de forma integral, teniendo en cuenta las posibles manifestaciones clínicas y comorbilidades relacionadas con síndromes hormonales o malignidad; un estudio hormonal completo (teniendo en cuenta las situaciones que pueden conllevar resultados falsamente positivos y negativos) y radiológico adecuado. En base a los resultados de la evaluación inicial se planificará el seguimiento y/o tratamiento


Initial evaluation of adrenal incidentalomas should be aimed at ruling out malignancy and functionality. For this, a detailed clinical history should be taken, and an adequate radiographic assessment and a complete blood chemistry and hormone study should be performed. The most controversial condition, because of the lack of consensus in its definition, is autonomous cortisol secretion. Our recommendation is that, except when cortisol levels < 1.8 μg/dL in the dexamethasone suppression test rule out diagnosis and levels ≥ 5 μg/dL establish the presence of autonomous cortisol secretion, diagnosis should be based on a combined definition of dexamethasone suppression test ≥ 3 μg/dL and at least one of the following: elevated urinary free cortisol, ACTH level < 10 pg/mL, or elevated nocturnal cortisol (in serum and/or saliva). During follow-up, dexamethasone suppression test should be repeated, usually every year, on an individual basis depending on the results of prior tests and the presence of comorbidities potentially related to hypercortisolism. The initial radiographic test of choice for characterization of adrenal incidentalomas is a computed tomography scan without contrast, but there is no unanimous agreement on subsequent monitoring. Our general recommendation is a repeat imaging test 6-12 months after diagnosis (based on the radiographic characteristics of the lesion). If the lesion remains stable and there are no indeterminate characteristics, no additional radiographic studies would be needed. We think that patients with autonomous cortisol secretion with comorbidities potentially related to hypercortisolism, particularly if they are young and there is a poor control, may benefit from unilateral adrenalectomy. The indication for unilateral adrenalectomy is clear in patients with overt hormonal syndromes or suspected malignancy. In conclusion, adrenal incidentalomas require a comprehensive evaluation that takes into account the possible clinical signs and comorbidities related to hormonal syndromes or malignancy; a complete hormone profile (taking into account the conditions that may lead to falsely positive and negative results); and an adequate radiographic study. Monitoring and/or treatment will be decided based on the results of the initial evaluation


Assuntos
Humanos , Achados Incidentais , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Sociedades Médicas/normas , Comorbidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Biópsia
9.
Eur J Endocrinol ; 183(4): 453-462, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32567556

RESUMO

Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Linfoma/diagnóstico , Linfoma/epidemiologia , Neoplasias das Glândulas Suprarrenais/complicações , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Fenótipo , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia
10.
Pediatr Blood Cancer ; 67(8): e28332, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32491270

RESUMO

BACKGROUND: Pheochromocytomas (PCs) are neuroendocrine tumors arising from the chromaffin cells of the adrenal gland, and paragangliomas (PGLs) are their extra-adrenal counterparts arising from ganglia along the sympathetic/parasympathetic chain. Surgery is the cornerstone of treatment. A sporatic or inherited germline mutation is commonly associated. MATERIALS AND METHODS: Among over 1000 patients registered into the Tumori Rari in Età Pediatrica-rare tumors in pediatric age project-from 2000 to 2019, 50 were affected by PC/PGL. All clinical and therapeutic data were evaluated. RESULTS: Twenty-eight patients had PC and 22 had PGL. Age at diagnosis ranged between 5 and 17 years. Thirty-five patients had symptoms related to catecholamine hypersecretion; in 7 of 50 patients, diagnosis was incidental or done during assessment of a familial syndrome. In all cases, conventional imaging was effective to assess the presence of a tumor. In addition, 18 of 38 functional imaging studies were positive (61%). Forty-eight patients were eligible for surgery: a complete resection was more frequently achieved in PC than in PGL (26/28 vs 11/22). All relapses were treated with surgery alone, surgery plus medical treatment, or chemotherapy alone; one PC with metastasis at diagnosis received radiotherapy only. Forty-four patients were in the first, second, or third complete remission (10/50 recurred; 8/10 carried a germline mutation). Five of 50 patients were alive with disease. One patient died of disease. CONCLUSIONS: Surgery can be curative in most tumors but it may not be always effective in removing PGLs. Severe postsurgical sequelae may affect these patients. Genetic tests should always be considered in individuals affected, and genetic counseling should be offered to their families.


Assuntos
Neoplasias das Glândulas Suprarrenais , Recidiva Local de Neoplasia , Paraganglioma , Feocromocitoma , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Itália , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Paraganglioma/diagnóstico , Paraganglioma/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/terapia , Estudos Prospectivos
11.
Best Pract Res Clin Endocrinol Metab ; 34(2): 101416, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32295730

RESUMO

Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumours characterized by a strong genetic determinism. Over the past 20 years, evolution of PPGL genetics has revealed that around 40% of PPGL are genetically determined, secondary to a germline mutation in one of more than twenty susceptibility genes reported so far. More than half of the mutations occur in one of the SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), which encode the different subunits and assembly protein of a mitochondrial enzyme, succinate dehydrogenase. These susceptibility genes predispose to early forms (VHL, RET, SDHD, EPAS1, DLST), syndromic (RET, VHL, EPAS1, NF1, FH), multiple (SDHD, TMEM127, MAX, DLST, MDH2, GOT2) or malignant (SDHB, FH, SLC25A11) PPGL. The discovery of a germline mutation in one of these genes changes the patient's follow-up and allows genetic screening of affected families and the presymptomatic follow-up of relatives carrying a mutation.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Testes Genéticos/tendências , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/história , Neoplasias das Glândulas Suprarrenais/patologia , Análise Mutacional de DNA/história , Análise Mutacional de DNA/tendências , Estudos de Associação Genética/história , Estudos de Associação Genética/tendências , Predisposição Genética para Doença , Testes Genéticos/história , Testes Genéticos/métodos , Mutação em Linhagem Germinativa , História do Século XX , História do Século XXI , Humanos , Mutação , Paraganglioma/diagnóstico , Paraganglioma/história , Paraganglioma/patologia , Feocromocitoma/diagnóstico , Feocromocitoma/história , Feocromocitoma/patologia , Succinato Desidrogenase/genética
12.
Cancer Genet ; 243: 1-6, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179488

RESUMO

Inherited germline mutations in the VHL gene cause predisposition to Von Hippel-Lindau (VHL) disease. Patients exhibit benign and cancerous lesions in multiple tissues, including hemangioblastomas, clear cell renal cell carcinoma, cysts in kidneys and pancreas, and pheochromocytomas. Although pathogenic germline mutations in the VHL gene have been widely described in different populations, only a single mutation was previously reported in a family from mixed Arab-Persian ethnicity. Here, we present five Arab patients with two new and two recurrent germline mutations in the VHL gene. These mutations include three in-frame deletions and a missense mutation. Infrequent in-frame deletions in previously described patients from other populations, as well as the presence of new mutations, suggests a distinct spectrum of VHL gene mutations in Arab patients. While pulmonary manifestation has been described rarely in VHL disease, we have identified two patients with a recurrent p.Phe76del in-frame deletion exhibiting multiple nodules in lungs. We also describe a first-ever in-frame deletion in the VHL gene in a patient with VHL type 2C disease, exhibiting bilateral pheochromocytoma. Overall, the study provides an insight into the genotype-phenotype relationship of VHL disease in Arab patients and provides a comparison with previously described patients from other ethnicities.


Assuntos
Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Idoso , Árabes/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/genética , Cerebelo/diagnóstico por imagem , Pré-Escolar , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Hemangioblastoma/diagnóstico , Hemangioblastoma/genética , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Imagem por Ressonância Magnética , Masculino , Anamnese , Pessoa de Meia-Idade , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Arábia Saudita , Tomografia Computadorizada por Raios X , Doença de von Hippel-Lindau/diagnóstico
13.
BMC Surg ; 20(1): 49, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178651

RESUMO

BACKGROUND: Pheochromocytoma (PCC) and Paraganglioma (PGL) are rare neuroendocrine neoplasms. These tumors harbour disastrous consequences during surgery due to catecholamine hypersecretion if they are undiagnosed or prepared inadequately preoperatively. CASE PRESENTATION: A 41- year- old lady presented with mild left flank discomfort. She had experienced recurrent anxiety attacks accompanied by palpitations and headache which were managed previously as panic attacks. Radiologic investigations showed a retroperitoneal mass that located anteromedial to the left kidney, separated from the left adrenal gland and adherent to the 4th duodenal segment. During admission, her vital signs showed slight elevation of blood pressure (140\90-160\110) mmHg, thus 24-h urine metanephrine and normetanephrine were requested and the results revealed normal values. Upper gastrointestinal endoscopy failed to pass beyond the 3th duodenal segment and showed no pathologic evidence. According to her findings, a diagnosis of duodenal gastrointestinal stromal tumor (GIST) was suspected. During laparotomy, crises of hypertension and tachycardia followed by severe hypotension made the resection of the misdiagnosed mass very tricky. Immunohistochemical staining studies confirmed the diagnosis of paraganglioma. CONCLUSION: Paraganglioma is a life threatening disease and should always be considered as a differential diagnosis of asymptomatic retroperitoneal mass. The aim of our study is to present a challenging case of an undiagnosed retroperitoneal paraganglioma and to alarm our colleagues from such troubles.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Paraganglioma/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Pressão Sanguínea , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Neoplasias Gastrointestinais/diagnóstico , Humanos , Hipertensão/diagnóstico , Laparotomia/efeitos adversos , Feocromocitoma/diagnóstico , Neoplasias Retroperitoneais/cirurgia
14.
Intern Med ; 59(11): 1437-1443, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32132335

RESUMO

Primary adrenal lymphoma (PAL) is rare and known to have a predilection for central nervous system (CNS) relapse. A 70-year-old man with a 2-year history of primary aldosteronism presented because of a fever. He was hypotensive, and his adrenal glands were unequivocally enlarged. PAL was diagnosed. Despite showing an initial response to immunochemotherapy, progressive paralysis ensued. Magnetic resonance imaging findings were negative, and rituximab was ineffective. His debilitated condition hindered further chemotherapy. A postmortem examination revealed lymphoma relapse in the systemic peripheral nerves. The sequential presentation of two rare lymphomas implies that PAL might have a predilection for not only the CNS but also peripheral nerves.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neurolinfomatose/diagnóstico , Neurolinfomatose/tratamento farmacológico , Rituximab/uso terapêutico , Idoso , Evolução Fatal , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico
15.
S D Med ; 73(2): 78-80, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32135056

RESUMO

Catecholamine-induced cardiomyopathy (CIC) and pheochromocytoma are both rare entities, and their exact incidence and prevalence are unknown. Pheochromocytoma has been implicated as one of the causes of CIC or Takotsubo syndrome (TTS) by means of case reports and retrospective reviews. However, the evaluation of any patient with TTS and pheochromocytoma is often faced with multiple challenges due to its rarity and atypical presentations, which subsequently leads to delay in diagnosis. Here, we present a case of a 51-year old female who had three distinct episodes of TTS and now presented in a hypertensive emergency with angina, palpitations, headache, nausea, and vomiting. She was treated for non-ST elevation myocardial infarction (NSTEMI) but coronary angiogram revealed patent coronary arteries. Due to the paroxysmal nature of her hypertensive emergencies and variable blood pressure response, pheochromocytoma was suspected. On further evaluation, she was found to have elevated metanephrines and a 6.3 cm left adrenal mass on CT scan. This case emphasizes the importance of considering or identifying pheochromocytoma as an underlying primary etiology for recurrent episodes of TTS and related concerns such as choice of anti-hypertensive agents.


Assuntos
Neoplasias das Glândulas Suprarrenais , Catecolaminas , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/induzido quimicamente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Catecolaminas/efeitos adversos , Emergências , Feminino , Humanos , Pessoa de Meia-Idade , Feocromocitoma/induzido quimicamente , Feocromocitoma/diagnóstico , Estudos Retrospectivos
16.
Eur J Endocrinol ; 182(5): 499-509, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32187575

RESUMO

Objective: Sympathoadrenal activity is decreased during overnight rest. This study assessed whether urinary-free normetanephrine, metanephrine and methoxytyramine in overnight/first-morning urine collections might offer an alternative to measurements in 24-h collections or plasma for diagnosis of pheochromocytoma and paraganglioma (PPGL). Design and methods: Prospective multicenter cross-sectional diagnostic study involving 706 patients tested for PPGL, in whom tumors were confirmed in 79 and excluded in 627 after follow-up. Another 335 age- and sex-matched volunteers were included for reference purposes. Catecholamines and their free O-methylated metabolites were measured in 24-h collections divided according to waking and sleeping hours and normalized to creatinine. Plasma metabolites from blood sampled after supine rest were measured for comparison. Results: Urinary outputs of norepinephrine, normetanephrine, epinephrine and metanephrine in the reference population were respectively 50 (48-52)%, 35 (32-37)%, 76 (74-78)% and 15 (12-17)% lower following overnight than daytime collections. Patients in whom PPGLs were excluded showed 28 (26-30)% and 6 (3-9)% day-to-night falls in normetanephrine and metanephrine, while patients with PPGLs showed no significant day-to-night falls in metabolites. Urinary methoxytyramine was consistently unchanged from day to night. According to receiver-operating characteristic curves, diagnostic accuracy of metabolite measurements in overnight/first-morning urine samples did not differ from measurements in 24-h urine collections, but was lower for both than for plasma. Using optimized reference intervals, diagnostic specificity was higher for overnight than daytime collections at similar sensitivities. Conclusions: Measurements of urinary-free catecholamine metabolites in first-morning/overnight urine collections offer an alternative for diagnosis of PPGL to 24-h collections but remain less accurate than plasma measurements.


Assuntos
Neoplasias das Glândulas Suprarrenais/urina , Dopamina/análogos & derivados , Metanefrina/urina , Paraganglioma/urina , Feocromocitoma/urina , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Dopamina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Adulto Jovem
17.
Biomed Res Int ; 2020: 4150735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190664

RESUMO

Objective: The aim of this study was to investigate the expression of Snail, galectin-3, and IGF1R in benign and malignant pheochromocytoma and paraganglioma (PPGL) and explore their role in the diagnosis of malignant PPGL. Methods: We retrospectively collected and analyzed surgical tumor tissue from 226 patients initially diagnosed with PPGL who underwent surgery from Jan. 2009 to Jan. 2016 at West China Hospital, Sichuan University. We observed and quantified the expression of Snail, galectin-3, and IGF1R in paraffin-embedded samples by immunohistochemical staining. Results: The significant difference in survival time among the three groups (benign PHEO, benign PGL, and potentially malignant PPGL) was compared by Kaplan-Meier survival analysis. The positive staining of Snail, galectin-3, and IGF1R in the benign PHEO group was significantly lower than that in the other three groups (P < 0.001). The Kaplan-Meier survival plots indicated that the survival time of the patients with intense positive staining was significantly lower than that of the patients with weak positive staining. Conclusion: The intense expression of Snail, galectin-3, and IGF1R may be valuable indicators for the diagnosis of malignant PPGL.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/metabolismo , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Receptor IGF Tipo 1/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , China , Diagnóstico Diferencial , Feminino , Galectina 3/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paraganglioma/metabolismo , Paraganglioma/cirurgia , Feocromocitoma/metabolismo , Feocromocitoma/cirurgia , Estudos Retrospectivos , Software
19.
BMC Med Genet ; 21(1): 42, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106822

RESUMO

BACKGROUND: von Hippel-Lindau (VHL) disease is a familial neoplasia syndrome that results from the germline mutation of VHL. Pathogenic VHL mutations include deletion, frameshift, nonsense and missense mutations. Synonymous mutations are expected to be phenotypically silent and their role in VHL disease remains poorly understood. CASE PRESENTATION: We report a Caucasian male with a family history of pheochromocytoma and the synonymous VHL mutation c.414A > G (p.Pro138Pro). At 47-years, MRI revealed pheochromocytoma in the left adrenal gland and hemangioblastomas in the spine and brain. Pheochromocytoma was treated by adrenalectomy. Radiotherapy, followed by craniotomy and resection were needed to reduce hemangioblastomas to residual lesions. Two of three of the proband's children inherited the mutation and both presented with retinal hemangioblastomas without pheochromocytoma at age 7: one twin needed four laser treatments. Primary skin fibroblasts carrying the heterozygous mutation or wild type VHL were established from the family. Mutant fibroblasts downregulated full-length VHL mRNA and protein, and upregulated the short VHL mRNA isoform (a result of exon 2 skipping in splicing) at the mRNA level but not at the protein level. CONCLUSIONS: Our study shows that the synonymous VHL mutation c.414A > G can within 7 years induce pediatric retinal hemangioblastoma in absence of pheochromocytoma. This highlights the need to include splicing-altering synonymous mutations into the screening for VHL disease. This is also the first report on detecting and validating a synonymous VHL mutation using patient-derived fibroblasts. The mutation c.414A > G translates to p.Pro138Pro, yet it is not functionally silent, because it causes aberrant splicing by skipping exon 2. The reduced but not completely abolished pVHL protein in a loss-of-heterozygosity genetic backdrop may underlie the etiology of VHL disease.


Assuntos
Neoplasias Cerebelares/genética , Hemangioblastoma/genética , Processamento de RNA/genética , Mutação Silenciosa , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/diagnóstico , Criança , Pré-Escolar , Família , Feminino , Mutação da Fase de Leitura/genética , Mutação em Linhagem Germinativa , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , Linhagem , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Prolina/genética , Neoplasias da Retina/complicações , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/genética , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética
20.
BMC Vet Res ; 16(1): 35, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014021

RESUMO

BACKGROUND: Ectopic Cushing's syndrome (ECS) associated with malignant tumors, such as small cell lung carcinoma, bronchial carcinoids, and pheochromocytoma, has been reported in human medicine. However, ECS related to pheochromocytoma has not been reported in dogs. CASE PRESENTATION: An 11-year-old castrated, male Scottish terrier was diagnosed with a left adrenal mass. Cushing's syndrome was suspected based on clinical signs, including pot belly, polyuria, polydipsia, bilateral alopecia, recurrent pyoderma, and calcinosis cutis. Cushing's syndrome was diagnosed on the basis of consistent clinical signs and repeated adrenocorticotropic hormone (ACTH) stimulation tests. In addition, tests for fractionated plasma metanephrine/normetanephrine suggested a pheochromocytoma. Unilateral adrenalectomy was performed after medical management with trilostane and phenoxybenzamine. Histopathology confirmed a diagnosis of pheochromocytoma without cortical lesions. After surgery, fractionated metanephrine/normetanephrine and the findings of low-dose dexamethasone suppression and ACTH stimulation tests were within the normal ranges without any medication. There were no clinical signs or evidence of recurrence and metastasis on thoracic and abdominal X-rays and ultrasonography up to 8 months after surgery. CONCLUSIONS: Pheochromocytoma should be considered a differential diagnosis for dogs with Cushing's syndrome with an adrenal tumor. A good prognosis can be expected with prompt diagnosis and surgical intervention.


Assuntos
Neoplasias das Glândulas Suprarrenais/veterinária , Síndrome de Cushing/veterinária , Doenças do Cão/diagnóstico , Feocromocitoma/veterinária , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/veterinária , Animais , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Di-Hidrotestosterona/análogos & derivados , Di-Hidrotestosterona/uso terapêutico , Doenças do Cão/etiologia , Doenças do Cão/terapia , Cães , Masculino , Fenoxibenzamina/uso terapêutico , Feocromocitoma/complicações , Feocromocitoma/diagnóstico
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