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1.
Arch Esp Urol ; 73(7): 611-623, 2020 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-32886076

RESUMO

OBJECTIVE: Perform a review on the diagnosis and treatment of pheochromocytomas and malignant paragangliomas. MATERIAL AND METHOD: A search was conducted in PubMed and Google Scholar of articles or clinical guides that referred to the diagnosis and treatment of these tumors. RESULTS: For the diagnosis of malignancy, a histological confirmation of a pheochromocytoma or paraganglioma should be provided, plus the presence of metastasis confirmed by images. Methanephrines are recommended over other biochemical determinations. For staging, PET-CT with 18F-FDG or 18F-DOPA is preferred because of its greater sensitivity than conventional images. The 123I-MIBG scan should be requested when radiotherapy with 131I-MIBG is planned.For treatment, control of adrenergic symptoms through the use of α-blockers is recommended. Active surveillance was an option in selected patients with slowly progressive tumors. Surgical treatment improved OS (148 months vs 36 months p=<0.01). Therapy with 131I-MIBG was indicated in patients with positive scintigraphy, reporting a global survival of 50% at 5 years with variable tumor responses. Chemotherapy was proposed in rapidly progressive disease, reporting a median overall survival of 6 years. Ablative therapies should be considered when there is a limited number of lesions, to achieve local tumor control and reduce the symptoms of excess catecholamines. External radiation therapy at high doses would be effective for patients with local symptoms due to their tumor burden. Prospective multi-institutional clinical trials are needed to determine the true benefits of molecular therapies in these patients. CONCLUSIONS: We recommend a multidisciplinary approach in centers of high complexity to be able to offer the entire diagnostic - therapeutic arsenal available so far that they improve the survival and quality of life of these patients.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma/diagnóstico , Paraganglioma/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/terapia , Humanos , Radioisótopos do Iodo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Qualidade de Vida
3.
Tokai J Exp Clin Med ; 45(3): 148-151, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901905

RESUMO

PURPOSE: Pheochromocytoma (PCC) and paraganglioma (PGL) associated with the succinate dehydrogenase (SDH) germline mutations are characterized by negative results of immunohistochemistry tests for SDH subunit B (SDHB). Genetic testing for the SDH complex (SDHA, SDHB, SDHC, SDHD, and SDHAF2) is indicated only in patients with those diseases in whom immunohistochemistry tests for SDHB as a surrogate marker to detect the SDH complex mutation yield negative results. Two novel SDHB germline mutations, L157X and P236S, in PGL were previously reported. We therefore examined immunohistochemistry testing for SDHB in the PGLs with the SDHB germline mutations of L157X and P236S. METHODS: Immunohistochemistry for SDHB was performed in PGLs with the SDHB germline mutations of L157X and P236S. Five cases of sporadic PCC were subject to immunohistochemistry testing for SDHB. Normal tissue from the adrenal cortex adjacent to the sporadic PCC was used as the external positive control. RESULTS: Immunohistochemistry results were positive for SDHB in PGLs with the SDHB germline mutation of L157X and P236S, all five cases of sporadic PCC, and the adrenal cortex as the external positive control. CONCLUSION: Immunohistochemistry tests for SDHB showed positivity in PGLs associated with the SDHB germline mutations of L157X and P236S. Thus, immunohistochemistry testing for SDHB might not always reveal a surrogate marker in formal genetic testing of the SDH complex.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Biomarcadores Tumorais/metabolismo , Mutação em Linhagem Germinativa , Paraganglioma/genética , Coloração e Rotulagem/métodos , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Córtex Suprarrenal/metabolismo , Humanos , Imuno-Histoquímica , Resultados Negativos
4.
Aust Vet J ; 98(9): 462-466, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32794177

RESUMO

BACKGROUND: Obstructive shock can be caused by any lesion leading to extraluminal compression or intraluminal occlusion of the cardiac chambers or major vessels. CASE REPORT: A 12-year-old, male castrated, Border Collie cross dog presented to a veterinary teaching hospital for collapse. A physical examination revealed severe vasoconstrictive shock and abdominal distension. Abnormalities on blood tests were consistent with systemic hypoperfusion. Cardiac underfilling, hepatomegaly with distended vasculature and ascites were identified by focused ultrasonography, raising suspicion of obstructive shock. This was supported by the radiographic findings of microcardia and a distended caudal vena cava (CVC). There was transient response to fluid therapy for blood volume expansion. Repeat focused ultrasonography during rapid intravenous fluid administration identified a right intra-atrial mass, assessed as likely to be causing obstruction of venous return. The dog was humanely euthanased given the guarded prognosis. At postmortem evaluation, a malignant pheochromocytoma in the left adrenal gland with tumour thrombus extending to the tricuspid valve through the CVC was found. The extensive thrombus caused the obstructive shock in this case. Metastasis in a peripheral lymph node and neoplastic emboli in the heart and lungs were also visible at the histopathological evaluation. CONCLUSION: To the best of authors' knowledge, this is the first report of severe obstructive shock secondary to extension of caval tumour thrombus into the right atrium in a dog with malignant pheochromocytoma. Tumour thrombus from a malignant pheochromocytoma should be included as a differential diagnosis of obstructive shock, with or without a visible right intra-atrial mass, in dogs. Serial focused ultrasonography during intravenous fluid administration can aid diagnosis.


Assuntos
Neoplasias das Glândulas Suprarrenais/veterinária , Fibrilação Atrial/veterinária , Doenças do Cão , Feocromocitoma/veterinária , Trombose/veterinária , Animais , Cães , Átrios do Coração , Masculino , Veia Cava Inferior
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 614-620, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773788

RESUMO

OBJECTIVE: Plasma free metanephrines (MNs) have been widely used as an initial test for pheochromocytoma and paraganglioma (PPGL). PPGL without MNs elevation has been reported on rare occasions. The objective of this study was to analyze the clinical profile of sporadic PPGL patients with normal MNs. METHODS: In the study, 104 patients with sporadic PPGL diagnosed by histopathology in Peking University First Hospital from March 2015 to January 2020 were enrolled. All the patients had plasma MNs result, of whom, eight (7.69%) were with normal MNs. The reasons for their medical visits, clinical manifestations, the levels of plasma free MNs, 3-methoxytyramine (3-MT), catecholamines and chromogranin A (CgA), and the imaging findings were documented. Their preoperative diagnosis, perioperative medical management, and intraoperative blood pressure were analyzed. All the data mentioned above were compared with the MNs elevated group. The postoperative follow-up for MNs normal patients were applied. RESULTS: For the eight PPGL patients with normal plasma MNs, the most common clinical symptoms were sweating (3/8), abdominal and back pain (3/8), headache (2/8), palpitations (2/8), and fatigue (2/8). There were no significant differences in plasma free 3-MT and catecholamines' diagnostic positive rate between the MNs normal group and MNs elevated group, but the rate for plasma CgA was significantly decreased in the MNs normal group (2/5 vs. 41/43, P=0.005). No significant difference was found for the incidence of typical findings by enhanced CT between the two groups. In these eight MNs normal patients, six were diagnosed with PPGL by the previous history of PPGL, typical symptoms and CT findings, or elevation of 3-MT, CgA levels or positive results of PET-CT; two patients were misdiagnosed as nonfunctioning adenoma or primary aldosteronism. All these MNs normal patients underwent preoperative management with alpha adrenergic receptor blockers, of whom, one had an average intraoperative arterial pressure < 60 mmHg during surgery. The median follow-up time for the eight patients was 1.5 (0.5-4.5) years. No evidence of new tumors was found on the enhanced CT scans. Two MNs normal patients' plasma 3-MT and (or) CgA decreased to normal. CONCLUSION: For patients with adrenal or retroperitoneal tumors, typical symptoms or a previous history of PPGL, normal plasma MNs is not a sufficient exclusion for PPGL. Plasma 3-MT, catecholamine, CgA results and the imaging findings are helpful for the diagnosis of PPGL. We recommend patients with suspected MNs normal PPGL take alpha adrenergic receptor blockers as preoperative blockade, but should avoid overdose. Postoperative follow-up for patients with normal MNs should focus on the positive biochemical markers before surgery.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Metanefrina , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
6.
J Comput Assist Tomogr ; 44(5): 766-771, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842071

RESUMO

OBJECTIVE: The aim of this study was to evaluate the use of texture analysis for differentiation between benign from malignant adrenal lesions on contrast-enhanced abdominal computed tomography (CT). METHODS: After institutional review board approval, a retrospective analysis was performed, including an electronic search of pathology records for all biopsied adrenal lesions. Patients were included if they also had a contrast-enhanced abdominal CT in the portal venous phase. Computed tomographic images were manually segmented, and texture analysis of the segmented tumors was performed. Texture analysis results of benign and malignant tumors were compared, and areas under the curve (AUCs) were calculated. RESULTS: One hundred twenty-five patients were included in the analysis. Excellent discriminators of benign from malignant lesions were identified, including entropy and standard deviation. These texture features demonstrated lower values for benign lesions compared with malignant lesions. Entropy values of benign lesions averaged 3.95 using a spatial scaling factor of 4 compared with an average of 5.08 for malignant lesions (P < .0001). Standard deviation values of benign lesions averaged 19.94 on the unfiltered image compared with an average of 34.32 for malignant lesions (P < .0001). Entropy demonstrated AUCs ranging from 0.95 to 0.97 for discriminating tumors, with sensitivities and specificities ranging from 81% to 95% and 88% to 100%, respectively. Standard deviation demonstrated AUCs ranging from 0.91 to 0.94 for discriminating tumors, with sensitivities and specificities ranging from 73% to 93% and 86% to 95%, respectively. CONCLUSION: Texture analysis offers a noninvasive tool for differentiating benign from malignant adrenal tumors on contrast-enhanced CT images. These results support the further development of texture analysis as a quantitative biomarker for characterizing adrenal tumors.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Abdome/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/classificação , Glândulas Suprarrenais/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
7.
Medicine (Baltimore) ; 99(28): e20918, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664087

RESUMO

RATIONALE: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neuropathic syndrome with typical clinical and radiological features. There are large amounts of risk factors resulting in RPLS, those including hypertension, eclampsia, neoplasia treatment, renal failure, systemic infections, chemotherapy, and immunosuppressive therapy after organ transplantation. PATIENT CONCERNS: A 27-year-old male patient was admitted for a 2-week history of paroxysmal tic of limbs along with consciousness disorder. Blood pressure elevation was discovered for the first time on admission, and the highest record was 210/150 mmHg during hospitalization. Neurological examinations were positive among mental state, speech, reaction and pathological reflex. The computed tomography scan of the abdomen demonstrated a mass derived from right adrenal gland. The magnetic resonance imaging of the brain showed reversible lesions in the centrum ovale, paraventricular, area and corpus callosum. DIAGNOSES: After control of blood pressure and rationally preoperative preparation, the mass was radically resected and verified to be pheochromocytoma by postoperative pathologic findings. He was diagnosed as having RPLS due to adrenal pheochromocytoma. INTERVENTIONS: The right adrenal gland mass was completely removed after 2 weeks of α-blockers and ß-blockers to treat hypertension. OUTCOMES: One week after surgery, the cerebral lesions of RPLS gradually faded and the blood pressure was easy to control well. LESSONS: A few case reports of RPLS related to pheochromocytomas had been documented in the literature. Therefore, we believe that pheochromocytomas may be a potential risk factor of RPLS. If patients receive timely diagnosis and treatment, it can often lead to a favorable prognosis.


Assuntos
Encéfalo/diagnóstico por imagem , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Síndrome da Leucoencefalopatia Posterior/etiologia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Assistência ao Convalescente , Encéfalo/patologia , Criança , Transtornos da Consciência/etiologia , Feminino , Hospitalização , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Imagem por Ressonância Magnética/métodos , Masculino , Exame Neurológico/métodos , Feocromocitoma/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Fatores de Risco , Transtornos de Tique/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(28): e20938, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664092

RESUMO

RATIONALE: Primary adrenal lymphoma (PAL) is an extremely rare and highly invasive malignant disease. Imaging examination usually shows bilateral adrenal involvement with large tumor masses and local infiltration. However, it is unclear how lymphoma dynamically develops into huge tumor masses in the adrenal glands. The overall survival rate of PAL is generally poor, and the underlying mechanism might be related to prooncogenic mutation but not fully elucidated. PATIENT CONCERNS: A 52-year-old woman complaining of a large mass in the left adrenal region for 1 month was admitted to our department. DIAGNOSIS: Computed tomography firstly showed a huge mass (8.9 × 7.5 cm) in the left adrenal gland and diffusely enlarged right adrenal gland. A month later, the mass in the left adrenal gland further enlarged (9.5x7.5 cm) with infiltration of the left renal artery and retroperitoneal lymphadenopathy, and the right adrenal gland rapidly progressed into a huge mass (8.0x4.7 cm). Additionally, her chest computed tomography revealed mediastinal and bilateral hilar lymphadenopathy. Then an adrenal biopsy confirmed the diagnosis of diffuse large B-cell lymphoma, nongerminal center B-cell type, stage IV by Ann Arbor staging system. Immunohistochemistry showed positivity for Ki-67 (approximately 90%), BCL2 (approximately 80%) and MYC (approximately 70%) double-expressor lymphoma. INTERVENTIONS: The patient's condition progressed rapidly, there was no opportunity to use pathology-based chemotherapy. Dexamethasone was given intravenously by thoracic and intraperitoneal injection; antibiotics and supporting treatment were also given. OUTCOMES: The patient's condition progressed rapidly, with the development of malignant chest and abdominal cavity fluid and lung infection, and eventually developed septic shock and respiratory failure. She responded poorly to treatment regimens, and eventually died 8 days after the diagnosis of PAL. LESSONS: PAL grows progressively throughout the adrenal glands, high Ki-67 positivity and BCL2/ MYC co-expression predict rapid progress and poor prognosis.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Linfoma Difuso de Grandes Células B/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica
9.
Eur J Endocrinol ; 183(3): 335-341, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717716

RESUMO

Objective: Autonomous cortisol secretion and possible autonomous cortisol secretion (ACS/pACS) are associated to an increase of cardiovascular risk factors such as hypertension, diabetes mellitus and dyslipidaemia. To our knowledge, the prevalence of smoking, another well-established risk factor for cardiovascular disease, has not been studied in detail in people with ACS/pACS or adrenal incidentalomas. Methods: Patients with adrenal incidentalomas were examined with the 1-mg overnight dexamethasone suppression test (cortisolONDST). Information about current smoking was collected from the patient's records. Results: We studied 1044 patients, of whom 370 (35%) were current smokers. Of these, 22% had bilateral AI compared to 12% of the non-smokers (P < 0.001). Among patients with unilateral adrenal incidentalomas, smokers had larger adrenal incidentalomas than non-smokers (22 mm vs 19 mm, P < 0.001). Smokers also more often had cortisolONDST ≥50 nmol/L than non-smokers, 54% vs 40% (P < 0.001), a finding independent of the size of the adrenal incidentaloma in patients with unilateral adrenal incidentalomas. Conclusions: In the present study of patients with adrenal incidentalomas, the prevalence of current smoking was higher than in the general population. Furthermore, smokers had larger unilateral adrenal incidentalomas, more often bilateral adrenal incidentalomas, and more frequently ACS/pACS. Whether smoking is a risk factor for adrenal incidentalomas and ACS/pACS or our findings are due to case selection needs to be further studied.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Fumar/epidemiologia , Neoplasias das Glândulas Suprarrenais/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dexametasona/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fumar/efeitos adversos
10.
Eur J Endocrinol ; 183(3): 325-333, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717717

RESUMO

Objective: To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis. Design: Cross-sectional study. Methods: In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software. Results: The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = -0.583, P < 0.001). Conclusions: The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Síndrome de Cushing/sangue , Síndrome de Cushing/patologia , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade
11.
Chirurg ; 91(9): 783-792, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32671423

RESUMO

Incidentally discovered adrenal alterations should be separated into those without any clinical importance and adrenal diseases that have to be surgically or conservatively treated. Before operative treatment, in addition to the possible different functional activity of tumors, a differentiation must be made between sporadically arising singular or multiple adrenal tumors or nodular adrenal hyperplasia, adrenal tumors as part of a familial syndrome and metastases of other primary malignant tumors into the adrenal glands. Benign hormonally active adrenal tumors as well as questionable malignant tumors of the adrenal cortex are resected by minimally invasive techniques. For large malignant tumors infiltrating into surrounding tissues and tumors with proven lymph node metastases, the primarily open approach is indicated. Patients with adrenal diseases should always undergo an interdisciplinary assessment and in cases with clear indications for surgery, sometimes transferred to a center with experience in surgery and postoperative management of these patients.


Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Adrenalectomia , Humanos , Período Pós-Operatório
12.
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
14.
Eur J Endocrinol ; 183(4): 369-379, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621582

RESUMO

Background: The '3PAs' syndrome, associating pituitary adenoma (PA) and pheochromocytoma/paraganglioma (PPGL), is sometimes associated with mutations in PPGL-predisposing genes, such as SDHx or MAX. In '3PAs' syndrome, PAs can occur before PPGL, suggesting a new gateway into SDHx/MAX-related diseases. Objective: To determine the SDHx/MAX mutation prevalence in patients with isolated PAs and characterize PAs of patients with SDHx/MAX mutations. Design: Genes involved in PAs (AIP/MEN1/CDKN1B) or PPGLs (SDHx/MAX) were sequenced in patients with isolated PAs. We then conducted a review of cases of PA in the setting of '3PAs' syndrome. Results: A total of 263 patients were recruited. Seven (likely) pathogenic variants were found in AIP, two in MEN1, two in SDHA, and one in SDHC. The prevalence of SDHx mutations reached 1.1% (3/263). Of 31 reported patients with PAs harboring SDHx/MAX mutations (28 published cases and 3 cases reported here), 6/31 (19%) developed PA before PPGL and 8/31 (26%) had isolated PA. The age of onset was later than in patients with AIP/MEN1 mutations. PAs were mainly macroprolactinomas and showed intracytoplasmic vacuoles seen on histopathology. Conclusions: We discovered SDHx mutations in patients bearing PA who had no familial or personal history of PPGL. However, the question of incidental association remains unresolved and data to determine the benefit of SDHx/MAX screening in these patients are lacking. We recommend that patients with isolated PA should be carefully examined for a family history of PPGLs. A family history of PPGL, as well as the presence of intracytoplasmic vacuoles in PA, requires SDHx/MAX genetic testing of patients.


Assuntos
Adenoma/genética , Mutação em Linhagem Germinativa , Neoplasias Hipofisárias/genética , Succinato Desidrogenase/genética , Adenoma/epidemiologia , Adenoma/patologia , Adolescente , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idade de Início , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Criança , Análise Mutacional de DNA/métodos , Feminino , França/epidemiologia , Predisposição Genética para Doença , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Paraganglioma/epidemiologia , Paraganglioma/genética , Paraganglioma/patologia , Feocromocitoma/epidemiologia , Feocromocitoma/genética , Feocromocitoma/patologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Prolactinoma/epidemiologia , Prolactinoma/genética , Prolactinoma/patologia , Subunidades Proteicas/genética , Estudos Retrospectivos , Adulto Jovem
15.
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
16.
Medicine (Baltimore) ; 99(25): e20905, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569238

RESUMO

RATIONALE: Chronic radiation enteritis, a disease secondary to radiation exposure, has been widely reported in adults. However, few studies have described chronic radiation enteritis in children. Early diagnosis is essential, and nutrition management plays an important role in pediatric chronic radiation enteritis management. PATIENT CONCERNS: A Chinese 3-year-10-month-old boy was admitted with vomiting, weight loss (1-2 kg) after radiotherapy for a neuroblastoma. DIAGNOSES: The patient was diagnosed as neuroblastoma (primary site: left adrenal grand; site of metastasis: multiple bone metastasis, bone marrow invasion, intraperitoneal lymph node metastasis) in 2015. Five months after radiotherapy, he showed vomiting and weight loss with stricture in intestine and thickening intestinal wall in imaging finding. His daily intake was not sufficient and extra supplements were needed by intravenous infusion. He had a weight-for-age z score of -5.04, a weight-for-height z score of -6.19, a height-for-age z score of -2.22, and a body mass index-for-age z score of -5.87. The highest level of alanine aminotransferase was 1433 U/L. Those findings established a diagnosis of chronic radiation enteritis with intestinal failure, intestinal stenosis, severe malnutrition, and hepatic dysfunction. INTERVENTIONS: This patient was treated by parenteral nutrition with minimal enteral feeding. Other treatments were aiming at complications during hospitalization. OUTCOMES: The patient weaned off parenteral nutrition finally with nutrition status and quality of life improved. There were no signs of tumor recurrence during the 4-year follow-up. LESSONS: Pediatric radiation enteritis is rare. Our study highlights the characteristics of pediatric chronic radiation enteritis. Nutrition therapy is an important part of the whole therapy strategy in pediatric chronic radiation enteritis.


Assuntos
Enterite/etiologia , Exposição à Radiação/efeitos adversos , Neoplasias das Glândulas Suprarrenais/radioterapia , Pré-Escolar , Nutrição Enteral , Enterite/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroblastoma/radioterapia , Radiografia
17.
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
19.
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
20.
PLoS Genet ; 16(6): e1008803, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511227

RESUMO

Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Biomarcadores Tumorais/genética , Mutação de Sentido Incorreto , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Células HEK293 , Humanos , Masculino , Metástase Neoplásica , Feocromocitoma/patologia
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