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1.
Am J Vet Res ; 82(2): 110-117, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33480281

RESUMO

OBJECTIVE: To develop a technique for isolation and culture of canine insulinoma cells and assess expression of cellular hexokinases (glucokinase and hexokinase I) and expression and secretion of insulin from these cells in vitro. SAMPLE: Pancreatic insulinomas and normal pancreatic tissue from 4 and 3 dogs, respectively. PROCEDURES: Tissues were collected by surgical excision or at necropsy. Insulinoma cells from 2 dogs were cultured for up to 10 weeks with standard techniques; insulin synthesis in vitro was confirmed by immunohistochemical analysis of freshly prepared slides of cultured cells, and insulin secretion was assessed by measurement of insulin concentrations in culture medium with an ultrasensitive mouse insulin ELISA. Expression of cellular hexokinases in insulinomas and adjacent normal (nontumor) pancreatic tissue from the same dog (n = 3) was examined by quantitative reverse transcriptase PCR assay. RESULTS: Insulinoma cells survived for up to 10 weeks but did not proliferate in culture. Insulin was detected in isolated cells and secreted into culture medium for up to 10 weeks. Both cellular hexokinases were expressed; glucokinase appeared to be overexpressed in insulinomas, compared with normal pancreatic tissue from the same dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Canine insulinomas expressed hexokinases responsible for glucose responsiveness. Insulinoma cells were successfully maintained in short-term culture; cultured cells remained functional for 10 weeks as evidenced by cellular insulin content and had detectable secretion of insulin into the culture medium for ≥ 5 weeks. Apparent glucokinase overexpression by insulinomas suggested a possible mechanism underlying excessive insulin release by these tumors.


Assuntos
Doenças do Cão , Insulinoma , Neoplasias Pancreáticas , Doenças dos Roedores , Animais , Cães , Glucoquinase/genética , Glucose , Hexoquinase/genética , Insulina , Insulinoma/veterinária , Camundongos , Neoplasias Pancreáticas/veterinária
3.
Rev. chil. endocrinol. diabetes ; 14(1): 17-20, 2021. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1146467

RESUMO

Insulinoma es un tumor neuroendocrino que surge de las células ß del páncreas y produce hiperinsulinemia endógena. Son neoplasias raras con una incidencia reportada de 4 casos por millón de habitantes por año. La presentación clínica típicamente cursa con síntomas adrenérgicos y neuroglucopénicos secundarios a hipoglicemia. Requiere estudios de niveles séricos de insulina, pro-insulina y péptido C, además de imágenes diagnosticas que confirmen los hallazgos. La mayoría de los insulinomas son benignos, su sitio primario más común es el páncreas y pueden extirparse quirúrgicamente. Se presenta el caso de un hombre de 36 años con déficit cognitivo leve y episodios de diaforesis con deterioro neurológico hasta convulsiones tónico clónicas generalizadas que curiosamente resolvían con uso doméstico de "panela molida". Se ingresó a urgencias por ataques recurrentes de hipoglicemia severa con requerimiento de altas dosis de dextrosa al 50% por acceso central, hasta confirmación diagnóstica, intervención y resección de tumor neuroendocrino pancreático bien diferenciado (G1 según clasificación OMS) tipo insulinoma en la cola del páncreas.


Insulinoma is a neuroendocrine tumor that arises from the ß cells of the pancreas and produces endogenous hyperinsulinemia. They are rare neoplasms with a reported incidence to 4 cases per million inhabitants per year. The clinical presentation typically presents with adrenergic and neuroglycopenic symptoms secondary to hypoglycemia. It requires studies of serum levels of insulin, pro-insulin and C-peptide, in addition to diagnostic images that confirm the findings. Most insulinomas are benign, their most common primary site is the pancreas, and they can be removed surgically. We present the case of a 36-year-old man with mild cognitive deficits and episodes of diaphoresis with neurological deterioration to generalized clonic tonic seizures that curiously resolved with domestic use of "ground brown sugar". He was admitted to the emergency department due to recurrent attacks of severe hypoglycemia with a high-dose requirement for 50% dextrose through central access, until diagnostic confirmation, intervention, and resection of a welldifferentiated pancreatic neuroendocrine tumor (G1 according to WHO classification) insulinoma in the tail of pancreas.


Assuntos
Humanos , Masculino , Adulto , Neoplasias Pancreáticas/diagnóstico , Insulinoma/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Imagem por Ressonância Magnética , Tumores Neuroendócrinos , Diagnóstico Diferencial , Epilepsia/diagnóstico , Glucose/uso terapêutico , Hiperinsulinismo/etiologia , Hipoglicemia/etiologia , Hipoglicemia/tratamento farmacológico , Insulinoma/cirurgia , Insulinoma/complicações
4.
Vnitr Lek ; 66(7): 447-448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380125

RESUMO

Hypoglycemia is a rather frequent complication of diabetes treatment, however it can occur also in non-diabetic patients. The article presents a brief differential diagnosis of hypoglycemia in non-diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulinoma , Neoplasias Pancreáticas , Diagnóstico Diferencial , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico
5.
Rev. cuba. cir ; 59(4): e994, oct.-dic. 2020.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1149851

RESUMO

RESUMEN Introducción: La Nesidioblastosis es una rara afección pancreática que provoca hipoglucemia por hipersinsulinismo endógeno en la infancia. Es poco habitual en el adulto; solo se han publicado casos aislados desde su descripción. Objetivo: Caracterizar la presentación de una hipoglucemia hiperinsulínica en un paciente adulto con Nesidioblastosis. Caso clínico: Paciente adulto de 35 años, blanco, sexo masculino, sospecha de insulinoma, con episodios de hipoglucemia en ayunas o tras un ejercicio que revertía con la ingesta de alimentos o soluciones glucosadas. Se le realizó pancreatectomía de un 85 por ciento y en el estudio histológico se detectó una Nesidioblastosis. Conclusiones: Es infrecuente en el adulto, realizar su diagnóstico es difícil, se llega a la cirugía con el conocimiento de un estado hiperinsulínico endógeno, sin la certeza de su origen(AU)


ABSTRACT Introduction: Nesidioblastosis is a rare pancreatic condition that causes hypoglycemia due to endogenous hypersinsulinism in childhood. It is unusual in adults; only isolated cases have been published including its description. Objective: To characterize a case of hyperinsulinic hypoglycemia, in an adult patient with nesidioblastosis. Clinical case: A 35-year-old, white, male, adult patient with suspected insulinoma, with episodes of hypoglycemia in the fasting state or after exercise that was reversed with ingestion of food or glucose solutions. 85 percent pancreatectomy was performed and nesidioblastosis was detected in the histological study. Conclusions: It is rare in adults, making its diagnosis is difficult, and surgery is reached with the knowledge of an endogenous hyperinsulinic state, without the certainty of its origin(AU)


Assuntos
Humanos , Masculino , Adulto , Pancreatectomia/métodos , Nesidioblastose/diagnóstico , Hipoglicemia/diagnóstico por imagem , Insulinoma/terapia
6.
Nat Commun ; 11(1): 5210, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060578

RESUMO

Human insulinomas are rare, benign, slowly proliferating, insulin-producing beta cell tumors that provide a molecular "recipe" or "roadmap" for pathways that control human beta cell regeneration. An earlier study revealed abnormal methylation in the imprinted p15.5-p15.4 region of chromosome 11, known to be abnormally methylated in another disorder of expanded beta cell mass and function: the focal variant of congenital hyperinsulinism. Here, we compare deep DNA methylome sequencing on 19 human insulinomas, and five sets of normal beta cells. We find a remarkably consistent, abnormal methylation pattern in insulinomas. The findings suggest that abnormal insulin (INS) promoter methylation and altered transcription factor expression create alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation. Finally, NFaT transcription factors, rather than the canonical PDX1 enhancer complex, are predicted to drive INS transactivation.


Assuntos
Regulação Neoplásica da Expressão Gênica , Insulina/genética , Insulina/metabolismo , Insulinoma/genética , Insulinoma/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Sítios de Ligação , Biologia Computacional , Metilação de DNA , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Transativadores/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Adulto Jovem
7.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 39(5): 279-283, sept.-oct. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-198289

RESUMO

ANTECEDENTES: El hiperinsulinismo congénito (HIC) es una enfermedad neuroendocrina con anomalías focales o difusas en el páncreas. Mientras que las formas difusas resistentes a los medicamentos requieren una pancreatectomía casi total o una farmacoterapia prolongada, el HIC focal podría ser tratado por resección quirúrgica dirigida. Por tanto, evaluamos la utilidad del 18F-DOPA PET/TC para identificar la forma pancreática focal. Objetivos y metodología: Diecinueve niños (11 niños y 8 niñas de 2 a 54meses de edad) con signos clínicos de HIC neonatal y exámenes genéticos positivos fueron registrados en el estudio. Después de la administración intravenosa del 18F-DOPA, una primera PET y posteriormente otra PET/TC cubriendo longitudinalmente la región toracoabdominal fueron llevadas a cabo. Ambas adquisiciones fueron realizadas en modo dinámico para permitir la exclusión de imágenes con artefactos de movimiento. Los valores de absorción estandarizados fueron ajustados al peso corporal (SUVbw). El hallazgo fue considerado como focal cuando la proporción de SUVbwmax entre la región sospechosa y el resto del páncreas fue mayor que 1,2. RESULTADOS: Las formas focales fueron registradas en 10/19 niños y 4 de ellos se sometieron a una resección quirúrgica con recuperación completa. La captación focal fue significativamente mayor que la captación en el tejido pancreático normal (p = 0,0059). Las formas focales y difusas del HIC no difieren significativamente en la captación del tejido pancreático normal. No encontramos ninguna ventaja en la medición de la relación SUVbwmean en comparación con la relación SUVbwmax (p = 0,50). CONCLUSIONES: 18F-DOPA PET/TC es una herramienta útil para la localización de HIC focal y la planificación de un tratamiento quirúrgico


BACKGROUND: Congenital hyperinsulinism (CHI) is a neuroendocrine disease with focal or diffuse abnormalities in pancreas. While drug-resistant diffuse forms require near-total pancreatectomy or prolonged pharmacotherapy, focal CHI may be treated by targeted surgical resection. We evaluated the usefulness of 18F-DOPA PET/CT to identify the focal pancreatic form. Subjects and methods: Nineteen children (11 boys, 8 girls, aged 2-54 months) with clinical signs of neonatal CHI and positive genetic examinations were enrolled in the study. After i.v. administration of 18F-DOPA, early PET and late PET/CT acquisition covering one-bed length over thoraco-abdominal region were performed. Both acquisitions were done in dynamic mode to allow exclusion of frames with motion artefacts. Standardized uptake values were adjusted to bodyweight (SUVbw). The finding was considered as focal when the ratio of SUVbwmax between the suspicious region and the rest of pancreas was greater than 1.2. RESULTS: Focal forms were recorded in 10/19 children and 4 of them underwent surgical resection with complete recovery. Focal uptake was significantly higher than the uptake in the normal pancreatic tissue (p = 0.0059). Focal and diffuse forms of CHI did not differ significantly in normal pancreatic tissue uptake. We found no advantage in the measurement of SUVbwmean ratio compared to SUVbwmax ratio (p = 0.50). CONCLUSION: 18F-DOPA PET/CT is a useful tool for the localization of focal CHI and planning of surgical treatment


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Hiperinsulinismo Congênito/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Pâncreas/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Insulinoma/diagnóstico por imagem , Traçadores Radioativos , Octreotida/uso terapêutico , Diazóxido/uso terapêutico
8.
Internist (Berl) ; 61(9): 964-968, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32734334

RESUMO

BACKGROUND: We report the case of a 46-year-old female patient who presented in the emergency department with intermittent disturbances of perception when fasting. DIAGNOSTICS: In the diagnostic fasting test, a hyperinsulinemic hypoglycemia already occurred after 7h. A sonographic examination was inconspicuous, therefore, a Ga 68-HA-DOTATATE positron emission tomography computed tomography (PET-CT) was carried out. The results were indicative of a neuroendocrine neoplasm, which gave rise to the suspicion of an insulinoma. CLINICAL COURSE: For surgical treatment the patient was transferred to an external hospital. Following surgery, the patient was free of symptoms. CONCLUSION: If multiple symptoms of hypoglycemia are present, an insulinoma as the cause must be considered in the differential diagnostics.


Assuntos
Jejum/efeitos adversos , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/complicações , Insulinoma/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Compostos Organometálicos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons , Cintilografia
10.
Yi Chuan ; 42(6): 586-598, 2020 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-32694117

RESUMO

Human islet amyloid polypeptide (hIAPP, also known as amylin) is a co-secreting protein of insulin in human pancreatic ß-cells. It is encapsulated in vesicles and secreted out of the cells with insulin. hIAPP can promote insulin secretion and regulate blood glucose homeostasis in the body under the normal physiological conditions. However, hIAPP misfolding or excessive accumulation can cause toxic effects on the ß cells, which in turn affect cell function, resulting in type 2 diabetes mellitus (T2DM) for the affected individuals. In order to eliminate the excessive accumulation of hIAPP in the cell and to maintain its normal synthetic function, we have adopted a new protein degradation technology called Trim-Away, which can degrade the target protein in a short time without affecting the mRNA transcription and translation synthesis function of the target protein. First, we overexpressed hIAPP in the rat insulinoma cells (INS1) to simulate its excessive accumulation and analyzed its effect in INS1 cells by measuring the release of LDH (lactate dehydrogenase), CCK8 activity and PI-Annexin V positive ratio. Results showed that excessive accumulation of hIAPP caused ß cell apoptosis. Second, real-time quantitative PCR analysis and ELISA detection showed that the synthesis and secretion of insulin were hindered. We used Trim-Way technology to specifically eliminate the excessive accumulation of hIAPP protein in hIAPP overexpressing INS1 cells. Cell activity experiments confirmed that clearance of hIAPP reduced the cell death phenotype. Further ELISA experiments confirmed that INS1 cells restored insulin secretion ability. This study examined the toxic effect of hIAPP excessive accumulation in INS1 cells and demonstrated the cytotoxicity clearance effect of Trim-Way technology in pancreatic ß-cells. Our research has provided a new strategy for using Trim-Away technology for treatment of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Insulinoma , Neoplasias Pancreáticas , Animais , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Neoplasias Pancreáticas/genética , Dobramento de Proteína , Ratos
12.
Clin Nucl Med ; 45(9): e386-e392, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558709

RESUMO

PURPOSE: Physiological pancreaticoduodenal uptake of radiolabeled exendin-4 in Brunner glands of the proximal duodenum is the most common pitfall for false interpretation of glucagon-like peptide-1 receptor (GLP-1R) imaging. The aim of this study was to analyze the pancreaticoduodenal uptake in GLP-1R PET/CT and SPECT/CT images and to identify additional potential reading pitfalls in patients with suspected insulinoma. METHODS: A post hoc analysis of a prospective study, including 52 consecutive patients, was performed. All patients underwent 1 Ga-exendin-4 PET/CT and 2 In-exendin-4 SPECT/CT scans (4 and 72 hours postinjection) in a randomized crossover order. Three board-certified nuclear medicine physicians read all scans independently. They were unaware of other results. Reference standard was surgery with histopathological confirmation of an insulinoma/nesidioblastosis and normalization of blood glucose levels after surgery. RESULTS: There were no false-positive readings. However, there were a number of false-negative PET/CT and SPECT/CT readings, respectively: (1) due to false interpretation of uptake in the pancreaticoduodenal region (falsely interpreted as physiological uptake in Brunner glands instead of an insulinoma in 0.6% vs 9.0%), (2) due to ectopic insulinoma (0% vs 2.6%), (3) due to small insulinoma (1.9% vs 5.1%), (4) due to insulinoma overlap with kidneys (1.9% vs 4.5%), and (5) due to nesidioblastosis (0.6% and 1.9%). Pitfalls were identified in all GLP-1R PET/CT and SPECT/CT scans. CONCLUSIONS: Peripancreatic uptake, small size of an insulinoma, insulinoma overlap with kidneys, and presence of nesidioblastosis are potential pitfalls in GLP-1R imaging, which can lead to false reading results.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Insulinoma/diagnóstico por imagem , Insulinoma/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Reações Falso-Positivas , Feminino , Humanos , Masculino , Estudos Prospectivos
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(2): 139-146, 2020 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-32385018

RESUMO

Objective To prospectively evaluate the correlation between intravoxel incoherent motion (IVIM)-derived parameters and CT perfusion parameters as well as the pathological grade in insulinoma. Methods A total of 55 patients with suspected insulinoma undergoing IVIM and CT perfusion scans were prospectively enrolled. The images were post-processed to obtain IVIM parameters including apparent diffusion coefficient (ADC),diffusion (D),perfusion correlated diffusion (D*),and f,and CT perfusion parameters including blood flow (BF),blood volume (BV),and permeability (PM). The pathological specimens were stained to obtain pathological parameters including the grading,ki-67 index,and the mitotic count. The IVIM derived parameters of normal pancreas including head,body,and tail as well as that of the pancreatic insulinoma were compared. The correlation between IVIM parameters and CT perfusion parameters as well as the pathological parameters was analyzed. Results ADC and D values of pancreatic tail were significantly lower than those of the pancreatic head and neck (all P<0.001). There were significant differences in all IVIM parameters between insulinoma and normal pancreas (all P<0.001). The ADC and f value of the normal pancreas was positively correlated with BF (r=0.437,P=0.003;r=0.357,P=0.010). There is no correlation between the remaining IVIM parameters and the CT perfusion parameters as well as between IVIM parameters and pathological parameters (all P>0.05). Conclusions IVIM parameters differ at different anatomical parts of normal pancreas. IVIM parameters can distinguish normal pancreatic parenchyma from insulinoma. The ADC value is weakly correlated with BF.


Assuntos
Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Movimento (Física) , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
14.
Ann Endocrinol (Paris) ; 81(2-3): 110-117, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32409005

RESUMO

Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves' disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis.


Assuntos
Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Adulto , Idade de Início , Antígenos CD/genética , Criança , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Jejum/sangue , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Hiperinsulinismo/epidemiologia , Insulinoma/sangue , Insulinoma/complicações , Insulinoma/epidemiologia , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Receptor de Insulina/genética , Fatores de Risco
15.
Clin Nucl Med ; 45(7): 519-524, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32453080

RESUMO

PURPOSE: Insulinomas are predominantly benign neuroendocrine tumors originating from beta cells within the islets of Langerhans of the endocrine pancreas. Because surgical resection represents the only curative therapy option, exact tumor localization and discrimination of insulinomas from focal or diffuse manifestations of congenital hyperinsulinism are crucial for optimal treatment strategies. We investigated the diagnostic value of glucagon-like peptide 1 receptor PET/CT using Ga-DOTA-exendin 4 for detecting insulinomas and compared the diagnostic value of PET scans performed at 2 time points. METHODS: In 10 patients with clinically and biochemically suspected insulinoma, PET/CT was performed at 1 hour (PET1) and 2 hours (PET2) after injection of Ga-DOTA-exendin 4. In this retrospective analysis, tracer uptake was visually assessed in both scans by 2 independent readers. SUVmax and tumor-to-background ratio (TBR) of focal lesions were assessed. Imaging results were compared with histopathologic findings, if patients underwent resection. RESULTS: Increased focal Ga-DOTA-exendin 4 uptake was observed in 8 of 10 patients concordantly by both readers. Seven patients with focal uptake underwent surgery with tumor enucleation and histopathologic proof of insulinoma (7/8). Two of 10 patients without focal uptake were considered to suffer from diffuse form of congenital hyperinsulinism and consequently received medical treatment. A significant increase of tumoral SUVmax on PET2 (PET1: SUVmax 20.2 ± 8.2 g/mL; PET2: SUVmax 24.7 ± 7.9 g/mL; P = 0.0018) did not result in a significant improvement in TBR (PET1: TBR 4.9 ± 1.7; PET2: TBR 4.3 ± 1.2; P = 0.2892). CONCLUSIONS: Focal uptake of Ga-DOTA-exendin 4 reliably indicated insulinomas as histopathologically confirmed in all patients undergoing consecutive surgery. The diagnostic value of PET2 was not found to be superior to PET1, indicating that a single 1-hour Ga-DOTA-exendin 4 PET/CT scan is a sufficient and convenient approach for patient care.


Assuntos
Insulinoma/diagnóstico por imagem , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Peptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
16.
Galicia clin ; 81(2): 54-56, abr. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-195199

RESUMO

Insulinomas are the most frequent etiology of hypoglycemia in a non-diabetic patient and the most common functional neuroendocrine tumors of the pancreas, with an annual incidence of about 4 cases per million. The majority of insulinomas are "well-differentiated endocrine tumors" or grade 1 tumors, as defined by World Health Organization. Most tumors are benign, solitary and occur sporadically. However, about 10% are associated with multiple endocrine neoplasia type 1 (MEN-1). Despite the majority being benign tumors, hypoglycemic symptoms caused by the hyperinsulinemia are frequently debilitating. Whipple triad (hypoglycemia, symptoms of hypoglycemia - either adrenergic or neuroglycopenic - and relief of these symptoms after administration of glucose) is usually present and should alert to the diagnosis.After the diagnosis is made, locating the tumor can be challenging because most tumors are small. Nonetheless, locating the tumor is crucial, once the only definite treatment is surgical excision. The majority of patients reach normalization of glucose levels after surgery. Incomplete resection leads to persistent symptoms and although uncommon in sporadic insulinomas, recurrence can be as high as 20% in patients with MEN-1 syndrome


No disponible


Assuntos
Humanos , Masculino , Adulto , Insulinoma/complicações , Insulinoma/diagnóstico por imagem , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico por imagem , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/cirurgia , Tumores Neuroendócrinos/cirurgia , Hipoglicemia/tratamento farmacológico , Octreotida/uso terapêutico , Diazóxido/uso terapêutico , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X
17.
PLoS One ; 15(3): e0224344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176701

RESUMO

A key event in the development of both major forms of diabetes is the loss of functional pancreatic islet ß-cell mass. Strategies aimed at enhancing ß-cell regeneration have long been pursued, but methods for reliably inducing human ß-cell proliferation with full retention of key functions such as glucose-stimulated insulin secretion (GSIS) are still very limited. We have previously reported that overexpression of the homeobox transcription factor NKX6.1 stimulates ß-cell proliferation, while also enhancing GSIS and providing protection against ß-cell cytotoxicity through induction of the VGF prohormone. We developed an NKX6.1 pathway screen by stably transfecting 832/13 rat insulinoma cells with a VGF promoter-luciferase reporter construct, using the resultant cell line to screen a 630,000 compound chemical library. We isolated three compounds with consistent effects to stimulate human islet cell proliferation, but not expression of NKX6.1 or VGF, suggesting an alternative mechanism of action. Further studies of the most potent of these compounds, GNF-9228, revealed that it selectively activates human ß-cell relative to α-cell proliferation and has no effect on δ-cell replication. In addition, pre-treatment, but not short term exposure of human islets to GNF-9228 enhances GSIS. GNF-9228 also protects 832/13 insulinoma cells against ER stress- and inflammatory cytokine-induced cytotoxicity. GNF-9228 stimulates proliferation via a mechanism distinct from recently emergent DYRK1A inhibitors, as it is unaffected by DYRK1A overexpression and does not activate NFAT translocation. In conclusion, we have identified a small molecule with pleiotropic positive effects on islet biology, including stimulation of human ß-cell proliferation and insulin secretion, and protection against multiple agents of cytotoxic stress.


Assuntos
Proliferação de Células/efeitos dos fármacos , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Insulinoma/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Animais , Linhagem Celular Tumoral , Células Secretoras de Glucagon/metabolismo , Células Secretoras de Glucagon/patologia , Glucose/farmacologia , Proteínas de Homeodomínio/metabolismo , Humanos , Células Secretoras de Insulina/patologia , Insulinoma/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Ratos
18.
JAAPA ; 33(4): 1-3, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32217911

RESUMO

Glycogen storage disease is a rare congenital disorder that can lead to hypoglycemic events. This article focuses on a patient in acute distress secondary to hypoglycemia that failed to respond to initial interventions. Because symptoms can be similar to severe hyperglycemia, a thorough history and physical examination are key to prompt diagnosis and appropriate management.


Assuntos
Doença de Depósito de Glicogênio Tipo I/complicações , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Adulto , Biomarcadores/sangue , Glicemia , Diagnóstico Diferencial , Feminino , Gluconeogênese , Glucose/administração & dosagem , Humanos , Hiperglicemia , Hipoglicemia/terapia , Injeções Intravenosas , Insulinoma , Ressuscitação , Tomografia Computadorizada por Raios X
19.
Rev. colomb. cancerol ; 24(1): 30-36, ene.-mar. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1115582

RESUMO

Resumen Los tumores neuroendocrinos pancreáticos (TNEsP) son un grupo poco frecuente de neoplasias, pueden ser funcionales y causan síndromes clínicos diversos, o no funcionales, con síntomas secundarios a invasión a estructuras cercanas o enfermedad metastásica (1). Se presenta el caso de una paciente de 55 años con insulinoma maligno con compromiso metastásico extenso, no candidata a intervención quirúrgica, hipoglucemia de difícil manejo sin respuesta a tratamiento con diazóxido y prednisolona, y que requirió manejo con quimioterapia y embolización de metástasis hepáticas, con posterior mejoría clínica, estabilidad de la enfermedad por imágenes diagnósticas y retiro de medicamentos para manejo de hipoglucemia. En seguimiento presenta síntomas de hiperglucemia con HbA1c en 12%, con lo cual se diagnosticó diabetes mellitus de novo y se inició manejo con insulina.


Abstract Pancreatic neuroendocrine tumors (TNEP) are a rare group of neoplasms, which can secrete peptide hormones causing various clinical syndromes, or be non-secretory, with symptoms secondary to invasion of neighboring or distant structures (1). The case of a 55-year-old patient with malignant insulinoma with extensive metastatic involvement, not operable, with persistent hypoglycemia refractory to treatment with diazoxide and prednisolone, who received management with chemotherapy and embolization of liver metastases, achieving the withdrawal of medications for the management of hypoglycemia and a tumor response of stable disease in the comparison of images during the 12-month follow-up. During the 15th cycle of chemotherapy, he presented symptoms of hyperglycemia with HbA1c in 12%, with which diabetes de novo mellitus was diagnosed and insulin management was initiated.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Insulinoma , Insulinoma/tratamento farmacológico , Tumores Neuroendócrinos , Capecitabina , Hipoglicemia
20.
Anesthesiol Clin ; 38(1): 149-163, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008649

RESUMO

Although endocrine emergencies are not common occurrences, their identification and careful perioperative management are of paramount importance for reduction of patient morbidity and mortality. The most common critical endocrine abnormalities are associated with functional tumors, such as pheochromocytomas, insulinomas, and carcinoid tumors, leading to carcinoid syndrome, abnormal thyroid function, or disturbances in the hypothalamus-pituitary-adrenal axis, causing adrenal insufficiency. This article aims to discuss the pathophysiology, diagnosis, and perioperative management of pheochromocytomas, hyperthyroidism, hypothyroidism, adrenal insufficiency, carcinoid disease, and insulinomas.


Assuntos
Anestesia/métodos , Doenças do Sistema Endócrino/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Insuficiência Adrenal/cirurgia , Emergências , Humanos , Hipotireoidismo/cirurgia , Insulinoma/cirurgia , Síndrome do Carcinoide Maligno/cirurgia , Assistência Perioperatória , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Tireotoxicose/diagnóstico , Tireotoxicose/cirurgia
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