Neoplasia endocrina múltiple tipo 1 en paciente con diagnóstico de nesidioblastosis. Presentación de un caso

Las neoplasias endocrinas múltiples engloban una serie de síndromes caracterizados por su origen genético y la afectación de una o más glándulas. Se describe el caso de un paciente masculino, de 23 años, con antecedentes de salud de nesidioblastosis diagnosticado a los 16 años de edad, quien acudió al Hospital General Docente Ambato por presentar convulsiones tónico clónicas, e hipoglucemia severa con posterior estatus epiléptico. Los estudios de laboratorio mostraron hiperparatiroidismo primario, y los de imagen identificaron lesiones sugerentes de adenoma paratiroideo e insulinoma de cabeza de páncreas. Después de analizar el caso, se identificaron dos criterios para plantear una neoplasia endocrina múltiple tipo 1: presencia de insulinoma e hiperparatiroidismo primario. Además de tratamiento con bifosfonato, se planificó interconsulta con el servicio de Genética, para estudio del paciente y familiares; y con Cirugía General, para programación de resolución quirúrgica. Debido a la poca frecuencia de esta enfermedad, resulta de interés describir el caso, con el objetivo de exponer las principales manifestaciones clínicas y conducta a seguir. Constituye una prioridad el diagnóstico de su causa en cada paciente.

Multiple endocrine neoplasias encompass a series of syndromes characterized by their genetic origin and the involvement of one or more glands. A 23-years-old male patient with a health history of nesidioblastosis diagnosed at 16 years of age, who attended the Ambato General Teaching Hospital with tonic-clonic seizures and severe hypoglycemia with subsequent epileptic status, is described. Laboratory studies showed primary hyperparathyroidism, and imaging identified lesions suggestive of parathyroid adenoma and insulinoma of the head of the pancreas. After analyzing the case, two criteria were identified to suggest multiple endocrine neoplasia type 1: presence of insulinoma and primary hyperparathyroidism. In addition to treatment with bisphosphonate, consultation with the Genetics service was planned for study of the patient and family members; and with General Surgery, for scheduling surgical resolution. Due to the infrequency of this disease, it is of interest to describe the case, with the aim of exposing the main clinical manifestations and conduct to follow. Diagnosing its cause in each patient is a priority.

Impacto del PET/CT en el diagnóstico de insulinoma

Introducción: La tomografía de emisión de positrones es una técnica diagnóstica no invasiva que permite tomar imágenes del organismo que muestra el metabolismo de los órganos del cuerpo. Objetivo: Destacar el valor de la PET/CT en el diagnóstico imagenológico prequirúrgico del enfermo. Presentación de caso: Se presentó un paciente masculino de 39 años sin antecedentes de importancia, con un cuadro de hipoglucemias severas de 5 años de evolución, a pesar de los múltiples estudios imagenológicos se incluyó la ecoendoscopía digestiva, lo que no fue posible evidenciar la lesión tumoral. Se le realiza PET/CT cuyo resultado fue crucial para localizar el tumor, se le dio al paciente la oportunidad de un tratamiento quirúrgico y la demostración anatomopatológica de insulinoma. Conclusiones: Los insulinomas son tumores pancreáticos poco frecuentes que provocan hiperinsulinismo endógeno y son difíciles de visualizar debido a su tamaño por las técnicas de imágenes convencionales, por lo que el PET/CT es un estudio bastante efectivo para localizar la lesión tumoral, y así realizar un procedimiento quirúrgico.

Introduction: Positron emission tomography is a non-invasive diagnostic technique, allowing images of the body to be taken that show the metabolism of the body's organs. Objective: To highlight the value of PET/CT in the pre-surgical imaging diagnosis of the patient. Case presentation: We report the case of a 39-year-old male patient with no significant medical history, but a 5-year history of severe hypoglycemia. Despite multiple imaging studies, digestive ultrasound endoscopy was included, which was not possible to demonstrate the tumor lesion. PET/CT was performed, the result of which was crucial in locating the tumor. The patient was given the opportunity for surgical treatment and the pathological demonstration of insulinoma. Conclusions: Insulinomas are rare pancreatic tumors that cause endogenous hyperinsulinism and are difficult to visualize due to their size using conventional imaging techniques, therefore PET/CT is a fairly effective study to locate the tumor lesion, and thus perform a surgical procedure.

Pâncreas ectópico: provocando gastrite e baixo peso / Ectopic pancreas: producing gastritis and low weight

O pâncreas ectópico é uma anomalia congênita rara representada por um aglomerado de tecido pancreático aberrante fora de seu lugar anatômico natural, visto em qualquer época da vida. A localização mais frequente é o duodeno ou tecido gástrico. Suas manifestações clínicas são inespecíficas e podem dificultar o diagnóstico. A ectopia pancreática pode ser vista também em outros órgãos ou regiões extra-abdominais como, por exemplo, no pulmão, mediastino e no umbigo. A incidência do pâncreas ectópico em achados de necropsias varia entre 0,6 a 5,6%. O autor relata um caso de um paciente com pâncreas ectópico localizado no antro gástrico que provocava sintomatologia gastrointestinal associado a baixo peso e faz uma breve revisão da literatura. [au]

Ectopic pancreas is a rare congenital anomaly represented by a cluster of aberrant pancreatic tissue outside its natural anatomical place seen at any time in life. The most frequent location is the duodenum or gastric tissue. Its clinical manifestations are nonspecific and can make diagnosis difficult. Pancreatic ectopy can also be seen in other organs or extra-abdominal regions, for example, in the lung, mediastinum and umbilicus. The incidence of ectopic pancreas in necropsy findings ranges from 0.6 to 5.6%. The author reports the case of a patient with ectopic pancreas located in the gastric antrum and reviews the literature. [au]

Paciente positiva a la COVID-19 operada de un insulinoma

RESUMEN Introducción: El insulinoma es una neoplasia neuroendocrina considerada una de las más raras. Surge en las células beta de los islotes de Langerhans, produce insulina de forma constante, por lo que provoca hipoglucemia. Su diagnóstico se basa en criterios clínicos, analíticos y pruebas de imagen. El tratamiento curativo es la cirugía, mediante la enucleación del tumor, la pancreatectomía parcial o total o duodenopancreatectomía cefálica. La actual pandemia dio a lugar a nuevos protocolos de actuación, con el fin de adaptar los recursos sanitarios sin comprometer la seguridad de los pacientes y el personal de salud. Objetivo: Presentar un caso clínico de una paciente con diagnóstico de insulinoma, que requirió tratamiento quirúrgico en el curso de la COVID-19. Caso clínico: Paciente femenina de 48 años de edad, con episodios de hipoglucemia intensa y dificultad para seguimiento clínico adecuado. Se le diagnosticó insulinoma y la COVID-19; esta última empeoró la sintomatología, de forma que resultó imposible el adecuado control metabólico. Se decidió tratamiento quirúrgico; se llevó a cabo la enucleación del tumor, sin complicaciones. Conclusiones: La cirugía es el tratamiento definitivo para lograr la curación en el caso de los tumores neuroendocrinos y la COVID-19 empeora el pronóstico. La decisión del tratamiento quirúrgico, debe ser tomada en discusión multidisciplinaria con el fin de evitar complicaciones postoperatorias.

ABSTRACT Introduction: Insulinoma is a neuroendocrine neoplasm considered one of the rarest, it arises in the beta cells of the islets of Langerhans, it produces insulin constantly, thus causing hypoglycemia. Its diagnosis is based on clinical, analytical and imaging criteria. Curative treatment is surgery, through enucleation of the tumor, partial or total pancreatectomy, or cephalic pancreaticoduodenectomy. The current pandemic gave rise to new action protocols, in order to adapt health resources without compromising the safety of patients and health personnel. Objective: To present a clinical case of a patient diagnosed with insulinoma who required surgical treatment in the course of COVID-19. Clinical case: 48-year-old female patient, with episodes of severe hypoglycemia and difficulty in proper clinical follow up. She was diagnosed with insulinoma and COVID-19, the latter worsened the patient's symptoms in such a way that adequate metabolic control was impossible. Surgical treatment was decided. The tumor was enucleated, without complications. Conclusions: Surgery is the definitive treatment to achieve cure in the case of neuroendocrine tumors, COVID-19 worsens the prognosis of patients with this tumor. Therefore, the decision of surgical treatment must be made in a multidisciplinary discussion in order to avoid postoperative complications.

Hipoglucemia tumoral dependiente y no dependiente de células ß-pancreáticas, un reto diagnóstico / Tumor and non-tumor mediated hypoglycemia by pancreatic beta cells, a diagnostic challenge

La hipoglucemia es una urgencia médica frecuente que en la mayoría de los casos es secundaria al uso de fármacos hipoglucemiantes, orales o inyectados, indicados en pacientes con diabetes mellitus. No obstante, puede presentarse en forma espontánea y severa relacionándose con múltiples condiciones clínicas, incluyendo las neoplasias. Ante una hipoglucemia de origen paraneoplásico se deben reconocer los mecanismos fisiopatológicos que la generan y establecer el diagnóstico oportuno y preciso para disminuir las complicaciones propias de este síndrome clínico. Presentamos dos pacientes con cuadro de hipoglucemia refractaria al manejo médico inicial, de aparición similar con patologías diferentes. El primer caso corresponde a un paciente con insulinoma y el segundo con un hemangiopericitoma.

Hypoglycemia is a common medical emergency which is mostly secondary to the use of oral or injected hypoglycemic drugs indicated in patients with diabetes mellitus. However, it can present spontaneously and severely in relation to multiple clinical conditions, including neoplasms. When faced with hypoglycemia associated with paraneoplastic disorders, the pathophysiological mechanisms of hypoglycemia must be recognized and a timely and accurate diagnosis must be established in order to diminish complications inherent to this clinical syndrome. We herein present two patients with hypoglycemia refractory to initial medical management, sharing similar appearance with other pathologies. The first case corresponds to a patient with an insulinoma and the second to a patient with a hemangiopericytoma.

Insulinoma simulando una epilepsia: reporte de caso / Insulinoma simulating epilepsy: case report

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.

Averaging Strategy to Form the Imaging for Routine Reading of Insulinoma from Pancreatic Perfusion Dataset / 中国医学科学院学报

Objective To determine the appropriate averaging strategy for pancreatic perfusion datasets to create images for routine reading of insulinoma.Methods Thirty-nine patients undergoing pancreatic perfusion CT in Peking Union Medical College Hospital and diagnosed as insulinoma by pathology were enrolled in this retrospective study.The time-density curve of abdominal aorta calculated by software dynamic angio was used to decide the timings for averaging.Five strategies,by averaging 3,5,7,9 and 11 dynamic scans in perfusion,all including peak enhancement of the abdominal aorta,were investigated in the study.The image noise,pancreas signal-to-noise ratio(SNR),lesion contrast and lesion contrast-to-noise ratio(CNR)were recorded and compared.Besides,overall image quality and insulinoma depiction were also compared.ANOVA and Friedman's test were performed.Results The image noise decreased and the SNR of pancreas increased with the increase in averaging time points(all P0.99)and were higher than that of the first group(all P<0.05).There was no significant difference in overall image quality among the 5 groups(P=0.977).Conclusions Image averaged from 5 scans showed moderate image noise,pancreas SNR and relatively high lesion contrast and lesion CNR.Therefore,it is advised to be used in image averaging to detect insulinoma.

Lanreotide and diazoxide have comparable effects on glucose levels in an elderly Japanese insulinoma patient: a case report / Journal of Rural Medicine

An insulinoma is a pancreatic neuroendocrine tumor that causes hypoglycemia. In the elderly, as surgery is not always possible, drugs are an important alternative. However, the effects of lanreotide on insulinomas have not yet been elucidated. We report the case of an 85-year-old Japanese woman who was admitted for loss of consciousness and hypoglycemia, which was resolved after intravenous glucose infusion. Insulin secretion was not inhibited during hypoglycemia. Enhanced computed tomography and OctreoScan scintigraphy revealed a pancreatic tumor (diameter, 13 mm) with radiotracer accumulation. Thus, clinical insulinoma was confirmed. However, the patient refused further examination and surgery. Diazoxide (150 mg/day) therapy resolved hypoglycemia but caused fluid retention. Consequently, we switched to lanreotide (120 mg/6 weeks). Continuous glucose monitoring revealed that both drugs had comparable effects on interstitial glucose normalization. Furthermore, 447 days after the initiation of lanreotide treatment, the patient had no hypoglycemic symptoms. Therefore, lanreotide may be a useful alternative treatment option for inoperable insulinomas in elderly individuals.

Hipoglucemia hiperinsulínica en un adulto con nesidioblastosis / Hyperinsulinic Hypoglycemia in an Adult with Nesidioblastosis

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)

Unique position of a pancreatic head insulinoma during laparoscopic enucleation: case report

Insulinomas are benign pancreatic neuroendocrine tumors that require surgical intervention as a therapeutic measure. We describe an 18-year-old male patient who presented to the emergency department with a history of syncope, blurred vision, and diaphoresis. His blood sugar level was low upon admission, and a 72-hour fasting plasma glucose test showed low serum glucose, high serum insulin, and high C-peptide. An abdominal computed tomography scan and magnetic resonant imaging revealed a solitary tumor in the pancreatic head with no sign of ductal dilatation. Laparoscopic enucleation was performed, and a histopathological examination revealed findings consistent with insulinoma. The patient’s postoperative course was uneventful, and his follow-up examination was unremarkable. In conclusion, physicians should have a high clinical suspicion index for insulinomas, especially in young patients with a history of syncope, blurred vision, and diaphoresis, in order to avoid delayed diagnosis.

You are not yourself when you are hungry: a rare case of malignant insulinoma

We present a rare case of high-grade functional neuroendocrine carcinoma of the pancreas secreting insulin. Our patient, an 80 years old woman, presented with neuropsychiatric symptoms consistent with hypoglycaemia that regressed with food intake and dextrose administration. Abdominal imaging showed a pancreatic tumour with invasion of the spleen and lymph node metastasis, highly suggestive of an insulinoma as the cause of the hypoglycaemia. The patient underwent left pancreatectomy with splenectomy and atypical gastric resection. The postoperative course of our patient was uneventful, with complete remission of the hypoglycaemic episodes, and the definitive histological examination showed three poorly differentiated large cell neuroendocrine carcinomas of the pancreas.

A rare case of recurrent hypoglycaemia

Very often clinicians are confronted with unconscious patients; the cause being hypoglycaemia. In addition to correction of hypoglycaemia promptly, a search for the cause of hypoglycaemia must be attempted at the earliest with a stepwise approach. Here, the authors present a rare case of recurrent hypoglycaemia where a stepwise approach ultimately led to a diagnosis, but there were various reports which were misleading. The diagnosis was insulinoma which was apparent from the history and presenting features. But, the initial investigations, even though having high sensitivity, were normal, thus leading to a more invasive approach. The patient was ultimately cured by enucleation.

Diabetes posterior a tratamiento no quirúrgico de un insulinoma maligno: reporte de caso y revisión literatura / Diabetes after non-surgical treatment of a malignant insulinoma: Case report and literature review

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.

Anesthesitic management for insulinoma resection in a patient having chronic inflammatory demyelinating neuropathy / Manejo anestésico para resección de insulinoma en un paciente portador de neuropatía desmielinizante crónica

Chronic Inflammatory Demyelinating Polyneuropathy associated with hypoglycemia 2 to insulinoma is unusual, and to our knowledge, very few patients have been reported in literature. Despite varying presentations in these patients, the clinical characteristics are usually the same. The syndrome usually occurs after several episodes of protracted hypoglycemia. The neuropathy is nearly always symmetrical. We report anesthetic management for a young female patient presenting with CIDP & repeated hypoglycemic episodes during a 2-year period scheduled for insulinoma enucleation.

La polineuropatía desmielinizante inflamatoria crónica asociada con hipoglicemia secundaria a insulinoma es inusual y, hasta donde sabemos, muy pocos pacientes han sido reportados en la literatura. A pesar de las diferentes presentaciones en estos pacientes, las características clínicas suelen ser las mismas. El síndrome generalmente ocurre después de varios episodios de hipoglicemia prolongada. La neuropatía es casi siempre simétrica. Presentamos el manejo anestésico para una paciente joven que se presenta con polineuropatía desmielinizante inflamatoria crónica y episodios repetidos de hipoglicemia durante un período de 2 años programado para la enucleación de insulinoma.

Correlation of Intravoxel Incoherent Motion-derived Parameters with Computer Tomography Perfusion Parameters in Insulinoma / 中国医学科学院学报

To prospectively evaluate the correlation between intravoxel incoherent motion (IVIM)-derived parameters and CT perfusion parameters as well as the pathological grade in insulinoma. 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. ADC and D values of pancreatic tail were significantly lower than those of the pancreatic head and neck (all 0.05). 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.

Descripción de la experiencia en pacientes diagnosticados con insulinoma. Estudio multicéntrico en Medellín, Colombia / Description of the experience with patients with insulinoma diagnosis. Multicentric study in Medellín, Colombia

RESUMEN Objetivo: describir la experiencia de los pacientes con insulinoma, diagnosticados y tratados entre los años 2002 y 2017 en tres hospitales de la ciudad de Medellín, Colombia. Métodos: estudio descriptivo y retrospectivo de pacientes con criterios bioquímicos para hipoglucemia hiperinsulínica y confirmación histopatológica de insulinoma. Resultados: se estudiaron 19 casos, 10 eran mujeres (52,6 %), la edad media al diagnóstico fue 43 años (D.E 15,5). Hubo cuatro casos de insulinoma multifocal (21,1 %), tres asociados con NEM-1 (15,8 %) y dos malignos (10,6 %). Todos presentaron hipoglucemia en ayunas y 63,2 % posprandial. En la prueba de ayuno, el nadir de glucemia sucedió antes de 48 horas en todos los casos, en promedio 9 horas (D.E 8,0). El diagnóstico bioquímico fue realizado con hipoglucemia e insulina elevada en todos los casos, aunque el péptido C fue reportado en nueve pacientes (47,3 %) y las sulfonilureas en dos (11,1 %). La localización preoperatoria se hizo por imágenes en 12 individuos (68,5 %) y las pruebas invasivas fueron necesarias en seis (31,5 %). Las pruebas diagnósticas fueron positivas en un 83 % para resonancia, 50 % para ecografía endoscópica y prueba de estímulo intraarterial con calcio y 100 % para ecografía intraoperatoria. La cirugía se realizó en 18 casos (94,7 %). La mortalidad (15,8 %) fue derivada de complicaciones en el posoperatorio temprano; la curación se logró en todos los casos. Conclusiones: el insulinoma en nuestro medio tiene características demográficas y clínicas similares a otras series. Existen limitaciones locales para el acceso a los estudios bioquímicos y en el rendimiento diagnóstico de las pruebas de localización.

SUMMARY Objective: The objective of the study was to describe the characteristics of patients with insulinoma in three hospitals in Medellín, Colombia, between 2002 and 2017. Methods: A retrospective analysis of patients with hyperinsulinemic hypoglycemia and histologic confirmation of insulinoma was conducted. Results: A total of 19 cases were identified. Ten women (52.6 %) and 9 males (47.4 %). The mean age at diagnosis was 43 years (S.D: 15.5). Four cases had multifocal insulinoma (21.1%), 3 cases were secondary to multiple endocrine neoplasia type 1 (15.8 %), and 2 of them were malignant (10.6 %). All patients presented fasting hypo-glycemia, and 63.2% presented post-prandial hypoglycemia. Glucose nadir in the fasting test occurred in the first 48 hours in all cases, with a mean time to hypoglycemia of 9 hours (S.D 8.0). The biochemical diagnosis was done with increased insulin in the presence of hypoglycemia. C-peptide was done in 9 patients (47.3 %), and sulfonylureas in 2 cases (11.1 %). Preoperative localization was done by imaging in 12 cases (68.5 %), and invasive tests were required in 6 cases (31.5 %). Localization tests were positive as follows: magnetic resonance imaging in 83%, endoscopic ultrasound in 50%, selective intra-arterial calcium injection in 50 %, and intraoperative ultrasound in 100%. Eighteen patients (94. 7%) underwent surgery. Mortality (15.8 %) was secondary to early post-operative complications. Conclusions: The characteristics of patients with insulinoma in Medellín are similar to other series. However, there are important local limitations for proper biochemical testing and imaging localization. This is the largest study in our country.

Recidiva tardía de insulinoma. Asociación con otras patologías

RESUMEN El insulinoma es un tumor neuroendocrino que se caracteriza por la producción de insulina. En individuos con MEN representa entre el 10 y el 30% de los tumores pancreáticos. Las metástasis son poco frecuentes. Presentamos el caso de una recidiva de un tumor productor de insulina después de varios años de la primera cirugía. La presencia de otras lesiones sugería un posible síndrome MEN1 aunque el estudio genético fue negativo. El hecho de que resultase negativo no descarta la posibilidad de que la paciente padezca el síndrome dado que hasta un 5-25% puede no tener mutación en dicho gen. El manejo del insulinoma a veces es complejo. Everolimus puede ser una opción de tratamiento en estos pacientes.

ABSTRACT Insulinoma is a pancreatic neuroendocrine tumor characterized by the production of insulin and represents 10 to 30% of pancreatic tumors in individuals with MEN 1. The metastases are rare. We present a recurrent pancreatic neuroendocrine tumor producing insulin after several years of the first surgery. The presence of other lesions suggests the possibility of a MEN1 syndrome; even the genetic study was negative. This fact does not rule out that the patient suffers from the syndrome since up to 5-25% ofthe reported cases with MEN1 syndrome may not have mutations. Management of these tumors may be complex Everolimus is a treatment option in these patients.

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells / 中国结合医学杂志

OBJECTIVE@#To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells.@*METHODS@#Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting.@*RESULTS@#The half-maximal inhibitory concentration (IC) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 μmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 μmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade.@*CONCLUSION@#High concentration (5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.

Type 2 diabetes coincides with insulinoma: One case report and literature review / 中华内分泌代谢杂志

Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells, which clinically manifests Whipple′ s triad and recurrent hypoglycemia. Insulinoma in a patient with type 2 diabetes mellitus is even a more rarely encountered case. In clinical practice, hypoglycemia in patients with diabetes is often considered to be associated with oral hypoglycemic agents, but insulinoma, as a possible etiology, is usually neglected. This article reported a case of a patient with type 2 diabetes mellitus, before the diagnosis of which she had experienced recurrent hypoglycemia for about 14 years. Hypoglycemia symptoms with hyperinsulinemia kept existing even after the withdrawal of antidiabetic agents. The pancreatic imaging and postoperative histopathology supported the diagnosis of insulinoma. After surgery, plasma glucose level of the patient increased and diabetes treatments continued. The co-existence of insulinoma and type 2 diabetes mellitus in this case may be attributed to the insulin resistance induced by chronic hyperinsulinemia due to insulinoma.

Relationship between the changes of plasma levels of leptin and obesity in patients with insulinoma / 中华消化杂志

Objective To analyze the relationship between the changes of fasting plasma level of leptin and obesity in patients with insulinoma before operation.Methods From January 2003 to May 2008,40 patients with insulinoma diagnosed at Peking Union Medical College Hospital were selected.Preoperative fasting plasma samples of them were collected.From January 2003 to May 2008,the plasma samples of 28 volunteers matched with age,gender and body weight matched with the patients were collected as the controls.All the subjects were divided into overweight-obesity group and normal weight group according to their body mass index (BMI).Plasma levels of leptin of all the subjects were measured by enzyme linked immunosorbent assay (ELISA).The Mann-Whitney U test and the correlation coefficient test were used for statistical analysis.Results The plasma leptin level of patients with insulinoma was 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL),which was higher than that of the control group (0.29 ng/mL,0.25 ng/mL to 1.15 ng/mL),and the difference was statistically significant (U =324.50,P =0.003).In the normal-weight group,the plasma leptin level of the patients with insulinoma was 0.35 ng/mL (0.27 ng/mL to 0.62 ng/mL),which was higher than that of the control group (0.28 ng/mL,0.25 ng/mL to 0.37 ng/mL),and the difference was statistically significant (U =28.000,P =0.001).While in the overweight-obesity group,the plasma leptin levels of the patients with insulinoma and the controls were 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL) and 0.34 ng/mL (0.26 ng/mL to 1.15 ng/mL),respectively,and the difference was not statistically significant (U =153.500,P =0.525).Plasma leptin levels in both the patients with insulinoma and the controls,were correlated with BMI (r =0.355,P =0.025;r =0.571,P =0.001,respectively).Conclusion Preoperative fasting plasma level of leptin increase in patients with insulinoma which is correlated with BMI.