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.

Insulinoma descubierto en paciente con aparente trastorno mental: reporte de un caso / Insulinoma found in patient with apparent mental disorder: a case report

El Insulinoma pancreático es un tumor neuroendocrino de las células beta de los islotes de Langerhans, tiene una incidencia de 4 casos por 1 000 000 habitantes. Se reporta el caso de una mujer de 36 años con alteración del comportamiento asociado a melancolía. Psiquiatría describe un examen mental anormal y diagnosticó depresión doble; sin embargo, la paciente tuvo la triada de Whipple y razón insulina/glucosa mayor a 0,3. El insulinoma fue localizado mediante resonancia magnética y tratado con cirugía. Los insulinomas pueden simular trastornos mentales, dificultando un diagnóstico temprano. Se compara los datos de la atención médica en nuestra localidad con otros obtenidos de la literatura a nivel mundial. Concluimos que a pesar de las limitaciones técnicas se debe incluir al insulinoma en el diagnóstico diferencial de trastornos mentales con hallazgo de hipoglucemia.

Pancreatic Insulinoma is a neuroendocrine tumor of the beta cells of the islets of Langerhans, has an incidence of 4 cases per 1 000 000 persons. We report the case of a 36-year-old woman with altered behavior associated with melancholy. Psychiatry describes an abnormal mental examination and diagnosed double depression; however, the patient had the Whipple triad and insulin/glucose ratio higher than 0.3. The insulinoma was localized by magnetic resonance imaging and treated with surgery. Insulinomas can mimic mental disorders, making early diagnosis difficult. We compare health care data in our locality with others obtained from the global literature. We conclude that despite the technical limitations, insulinoma should be included in the differential diagnosis of mental disorders with hypoglycemia.

Hiperinsulinismo endógeno: dois desafios diagnósticos / Endogenous hyperinsulinism: two diagnostic challenges

A hipoglicemia em um adulto aparentemente saudável é um achado raro na prática clínica que exige uma investigação exaustiva da causa. A identificação de glicemia plasmática diminuída associada a concentrações plasmáticas de insulina e peptídeo-C não suprimidos deverá levar à exclusão de causas raras de hipoglicemia, entre elas, doença das células betapancreáticas e hipoglicemia autoimune. Neste artigo, descrevemos dois casos de hipoglicemia associada a hiperinsulinismo endógeno, cujas causas são pouco habituais na prática clínica. A propósito desses casos clínicos revemos aspectos importantes de diagnósticos e tratamento da hipoglicemia no contexto de hiperinsulinismo endógeno.

Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately high levels of insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia, including pancreatic islet-cells disease and autoimmune hypoglycemia. In this paper, we describe two cases of hypoglycemia associated with endogenous hyperinsulinism, whose causes are uncommon in clinical practice, and review important aspects of the diagnosis and treatment of hyperinsulinemic hypoglycemia.

Estados hiper e hipoglicêmicos agudos: conduta atual / Acute hyper and hypoglycaemic states: current conduct

Os estados hiperglicêmicos e hipoglicêmicos agudos são exemplos das mais comuns emergências médicas com que nos deparamos no campo das alterações do metabolismo. Os estados hiperglicêmicos agudos compreendem a cetoacidose diabética e o coma hiperosmolar hiperglicêmico não cetótico. Neste artigo, analisamos essas condições hiperglicêmicas, que representam um desafio para o clínico e o médico generalista que trabalham no terreno nas emergências médicas

The acute hypoglycemic and hyperglycemic situations are examples of the most common medical emergencies that we face in the field of metabolic disorders. The acute hyperglycemic situations include diabetic ketoacidosis and hyperosmolar hyperglycemic coma hyperosmolar nonketotic. In this article, we analyze these two hyperglycemic conditions that represent a challenge to the clinician and general practitioner working in the field in medical emergencies

Síntomas psiquiátricos e insulinoma: reporte de caso / Psychiatric symptoms and insulinoma: a case report

Insulinomas are pancreatic endocrine neoplasms with a low incidence between 1-4 cases per million per year. Case description: A female 49 years-old with neurological and psychiatric symptoms were treated for two years as a psychiatric patient. Presented a glucose value, which reflects hypoglycemia. The patient was operated with resolution of symptoms. Conclusion: Assess all patients with psychiatric symptoms and perform a complete medical history and laboratory findings, being the most opportune glucose...

Insulinoma: diagnóstico y tratamiento tras 5 años de manejo psiquiátrico / Insulinoma: diagnosis and treatment after 5 years of psychiatric management

El insulinoma es un tumor endocrinológico derivado de las células beta del páncreas, de baja frecuencia y de mayor prevalencia en la 5a década de la vida. Son pequeños, benignos y únicos, en la mayoría de los casos. Presentamos un caso, diagnosticado en el Servicio de Medicina Interna del Hospital Regional de Talca, en una paciente de 38 años de edad con antecedentes de depresión de 5 años de evolución en tratamiento farmacológico, que ingresó para estudio de hipoglicemias de larga data, persistentes, de ayuno. Se objetivaron hipoglicemias de ayuno e insulinemia inapropiadamente alta. TAC abdomen con contraste demostró masa hipervascular en relación al páncreas. Se realizó resección quirúrgica del tumor y el estudio inmunohistoquímico confirmó insulinoma. La evolución postoperatoria fue satisfactoria, con normalización de glicemias y notable mejoría de su cuadro depresivo.

Insulinoma, presentación y evolución de dos casos clínicos / Insulinoma, evolution and presentation of 2 clinical cases

Insulinoma is a very uncommon tumor in children, with an incidence in adults of 2 per million inhabitants. Clinical manifestations include neuroglycopenic or autonomic manifestations due to hypoglycemia. We describe 2 pediatric patients with insulinoma, characterized by repeated episodes of hypoglycemia associated to high insulin serum levels and presence of a small mass in the pancreas by imaging studies. The diagnosis was very prompt in one case and delayed in the other, emphasizing the need for an appropriate diagnosis of hypoglycemia during childhood.

El insulinoma es un tumor muy infrecuente en la edad pediátrica y la incidencia reportada en adultos es de 2 casos por millón de habitantes. La presentación de la enfermedad consiste en la presencia de síntomas neuroglicopénicos y autonómicos desencadenados por los episodios de hipoglicemia. Se describen dos pacientes con insulinoma esporádico. El cuadro clínico consistió en episodios repetidos de hipoglicemia asociados a niveles aumentados de insulina sérica y a imágenes sugerentes de un tumor pancreático. El diagnóstico fue muy oportuno en uno de los casos y muy tardío en el otro, lo que resalta la necesidad de estar muy alerta ante casos de hipoglicemia durante la niñez.

Insulinoma induced hypoglycaemia in a Jamaican patient / Hipoglicemia inducida por insulinoma en un paciente de Jamaica

Herein reported is the case of a young woman who had hyperinsulinaemic hypoglycaemia which was biochemically consistent with an insulinoma. Initial imaging was negative and definitive treatment was delayed until repeat imaging localized the tumour several years later. This case demonstrates the importance of clinical judgment and biochemical testing in the diagnosis of insulinoma despite negative imaging.

Aquí se reporta el caso de una joven que presentó hipoglicemia hiperinsulinémica, bioquímicamente concordante con un insulinoma. La imagen inicial fue negativa y el tratamiento fue retardado hasta que mediante la repetición de la técnica de imaginología años más tarde localizó el tumor. Este caso demuestra la importancia de juicio clínico y las pruebas bioquímicas en el diagnóstico del insulinoma, especialmente frente a la obtención de una imagen negativa.

Insulinoma apresentando-se como crise convulsiva: relato de caso / Insulinoma presenting as seizure: case report

O insulinoma é doença rara que cursa com sintomas episódicos neuroglicopênicos e/ou adrenérgicos. Descrevemos o caso de uma paciente de 36 anos, que estava sendo tratada por crises convulsivas parciais complexas há 4 anos sem melhora do quadro. Apresentava história de vários episódios de crise convulsiva associada a hipoglicemia marcante. Tomografia de crânio e eletrencefalograma eram normais. No teste de jejum de 72 horas evidenciaram-se sintomas hipoglicêmicos, que eram revertidos com reposição de glicose, associados com insulina e peptídeo C elevados. A localização do insulinoma foi possível apenas após laparotomia exploradora; os métodos de imagem utilizados não revelaram o tumor. O exame histopatológico confirmou neoplasia endócrina diferenciada. Concluímos que a dosagem da glicemia deve fazer parte da investigação de transtornos convulsivos ou do comportamento, pois o insulinoma pode inicialmente apresentar-se desta forma.

Insulinoma--a case report.

Insulinoma is a rare pancreatic endocrine tumour characterised by hyperinsulinemic hypoglycemia. It is important to surgically remove this tumour as it can cause potentially lethal hypoglycemia. We report a case of insulinoma presenting with unconsciousness following repeated episodes of inability to arise from sleep and convulsions. Biochemical investigation revealed hypoglycemia and hyperinsulinemia. The diagnosis of Insulinoma is often delayed due to misattribution of symptoms to psychiatric or neurological disorders. In this case, same delay lead to fatal outcome for this patient.

The surgical management of insulinoma

Insulinoma is the most common endocrine tumor of the pancreas. Over 90 of the insulinomas are benign and single, and can be cured by simple excision. Depending on the location, insulinomas can be enucleated, might require partial or distal pancreatectomy or pancreaticoduodenectomy. Five cases with insulinoma successfully treated by surgical intervention, two by enuclation, two by distal pancreatectomy and splenectomy, and preservation of the spleen have been summarized. The management of insulinoma involves the diagnosis, localization of the tumor and treatment. Insulinomas are rare tumors of the pancreas. Nevertheless, it is the most common endocrine tumor of the pancreas. Specifically arising from the beta cells, of the islets of Langerham, that produce insulin (fig.1). Its incidence is one in 250,000 inhabitants. It can be seen at any age, but is more frequent in females between 4 and 82 years of age, with a mean of 45.5 years. Insulinomas are evenly distributed between the head, body and tail of the pancreas. Over 90 are benign and single and can be cured by simple excision. Depending on the location insulinomas can be enucleated, might require partial or distal pancreatectomy or a pancreaticoduodenectomy. Ten percent could be malignant when metastasis to peripancreatic lymph nodes or to the liver is detected. The course of the patient with malignant insulinoma is an indolent one. The release of insulin leads to fasting hypoglycemia producing confusion, loss of consciousness, coma or convulsions. The hypoglycemia in turn can induce the release of cathecolamines producing tachycardia, tremulousness and diaphoresis. The Whipple's triad must be present for the diagnosis of insulinoma; symptoms of hypoglycemia, glucose level below 50 mgs/dl and relief of symptoms by the administration of glucose. In large series the interval between the onset of symptoms and a definitive diagnosis of insulinoma was 37 months, with a range of 0 to 14 years

Insulinoma in childhood.

A 9-year-old boy with convulsions is herein described. He was diagnosed and treated for epilepsy and insufficient adrenal function for four years with no response. Hypoglycemia from hyperinsulinism was found and the source of the hyperinsulinism was a tumor of the tail of the pancreas--located by computerized tomographic scan and magnetic resonance imaging. Distal pancreatectomy was performed with good results. Histology of the tumor showed islet cell tumors with capsular invasion. For this type of patient, long-term follow-up should include: prevention of metastasis or recurrence, and testing for multiple endocrine neoplasia type 1.

Malignant insulinoma presenting with recurrent episodic loss of consciousness.

A 57 year old male presented with episodic behavioural abnormalities and loss of consciousness for 2 years. His fasting blood glucose was 20 mg/dl and corresponding insulin level 119 uU/ml. His EEG showed intermittent rhythmic delta activity. Abdominal CT scan revealed an enhancing mass in the tail of the pancreas and secondaries in the liver. After distal pancreatectomy, resection of the left lobe of the liver and chemotherapy, the hypoglycaemic spells subsided. Histopathology revealed an islet cell tumour with metastases in the liver. Episodic neurobehavioural dysfunction should alert towards the possibility of hypoglycaemia.

Polineuropatia hipoglicêmica: registro de caso com insulinoma / Hypoglycemic polyneuropathy: report of a case with insulinoma

Os autores registram o caso de jovem do sexo masculino que desenvolveu polineuropatia sensitivo-motora, com grande amiotrofia das mäos, no curso de crises de hipoglicemia, provocadas por provável insulinoma. A eletroneuromiografia revelou predominância de alteraçöes axonais. O nervo sural, estudado à microscopia óptica e eletrônica, mostrou perda axonal de fibras mielínicas de grande calibre e de fibras amielíncias. Consideraçöes sobre a etiopatogenia desta síndrome säo feitas, parecendo ser devida a hipoglicemia e näo a excesso de insulina