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.

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult

ABSTRACT Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), without previous bariatric surgery, is a rare form of hypoglycemia in adult patients and is associated with nesidioblastosis. Adult-onset nesidioblastosis in diabetic patients is rare and histologically identical to "non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)". Nesidioblastosis is rare in adults and clinically and biochemically mimics Insulinoma. In the literature, there have only been four cases of adult nesidioblastosis that followed diabetes mellitus. We report a case of nesidioblastosis in a 36-year-old diabetic female presenting with dizziness, sweating, and palpitations for three years. Selective non-invasive techniques failed to detect a tumor. Based on the pursuit of an insulinoma, a distal pancreatectomy specimen was received at our laboratory, and a diagnosis of nesidioblastosis was made. She is currently on follow-up with a favorable outcome. The definitive diagnosis of nesidioblastosis is made on a histological basis. The preferred form of treatment is pancreatic surgical resection. Nesidioblastosis should be taken into consideration in cases where diabetes transforms into hyperinsulinemic hypoglycemia.

Nesidioblastosis del adulto. Informe de un caso / Adult's Nesidioblastosis. Case report

Resumen La nesidioblastosis del adulto es rara. Se define como cambios en el páncreas endocrino caracterizado por la proliferación anormal de las células de los islotes pancreáticos, que afecta en forma difusa a la glándula, y que causa hipoglucemia hiperinsulinémica persistente en ausencia de un insulinoma. Se presenta el caso de un paciente que ingresa en el servicio de medicina interna del Hospital "Dr. Gustavo Aldereguía Lima" de Cienfuegos con un síndrome hipoglucémico para estudio. Se le realizó prueba de tolerancia a la glucosa oral de 6 h con hipoglucemia (1.9mmol/L) a la hora 5. Prueba de ayuno de 72h: con hipoglucemia a las 2 h con respuesta paradójica de la insulina, glicemia e insulinemia con los síntomas. En la tomografía axial computarizada abdominal multicorte no se evidenció lesión en el páncreas. Se realiza pancreatectomía distal de ± 85% de la glándula con conservación esplénica. La anatomía patología confirmó nesidioblastosis. La nesidioblastosis del adulto es una entidad muy poco frecuente, pero debe ser tenida en cuenta como diagnóstico diferencial de los insulinomas ante la ausencia de lesión evidente en los estudios convencionales de imágenes.

ABSTRACT Adult nesidioblastosis is rare, defined as changes in the endocrine pancreas characterized by abnormal proliferation of pancreatic islet cells, diffusely affecting the gland, and causing persistent hyperinsulinemic hypoglycemia in the absence of an insulinoma. A case of a patient who is admitted to the internal medicine service at the "Dr. Gustavo Aldereguía Lima" Cienfuegos Hospital with a hypoglycemic syndrome for study. A 6-hour oral glucose tolerance test was performed with hypoglycemia (1.9mmol / L) at hour 5. 72-hour fasting test: with hypoglycemia at 2 hours with a paradoxical response to insulin, Glycemia and Insulinemia with the symptom. In the multislice abdominal computerized axial tomography, no lesion in the pancreas was evidenced. A distal pancreatectomy of ± 85% of the gland is performed with splenic preservation. The pathology anatomy confirmed nesidioblastosis. Nesidioblastosis in adults is a very rare entity, but it should be taken into account as a differential diagnosis of insulinomas in the absence of an evident lesion in conventional imaging studies.

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)

Hiperplasia de células neuroendocrinas que simula tumor sólido de páncreas / Neuroendocrine cell hyperplasia mimicking a solid pancreatic tumor

RESUMEN La hiperplasia de células neuroendocrinas pancreáticas es una patología donde se produce un aumen to en el número de células de los islotes de Langerhans y a veces puede simular un proceso tumoral. Caso clínico: presentamos el caso de un paciente con tumor sólido de cola de páncreas, sintomático, al que se le realizó esplenopancreatectomía corporocaudal laparoscópica. El resultado anatomopatoló gico posterior informó una hiperplasia neuroendocrina. Conclusión: la hiperplasia de células neuroen docrinas debería considerarse en el diagnóstico diferencial de tumores sólidos de páncreas. La alterna tiva quirúrgica laparoscópica es factible cuando no es posible establecer el diagnóstico prequirúrgico con estudios de imágenes o biopsia.

ABSTRACT Pancreatic endocrine cell hyperplasia is defined as an increase in the number of cells of Langerhans islets and can sometimes mimic a tumoral process. Case report: a male patient with a symptomatic solid tail of pancreas tumor underwent laparoscopic distal pancreatectomy and splenectomy. The pathological examination reported neuroendocrine cell hyperplasia. Conclusion: pancreatic endocrine cell hyperplasia should be considered in the differential diagnosis of solid pancreatic tumors. Laparoscopic surgery is feasible when the preoperative diagnosis with imaging tests of biopsy is not possible.

Islets of hypoglycaemia: a rare case of adult onset nesidioblastosis

A case of diffuse nesidioblastosis in an adult patient is reported in this study. A 24-year-old female with no known comorbidities presented with multiple episodes of documented recurrent hypoglycaemia and Hypoglycaemia induced seizures both in fasting and postprandial state. Her blood investigations revealed low plasma glucose levels, high insulin and C-peptide levels with positive 72-hour fast test. Her transabdominal USG and CECT abdomen did not reveal any abnormality, 68Ga DOTANOC PET CT done showed ill-defined diffuse somatostatin receptor expression in the pancreatic head and tail suggestive of nesidioblastosis. As patient was not willing for surgical treatment, hence started on medical treatment with oral nifedipine. Nesidioblastosis is very rare in adults. It is an important differential diagnosis in adults with hyperinsulinemic hypoglycemia although the incidence is very rare in adults. PET SCAN was used to non-invasively diagnose nesidioblastosis in this case. Surgery being the preferred choice of treatment in nesidioblastosis, there is limited data on medical line of management in nesidioblastosis.

Hipoglicemia posprandial secundaria a síndrome dumping / Postprandial hypoglycemia secondary to dumping síndrome

La hipoglicemia en pacientes no diabéticos se define como un nivel sérico menor de 55 mg/dL que puede ser parte de la tríada de Whipple (síntomas de hipoglicemia, niveles bajos de glucosa sérica y resolución de la sintomatología tras la normalización de la glicemia). Puede ser mediada o no por insulina, dando manifestaciones en ayunas (posabsorptiva) o posprandiales (reactiva). Con el aumento de la cirugía bariátrica se ha observado una mayor incidencia de complicaciones como la hipoglicemia posprandial por el síndrome de dumping. Presentación del caso: paciente con antecedente de cirugía bariátrica y evidencia posoperatoria de hipoglicemia posprandial. Las pruebas de ayuno y de alimentos mixtos confirmó el síndrome de dumping. Discusión y conclusiones: la hipoglicemia es una urgencia médica frecuente, en la mayoría de los casos secundaria al uso de medicamentos en pacientes con diabetes mellitus. No obstante, en los no diabéticos puede presentarse de forma espontánea y estar relacionada con múltiples condiciones clínicas. En el posoperatorio de cirugía bariátrica, la aparición del síndrome de dumping puede ser incapacitante, con manifestaciones tempranas o tardías. El diagnóstico se basa en la clínica y en estudios funcionales e imagenológicos que confirmen la presencia de hipoglicemia posprandial y un rápido vaciamiento gástrico. El tratamiento inicial se basa en cambios en la alimentación, aunque pueden ser necesarios fármacos e incluso procedimientos quirúrgicos cuando hay refractariedad. Es por esto que la elección de los pacientes llevados a cirugía bariátrica debe ser realizado por un grupo multidisciplinario.

Hypoglycemia in non-diabetics has been defined as a post-prandial glucose level of less than 55 mg/dl which may be part of Whipple ́s triad (symptoms of hypoglycemia, low plasma glucose and relief of symptoms with the correction of low glucose). It may be mediated by insulin or may not be mediated by insulin, with fasting (postabsorbative) or postprandial (reactive) manifestations. The incidence of complications, such as, postprandial hypoglycemia related to dumping syndrome, has increased with the use of bariatric surgery. A case is presented in a patient who underwent bariatric surgery experiencing postoperative postprandial hypoglycemia. Dumping syndrome was confirmed by fasting and mixed-meal tests. Discussion and Conclusions: hypoglycemia is a common medical emergency and is usually secondary to medications used to treat diabetes. However, it may be spontaneous in non-diabetics and may be associated with multiple clinical disorders. Postoperative dumping syndrome following bariatric surgery may be disabling, with early or late manifestations. Diagnosis is based on symptoms and functional and imaging studies which confirm postprandial hypoglycemia and a rapid gastric emptying. Initial treatment is based on dietary modification, although medical therapy or surgical intervention may be required in refractory cases. Thus, the selection of candidates to undergo bariatric surgery must be conducted by a multidisciplinary group.

Masa pancreática: una presentación inhabitual de nesidioblastosis en el adulto / Pancreatic mass: an unusual presentation of nesidioblastosis in adults

A 41-year-old woman, multiparous of 4, with personal or familiar history of diabetes, with a history of Nissen fundoplication due to pathological gastro-oesophageal reflux, is refer to an endocrinologjst during her post-operatiye follow up, 4 months after her surgery for a 14 kg weight loss in 10 months and symtomatic hypoglycemia to repetition. A positive prolonged fasting test for hypoglycemia was performed. In addition, abdominal computed axial tomography was performed, which resulted normal and endosonography, showing a lesion on the head of the pancreas. Octreoscan positive for pancreatic head focal lesion with positive somatostatin receptors compatible with insulinoma. Whipple surgery was performed where surgeon palpated pancreatic tumor, biopsy showed tissue compatible with diffuse nesidioblastosis. In the postoperative period, the patient decreased frequency and intensity of hypoglycemic episodes compared to their previous stage. Control prolonged fasting test and Octreoscan were within normal ranges. However, 4 months after surgery, the patient presented hypoglycemia of lower intensity and frequency than before surgery. Currently he remains in control with nutritionist and endocrinologist, mainly adjusting diet and with good control glycemias.

Nesidioblastosis del adulto tras derivación gástrica / Nesidioblastosis in the adult following gastric bypass

La hipoglucemia por hiperinsulinismo endógeno ha sido descrita como una complicación de la cirugía bariátrica. Se presenta el caso de un hombre de 34 años con tríada de Whipple que se manifestó ocho años después de someterse a derivación (bypass) gástrica. La hipoglucemia se asociaba con niveles elevados de insulina y péptido C, pero la localización del hiperinsulinismo endógeno solo se pudo precisar mediante cateterismo de arterias pancreáticas con estimulación intraarterial selectiva con calcio. Se decidió practicar una pancreatectomía subtotal laparoscópica, después de la cual el paciente presentó una excelente evolución posoperatoria y mejoró significativamente su sintomatología. Mediante la evaluación histopatológica e inmunohistoquímica, se confirmó una nesidioblastosis del adulto. Es importante reconocer esta enfermedad como una complicación de la cirugía bariátrica, más aún cuando estos procedimientos son tan frecuentes en la actualidad debido a la epidemia de obesidad. Los síntomas se pueden confundir con los de un síndrome de evacuación gástrica rápida (dumping), el cual no tiene repercusiones tan graves sobre la salud del paciente, como sí la tiene la nesidioblastosis

Hypoglycemia due to endogenous hyperinsulinism has been described as a complication of bariatric surgery. We present the case of a 34-year-old man who developed a Whipple's triad eight years after undergoing gastric bypass. Hypoglycemia was associated with high serum levels of insulin and C peptide; anatomic localization of endogenous hyperinsulinism was finally demonstrated with a selective intra-arterial calcium-stimulation test. Patient was offered a laparoscopic subtotal pancreatectomy, which resulted in an excellent postoperative course and significant symptoms resolution. Pathology report and inmunohistochemical analysis confirmed the diagnosis of adult nesidioblastosis. We believe it is important to recognize this condition as a complication of bariatric surgery, a procedure performed more frequently nowadays due to the obesity epidemic. Symptoms might be confused with those of dumping syndrome which does not have severe consequences in the patient´s health as nesidioblastosis does

Difficult diagnosis and localization of focal nesidioblastosis: clinical implications of ⁶⁸Gallium-DOTA-D-Phe¹-Tyr³-octreotide PET scanning

Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. ⁶⁸Gallium-DOTA-D-Phe¹-Tyr³-octreotide PET scanning and ¹¹¹indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results.

Difficult diagnosis and localization of focal nesidioblastosis: clinical implications of ⁶⁸Gallium-DOTA-D-Phe¹-Tyr³-octreotide PET scanning

Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. ⁶⁸Gallium-DOTA-D-Phe¹-Tyr³-octreotide PET scanning and ¹¹¹indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results.

Nesidioblastosis en adolescentes: A propósito de un caso

Objetivos: Describir la presentación de un caso clínico de nesidioblastosis en una paciente adolescente. Caso clínico: Adolescente femenina de 14 años de edad, con inicio de enfermedad actual en Febrero/2013, caracterizada por cefalea de moderada intensidad, concomitantemente diaforesis y mareos; en Marzo/2013 presenta movimientos tónico-clónicos generalizados, retroversión ocular con pérdida del estado de conciencia (en 2 oportunidades), es trasladada a centro médico donde evidencian glucemia en 48 mg/dl y 40 mg/dl respectivamente, colocan solución dextrosa con mejoría. Estudios complementarios revelan: hipoglucemia en ayunas: glucemia 40 mg/dl, para vun valor de insulina de 46,7 μUI/ml; es ingresada realizándose prueba de ayuno de 72 horas, a las 10 horas del inicio de la misma se evidencia triada de Whipple, y las muestras confirmaron hipoglucemia por hiperinsulinismo endógeno; se realizan estudios de localización sin evidencia de lesión. El 24/07/13 se realiza laparotomía abierta. Biopsia post-operatoria reportó: hiperplasia de las células de los islotes de Langerhans. En su post-operatorio tardío presenta síntomas de hipoglucemia. Se sugiere completar la cirugía, se inicia manejo farmacológico con Verapamilo a dosis de 40 mg cada 8 horas, con respuesta satisfactoria. Conclusión: La nesidioblastosis en una causa rara de hipoglucemia por hiperinsulinismo endógeno en el adulto, sin casos reportados en adolescentes, clínicamente es indistinguible del insulinoma; bioquímicamente es necesario documentar la hipoglucemia hiperinsulinémica mediante una prueba de ayuno de 72 horas, los estudios de extensión no aportan datos específicos, el tratamiento de elección es la cirugía, el tratamiento médico está reservado principalmente para casos con alto riesgo quirúrgico y recidivas.

Objectives: To describe a clinical case of nesidioblastosis in a teenage patient. Clinical case: This is a fourteen-year-old female teenage patient, with current illness starting on February/2013 characterized by headache of moderate intensity, concomitantly diaphoresis and dizziness. In March/2013 she presents generalized tonic-clonic movements, ocular retroversion with loss of consciousness (2 opportunities) and is referred to a medical center where they find a glycemia of 48 mg/dl and 40 mg/dl respectively, improving with glucose solution. Since complementary studies revealed fasting hypoglycemia: glycemia 40 mg/dl for insulin value 46.7 μUI/ml, the patient is hospitalized for a 72 hours fasting test, and at 10 hours from the start, a Whipple triad is evidenced, and blood tests confirmed hypoglycemia due to endogenous hyperinsulinism. Localization studies are performed with no evidence of a lesion. On 07/24/2013 an open laparotomy is carried out. Postoperatory biopsy reported: Langerhans islet cell hyperplasia. During late postoperative period, hypoglycemic symptoms reappear. It is suggested to complete surgery and pharmacological management with Verapamil at 40 mg every 8 hours is started, with a satisfactory response. Conclusion: Nesidioblastosis is a rare cause of hypoglycemia by endogenous hyperinsulinism in adults, with no case reports in teenagers. It is clinically indistinguishable from insulinoma and it is necessary to biochemically demonstrate hyperinsulinemic hypoglycemia with a 72 hour fasting test. Imaging studies don’t provide specific data. Surgical treatment is first choice and pharmacological treatment is reserved mainly for high-risk surgical patients and recurrence.

Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. METHODS: To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. RESULTS: Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 microIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. CONCLUSION: The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Nesidioblastosis: hipoglucemia hiperinsulinémica persistente en la infancia / Nesidioblastosis: persistent hyperinsulinemic hypoglycemia in the childhood

Se presentan 2 casos clínicos de recién nacidas que, entre otros síntomas, presentaron cifras bajas de glucemia mantenidas (menores 2,2 mmol/L), por lo que fueron evaluadas en el Servicio de Endocrinología del Hospital Provincial Pediátrico Docente "Eduardo Agramonte Piña" de Camagüey, donde se les diagnosticó nesidioblastosis -- hipoglucemia neonatal persistente --. En una de las pacientes el tratamiento médico resultó favorable, pero en la otra fue necesario realizar la pancreatectomía subtotal. Actualmente ambas afectadas reciben esquemas terapéuticos adecuados a sus necesidades clínicas.

Two case reports of female newborns are presented who, among other symptoms, presented with low concentrations of maintained glucemia (lower than 2,2 mmol/L), so they were evaluated in the Endocrinology Service of "Eduardo Agramonte Piña" Teaching Pediatric Provincial Hospital in Camagüey, where they were diagnosed nesidioblastosis -- persistent neonatal hypoglycemia --. In one of the patients the medical treatment was favorable, but in the other it was necessary to carry out a subtotal pancreatectomy. At present both patients receive therapeutic schedules adjusted to their clinical needs.

A Case of Alpha-cell Nesidioblastosis and Hyperplasia with Multiple Glucagon-producing Endocrine Cell Tumor of the Pancreas / 대한소화기학회지

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.

Hipoglicemia hiperinsulinêmica da infância: Análise de dados clínicos de uma amostra brasileira / Hyperinsulinemic hypoglycemia of the infancy: Analysis of clinical data from a Brazilian sample

OBJETIVO: Rever a apresentação dos casos de hipoglicemia hiperinsulinêmica da infância (HHI), tratamento e histologia nos serviços de endocrinologia pediátrica no Brasil. MATERIAIS E MÉTODO: Os serviços receberam protocolo para resgatar dados de nascimento, resultados laboratoriais, tipo de tratamento instituído, necessidade de pancreatectomia e histologia. RESULTADOS: Vinte e cinco casos de HHI de seis centros foram resgatados, 15 do sexo masculino, 3/25 nascidos de parto normal. A mediana de idade do diagnóstico foi 10,3 dias. As dosagens de glicose e insulina na amostra sérica crítica apresentaram mediana de 24,7 mg/dL e 26,3 UI/dL. A velocidade de infusão de glicose endovenosa foi superior a 10 mg/kg/min em todos os casos (M:19,1). Diazóxido foi utilizado em 15/25, octreotide em 10, corticoide em 8, hormônio de crescimento em 3, nifedipina em 2 e glucagon em 1. Quarenta por cento (10/25) foram pancreatectomizados, nos quais a análise histológica revelou a forma difusa da patologia. CONCLUSÃO: Primeira análise crítica de uma amostra brasileira de portadores de HHI congênita. Arq Bras Endocrinol Metab. 2012;56(9):666-71.

OBJECTIVE: To review the presentation of hyperinsulinemic hypoglycemia of the infancy (HHI), its treatment and histology in Brazilian pediatric endocrinology sections. MATERIALS AND METHOD: The protocol analyzed data of birth, laboratory results, treatment, surgery, and pancreas histology. RESULTS: Twenty-five cases of HHI from six centers were analyzed: 15 male, 3/25 born by vaginal delivery. The average age at diagnosis was 10.3 days. Glucose and insulin levels in the critical sample showed an average of 24.7 mg/dL and 26.3 UI/dL. Intravenous infusion of the glucose was greater than 10 mg/kg/min in all cases (M:19,1). Diazoxide was used in 15/25 of the cases, octreotide in 10, glucocorticoid in 8, growth hormone in 3, nifedipine in 2 and glucagon in 1. Ten of the cases underwent pancreatectomy and histology results showed the diffuse form of disease. CONCLUSION: This is the first critic review of a Brazilian sample with congenital HHI. Arq Bras Endocrinol Metab. 2012;56(9):666-71.

Nesidioblastosis: hipoglucemia hiperinsulínica persistente en un recién nacido / Nesidioblastosis: persistent hyperinsulinemic hypoglycemia in a newborn

Se presenta el caso clínico de un recién nacido a término por parto distócico (cesárea), debido a una toxemia gravídica, con antecedente de polihidramnios, que manifestó dificultad respiratoria a los pocos minutos del nacimiento y fue ingresado en el Hospital Infantil Norte Dr Juan de la Cruz Martínez Maceira de Santiago de Cuba. Le fueron detectadas cifras de glucemia muy bajas que, evolutivamente, trajeron aparejadas convulsiones tónico-clónicas generalizadas, cuyas frecuencias no se lograban disminuir. Se le diagnosticó una hipoglucemia hiperinsulínica persistente (nesidioblastosis) y fue trasladado a La Habana para recibir tratamientos clínico y quirúrgico definitivos. Actualmente es atendido por un equipo médico multidisciplinario

The case of a term infant by dystocia (cesarean section) due to pregnancy toxemia with history of polyhydramnios is presented, who had respiratory distress a few minutes after birth and he was admitted to Dr Juan de la Cruz Martínez Maceira Northern Children Hospital of Santiago de Cuba. Very low blood glucose levels were detected that progressively caused tonic-clonic seizures, which frequencies could not be reduced. He was diagnosed with persistent hyperinsulinemic hypoglycemia (nesidioblastosis) and was transferred to Havana to receive definitive clinical and surgical treatments. Currently, he is treated by a multidisciplinary medical team

A case of adult nesidioblastosis mimicking an insulinoma and autoimmune hypoglycemia / 대한내과학회지

Hyperinsulinemic hypoglycemia in the absence of exogenous insulin use is caused by disorders such as insulinoma, diffuse beta-cell hyperplasia/nesidioblastosis, and autoimmune hypoglycemia. Nesidioblastosis is a rare cause of hypoglycemia in adults, accounting for 0.5~7.0% of organic hyperinsulinemia cases. Although pancreatic resection is considered the best treatment modality for curing nesidioblastosis, there is no consensus regarding the indications for and extent of the surgery due to its high risk and complication rate. A 75-year-old woman presented with an altered mental state, a mass suspected of being an insulinoma, and insulin receptor antibodies. The patient underwent surgery because of recurrent life-threatening hypoglycemia. Postoperative pathology of her pancreas revealed nesidioblastosis.

Nesidioblastosis del adulto coexistente con insulinoma / Adult Nesidioblastosis Concurrent with Insulinoma

La nesidioblastosis es poco común, pero ampliamente reconocida como causa de la hipoglucemia hiperinsulinémica persistente de la infancia. En adultos, el insulinoma es la principal causa de hipoglucemia hiperinsulinémica, pero también se han identificado casos de nesidioblastosis, los cuales se denominan ‘síndrome de hipoglucemia pancreatógena no insulinoma’. Los primeros casos de nesidioblastosis del adulto que fueron descritos se asociaron con otras condiciones, como insulinoma y tumores neuroendocrinos pancreáticos y MEN-1. En este artículo se describe un caso de nesidioblastosis coexistente con insulinoma en una paciente de 20 años; se hace una revisión de la literatura; se plantea la discusión sobre su posible etiología, presentación clínica, diagnóstico, tratamiento y, finalmente, se presenta un algoritmo para su estudio.

Nesidioblastosis is infrequent; however, it is widely recognized as the cause of persistent infant hyperinsulinemic hypoglycemia. Among adults, insulinoma is the major cause of hyperinsulinemia hypoglycemia, but identification has also been made of cases of nesidioblastosis which are designated as ´non insulinoma pancreatogena hypoglycemic syndrome´. The first case descriptions of adult nesidioblastosis were associated with other conditions such as insulinoma and neuroenodocrinal pancreatic tumors, and MEN-1. This article describes a case of nesidioblastosis concurrent with insulinoma in a 20-year old patient; the literature is reviewed; discussion is provided on possible etiology, clinical manifestation, diagnosis, treatment, and a concluding algorithm.

Hypoglycemia due to Focal Nesidioblastosis in a Patient with Type 2 Diabetes Mellitus / 당뇨병

We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.