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.

Indications for genetic study in gastro-entero-pancreatic and thoracic neuroendocrine tumors.

Gastro-entero-pancreatic (GEP-NET) and thoracic neuroendocrine tumours (NETs) are one of the most heritable groups of neoplasms in the body, being multiple endocrine neoplasia syndrome type 1 (MEN1), the genetic syndrome most frequently associated with this type of tumours. Moreover, Von Hippel Lindau syndrome, tuberous sclerosis, type 4 multiple neoplasia syndrome, and type 1 neurofibromatosis are associated with an increased risk of developing GEP-NETs. Another important aspect in GEP-NETs and thoracic NETs is the knowledge of the molecular background since the molecular profile of these tumours may have implications in the prognosis and in the response to specific treatments. This review summarizes the main indications for performing a genetic study in patients with GEP-NETs and thoracic NETs, and the methods used to carry it out. Moreover, it offers a description of the main hereditary syndromes associated with these NETs and their molecular background, as well as the clinical implications of the molecular profile.

RET gene mutational diagnosis and precision medicine in Mexico.

Precision medicine is a reality in some diseases; it supports the development of accurate and specific diagnostic methods, new drugs and molecules. Our research team in Mexico, made up of clinical and biomedical researchers, has been performing free RET gene mutational diagnosis for medullary thyroid cancer and multiple endocrine neoplasia (MEN) 2 and 3 for 20 years. RET pathogenic variants in the Mexican population are consistent with reported data: most common mutations are 634/NEM2 and 918/NEM3. Currently, new nanobiotechnology methods are being developed for this type of determination in order to obtain faster, simpler, more sensitive and specific results applicable in all types of laboratories.

La medicina de precisión en algunas enfermedades es una realidad; respalda el desarrollo de métodos diagnósticos certeros y específicos, de nuevas drogas y moléculas. Nuestro equipo de investigación en México, conformado por investigadores clínicos y biomédicos, desde hace 20 años realiza de forma gratuita el diagnóstico mutacional del gen RET y su relación con el cáncer medular de tiroides y la neoplasia endocrina múltiple (NEM) 2 y 3. Las variantes patogénicas de RET en la población mexicana coinciden con los datos reportados: la mayoría con 634/NEM2 y 918/NEM3. Actualmente se están desarrollando nuevos métodos de nanobiotecnología para este tipo de determinaciones, de tal forma que puedan obtenerse resultados más rápidos, simples, sensibles y específicos aplicables en todo tipo de laboratorio.

Diagnóstico del carcinoma medular de tiroides / Diagnosis of medullary thyroid carcinoma

Introducción: El carcinoma medular de tiroides (CMT) es un tumor maligno neuroendocrino poco frecuente derivado de las células parafoliculares o células C del tiroides. En el momento del diagnóstico presentan metástasis ganglionares más del 50% y a distancia el 10%. Su pronóstico depende en gran parte del estadio del tumor, por lo que su diagnóstico temprano es fundamental.Objetivo: El objetivo de este trabajo es realizar una revisión actualizada sobre el abordaje diagnóstico del CMT.Síntesis: La ecografía es la principal herramienta en la estratificación del nódulo tiroideo, pero la mayor parte de los estudios se han centrado en el carcinoma papilar de tiroides. En el caso del CMT las características ecográficas sospechosas de malignidad suelen ser menos frecuentes y esto podría conducir a un retraso diagnóstico y terapéutico, por lo que se debe combinar con técnicas diagnósticas adicionales. En estos tumores la sensibilidad del estudio citológico del nódulo mediante punción aspiración con aguja fina generalmente es baja, y en aquellos casos de sospecha de CMT se recomienda realizar inmunohistoquímica para calcitonina y determinar la calcitonina en el aspirado de la punción. La calcitonina plasmática es el marcador más sensible para el diagnóstico de estos pacientes, pero su determinación rutinaria en el estudio del nódulo tiroideo es controvertida. Sus niveles se relacionan con la masa de células C y la presencia de metástasis ganglionares. Si son superiores a 500 pg/ml se recomienda realizar estudio de extensión con pruebas de imagen complementarias por sospecha de enfermedad metastásica. Es importante solicitar estudio genético a todos los pacientes, ya que el 25% son hereditarios formando parte de la neoplasia endocrina múltiple tipo 2 asociada a mutación en el gen RET. (AU)

Introduction: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignant tumor derived from the parafollicular cells or thyroid C cells. At the time of diagnosis, over 50 % of patients have lymph node metastases, and 10 % have distant metastases. Prognosis is largely dependent on tumor stage and, therefore, early diagnosis is essential. Objective: The aim of this work is to present an updated review of the diagnostic approach for MTC. Summary: Thyroid ultrasound is the main tool used for thyroid nodule stratification; however, most studies have focused on papillary thyroid carcinoma. In MTC, ultra-sonographic findings suggestive of malignancy are usually less frequent and this could delay diagnosis and treatment. Therefore, ultrasound examination should be combined with additional diagnostic techniques. The sensitivity of the fine-needle aspiration cytology is generally low for these types of tumors and when MTC is suspected, it is recommended to perform immunohistochemical for calcitonin and measurement of calcitonin in washout fluid of thyroid nodule aspirate. Serum calcitonin is the most sensitive marker for diagnosing this condition; however, its routine measurement in the evaluation of thyroid nodule is contro-versial. Serum calcitonin levels are related to C-cell mass and the presence of lymph node metastases. When these levels are above 500 pg/mL suggest distant metastatic disease and additional imaging procedures are indicated. Genetic testing should be offered to all patients because 25 % of these carcinomas are hereditary and are part of multiple endocrine neoplasia type 2 syndrome associated with a germline RET mutation. (AU)

Diagnóstico mutacional del gen RET y la medicina de precisión en México / RET gene mutational diagnosis and precision medicine in Mexico

Resumen La medicina de precisión en algunas enfermedades es una realidad; respalda el desarrollo de métodos diagnósticos certeros y específicos, de nuevas drogas y moléculas. Nuestro equipo de investigación en México, conformado por investigadores clínicos y biomédicos, desde hace 20 años realiza de forma gratuita el diagnóstico mutacional del gen RET y su relación con el cáncer medular de tiroides y la neoplasia endocrina múltiple (NEM) 2 y 3. Las variantes patogénicas de RET en la población mexicana coinciden con los datos reportados: la mayoría con 634/NEM2 y 918/NEM3. Actualmente se están desarrollando nuevos métodos de nanobiotecnología para este tipo de determinaciones, de tal forma que puedan obtenerse resultados más rápidos, simples, sensibles y específicos aplicables en todo tipo de laboratorio.

Abstract Precision medicine is a reality in some diseases; it supports the development of accurate and specific diagnostic methods, new drugs and molecules. Our research team in Mexico, made up of clinical and biomedical researchers, has been performing free RET gene mutational diagnosis for medullary thyroid cancer and multiple endocrine neoplasia (MEN) 2 and 3 for 20 years. RET pathogenic variants in the Mexican population are consistent with reported data: most common mutations are 634/NEM2 and 918/NEM3. Currently, new nanobiotechnology methods are being developed for this type of determination in order to obtain faster, simpler, more sensitive and specific results applicable in all types of laboratories.

Neoplasia endócrina múltipla tipo 2A: relato de caso / Multiple endocrine neoplasia type 2A: a case report / Neoplasia endocrina múltiple tipo 2A: reporte de caso

As neoplasias endócrinas múltiplas (NEM) são síndromes genéticas autossômicas dominantes implicadas no desenvolvimento de neoplasias benignas ou malignas, envolvendo ao menos duas glândulas endócrinas. Entre seus subtipos, está a NEM2A, que consiste em carcinoma medular de tireoide (CMT), feocromocitoma e hiperparatireoidismo. Este texto apresente o relato de caso de um paciente de 40 anos, previamente hígido, que passou a apresentar episódios de cefaleia associada a sudorese profusa, vômitos e taquicardia. Evoluiu com distensão abdominal intensa após alimentação por via oral, perda ponderal, desnutrição, astenia, obstipação, humor deprimido e picos pressóricos. Exames laboratoriais evidenciaram alterações dos hormônios tireoidianos, PTH e hormônios da adrenal. Foi levantada a suspeita clínica de NEM2A, posteriormente corroborada pelos diagnósticos anatomopatológicos de feocromocitoma e CMT, associados à presença de hiperparatireoidismo. Foi possível concluir que, a despeito de sua baixa prevalência na população geral, a NEM é uma síndrome clínica de grande relevância, tendo em vista os impactos para os pacientes e famílias acometidas. Dessa forma, é necessário que os profissionais de saúde tenham conhecimento acerca da síndrome e que o Sistema Único de Saúde (SUS) esteja apto a assistir aos pacientes portadores de NEM, possibilitando diagnóstico precoce e tratamento adequado.

Multiple endocrine neoplasias (MEN) are dominant autosomal genetic syndromes involved in the development of benign or malignant tumors in at least two endocrine glands. MEN2A is one of its subtypes, which consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. This study reports the case of a healthy 40-year-old male patient presenting with episodes of headache associated with profuse sweating, vomiting, and tachycardia. The patient evolved with severe abdominal distension after oral feeding, weight loss, malnutrition, asthenia, constipation, depressed mood, and pressure peaks. Laboratory tests showed abnormalities in thyroid, parathyroid (PTH), and adrenal hormones ­ thus raising the hypothesis of MEN2A, which was later corroborated by the histological diagnosis of pheochromocytoma and MTC, associated with hyperparathyroidism. The results indicate that, despite its low prevalence in the general population, MEN has a great impact on affected patients and families, thus being a relevant clinical syndrome. For enabling early diagnosis and adequate treatment, health professionals must be familiarized with such a condition, and the Brazilian Unified Health System (SUS) must be able to assist affected patients.

Las neoplasias endocrinas múltiples (NEM) son síndromes genéticos autosómicos dominantes involucrados en el desarrollo de neoplasias benignas o malignas, que afectan al menos dos glándulas endocrinas. Entre sus subtipos se encuentra NEM2A, que consiste en carcinoma medular de tiroides (CMT), feocromocitoma e hiperparatiroidismo. Este es un reporte de caso de un paciente de 40 años de edad, previamente sano, que comenzó a presentar episodios de cefalea asociada a sudoración profusa, vómitos y taquicardia. Evolucionó con distensión abdominal severa después de alimentarse, pérdida de peso, desnutrición, astenia, estreñimiento, estado de ánimo deprimido y picos de presión. Las pruebas de laboratorio mostraron alteraciones en las hormonas tiroideas, PTH y hormonas suprarrenales. Se planteó la hipótesis de MEN2A, posteriormente corroborada por el diagnóstico anatomopatológico de feocromocitoma y CMT, asociado a hiperparatiroidismo. Se pudo concluir que, a pesar de su baja prevalencia en la población general, el NEM es un síndrome clínico de gran relevancia, dado el impacto que tiene en los pacientes y familiares afectados. Por tanto, es necesario que los profesionales sanitarios tengan conocimiento sobre el síndrome y que el Sistema Único de Salud (SUS) sea capaz de asistir a los pacientes con NEM, posibilitándoles diagnóstico precoz y tratamiento adecuado.

Pheochromocytoma: A three-decade clinical experience in a multicenter study.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ±â€¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ±â€¯14.2 years vs 54.5 ±â€¯13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3-6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4-5.0 cm] vs 5.6 cm [4.0-7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.

Neoplasia endocrina múltiple IIA: feocromocitoma bilateral. A propósito de un caso y revisión de la literatura / Multiple Endocrine Neoplasia IIA: Bilateral Pheochromocytoma. About a Case and Literature Review

Resumen: Presentamos el caso de una paciente del sexo femenino, de 54 años de edad, con antecedente familiar de neoplasia endocrina múltiple tipo II, con estudio genético positivo para NEM 2 IIA EXON 11, c634 CGCIB. Inició padecimiento con cardiopatía hipertensiva y disfunción diastólica, hallazgo to mográfico de tumor suprarrenal bilateral por imagenología, se realizó adrenalectomía convencional transabdominal, se encontró tumor derecho con cápsula correspondiente a feo cromocitoma con un peso de 1,100 g de 14.5 cm de diámetro mayor con invasión a cápsula sin romperla, tumor suprarrenal izquierdo correspondiente a feocromocitoma con un peso de 950 g de 15 cm de diámetro mayor.

Abstract: We present the case of a 54-year-old female patient with a family history of multiple endocrine neoplasia type II, with a genetic study for MEN 2 IIA EXON 11, CG6B c634, onset with hypertensive heart disease and diastolic dysfunction, tomographic finding of bilateral adrenal tumor by imaging. A conventional transabdominal adrenalectomy was performed, finding a right tumor with a capsule corresponding to pheochromocytoma with a weight of 1,100 g of 14.5 cm of greater diameter with invasion of the capsule without breaking it, and a left adrenal tumor corresponding to pheochromocytoma with a weight of 950 g of 15 cm of greater diameter.

Feocromocitoma: experiencia clínica de tres décadas en un estudio multicéntrico / Pheochromocytoma: A three-decade clinical experience in a multicenter study

Objetivo Analizar las características clínicas y analíticas, las pruebas diagnósticas, los tratamientos y los resultados del feocromocitoma (FCC). Diseño y métodos Estudio multicéntrico retrospectivo en pacientes con FCC tratados quirúrgicamente y seguidos en 3 hospitales terciarios de referencia españoles. Resultados Se analizó a un total de 106 pacientes (61 [57,5%] mujeres, edad media 52,3 ± 14,8 años). En el diagnóstico, el FCC fue sintomático en el 62% de los casos y esporádico en el 83%. Los pacientes con FCC familiar eran significativamente más jóvenes que aquellos que presentaban la enfermedad esporádica (40,8 ± 14,2 años vs. 54,5 ± 13,9 años, p < 0,001). El FCC familiar se asociaba con mayor frecuencia a la MEN2A (n = 8). Los niveles de metanefrinas en orina de 24h se relacionaron positivamente con el tamaño del tumor. El diámetro tumoral máximo fue 4,3cm (3-6cm); el 27,8% de los pacientes tenían tumores ≥ 6cm. Los FCC incidentales eran significativamente más pequeños que los FCC sintomáticos (3,4cm [2,4-5,0cm] vs. 5,6cm [4,0-7,0cm], p < 0,001). La gammagrafía con 123I-metaiodobencilguanidina mostró una alta sensibilidad (81,9%). En el 93,6% de los casos se usó el bloqueo alfa preoperatorio con fenoxibenzamina y con doxazosina en los demás casos. En 2/3 de los pacientes se empleó la cirugía laparoscópica, con una baja tasa de conversión (1,9%) a cirugía abierta. Aproximadamente en el 20% de los pacientes aparecieron complicaciones perioperatorias, principalmente crisis hipertensivas (9,4%). La enfermedad recurrente apareció en el 10% de los casos y el FCC maligno fue raro (6,3%). Conclusiones Los FCC tratados quirúrgicamente en España suelen ser tumores grandes, sintomáticos y esporádicos diagnosticados alrededor de la sexta década de vida. El FCC hereditario está generalmente asociado con MEN2A. La cirugía laparoscópica es el tipo principal de técnica quirúrgica utilizada y la prevalencia del FCC metastásico es baja (AU)

Objective To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). Design and methods A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. Results A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). Conclusion PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low (AU)

Pheochromocytoma: A three-decade clinical experience in a multicenter study. / Feocromocitoma: experiencia clínica de tres décadas en un estudio multicéntrico.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.

Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT. / Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina.

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.

Zollinger-ellison syndrome. case report

ABSTRACT Introduction: The Zollinger-Ellison syndrome (ZES) is a pathology caused by a neuroendocrine tumor, usually located in the pancreas or the duodenum, which is characterized by elevated levels of gastrin, resulting in an excessive production of gastric acid. Case presentation: A 42-year-old female patient with a history of longstanding peptic ulcer disease, who consulted due to persistent epigastric pain, melena and signs of peritoneal irritation. Perforated peptic ulcer was suspected, requiring emergency surgical intervention. Subsequently, a tumor lesion in the head of the pancreas was documented and managed with Whipple procedure. The pathology results reported a tumor suggestive of neuroendocrine neoplasm. Discussion: The Zollinger-Ellison syndrome occurs in 0.1 to 3 people per 1 000 000 inhabitants worldwide and is predominant in women between 20 and 50 years of age. It usually appears as a refractory acid-peptic disease or as a complication of gastric acid hypersecretion. Medical therapy is the standard management, being proton pump inhibitors (PPI) the most effective option. Surgery is recommended for sporadic ZES. Conclusions: ZES has a low incidence rate. It is rarely considered in the differential diagnosis of chronic epigastric pain and high clinical suspicion is required to achieve adequate management. This article is highly relevant as it presents a confirmed clinical case of ZES in Colombia, highlighting the importance of producing local scientific literature to improve the diagnosis and treatment of this pathology.

RESUMEN Introducción. El síndrome de Zollinger-Ellison (SZE) es una patología producida por un tumor neuroendocrino habitualmente localizado a nivel duodenal o pancreático, el cual produce niveles elevados de gastrina, derivando en hipersecreción de ácido gástrico. Presentación del caso. Paciente femenino de 42 años con antecedente de enfermedad ulceropéptica de larga data, quién consulta por epigastralgia persistente y deposiciones melénicas y presenta signos de irritación peritoneal. Se sospecha una ulcera péptica perforada, requiriendo intervención quirúrgica de urgencia. Posteriormente se documenta una lesión tumoral en la cabeza del páncreas, manejada con cirugía de Whipple; en el reporte de patología se detecta un tumor sugestivo de neoplasia neuroendocrina. Discusión. El SZE se presenta en 0.1-3 personas por cada 1 000 000 de habitantes a nivel mundial, predominantemente en mujeres entre 20 y 50 años de edad. Suele debutar como enfermedad ácido-péptica refractaria o por complicaciones de la hipersecreción gástrica. La terapia médica es el manejo estándar, siendo la más efectiva la que involucra inhibidores de la bomba de protones. En SZE esporádico está recomendada la cirugía. Conclusiones. El SZE tiene una incidencia baja, raramente se considera en el diagnóstico diferencial de epigastralgia crónica y se requiere alta sospecha clínica para lograr un manejo adecuado. Este artículo es valioso al presentar un caso clínico confirmado de SZE en Colombia, destacando la importancia de producir bibliografía científica local para mejorar el diagnóstico y tratamiento de esta patología.

Rara presentación de polineuropatía distal hipoglicémica causada por un insulinoma en el contexto de una neoplasia endocrinamúltiple tipo 1 / An unusual presentation of hypoglycemic distal polyneuropathy caused by an insulinoma in the context of multiple endocrine neoplasia 1

La neoplasia endocrina múltiple tipo 1 es una enfermedad de rara presentación. Se caracteriza por el compromiso tumoral neuroendocrino, de paratiroides, hipófisis y enteropancreático. Presentamos el caso de una paciente de 19 años con síntomas de cefalea, convulsiones y debilidad de las cuatro extremidades. Se confirmó la presencia de hipoglicemia 33mg/dL. El estudio elecromiográfico evidenció polineuropatía sensitivo motora en las cuatro extremidades. La resonancia magnética abdominal mostró un tumor en la cola del páncreas que luego de la pancreatectomía se confirmó como insulinoma. La glicemia se normalizó. Además, presentó un macroadenoma hipofisario, hiperparatiroidismo primario y tumor adrenal no funcionante. A los 25 años presentó cefalea intensa y amaurosis de ojo derecho, en la tomografía axial se evidenció tumoración hipofisaria gigante y en estudio de patología se diagnosticó neoplasia maligna condroide (cordoma).

Multiple endocrine neoplasia type 1 is a rare disease. It is characterized by the neuroendocrine, parathyroid, pituitary, and enteropancreatic tumor involvement. We present the case of a 19 year old patient with symptoms of headache, convulsions and weakness of the four extremities. The presence of hypoglycemia 33mg/dL was confirmed. The electromyographic study showed motor sensory polyneuropathy in all four extremities. The abdominal magnetic resonance showed a tumor in the tail of the pancreas that after the pancreatectomy was confirmed as insulinoma. The glycemia was normalized. In addition, he presented a pituitary macroadenoma, primary hyperparathyroidism and non-functioning adrenal tumor. At 25 years of age, he presented severe headache and amaurosis of the right eye. Axial tomography showed a giant pituitary tumor and in the study of pathology chondroid malignancy (chordoma) was diagnosed.

Síndromes de neoplasia endocrina múltiple: revisión radiológica / Multiple Endocrine Neoplasia Syndromes: Radiological Review

Los síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Primary hyperparathyroidism associated with MEN 1: Experience in 71 cases. / Hiperparatiroidismo primario asociado a neoplasia endocrina múltiple tipo 1 (MEN 1). Experiencia en 71 casos.

INTRODUCTION: Primary hyperparathyroidism (pHPT) in MEN 1 is characterized by multiglandular disease and early involvement of parathyroid glands at different times. Persistence and recurrence range from 25%-35%. The purpose was: a) to describe the experience and the treatment of patients with pHPT in MEN 1; b) to analyze the variables related with clinical presentation and recurrence. METHOD: A total of 97 patients with MEN 1 were diagnosed in a tertiary hospital. A retrospective analysis was made in patients with pHPT (n=71). STUDY VARIABLES: age at diagnosis, mutation, clinical presentation, laboratory tests, surgical technique, and recurrence of HPT. RESULTS: Mean age was 38 years, and 50 patients were asymptomatic. The surgical technique was: subtotal parathyroidectomy (n=55), resection of three glands (n=7), and resection of less glands (n=9). Transcervical thymectomy was performed in 53 patients. Mean follow-up was 102.9 months. There were 21 recurrences, There were correlations between age at diagnosis and serum calcium levels with the presence of symptoms (P<.0001). There were also correlations between recurrence and surgical technique (P<.03), non-association with thymectomy (P<.0001), and follow-up time (P<.03). CONCLUSION: Performing genetic and clinical screening allows us to make a diagnosis in the asymptomatic period and to provide early treatment for HPT in MEN 1. The recurrence rate is high, and follow-up time and the surgical technique used are risk factors for recurrence.

Caracterización de familia hondureña afectada por neoplasia endócrina múltiple (NEM-2A), Instituto Nacional Cardiopulmonar, Tegucigalpa, Honduras / Characterization of Honduran family affected by Multiple Endocrine Neoplasia (MEN-2A), Instituto Nacional Cardio-Pulmonar, Tegucigalpa, Honduras

RESUMEN. Introducción . Las Neoplasias Endocrinas Múltiples (NEM) son síndromes clínicos autosómico-dominantes. Se maniies - tan por tumores benignos y malignos que involucran órganos endócrinos y no endócrinos. Incidencia de 1/30,000 personas. Objetivo : Caracterizar una familia hondureña cuyos miembros presentan tumores endócrinos, Instituto Nacional Cardio-Pulmonar (INCP), Tegu - cigalpa, 2017. Métodos . Estudio descriptivo longitudinal. Análisis de información clínica, epidemiológica y de laboratorio, consignada en expedientes clínicos (INCP) y brindada por pacientes, previo consentimiento informado. Conirmación de dos casos mediante estudios genéticos. Resultados . Familia de 9 hijos, procedente de Olancho. Madre falleció por Adenocarcinoma Pancreático; padre sin información. Hija3, caso índice, se le realizó Tiroidectomía Total por Cáncer Medular de Tiroides (CMT). Hijo2 no evaluado. Hija4 portadora asintomática de la mutación del proto-oncogén RET. Hija1 se realizó Tiroidectomía Proiláctica por Hiperplasia Folicular de Tiroides e Hiperplasia Linfática Benigna en nódulo post-auricular derecho. Hija7 se practicó Parotidectomía izquierda por Adenoma Pleomórico Benigno. Hijo5 fue diagnosticado con CMT multifocal. Hija9 se le hizo Tiroidectomía Total con linfadenectomía por CMT multifocal. Hijos 6 y 8, residentes en Estados Unidos de América, se les realizó Adrenalectomía por Feocromocitoma y Tiroidectomía Total por CMT multifocal, respectivamente. Además, se les realizaron pruebas genéticas y moleculares, cuyos resultados conirmaron la mutación en los exones 10, 11, 13, 14, 15 y 16 del proto-oncogén RET, del codón 634 con la sustitución del amino ácido cisteína por triptófano (Cys634Trp), conirmatorio de NEM-2A. Discusión . Constituye el primer trabajo publicado de esta patología en Honduras. Sugerimos la búsqueda epidemiológica de NEM en todo paciente diagnosticado con CMT.

[Intrathyroidal location of parathyroid glands. Atypical presentation of multiple endocrine neoplasia type 1 syndrome]. / Localización intratiroidea de glándulas paratiroides. Presentación atípica del síndrome de neoplasia endocrina múltiple tipo 1.

BACKGROUND: The most common manifestation of MEN 1 syndrome is primary hyperparathyroidism (PHPT) with parathyroid multiglandular affectation. The intrathyroidal situation represents 3-4% of all glands, and it is the second most frequent location in the cervical ectopias. CLINICAL CASE: 11 year old patient, with a family history of MEN1 syndrome and carrier of this same mutation. Patient presents HPTP with osteopenia. The cervical ultrasound shows three compatible images with pathological parathyroid glands (bilateral lower and upper left). The Scan and MRI are normal. Bone densitometry displays data on osteopenia. The patient is surgically intervened, only the upper parathyroid glands are located and removed, after this implantation is performed on the forearm, to prevent the possible devascularization in the dissection of the other glands. However, osteopenia persists and an elevated PTH, therefore new diagnostic tests are held which seem to show two lower parathyroid glands with intrathyroidal location. The patient is reoperated. A subtotal parathyroidectomy of the lower right gland and the resection of the left gland is performed, with the use of intraoperative ultrasound and placement of harpoon. The intraoperative pathology study confirms parathyroid tissue in both cases. DISCUSSION: It is necessary to locate the parathyroid glands preoperatively in order to alert us of the existence of topographical and ectopia abnormalities, as well as their intrathyroidal location (0.5-3.6%). CONCLUSION: The intraoperative ultrasound can be a complement to the experience of the endocrine surgeon for the localization of the parathyroid glands and therefore can help determine the best surgical strategy for each clinical case.

Neoplasia endocrina múltiple tipo 1 A propósito de un caso / Multiple endocrine neoplasia type 1 About a case

La neoplasia endocrina múltiple tipo 1 (NEM1) es un raro síndrome hereditario, autosómico dominante, clásicamente caracterizado por tumores en varias glándulas (paratiroides, adenohipófisis e islotes pancreáticos). La prevalencia del NEM1 es de aproximadamente 2 por 100.000 habitantes.El síndrome de Zollinger Ellison (SZE) es una de las 3 neoplasias que forman parte del NEM1 y corresponde al 20 a 60%. A continuación se presenta el caso clínico de un paciente de sexo masculino, 66 años de edad, con cuadro clínico de síndrome de Zollinger Ellison que, en investigación posterior, evidencia alteración funcional de las glándulas paratiroides, cumpliendo criterios diagnósticos de neoplasia endocrina múltiple tipo 1 (NEM1).(AU)

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary syndrome, classically characterized by the presence of tumors in several glands (parathyroid, anterior pituitary and pancreatic islets) The prevalence of MEN 1 is approximately 2 per 100,000 inhabitants. The Zollinger Ellison syndrome (ZES) is one of the three neoplasias that form part of the MEN 1, and corresponds to 20 to 60%. The clinical case of a 66-year-old male patient, with a clinical of Zollinger Ellison Syndrome, who in a subsequent investigation shows functional abnormality of the parathyroid glands, fulfilling diagnostic criteria of Multiple Endocrine Neoplasia type 1 (NEM1) (AU)

Síndrome de Zollinger-Ellison: revisión del conocimiento actual / Zollinger-Ellison syndrome: review of current knowledge

El síndrome de Zollinger-Ellison se caracteriza por la presencia de úlceras pépticas resistentes al tratamiento que se deben a la hipersecreción ectópica de gastrina por un tumor neuroendocrino, que es el gastrinoma y que resulta en la hipersecreción de ácido clorhídrico en el estómago. Este síndrome se presenta en forma esporádica y también se asocia al síndrome de neoplasia neuroendocrina múltiple de tipo 1. Se describen ambas presentaciones clínicas, así como también la fisiopatología, el diagnóstico, el estudio, el tratamiento y el pronóstico, enfatizando en los detalles técnicos de la cirugía. El pronóstico de los gastrinomas cuando son identificados precozmente es bueno, aun en aquellos casos malignos, por lo que la sospecha clínica asociada al estudio específico y al tratamiento de estos pacientes es fundamental. Dada la tecnología diagnóstica disponible en la actualidad, la identificación de estos tumores será cada vez más frecuente, por lo que el conocimiento de los detalles esenciales para su tratamiento es importante para el cirujano.

Zollinger-Ellison syndrome is characterized by peptic ulcers refractory to treatment secondary to ectopic gastrin hypersecretion by a neuroendocrine tumor called gastrinoma resulting in gastric hydrochloride acid hypersecretion. This syndrome occurs sporadically and is also associated to Multiple Neuroendocrine Neoplasia type 1. The present article describes their clinical presentations, as well as their pathophysiology, diagnosis, study, treatment and prognosis, emphasizing the surgical technical details. Early diagnosis of gastrinoma carries a good prognosis, even in those malignant cases. Consequently, clinical suspicion associated to specific study leading to diagnosis and treatment is fundamental for these patients. Due to the available current technology, the diagnosis of these tumors should be more common, as a consequence the knowledge of important details within their management is important for the surgeon.

Síndrome de zolinger - Elison / Syndrome of Zolinger - Elison

Resumen:El síndrome de Zollinger - Ellison es una endocrinopatía que fue descrita en 1955 por los doctores Robert Zollinger y Edwin Ellison, quienes propusieron la triada diagnóstica que incluye hipersecreción gástrica ácida, úlcera péptica y gastrinoma. Esta enfermedad predomina en mujeres entre los 50 y 60 años de edad. Según su etiología, este síndrome se clasifica en una forma esporádica o asociada a neoplasia endocrina múltiple tipo 1 (NEM - 1).Más de la mitad de los gastrinomas se localizan en la pared duodenal, el páncreas es la segunda ubicación en frecuencia. Existen localizaciones ectópicas en ovario, mesenterio, hígado y ducto biliar. A nivel histopatológico se encuentran células tumorales redondas, con núcleos pequeños y nucléolos prominentes. La hipersecreción ácida gástrica está asociada a un defecto en la inhibición del retrocontrol negativo de la somatostatina sobre las células G antrales productoras de gastrina. Clínicamente, los pacientes manifiestan dolor abdominal, diarrea, pirosis, náuseas y vómitos; relacionados principalmente a la formación de úlceras pépticas. El diagnóstico debe incluir una medición en los niveles séricos de gastrina y valores de pH gástrico. El tratamiento de primera línea es la terapia antisecretora, principalmente con inhibidores de la bomba de protones. Los estudios de imágenes son deutilidad para detectar metástasis y evaluar la enfermedad quirúrgicamente resecable. Se debe hacer diagnóstico diferencial con otros tumores neuroendocrinos y causas de hipergastrinemia.

Abstract:Zollinger - Ellison syndrome is an endocrinopathy that was first described in 1955 by doctors Robert Zollinger and Edwin Ellison, who proposed the diagnostic triad that includes gastric acid hypersecretion, peptic ulcer and gastrinoma. This disease predominates in women between 50 and 60 years old. Based on the etiology, the syndrome is classified in sporadic or associated with multiple endocrine neoplasia type 1 (NEM - 1). Over half of gastrinomas are located in the duodenal wall, the pancreas is the second frequency location. There are ectopic locations, such as ovary, mesentery, liver and bile duct. Round cells, small nuclei and prominent nucleoli, are the main hispathologycal characteristics. Gastric acid hypersecretion is associated with a defect in the negative feedback inhibition of somatostatin on G antral gastrin-producing cells. Clinically, patients present abdominal pain, diarrhea, heartburn, nausea and vomiting; primarily related to the development of peptic ulcers. Diagnosis includes a measurement in serum gastrin levels and gastric pH values. The first line treatment is the antisecretory therapy, primarily proton-pump inhibitor. Imaging studies are useful to detect metastases and evaluate the surgically resectable disease. Neuroendocrine tumors and hypergastrinemia causes are the main differential diagnoses, the clinician should consider.