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.

Manifestaciones maxilofaciales en una familia chilena con adenomatosis poliposa familiar / Maxillofacial manifestations in a Chilean family with familial adenomatous polyposis

RESUMEN: La Poliposis Adenomatosa Familiar (PAF) es un síndrome hereditario autosómico dominante causado por la mutación del gen APC. En su forma clásica se desarrollan más de 100 pólipos adenomatosos intestinales que progresan a cáncer colorrectal en casi el 100% de los casos no tratados. Dentro de las manifestaciones extracolónicas de PAF, se encuentran las maxilofaciales, como: osteomas y alteraciones dentales, que pueden preceder por años al desarrollo de poliposis colónica. A pesar de que en Chile hay estudios de PAF y cáncer de colon, son escasos los reportes de manifestaciones maxilofaciales en estos pacientes. En la familia en estudio se encontró manifestaciones descritas previamente como: odontoma, osteomas y malformaciones de incisivos; adicionalmente tags mucosos que no se han asociado previamente al síndrome.

ABSTRACT: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary syndrome caused by the mutation of the APC gene. In its classic form, more than 100 intestinal adenomatous polyps progress to colorectal cancer in almost 100% of cases if they are not treated. Within the extracolonic manifestations of FAP are the maxillofacial, such as: osteomas and dental alterations, which may precede the development of colonic polyposis. Although studies of colonic adenomatous polyposis and colon cancer exist in Chile, there are few reports of maxillofacial manifestations in these patients. In the family under study, previously described manifestations were found, such as: odontoma, osteomas and dental malformations; mucosal tags were also observed, with no previous association with the syndrom.

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.

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.

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.

Tumor neuroendócrino pancreático metastásico, caso clínico / Metastatic pancreatic neuroendocrine tumor: clinical case

Introducción: los insulinomas son tumores neuroendocrinos pancreáticos secretores de insulina, la incidencia en la población en general estimada es de 1 a 4 casos en un millón de habitantes por año. Los insulinomas constituyen el 60% de los tumores de páncreas, de los cuales el 90% son benignos y únicos; el 10% son múltiples, la mayoría asociados a MEN 1 (Neoplasia Endocrina Múltiple) y del 5 al 10% son malignas. La posibilidad de recidiva obliga a un diagnóstico y seguimiento a largo plazo. La característica clínica del insulinoma es la hipoglucemia en ayunas, con signos y síntomas de neuroglucopenia, que pueden estar precedidos o no por manifestaciones adrenérgicas. El tratamiento de elección es el quirúrgico; en etapas irresecables o avanzadas se proponen tratamientos paliativos o sintomáticos con quimioterapia o procedimientos mediante radiología intervencionista con pobres respuestas. Se ha demostrado que con nuevos tratamientos con inhibidores de la tirosina kinasa e inhibidores de la vía de la rapamicina en tumores neuroendocrinos pancráticos bien diferenciados las respuestas tanto en sobrevida libre de progresión así como sobrevida global mejoran importantemente. Caso: presentamos el caso de un hombre de 44 años, con diagnóstico de insulinoma y MEN 1, debutó con convulsiones tónico clónicas generalizadas tratado con pancreatectomia parcial, siete años más tarde, tras haber permanecido asintomático nuevo episodio de convulsiones, documentándose hipoglicemias severas y múltiples metástasis hepáticas, sometido a una pancreatoduodenectomia y como tratamiento sintomático recibió corticoides en altas dosis, diazóxido, octreotide mensual y dos líneas de quimioterapia, además de embolización de las metástasis hepáticas de mayor tamaño y por progresión de enfermedad se inició inhibidores de tirosin-kinasa por un período de tres meses y el paciente fallece.

Introduction: the Insulinomas are pancreatic neuroendocrine tumors secreting insulin. The incidence in the general population is estimated 1-4 per 1 000 000 yearly Insulinoma accounts for 60% of pancreatic tumors, of which 90% are benign and unique, 10% are multiple, mostly associated with MEN 1 (Multiple Endocrine Neoplasia), and 5-10% is malignant. The possibility of recurrence requires diagnosis and long-term monitoring. The clinical characteristic of insulinoma is fasting hypoglycemia, with signs and symptoms of neuroglucopenia, which may be preceded or not by adrenergic manifestations. Surgery is the treatment of choice, in irrsecable; and in advanced stages the proposed palliatives or symptomatic treatments are with chemotherapy or procedures through interventional radiologist with poor responses. It has been shown that new treatments with inhibitors of tyrosine kinase inhibitors and rapamycin pathway for pancreatic neuroendocrine well differentiated tumors, the response in both progression-free survival and overall survival signifcantly improved. Case study: we report the case of a 44 year old male of, diagnosed with insulinoma and MEN 1, debuted with tonic clonic seizures treated with partial pancreatectomy, 7 years later after a new episode of seizures documented severe hypoglycemia and multiple liver metastases, underwent a pancreatoduodenectomy and as symptomatic treatment received high-dose corticosteroids, diaxozido, octreotide monthly and 2 lines of chemotherapy, in addition to embolization of the larger liver metastases masses, and due to disease progression tyrosine kinase inhibitors was initiated for a period of 3 months and the patient dies.

Complexo de Carney esporádico com tumor testicular e mixoma atrial: relato de caso / Sporadic Carney complex with testicular tumor and atrial myxoma: case report

O complexo de Carney é uma rara forma de neoplasia endócrina múltipla familial autossômica dominante. Está associado à alteração de pigmentação cutânea e mucosa, doença nodular adrenal pigmentosa primária, mixomas cardíacos e cutâneos, adenomas hipofisários funcionantes, neoplasia testicular, adenoma ou carcinoma de tireoide, além de cistos ovarianos. Aproximadamente 70% dos indivíduos diagnosticados com complexo de Carney têm pais afetados, e 30% apresentam forma esporádica. O objetivo deste estudo foi relatar um caso de complexo de Carney esporádico por mixoma cardíaco e tumor testicular. Ressalta-se a importância do caso por sua raridade e sua forma curiosa de apresentação. Homem, 33 anos, manifestou dois quadros de acidentes vasculares cerebrais em 4 meses. Na investigação apresentou pressão arterial elevada com sopro sistólico discreto e fraqueza muscular (força grau 4 em membro superior direito e grau 3 em membro inferior direito). História mórbida de tumor testicular de células de Sertoli há 7 anos com orquiectomia bilateral. História familiar sem particularidades. Na investigação, evidenciaram-se sobrecarga atrial esquerda ao eletrocardiograma e massa tumoral pedunculada compatível com mixoma atrial esquerdo ao ecocardiograma transesofágico. Foi configurada síndrome de Carney pela presença de dois critérios maiores, e o paciente foi submetido à atriotomia esquerda, com ressecção da massa tumoral e confirmação anatomopatológica. A curiosa apresentação do caso recorda que, diante de um caso de acidente vascular cerebral em paciente jovem, a suspeita clínica seja direcionada a causas mais raras. O complexo de Carney esporádico é raro, dificultando ainda mais a elucidação.

Carney complex is a rare form of autosomal dominant multiple endocrine neoplasia familial. Changing skin pigmentation and mucos, primary pigmented nodular adrenal disease, cardiac and cutaneous myxomas, functioning pituitary adenomas, testicular cancer, thyroid adenoma or carcinoma is associated, and ovarian cysts. Approximately 70% of individuals diagnosed with Carney complex have affected parents and 30% have sporadically. The aim of this study was to report a case of sporadic Carney complex due to cardiac myxoma and testicular tumor. We emphasized the importance of the case for its rarity and curious form of presentation. Man, 33, showed two episodes of strokes in 4 months. In research presented high blood pressure with mild systolic murmur and muscle weakness (grade 4 strengthin the right arm and grade 3 in the right lower limb). Morbid history of testicular Sertoli cell tumor 7 years ago with bilateral orchiectomy. No special family history. On investigation, left atrial enlargement and was evident on the electrocardiogram, and transesophageal echocardiogram revealed the presence of pedunculated tumor mass setting a left atrial myxoma. Carney's syndrome was characterized by the existence of two major criteria and patient underwent left atriotomy with resection of the tumor mass and anatomic-pathologic confirmation. The curious case presentation reminded us that before a case of stroke in a young patient should direct the clinical suspicion for rarer causes. The Carney complex sporadic is rare, yet difficult to elucidate.

Factors associated with reporting of abuse against children and adolescents by nurses within Primary Health Care / Fatores associados à notificação de maus-tratos em crianças e adolescentes realizada por enfermeiros na Atenção Primária à Saúde / Factores asociados a la notificación del maltrato en niños y adolescentes realizada por enfermeros en la Atención Primaria a la Salud

OBJECTIVE: to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents. METHOD: cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used. RESULTS: female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting. CONCLUSION: the study's results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents. .

OBJETIVO: analisar os fatores associados à notificação de maus-tratos em crianças e adolescentes, realizada por enfermeiros que atuam na Atenção Primária à Saúde. MÉTODO: estudo transversal, realizado com 616 enfermeiros. Foi utilizado um questionário contendo dados sociodemográficos, formação profissional, instrumentação e conhecimento sobre o tema, identificação e notificação de casos de maus-tratos. Análises bivariada e multivariada por regressão logística foram realizadas. RESULTADOS: predominaram enfermeiros do sexo feminino, na faixa etária entre 21 e 32 anos, não casados, com cinco ou mais anos de formado, com pós-graduação e com cinco ou mais anos de trabalho. O modelo logístico final evidenciou que fatores como tempo de trabalho de cinco ou mais anos, a unidade de saúde possuir a ficha de notificação, saber para onde encaminhar os casos, não ter medo de envolvimento legal e achar vantajosa a notificação na atenção primária facilitam a efetivação do ato notificatório. CONCLUSÃO: os resultados desta pesquisa, além de sensibilizar os enfermeiros para o problema, poderão ser utilizados pelos profissionais da gestão na orientação de estratégias para o cumprimento da notificação como dispositivo legal de garantia dos direitos de crianças e adolescentes. .

OBJETIVO: analizar los factores asociados a la notificación de maltrato en niños y adolescentes realizado por enfermeros que actúan en la Atención Primaria a la Salud. MÉTODO: estudio transversal realizado con 616 enfermeros. Fue utilizado un cuestionario conteniendo datos sociodemográficos, formación profesional, instrumentación y conocimiento sobre el tema, identificación, y notificación de casos de maltrato. Análisis bivariado y multivariado por regresión logística. RESULTADOS: predominaron enfermeros del sexo femenino, en la franja etaria de 21 a 32 años, no casados, con cinco o más años de graduación, con postgraduación y con cinco o más años de trabajo. El modelo logístico final evidenció que factores como tiempo de trabajo de cinco o más años, la unidad de salud poseer ficha de notificación, saber para donde encaminar los casos, no tener miedo de involucramiento legal y encontrar ventaja en la notificación en la atención primaria, son aspectos que facilitan la efectividad del acto de la notificación. CONCLUSIÓN: los resultados de esta investigación, además de sensibilizar a los enfermeros para el problema, podrán ser utilizados por profesionales de la gestión en la orientación de estrategias para el cumplimiento de la notificación como dispositivo legal de garantía de los derechos de niños y adolescentes. .

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed.

Feocromocitoma asintomático / Asymptomatic pheochromocytoma

El feocromocitoma es un tumor que produce catecolaminas,mayor responsable de la hipertensión arterial en jóvenes,con mayor frecuencia se localiza en la medula suprarrenal, unilateral.Generalmente asociado con neoplasia endócrina múltiple.Los pacientes presentan una serie de síntomas, entre ellosla hipertensión arterial.Se presenta el caso de una paciente de 31 años, con doloren hipocondrio derecho de un año de evolución, tipo pesadezy pérdida de peso de 3 kg. Al examen físico se constató tumoraciónen hipocondrio derecho que llega a epigastrio, de 12cm de diámetro. Con el diagnóstico de tumor retroperitonealobtenido por imágenes se decide una laparotomía exploradoradonde se visualizó un tumor de 18cm. de diámetro, sólido, enpolo superior del riñón derecho, adherido a vena cava. Se realizóuna exéresis tumoral y el informe de anatomía patológicaconfirmó feocromocitoma

Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil

The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical followup); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine.

MENX and MEN4

Multiple endocrine neoplasias are autosomal dominant disorders characterized by the occurrence of tumors in at least two endocrine glands. Two MEN syndromes have long been known and are well characterized: the MEN type 1 (MEN1) and type 2 (MEN2). These syndromes are caused by germline mutations in the MEN1 and RET genes, respectively, and have a different tumor spectrum. Recently, a variant of the MEN syndromes arose spontaneously in a rat colony and was named MENX. Affected animals consistently develop multiple endocrine tumors, with a spectrum that shares features with both MEN1 and MEN2 human syndromes. Genetic studies identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle inhibitor, as the causative mutation for MENX. Capitalizing on these findings, heterozygous germline mutations in the human homologue, CDKN1B, were searched for and identified in patients with multiple endocrine tumors. As a consequence of this discovery, a novel human MEN syndrome, named MEN4, was recognized, which is caused by mutations in p27. Altogether, these studies identified Cdkn1b/CDKN1B as a novel tumor susceptibility gene for multiple endocrine tumors in both rats and humans. Here we review the characteristics of the MENX and MEN4 syndromes and we briefly address the main function of p27 and how they are affected by MENX/4-associated mutations.

Mutación del gen de la menina: desde el hiperparatiroidismo familiar aislado a la neoplasia endocrina múltiple de tipo 1: [revisión] / Mutation of the menin gen: from isolated familial hyperparathyroidism to the multiple endocrine neoplasia syndrome type 1: [review]

La menina es una proteína supresora de tumor codificada por el gen MEN1, cuya mutación produce procesos neoplásicos en múltiples tejidos del organismo que pueden manifestarse por generaciones como síndromes familiares. La mutación genera un espectro de enfermedad que va desde el hiperparatiroidismo familiar aislado hasta la neoplasia endocrina múltiple de tipo 1, caracterizada por neoplasias de paratiroides, hipófisis anterior, páncreas endocrino y duodeno, entre otras. Como ejemplo, se presentan dos casos de pacientes con neoplasias endocrinas secundarias a la mutación del gen MEN1. Se revisa la información actual sobre la etiopatogenia y carcinogénesis entendidos apenas recientemente, al igual que otras mutaciones involucradas en los síndromes neoplásicos expuestos y se dan unas recomendaciones finales.

Menin is a tumor suppressor protein, encoded by the MEN1 gene, whose mutation can generate neoplastic disease in multiple tissues of the human body, which for generations can manifest as familial syndromes. The mutation generates a spectrum of diseases ranging from familial isolated hyperparathyroidism to multiple endocrine neoplasia type 1, characterized by neoplasm of parathyroid glands, anterior pituitary, endocrine pancreas and duodenum, among others. We present two cases of patients with endocrine neoplastic disease secondary to menin’s mutation. We review current information regarding its ethiopathogeny and its mechanism of carcinogenesis just recently understood. Additionally we review other mutations involved in the neoplastic syndromes exposed and present some final recommendations.

Carcinoma medular de tiroides metastásico a hígado y pulmón. Paciente asintomática con enfermedad activa / Medullary carcinoma of the thyroid with liver and lung metastases an asymptomatic. Patient with an active disease

El carcinoma medular de tiroides es un tumor poco frecuente y con baja prevalencia, derivado de las células C parafoliculares secretoras de calcitonina. De comportamiento agresivo suele invadir ganglios linfáticos, tejido glandular adyacente y hacer metástasis a hueso, pulmón e hígado. Presentamos una paciente de 26 años con dicho tumor metastático a pulmón e hígado. A pesar del manejo quirúrgico y médico concomitante persiste con actividad de la enfermedad y niveles elevados de calcitonina. Llama la atención la escasa sintomatología.

Medullary thyroid carcinoma is a rare malignancy with low prevalence. It arises from the parafollicular calcitonin- producing C-cells. It may have an aggressive course spreading to regional lymph nodes and glandular tissue and distant metastases may involve bone, lung and liver. Here, we present the case of a 26-year old female patient with such a malignancy with lung and liver metastases. Despite surgical and pharmacological management her disease remains active with high calcitonin levels. Remarkably, scarce or no symptoms are noted.

Análise do gene AIP na acromegalia familial isolada / Analysis of the AIP gene in familial isolated acromegaly

A acromegalia é doença insidiosa e desfigurante caracterizada por um crescimento desproporcional dos ossos das mãos, pés e do crânio devido à exposição crônica a altos níveis de hormônio de crescimento (GH) e de seu efetor insuline growth factor 1 (IGF-1). Trata-se de uma doença rara, com incidência estimada de 3-4 casos por milhão, com prevalência de aproximadamente 50 casos por milhão de pessoas. A principal causa da acromegalia é a presença de um tumor hipofisário secretor de GH (somatotropinoma). Caso o somatotropinoma ocorra durante a infância ou adolescência, antes do fechamento das epífises dos ossos longos, a criança crescerá longitudinalmente de forma descontrolada, caracterizando a forma clínica gigantismo. Na grande maioria dos casos a acromegalia se apresenta na forma esporádica, entretanto casos familiais da doença podem ocorrer associados à Neoplasia Endócrina Múltipla tipo 1 (NEM-1), ao complexo de Carney (CNC) e à acromegalia familial isolada (IFS). Os genes responsáveis pela NEM-1 (MEN1) e CNC (PRKAR1A) foram clonados há mais 10 anos, entretanto etiologia molecular da IFS permaneceu desconhecida até recentemente. Vierimaa et al. (2006) combinaram estudos de ligação por análise de polimorfismos e estudos de expressão gênica e identificaram mutações no gene AIP em famílias com acromegalia não-NEM-1 e não-CNC; além de perda de heterozigose (LOH) nos somatotropinomas dos pacientes com mutação AIP. No presente estudo, investigamos o gene AIP em três famílias brasileiras com IFS e em seus tumores (hipofisários e não-hipofisários). Descrevemos uma nova mutação AIP (Y268X) em uma família brasileira com IFS, confirmando o papel desse novo gene na predisposição a tumores hipofisários. A partir de dados gerados em uma extensa revisão da literatura, sugerimos que os tumores hipofisários familiais isolados são doenças multigênicas que possuiriam um gene principal, mas que sofreriam influência de outros genes/loci ainda pouco caracterizados...

Acromegaly is a rare disfigurating and insidious disease characterized by enlargement of hands, feet and skull bones due to excess of growth hormone (GH) secreted by a pituitary tumor (somatotropinoma). The majority of the cases with acromegaly is sporadic, however it may occur in association with inherited disorders as Multiple Endocrine Neoplasia type 1 (MEN1), Carney complex (CNC) and Isolated Familial Somatotropinoma (IFS). The genes associated with MEN1 syndrome (MEN1) and CNC (PRKAR1A) have been described more than a decade ago, however until very recently the molecular etiology of IFS remained unknown. Using a combined strategy of single nucleotide polymorphism (SNP) analysis and gene expression analysis, Vierimaa et al. (2006) described mutations in the AIP gene occurring in families with acromegaly not associated with MEN1 and CNC. In the current study, we investigated three Brazilian families with IFS and were able to describe two germline mutations in the AIP gene, confirming the role of this new gene in the predisposition to familial somatotropinoma. We revised the literature of genetic studies of isolated pituitary adenoma syndromes, which indicated a genetic heterogeneity as well as possible multigenic inheritance for these diseases. Thus, we investigated the role of several genes/loci (SSTR2, SSTR5, CDKN1B, AHR, PRKAR1A, PTTG, PROP1, MEG3, RB1 and 2p16) selected as potentially acting as phenotypic modulators in IFS. Our data indicate that AIP-mutated patients are prone to pituitary disease, however it is necessary the co-segregation of markers located at oncogenic regions to the development of the pituitary tumors and manifestation of the disease. Herein, we also present the first somatic analysis of non-pituitary tumors of AIP-mutated patients. A potential role of AIP, which is implicated in the cAMP pathway, could not be excluded in the development of an adrenocortical carcinoma.

Neoplasia endocrina múltiple tipo 1 / Multiple endocrine neoplasia type 1

Se reporta un caso infrecuente de neoplasia endocrina múltiple tipo 1, en una mujer de 44 años de edad. El diagnóstico se basó en el hallazgo de úlceras gástricas múltiples asociadas a hipergrastinemia, hipercalcemia relacionada con un adenoma paratiroideo e hiperprolactinemia debida a un microadenoma hipofisiario.

We report an infrequent case of multiple endocrine neoplasia type 1 in a 44 year-old woman. The diagnosis was based after the finding of multiple duodenal ulcers associated to hypergastrinemia, hypercalcemia related to a parathyroid adenoma and hyperprolactinemia due to a hypophyseal microadenoma.

Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma: [revision]

Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2-4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventivethyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis...