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.

Feocromocitotoma bilateral maligno como componentes de adenomatosis endocrina multiple tipo II-A: presentacion de un caso y revision de la literatura / Bilateral malignant pheochromocytoma as component of multiple endocrine adenmatosis type II-A: presentation of a case and review of the literature

Se presenta el caso de un joven de 25 anos hospitalizado por un cuadro de hipertension arterial sistemica severa acompanado de bocio multinodular, a quien se le diagnostico adenomatosis endocrina multiple tipo II-A (AEM II-A). Se comprobo la presencia de feocromocitoma bilateral metastasico al encontrarse niveles elevados de acido venilmandelico en orina, dos masas suprarrenales bilaterales y una masa tumoral hepatica en el estudio tomografico de abdomen. En forma similar se evidenciaron nodulos hipocaptantes en tiroides, demostrandose que correspondian a un carcinoma medular de tiroides al realizar el estudio histopatologico. se logro el control de las cifras tensionales con la administracion de prazosin (12 mg/da) y labetalol (600 mg/dia) en el periodo preoperatorio, practicandose posteriormente la adrenalectomia subtotal bilateral y tiroidectomia total. En su evolucion postoperatoria el paciente presento episodios de hemorragia digestiva superior masiva debidos a multiples ulceras del tracto gastrointestinal, que ameritaron realizar una gastrectomia total para el control de la hemorragia. Se hace revision de la literatura con referencia particular al diagnostico y manejo del feocromocitoma maligno

Adenomatose endócrina múltipla: tipo combinado, associado a lipoma / Multiple endocrine adenomatosis: combined type, associated with lypoma

Descreve-se um caso de adenomatose endócrina múltipla (MEA) composto de insulinoma pancreático, lipoma da supra-renal E, cisto de mama e da tireóide. Após revisäo da literatura, discutem-se os aspectos conceituais da síndrome e propöe-se uma denominaçäo nova: a de adenomatose endócrina múltipla "tipo combinado", toda vez que os casos de alteraçäo multiglandular näo se adaptarem às alteraçöes clínicas que ocorrem nos Tipos I, II e III. Esta proposta visa evitar uma enumeraçäo extensa de síndromes que säo, afinal, de adenomatoses endócrinas com pequenas diferenças em suas manifestaçöes clínicas, espelhando a alteraçäo endócrina predominante em cada caso. Propöe-se também que seja acrescentada a expressäo "associada a", seguindo-se a alteraçäo ou conseqüência, p. ex.: MEA associada a lipoma, a úlcera péptica, a tumor carcinóide