Beckers Albert, Daly Adrian F
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, University of Liège, 4000 Liège, Belgium.
Eur J Endocrinol. 2007 Oct;157(4):371-82. doi: 10.1530/EJE-07-0348.
Pituitary adenomas occur in a familial setting in multiple endocrine neoplasia type 1 (MEN1) and Carney's complex (CNC), which occur due to mutations in the genes MEN1 and PRKAR1A respectively. Isolated familial somatotropinoma (IFS) is also a well-described clinical syndrome related only to patients with acrogigantism. Pituitary adenomas of all types--not limited to IFS--can occur in a familial setting in the absence of MEN1 and CNC; this phenotype is termed familial isolated pituitary adenomas (FIPA). Over the past 7 years, we have described over 90 FIPA kindreds. In FIPA, both homogeneous and heterogeneous pituitary adenoma phenotypes can occur within families; virtually all FIPA kindreds contain at least one prolactinoma or somatotropinoma. FIPA differs from MEN1 in terms of a lower proportion of prolactinomas and more frequent somatotropinomas in the FIPA cohort. Patients with FIPA are significantly younger at diagnosis and have significantly larger pituitary adenomas than matched sporadic pituitary adenoma counterparts. A minority of FIPA families overall (15%) exhibit mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene; AIP mutations are present in only half of IFS kindreds occurring as part of the FIPA cohort. In families with AIP mutations, pituitary adenomas have a penetrance of over 50%. AIP mutations are extremely rare in patients with sporadic pituitary adenomas. This review deals with pituitary adenomas that occur in a familial setting, describes in detail the clinical, pathological, and genetic features of FIPA, and addresses aspects of the clinical approach to FIPA families with and without AIP mutations.
垂体腺瘤在1型多发性内分泌腺瘤病（MEN1）和卡尼综合征（CNC）的家族背景中发生，这两种疾病分别由于MEN1基因和PRKAR1A基因的突变所致。孤立性家族性生长激素瘤（IFS）也是一种已被充分描述的临床综合征，仅与肢端肥大症患者相关。所有类型的垂体腺瘤——不限于IFS——都可在无MEN1和CNC的家族背景中发生；这种表型被称为家族性孤立性垂体腺瘤（FIPA）。在过去7年中，我们描述了90多个FIPA家系。在FIPA中，家族内可出现同质和异质的垂体腺瘤表型；几乎所有FIPA家系都至少包含一个催乳素瘤或生长激素瘤。FIPA与MEN1的不同之处在于，FIPA队列中催乳素瘤的比例较低，生长激素瘤更为常见。FIPA患者诊断时年龄显著更小，垂体腺瘤也比匹配的散发性垂体腺瘤患者的腺瘤大得多。总体而言，少数FIPA家族（15%）表现出芳烃受体相互作用蛋白（AIP）基因突变；作为FIPA队列一部分的IFS家系中，只有一半存在AIP突变。在有AIP突变的家族中，垂体腺瘤的外显率超过50%。AIP突变在散发性垂体腺瘤患者中极为罕见。本综述探讨了在家族背景中发生的垂体腺瘤，详细描述了FIPA的临床、病理和遗传特征，并讨论了对有和无AIP突变的FIPA家族的临床处理方法。
