Corticotroph adenoma of the pituitary in a patient with X-linked adrenal hypoplasia congenita due to a novel mutation of the DAX-1 gene
Corticotroph adenoma of the pituitary in a patient with X-linked adrenal hypoplasia congenita due to a novel mutation of the DAX-1 gene
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DOI：
10.1530/eje.1.01958
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Cremonini, N
中科院分区：
文献类型：
--
作者：
De Menis, E;Roncaroli, F;Cremonini, N
目的：DAX-1基因突变导致X连锁先天性肾上腺发育不全。经典的临床表现是生命早期的原发性肾上腺功能不全和预期青春期时的低促性腺激素性性腺功能减退症，但最近的数据扩大了DAX-1突变的表型谱。我们报告的发生ACTH分泌腺瘤的患者与X连锁先天性adrenal hypoplasia.Design和方法：详细的临床，放射学和病理调查的垂体腺瘤。DAX-1基因在患者和他的mother.Results的基因组分析：在这个病人中，原发性肾上腺功能衰竭已被诊断为在3岁，尽管替代治疗，在30岁的进行性色素沉着发展和损害的视野。ACTH为24980 pg/ml，核磁共振示巨大垂体腺瘤。三次经蝶手术及放射线治疗是必要的，以消除肿瘤肿块和控制ACTH分泌。组织学上，腺瘤由嗜色性和嗜碱性肿瘤细胞组成，ACTH免疫染色阳性。此外，一个新的突变被发现在病人和他的母亲：一个4 bp的插入（AGCG）在核苷酸2 - 5 - 9，在外显子1导致的移码和提前终止。结论：这种情况下表明，在先天性肾上腺发育不全的垂体腺瘤的发展，应考虑当突然上升的ACTH发生，尽管有足够的类固醇替代。
Objective: Mutations in the DAX-1 gene result in X-linked congenital adrenal hypoplasia. The classic clinical presentation is primary adrenal insufficiency in early life and hypogonadotropic hypogonadism at the time of expected puberty, but recent data have expanded the phenotypic spectrum of DAX-1 mutations. We report the occurrence of an ACTH-secreting adenoma in a patient with X-linked congenital adrenal hypoplasia.Design and methods: Detailed clinical, radiological and pathological investigation of the pituitary adenoma. Genomic analysis of the DAX-1 gene in the patient and his mother.Results: In this patient, primary adrenal failure had been diagnosed at 3 years of age and, despite replacement therapy, at 30 years of age progressive pigmentation developed and impairment of the visual field followed. ACTH was 24 980 pg/ml and nuclear magnetic resonance disclosed a huge pituitary adenoma. Three transsphenoidal operations and radiotherapy were necessary to remove the tumor mass and control ACTH secretion. Histologically, the adenoma was composed of chromophobic and basophilic neoplastic cells with positive immunostaining for ACTH. Moreover, a novel mutation was found both in the patient and his mother: a 4 bp insertion (AGCG) at nucleotide 2 5 9, in exon 1 resulting in a frame shift and premature termination.Conclusions: This case suggests that in adrenal hypoplasia congenita the development of a pituitary adenoma should be considered when a sudden rise of ACTH occurs despite adequate steroid substitution.