Faculty of Medicine, University of Belgrade, Serbia.
Hormones (Athens). 2012 Apr-Jun;11(2):189-98. doi: 10.14310/horm.2002.1346.
Congenital hypopituitarism is a syndrome which is associated with single or multiple pituitary hormone deficiencies. Mutations in a number of developmental genes have been linked to combined pituitary hormone deficiencies, the most common being mutation in the pituitary homeobox protein prophet of the Pit 1 gene (PROP1). PROP1 exhibits DNA-binding and transcriptional activities. On magnetic resonance imaging, most patients with PROP1 mutation have a hypoplastic pituitary gland. Occasionally, transient pituitary enlargement before definite involution is reported. Kallmann syndrome (KS) is a human developmental genetic disorder which is a clinically (isolated hypogonadotropic hypogonadism-IHH) and genetically heterogeneous disease. Routine neuroimaging in classical IHH is thought to be of limited clinical value and normal anatomy of the hypothalamic-pituitary region is often reported. For neither disorder are there many reports on imaging during adulthood. Nor are there any guidelines concerning long-term imaging follow-up in patients with developmental pituitary disorders.
Our aim was to present unusual endocrine and imaging abnormalities which developed in adulthood in two patients with developmental pituitary disorders.
We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas.
Both patients with developmental gene mutations, after long-term correction of their sex steroid status, developed prolactinomas. Although the exact mechanism of pituitary tumorigenesis is not known, we speculate that sex steroids may have facilitated prolactinoma development from the prolactin cell pool which underwent uncontrolled proliferation in the setting of a developmental disorder.
先天性垂体功能减退症是一种与单一或多种垂体激素缺乏相关的综合征。许多发育基因的突变与联合垂体激素缺乏有关，最常见的是垂体同源框蛋白 Pit-1 基因（PROP1）的突变。PROP1 表现出 DNA 结合和转录活性。在磁共振成像上，大多数 PROP1 突变患者的垂体腺发育不全。偶尔也有报道称，在明确的萎缩之前会出现短暂的垂体增大。卡尔曼综合征（KS）是一种人类发育遗传疾病，临床上表现为（孤立性促性腺激素缺乏性性腺功能减退症-IHH）和遗传异质性疾病。经典 IHH 的常规神经影像学被认为临床价值有限，下丘脑-垂体区域的正常解剖结构经常被报道。对于这两种疾病，成年期的影像学都没有很多报道。也没有关于发育性垂体疾病患者长期影像学随访的指南。
我们的目的是报告两名发育性垂体疾病患者成年后出现的异常内分泌和影像学异常。
我们报告了一名女性患者，由于 PROP1 突变，除了催乳素外，还存在多种垂体激素缺乏（GH、TSH、促性腺激素和 ACTH），以及一名男性患者，由于 Kallmann 2 基因（成纤维细胞生长因子受体 1-FGFR1）突变，患有 KS（嗅觉缺失和 IHH），这两名患者成年后均出现催乳素瘤。
两名发育基因突变患者在长期纠正其性激素状态后，均发生了催乳素瘤。虽然确切的垂体肿瘤发生机制尚不清楚，但我们推测性激素可能在发育障碍的背景下，促进了催乳素细胞池的不受控制增殖，从而导致催乳素瘤的发生。
