Triulzi F, Scotti G, di Natale B, Pellini C, Lukezic M, Scognamiglio M, Chiumello G
Department of Neuroradiology, Scientific Institute H San Raffaele, Milan, Italy.
Pediatrics. 1994 Mar;93(3):409-16.
Magnetic resonance imaging (MRI) of the brain in pituitary dwarfs has revealed a previously unknown entity: ectopia of the posterior pituitary (PPE), absence or hypoplasia of the pituitary stalk and hypoplasia of the anterior pituitary. The pathogenesis of these findings was explained originally by a traumatic transection of the pituitary stalk during delivery. A high incidence of breech delivery has been reported in these groups, but the traumatic hypothesis cannot explain the findings in the relatively high percentage of patients with normal delivery, nor account for a different feature also found in other pituitary dwarfs consisting of pituitary hypoplasia with normal posterior pituitary. A second hypothesis could then been proposed, based on dysgenesis or abnormal embryonic development of both adenohypophysis and neurohypophysis.
To review the value and significance of these two different etiopathogenetic hypotheses by analyzing clinical, endocrinological, and MRI findings in a large population of pituitary dwarfs.
One hundred and one consecutive patients with congenital idiopathic growth hormone deficiency (CIGHD) were studied by MRI; they were compared with a control group of 46 healthy short children. A complete clinico-endocrinological evaluation was obtained in both patients and controls to assess the perinatal history, the pituitary-hypothalamic function, and the neurological status. MRI studies were evaluated both qualitatively and quantitatively and the pituitary volume (PV) was calculated in both patients and controls. Quantitative data were statistically analyzed to compare the mean PV of the patients with the mean PV of controls, the hormonal therapy, the single or multiple pituitary hormone deficiency, and the presence of breech delivery.
MRI revealed PPE in 59 patients and a normal posterior pituitary (NPP) in 42. PV was extremely small in patients with PPE and in patients with NPP associated with a severely narrowed pituitary stalk; mean PV was significantly lower in CIGHD patients when compared with that of healthy short children. PV was not influenced by hormonal therapy and did not differ between patients with single and multiple pituitary hormone deficiency and between patients with normal and breech delivery. PPE patients differed from NPP patients for a higher male/female ratio (3:1 vs 1:1) and for a greater frequency of multiple pituitary hormone deficiency (49% vs 12%), breech delivery (32% vs 7%), and associated congenital brain anomalies (12% vs 7%). In PPE patients breech delivery was strongly associated with multiple pituitary hormone deficiency.
On the basis of this study the traumatic hypothesis could theoretically explain the pathogenesis of PPE only in 32% of the patients with this condition. On the basis of modern understanding of embryogenesis of anterior and posterior pituitary, it is then justified to propose that a defective induction of mediobasal structure of the brain in the early embryo could account for both the complex morphological MRI abnormality and the clinico-endocrinological features encountered in all PPE patients. The close contiguity between the future pituitary and hypothalamus, the peculiar association with congenital midline brain anomalies, and the recent data about a possible role of Pit-1 gene, all support the hypothesis of a congenital defect. Finally, breech delivery can be considered not as a cause of PPE, but as an effect of the embryonic pituitary-hypothalamic abnormalities.
垂体性侏儒症患者的脑部磁共振成像（MRI）显示出一种此前未知的情况：垂体后叶异位（PPE）、垂体柄缺如或发育不全以及垂体前叶发育不全。这些发现的发病机制最初被解释为分娩过程中垂体柄的创伤性横断。据报道，这些患者群体中臀位分娩的发生率很高，但创伤假说无法解释正常分娩患者中相对较高比例的这些发现，也无法解释在其他垂体性侏儒症患者中发现的另一个特征，即垂体前叶发育不全但垂体后叶正常。基于此，有人提出了第二种假说，即腺垂体和神经垂体发育异常或胚胎发育异常。
通过分析大量垂体性侏儒症患者的临床、内分泌和MRI表现，探讨这两种不同病因假说的价值和意义。
对101例连续的先天性特发性生长激素缺乏症（CIGHD）患者进行MRI检查，并与46例健康矮小儿童组成的对照组进行比较。对患者和对照组进行全面的临床 - 内分泌评估，以评估围产期病史、垂体 - 下丘脑功能和神经状态。对MRI研究进行定性和定量评估，并计算患者和对照组的垂体体积（PV）。对定量数据进行统计分析，以比较患者的平均PV与对照组的平均PV、激素治疗情况、单一或多种垂体激素缺乏情况以及臀位分娩情况。
MRI显示59例患者存在PPE，42例患者垂体后叶正常（NPP）。PPE患者以及垂体后叶正常但垂体柄严重狭窄的患者的PV极小；与健康矮小儿童相比，CIGHD患者的平均PV显著更低。PV不受激素治疗影响，单一和多种垂体激素缺乏患者之间以及正常分娩和臀位分娩患者之间的PV无差异。PPE患者与NPP患者相比，男女比例更高（3:1对1:1），多种垂体激素缺乏的频率更高（49%对12%），臀位分娩的频率更高（32%对7%），以及合并先天性脑异常的频率更高（12%对7%）。在PPE患者中，臀位分娩与多种垂体激素缺乏密切相关。
基于本研究，创伤假说理论上仅能解释32%患有PPE患者的发病机制。基于对垂体前叶和后叶胚胎发生的现代理解，有理由提出早期胚胎中脑底结构诱导缺陷可解释所有PPE患者中出现的复杂形态学MRI异常和临床 - 内分泌特征。未来垂体与下丘脑的紧密相邻、与先天性中线脑异常的特殊关联以及关于Pit - 1基因可能作用的最新数据，均支持先天性缺陷假说。最后，臀位分娩不应被视为PPE的原因，而应被视为胚胎垂体 - 下丘脑异常的结果。
