EVIDENCE OF A CONGENITAL MIDLINE BRAIN ANOMALY IN PITUITARY DWARFS - A MAGNETIC-RESONANCE-IMAGING STUDY IN 101 PATIENTS

Background. Magnetic resonance imaging (MRI) of the brain in pituitary dwarfs has revealed a previously unknown entity: ectopia of the poste rior pituitary (PPE), absence or hypoplasia of the pituitary stalk and hypoplasia of the anterior pituitary. The pathogenesis of these findi ngs was explained originally by a traumatic transection of the pituita ry 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 norma l delivery, nor account for a different feature also found in other pi tuitary dwarfs consisting of pituitary hypoplasia with normal posterio r pituitary. A second hypothesis could then been proposed, based on dy sgenesis or abnormal embryonic development of both adenohypophysis and neurohypophysis. Objective. To review the value and significance of t hese two different etiopathogenetic hypotheses by analyzing clinical, endocrinological, and MRI findings in a large population of pituitary dwarfs. Methods. One hundred and one consecutive patients with congeni tal 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 pa tients and controls to assess the perinatal history, the pituitary-hyp othalamic function, and the neurological status. MRI studies were eval uated both qualitatively and quantitatively and the pituitary volume ( PV) was calculated in both patients and controls. Quantitative data we re 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. Res ults. MRI revealed PPE in 59 patients and a normal posterior pituitary (NPP) in 42. PV was extremely small in patients with PPE and in patie nts 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 a nd did not differ between patients with single and multiple pituitary hormone deficiency and between patients with normal and breech deliver y. PPE patients differed from NPP patients for a higher male/female ra tio (3:1 vs 1:1) and for a greater frequency of multiple pituitary hor mone deficiency (49% vs 12%), breech delivery (32% vs 7%), and associa ted congenital brain anomalies (12% vs 7%). In PPE patients breech del ivery was strongly associated with multiple pituitary hormone deficien cy. Conclusion. On the basis of this study the traumatic hypothesis co uld theoretically explain the pathogenesis of PPE only in 32% of the p atients with this condition. On the basis of modern understanding of e mbryogenesis 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 morpholog ical MRI abnormality and the clinico-endocrinological features encount ered in all PPE patients. The close contiguity between the future pitu itary and hypothalamus, the peculiar association with congenital midli ne brain anomalies, and the recent data about a possible role of Pit-1 gene, all support the hypothesis of a congenital defect. Finally, bre ech delivery can be considered not as a cause of PPE, but as an effect of the embryonic pituitary-hypothalamic abnormalities.