Anterior pituitary agenesis (APA) has very rarely been reported. Therefore, its phenotypical and genotypical features are not well known. The aim of this study was to ascertain whether the clinical picture in 4 subjects with APA and multiple pituitary hormone deficiencies (MPHD) was different compared to the one observed in a selected control group consisting of 7 MPHD individuals with hypoplastic (and not aplastic) adenohypophysis and pituitary stalk interruption syndrome. Another goal was to investigate genetic basis of APA by analyzing for the first time in this condition many of the transcriptional factors which are required for both structural development and cellular differentiation of hypophysis. Age at diagnosis was significantly lower in APA children than in controls (1.5+/-2.3 vs 11.1+/-7.6 yr, p<0.0005). Microphallus and neonatal cholestasis were observed only in APA subjects (chi-squared=4.3, p<0.05) and also neonatal hypoglycemia was more frequent in APA patients than in controls (X2=4.05, p<0.05). Molecular analyses of the genes of the transcriptional factors POU1F1, PROP1, LHX3, LHX4, ISL1 and HESX1 detected no mutations in APA patients.
Conclusions: a) if compared with a selected cohort of MPHD patients with both adenohypophysis hypoplasia and pituitary stalk interruption syndrome, the ones with APA show an earlier and more severe picture of hypopituitarism; b) mutations in several transcription factors that are known to be essential for the development of Rathke's pouch are not necessarily found in humans with APA.