Residual activity of mutant androgen receptors explains wolffian duct development in the complete androgen insensitivity syndrome.

Development of the Wolffian ducts (WD) into epididymides and vasa deferentia is dependent on testosterone. Patients with the complete androgen insensitivity syndrome (CAIS) are therefore not expected to develop these structures. However, WD derivatives have been described in cases of CAIS. It is thought that these may be remnants. This study assesses the degree of WD development in 33 patients with CAIS and investigates whether this development was androgen dependent. Epididymides and vasa deferentia were identified in 70% of patients with substitution mutations in the androgen receptor ligand-binding domain. They were more developed than epididymides and vasa deferentia from 16- to 20-wk-old male fetuses, suggesting that the WD had been stimulated to grow, rather than failed to regress. Receptors with substitutions in the ligand-binding domain were normally expressed and showed residual response to androgens in transactivation assays. Patients with premature stop codons or frameshift mutations, which prevented androgen receptor expression, or DNA-binding domain mutations that abolished transcriptional activity did not have epididymides or vasa deferentia. We hypothesize that mutant receptors with residual activity in vitro respond to high local testosterone concentrations in vivo, thereby stimulating WD development. The classification of androgen insensitivity in such patients should be considered severe rather than complete.

Pelvic floor magnetic resonance imaging after neonatal single stage reconstruction in male patients with classic bladder exstrophy.

PURPOSE: We evaluate a magnetic resonance imaging (MRI) protocol used to study the pelvic floor anatomy in male patients following neonatal single stage complete bladder exstrophy and epispadias repair with osteotomies. MATERIALS AND METHODS: From 1996 to 2002, 9 males underwent surgical correction of bladder exstrophy and epispadias with osteotomies within 1 to 12 days of birth. Pelvic floor MRI was conducted comparing this group to 5 aged matched male patients with no pelvic anatomical abnormality who underwent MRI for other illness. We compared various measurement of pelvic musculature by unpaired Wilcoxon test. RESULTS: Median followup was 3 years (range 0.5 to 5.3). All surgical procedures succeeded in closure of abdominal wall and genitalia defects. MRI data showed that in the exstrophy group symphyseal distance was significantly wider than that in controls (median 3.8 vs 1.1 cm). In addition, the levator ani fibers diverted more laterally (42 vs 22 degrees), the pelvic floor in coronal view was more flat (103 vs 80 degrees) and the anus was more anteriorly displaced (2.8 vs 4.4 cm). We also documented shorter anterior corporeal bodies in the exstrophy group (1 vs 2 cm). No statistical difference between the 2 groups was found in the dimensions of the levator and obturator muscles, sagittal angle of the pelvic floor, and the dimensions and angle of the posterior corporal bodies. Two patients achieved some degree of continence around the age of 4 years. They had the shortest symphyseal distance and sharpest angle of levator ani fiber divergence, and the bladder neck was more deeply located in the pelvic. CONCLUSIONS: We applied novel MRI parameters to the pelvic floor anatomy providing a new quantifiable approach. Our protocol is feasible and reproducible, allowing for future comparison of the impact of different surgical modalities, and correlation between anatomical findings and continence.