Hierarchical cluster analysis identified the structure at C3-C5 as a key distinguishing feature of the major catabolic streams and demonstrated a split point in metabolic pattern in patients at 7 days. Changes with time in steroid metabolism, larger in patients than in controls, could be interpreted as reflecting increased cortisol demand post partum, the clinical onset of salt-wasting and a transition in catabolism from fetal to postnatal life. Faster involution of the fetal zone and pronounced enhancement of steroid production in zona fasciculata and zona glomerulosa were indicated in patients. Predominant at birth were 鈥榩lanar鈥?fetal-type 5伪-reduced metabolites, adapted to placental excretion, which gave way to additionally hydroxylated neonatal-type metabolites, facilitating renal excretion. Classical metabolism made gains over the study period. Overproduction of steroids in utero in 21-hydroxylase deficiency would have induced fetal catabolic pathways dependent on 5伪-reduction. A progressive increase of steroids likely to arise from 5伪-reductase type 2 activity, again more distinct in disease, was observed.
We demonstrate that the key intermediates in the hypothetical 鈥榖ackdoor鈥?pathway of androgen synthesis are part of a broader catabolic network and should not be examined in isolation.