Much of our modern understanding and treatment of CAH comes from research conducted at Johns Hopkins Medical School in Baltimore in the middle of the 20th century. Lawson Wilkins , "founder" of pediatric endocrinology , worked out the apparently paradoxical pathophysiology: that hyperplasia and overproduction of adrenal androgens resulted from impaired capacity for making cortisol. He reported use of adrenal cortical extracts to treat children with CAH in 1950. Genital reconstructive surgery was also pioneered at Hopkins. After application of karyotyping to CAH and other intersex disorders in the 1950s, John Money , JL Hampson, and JG Hampson persuaded both the scientific community and the public that sex assignment should not be based on any single biological criterion, and gender identity was largely learned and has no simple relationship with chromosomes or hormones. See Intersex for a fuller history, including recent controversies over reconstructive surgery.
Shackleton et al. (2004) studied steroid excretion in 8 patients diagnosed with ABS and 1 patient with a milder but related phenotype without skeletal or genital abnormalities. The steroid excretion pattern was consistent and distinctive in all 9 patients, and was significantly different from that measured in controls (p less than ). A high ratio of metabolites of the primary adrenal steroid precursors pregnenolone and progesterone to cortisol metabolites was the most characteristic feature for diagnosis. The authors stated that pregnanediol could be considered a hallmark analyte since it is essentially absent from the urine of normal individuals or those with other defects in steroid biosynthesis. Shackleton et al. (2004) proposed the use of this distinctive steroid metabolic profile as the primary biochemical parameter for the diagnosis of the ABS-like phenotype not associated with FGFR2 mutations.