17 Urinary C21 Corticosteroid Sulfates in the Urine of Premature Infants Pre and Post ACTH

We have studied the urinary excretion of cortisol (F), cortisone (E), tetrahydrocortisol (THF), tetrahydrocortisone (THE), 6β-hydroxycortisol (6β-OHF) and corticosterone (B) in premature infants. Each specimen was extracted sequentially for free, β-glucuronidase and solvolysis liberated steroids; each metabolite was identified by constant isotope ratios, and quantitated by a double-isotope derivative assay. In 3 normal prematures studied within the first 48 hours of life, 6β-OHF, THF, F and B were mainly recovered as free or sulfated compounds. THE and E were mainly sulfurylated. In a 4th infant, with respiratory distress syndrome, studied similarly, 6β-OHF was mainly sulfated while THF was mostly as a glucuronoside. THE and B were equally glucuro and sulfo-conjugated while F and E were equally recovered in free or sulfated form. In a pool of 8 premature infants studied from two weeks of age, prior to ACTH, approximately 60 % of F and E were sulfo-conjugated, while a larger proportion of B was in the sulfate form. 6β-OHF and THF were predominantly excreted as sulfates, while THE was mostly unconjugated. Post ACTH, there was a considerable increase of all steroids and glucuro-conjugation seemed genererally enhanced except for F. These studies suggest that: 1. in resting state, most C21 steroids are excreted unconjugated or conjugated with sulfuric acid, in accord with limited glucuro-conjugation; 2. some limitation in reduction of Ring A of the steroid molecule exists since more unreduced metabolites are recovered than in older children and adults; 3. glucuroconjugation can be enhanced under stress or ACTH, suggesting that glucuro-conjugation is not maximal in resting state; 4. these metabolic particularities persist at least up to four weeks of age. (SPR)