ESPE Abstracts

Introduction: The steroid metabolism of the newborn and infant is subject to rapid changes and is extremely difficult and complex to assess. Of all analytical techniques, the platform technology of GC-MS allows the most comprehensive assessment of the entire steroid metabolome and this approach is also non-invasive.

Method: In order to characterize the essential changes in steroid metabolism during infancy, a total of 355 urine samples from healthy, maturely born infants (129 females, 226 males) aged 1 to 352 days (median 77 days) was examined and divided into 6 various age groups: week 1, week 2-4, up to 6 months, up to 8 months, up to 10 months, up to 12 months. Urinary steroid metabolites were quantified by GC-MS after solid phase extraction, enzymatic hydrolysis, and derivatisation. We measured n = 56 urinary C₂₁-, C₁₉-, and C₁₈-steroids, resembling metabolites of the precursor hormones pregnenolone, 17-OH-pregnenolone, and DHEA (fetal zone steroids), progesterone, 17-OH-progesterone, several intermediates, cortisol, cortisone, corticosterone, androgens, and estrogens.

Results: for all age groups and sexes, reference values (centiles) were created regarding individual steroid metabolites and typical precursor/product ratios allowing assessment of relative enzyme activities. This is illustrated by the following examples: In males 5-pregnen--3β,20α,21-triol, a marker of adrenal fetal cortex activity, decreased steadily from 7918 µg/l (4732-28,371) in the first week of life to 404µg/l (163-676) in the 8^th month of the life. Furthermore, maturation of 5α-reductase-activity was reflected by α-tetrahydrocortisol (THF) which e.g. in males increased from 0 in week 1 up to 85 µg/l (12-445) in month 6. Finally, change of 11β-hydroxysteroiddehydrogenase activity was reflected by an increase in THF concentrations: e.g. in males THF increased from 0 (0-21) in week 1 to 296 µg/l (55-696) in the 12th month of life.

Conclusion: 1) Our GC-MS based approach of characterizing the steroid metabolome of infants allows assessment of all relevant physiologic changes of steroid metabolism during infancy. 2) Furthermore, it enables delineation of practically all steroid related disorders. 3) Since spot urine samples are used, the procedure is non invasive and sample material is easy to obtain.