Reported literature data strongly suggest that
steroid metabolism is dysregulated in
Type 1 diabetes mellitus. The aim of this study was to non-invasively examine the
cortisol metabolism in children with
Type 1 diabetes mellitus (T1DM) in detail and to test the hypothesis that adrenarche is affected under conventional intensive
insulin therapy. In 24-h urine samples of 109 patients aged 4-18 years with T1DM of more than 1 year,
steroids were profiled using gas chromatography-mass spectrometry. Additionally, urinary free
cortisol (UFF) and
cortisone (UFE) were quantified by RIA after extraction and chromatographic purification. Data on urinary
steroids from 400 healthy controls served as reference values.
Enzyme activities were assessed by established
steroid metabolite ratios, e.g. 5alpha-reductase and
11beta-hydroxysteroid dehydrogenase Type 2 (11beta-HSD2) by 5alpha-
tetrahydrocortisol/
tetrahydrocortisol and UFE/UFF, respectively. Urinary markers of adrenarche, especially
dehydroepiandrosterone and its direct metabolites were elevated in patients, as were urinary
6beta-hydroxycortisol, UFE, and
11beta-HSD2 activity. However, overall
cortisol secretion, as reflected by the sum of major urinary
cortisol metabolites, was mostly normal and activity of 5alpha-reductase clearly reduced. Our study provides evidence for an exaggerated adrenarche in T1DM children, which may help to understand reported sequelae in female patients like hyperandrogenic symptoms. The findings also suggest a reduced
cortisol inactivation via 5alpha-reductase that is not compensated by a fall in
cortisol secretion. Whether the elevated urinary
6beta-hydroxycortisol and
cortisone excretion, observed in the patients, are also present in other forms of
hypercortisolism and may thus serve as non-invasive clinical stress markers deserves further study.