Exaggerated adrenarche and 11beta-hydroxysteroid dehydrogenase type 2 activity appear to be major features of the altered adrenal steroid metabolism in children and adolescents with type 1 diabetes mellitus

Our aim was to study the alterations in adrenal steroid metabolism in children with type 1 diabetes mellitus (T1DM). We profiled steroids in 24-h urinary samples using gas chromatography-mass spectrometry (GC-MS) in 109 patients aged 4–18 years with T1DM of more than 1 year. 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 participating in the DONALD (Dortmund Nutritional and Anthropometric Longitudinally Designed) study served as reference values. 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) activity was assessed by the ratio of UFE/UFF and potential bioactive free glucocorticoids (PBFG) by the sum of UFF+UFE. PBFG, 11ß-HSD2 activity, and UFE were higher in both children (<10 years of age) and adolescents (>=10 years) with T1DM (mean SDS of all patients ranging from +1.09 [SE 0.17] to +1.86 [0.18]; each with P<0.0001) as was the combined daily excretion of the predominant adrenal androgen dehydroepiandrosterone and its major 16-hydroxylated downstream metabolites (DHEA&M; +0.57 [0.11]; P<0.0001). Cortisol secretion, reflected by the sum of 7 major cortisol metabolites, was elevated only in children ≤ 10 years (+0.83 [0.33]; P<0.05), whereas UFF did not differ significantly from the DONALD controls (+0.04 [0.14]). Our results point to an increased secretion of adrenal androgens in T1DM during growth. We speculate that the overall elevated peripheral insulin levels in treated T1DM might induce adrenarche-specific steroidogenic enzymes. Although cortisol secretion was not consistently increased, all subgroups of diabetics showed a clearly elevated excretion of PBFG. Whether renal effects of administered insulin may have stimulated the cortisol to cortisone conversion is not yet known. Our findings suggest that children and adolescents with T1DM have exaggerated adrenarche and 11ß-HSD2 activity.

(Supported by grant from the foundation „The child with diabetes“ and DFG grant RE 753/5)