ESPE Abstracts (2022) 95 FC5.5

ESPE2022 Free Communications Adrenals and HPA Axis (6 abstracts)

Influence of prenatal environment and genetic background on glucocorticoid steroid metabolism in monozygotic twins with intra-twin birthweight-differences

Sandra Schulte 1 , Felix Schreiner 1 , Michaela Plamper 1 , Charlotte Kasner 1 , Mathias Gruenewald 1 , Peter Bartmann Bartmann 2 , Rolf Fimmers 3 , Michaela F. Hartmann 4 , Stefan A. Wudy 4 , Joachim Woelfle 5 & Bettina Gohlke 1

1Children’s University Hospital Bonn, Dept. of Paediatric Endocrinology and Diabetology, Bonn, Germany; 2Children’s University Hospital Bonn, Dept. of Neonatology, Bonn, Germany; 3University Hospital Bonn, Institute of Medical Biometry, Informatics and Epidemiology (IMBIE), Bonn, Germany; 4Centre of Child and Adolescent Medicine, Justus Liebig University Giessen, Division of Paediatric Endocrinology and Diabetology, Steroid Research and Mass Spectrometry Unit, Giessen, Germany; 5Children’s University Hospital Erlangen, Erlangen, Germany

Preliminary results:

Objective: Although low birthweight (bw) and unfavourable intrauterine conditions have been associated with metabolic sequelae in later life, little is known about their impact on steroid metabolism. We studied genetically identical twins with intra-twin bw-differences from birth to adolescence to analyse the long-term impact of bw on steroid metabolism.

Methods: 68 monozygotic twin-pairs with bw-difference of <1SDS (concordant; n=41, 18 female) and ≥1SDS (discordant; n=27, 15 female, 6 female and male pairs with catch-up) were recruited. At mean age of 14.9 yrs morning urine samples were collected and analysed by gas chromatography–mass spectrometry.

Results: In the concordant group no significant differences in urinary steroid metabolites were detected in females or males. In contrast, in the discordant female group with catch-up growth, we found significantly higher concentrations in the smaller twins for α-Cl, a cortisone metabolite (P=0.028, 1941 vs 1169 µg/l). Ratio of 11β-hydroxy-steroiddehydrogenase activity (cortols/cortolones) was significantly lower in smaller discordant females (P=0.032, 0.23 vs 0.27). Overall cortisol metabolite secretion was higher in female smaller twins with catch-up (11783 vs 7256 µg/l), although not significantly. Smaller female twins without catch-up showed slightly lower concentrations than their larger co-twins (11842 vs 13713 µg/l), again without significant difference. In the male pairs, the smaller discordant twins without catch-up showed significantly lower metabolite concentrations in 9/13 (69.2%) metabolites analysed and significantly lower cumulative major cortisol metabolites (P=0.046, 8053 vs 10060 µg/l) and overall cortisol metabolite secretion (P=0.028, 11879 vs 14867 µg/l). Male smaller twins with catch-up showed concentrations not significantly different than their larger co-twins (13483 vs 14284 µg/l). Within all twin pairs, we found significant intra-twin correlations in all steroid metabolites, cumulative metabolites, and enzyme activities analysed. Multiple regression analyses of the smaller twins showed that individual steroid concentrations of the larger co-twin were the strongest influencing factor among nearly all parameters analysed.

Conclusion: In monozygotic twins with intra-twin bw-differences, we could show that bw has a long-lasting impact on steroid metabolism with significant differences regarding cortisol metabolites and enzyme activities in pairs with greater bw-differences. Pronounced in the male group, we could see that lower overall cortisol metabolite secretion was represented in smaller twins without catch-up. Whether this might be source or result of a missing catch-up growth in childhood remains unclear. However, most parameters showed highly significant intra-twin correlations, suggesting also a major importance of the genetic background.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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