ESPE Abstracts

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 glucocorticoid metabolism. We studied monozygotic twins with intra-twin bw-differences from birth to adolescence to analyse the long-term impact of bw and catch-up growth on glucocorticoid metabolism.

Methods: 46 monozygotic prepubertal twin-pairs with bw-difference of <1SDS (concordant; n=29, 13 female) and ≥1SDS (discordant; n=17, 6 female) were recruited. At a mean age of 6.9 yrs saliva samples were collected (at 7 am/waking, 1 pm, 6 pm and 9 pm/before bed) and analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Cortisol and cortisone concentrations showed statistically significant or highly significant intra-twin correlations in all twin pairs at 3/4 (cortisol), respectively 4/4 (cortisone) time points. Graphic evaluation of the diurnal cortisol patterns for each twin pair showed a distinct alignment in all groups. However, significant differences were found in the discordant group: the formerly smaller twins showed lower cortisone concentrations at 6 pm (2.77 vs 3.88 nmol/L, P=0.033) and statistically significant higher 11-deoxycortisone concentrations at 7 am (0.34 vs 0.13 nmol/L, P=0.042). Other time points showed no intra-twin differences. Analyses of the change of intra-twin differences over the day by mixed linear modelling showed no intra-twin differences in diurnal patterns. Regression analyses of intra-twin differences (smaller twin - larger twin) at 7 am showed a statistically significant influence for catch-up growth, indicating lower cortisol concentrations in smaller twins with more catch-up growth (adj.R²=0.159, P=0.014, ß=-3.71). Regarding 7 am cortisone concentration, regression analyses showed that intra-twin differences were statistically significantly influenced by being in the concordant or discordant group, with lower cortisone concentrations in the formerly smaller twins of the discordant group (adj.R²=0.121, P=0.012, ß=-5.74).

Conclusion: In monozygotic twins with intra-twin bw-differences, we found only few statistically significant differences regarding single time points and no differences regarding diurnal patterns. Additionally, a moderate influence on intra-twin differences in morning cortisol concentrations for intra-twin catch-up growth was found, as well as a weak influence on morning cortisone concentrations for being in the concordant or discordant group. However, we found statistically significant intra-twin correlations for cortisol and cortisone over the day in all groups and a pronounced graphic alignment of cortisol diurnal patterns in the individual twin pairs. We therefore suggest a major importance of the genetic background in cortisol metabolism.