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Context Low birthweight (bw) and unfavorable intrauterine conditions have been associated with metabolic sequelae in later life, but little is known about their impact on glucocorticoid metabolism. Objective We studied monozygotic twins with intratwin bw differences to analyze the long-term impact of bw on glucocorticoid metabolism. Methods 46 monozygotic twin pairs with bw differences of <1 SDS (concordant; n = 29) and ≥1 SDS (discordant; n = 17) were recruited. At 6.9 years (mean age), saliva samples were collected (at 7 hours, 13 hours, 18 hours and 21 hour) and analyzed with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results We found significant or highly significant intratwin correlations in all twin pairs at 3 of 4 (cortisol), and 4 of 4 (cortisone) time points. Graphic evaluation of the diurnal cortisol patterns for each twin pair showed a distinct alignment in all groups. Analyses of the change of intratwin differences over the day by mixed linear modeling showed no intratwin differences in diurnal patterns. Regression analyses of intratwin differences at 7:00 hours showed a significant influence of catch-up growth, indicating lower cortisol concentrations in smaller twins with more catch-up growth (adj. R2 = 0.159, P =.014, ß = −3.71, F(1,42) = 9.15, f2 = 0.19). Conclusion In monozygotic twins with intratwin bw differences, intratwin catch-up growth showed a moderate influence on intratwin differences in morning cortisol concentrations. We observed no differences regarding diurnal patterns. In contrast, in all groups, we found significant intratwin correlations for cortisol and cortisone over the day and a pronounced graphic alignment of cortisol diurnal patterns. We therefore suggest a predominant significance of the genetic background compared with bw differences on cortisol metabolism. [ABSTRACT FROM AUTHOR]

Objective: To study the impact of the quality of therapeutic control on f ertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adre nal hyperplasia (CAH). Design: Combined cross-sectional and retrospective clinical study. Methods: Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as 'poor', 'moderate' or 'medium'. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes. Results: Semen quality was similar in males with CAH and controls (P = 0.066), however patients with 'poor' past control and large TART, or with 'poor' current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was 'poor' (1.8 ± 0.9 U/L; 'good': 3.9 ± 2.2 U/L); P = 0.015); luteinizing hormone was decreased if it was 'poor' (1.8 ± 0.9 U/L; P = 0.041) or 'moderate' (1.9 ± 0.6 U/L; 'good': 3.0 ± 1.3 U/L; P = 0.025). None of the males with 'good' past CAH control, 50% of those with 'moderate' past control and 80% with 'poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively. Conclusions: TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis. [ABSTRACT FROM AUTHOR]

Objective: Although low birthweight (bw) and unfavorable 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 analyze the long-term impact of bw on steroid metabolism.Methods: 68 monozygotic twin pairs with a bw-difference of <1 standard deviation score (SDS; concordant; n = 41) and ≥1 SDS (discordant; n = 27) were recruited. At 14.9 years (mean age), morning urine samples were collected and analyzed with gas chromatography-mass-spectrometry.Results: No significant differences were detected in the concordant group. In contrast, in the smaller twins of the discordant group, we found significantly higher concentrations not only of the dehydroepiandrosterone sulfate (DHEAS) metabolite 16α-OH-DHEA (P = 0.001, 656.11 vs 465.82 µg/g creatinine) but also of cumulative dehydroepiandrosterone and downstream metabolites (P = 0.001, 1650.22 vs 1131.92 µg/g creatinine). Relative adrenal (P = 0.002, 0.25 vs 0.18) and overall androgen production (P = 0.001, 0.79 vs 0.65) were significantly higher in the formerly smaller discordant twins. All twin pairs exhibited significant intra-twin correlations for all individual steroid metabolites, sums of metabolites, indicators of androgen production, and enzyme activities. 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 analyzed.Conclusion: In monozygotic twin pairs with greater intra-twin bw-differences (≥1 SDS), we found that bw had a long-lasting impact on steroid metabolism, with significant differences regarding DHEAS metabolites and relative androgen production. However, most parameters showed significant intra-twin correlations, suggesting a consistent interrelationship between prenatal environment, genetic background, and steroid metabolism. [ABSTRACT FROM AUTHOR]