Influence of Fetal Growth Velocity and Smallness at Birth on Adrenal Function in Adolescence

Abstract

The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth weight <10 percentile). In 52 adolescent boys (17.5 years) we assessed circulating androgen levels (T, Δ⁴-adione, DHEAS), overnight serum cortisol profiles (every 20 min), ACTH stimulation test (250 µg i.v.) and analysis of 24-hour urinary adrenal steroid excretion. Urinary excretion of adrenal androgen and cortisol metabolites were significantly lower in the SGA compared to the AGA group. Basal morning cortisol levels were lower in adolescents born SGA compared to those born AGA (365 mmol/l, interquartile range (IQR) 284–413 vs. 445 mmol/l, IQR 377–495, p = 0.04), but overnight cortisol profiles (AUC) did not differ. The ACTH test showed equally stimulated levels of cortisol for those born SGA and AGA. There was no difference in serum testosterone, dehydroepiandrosterone sulfate and Δ⁴-adione levels between the SGA and AGA subjects. This suggests impaired excretion of adrenal androgen and cortisol metabolites in young men born SGA compared to AGA. In conclusion, this study demonstrated subtle changes in adolescent adrenal function associated with birth weight.

Adrenocortical Hormonal Activity in 20-Year-Old Subjects Born Small or Appropriate for Gestational Age

“…In agreement with our findings, Jensen et al [36] reported similar serum DHEAS levels in full-term born 17-year-olds, and Allvin et al [38] in about 20-year-old SGA and AGA men. Jaquet et al [39] also reported similar serum DHEAS and androstenedione levels in 20-year-old full-term born SGA and AGA women.…”

“…A recent study on very preterm born and growth-restricted young adults reported higher DHEAS concentrations compared to the control subjects [23]. SGA children at prepubertal and pubertal age have been shown to have increased DHEAS levels in several [10,11,12,13,14] but not in all studies [35,36]. In the study of Boonstra et al [35], the SGA born children were selected on the basis of short stature at the age of 3–9 years.…”

Response to the Letter to the Editor Regarding the Article: Reference values for serum dehydroepiandrosterone‐sulphate in healthy children and adolescents with emphasis on the age of adrenarche and pubarche

“…Based on these findings, we believe that potential bias of IUGR on suggested DHEA‐S values was excluded. Additionally, findings of several previous studies also did not confirm associations between SGA status and premature adrenarche/serum DHEA‐S levels . Similarly in follow‐up studies of SGA cohorts, very few SGA‐born children have been reported to develop premature adrenarche …”

“…Additionally, findings of several previous studies also did not confirm associations between SGA status and premature adrenarche/ serum DHEA-S levels. [6][7][8] Similarly in follow-up studies of SGA cohorts, very few SGA-born children have been reported to develop premature adrenarche. 9 Ahmet Ucar also indicated that due to DHEA-S and androstenedione being week androgens, the validity of the serum DHEA-S cut-off values at the transition from PH1 to PH2 suggested by Guran et al warrants reconsideration and that such a cut-off value is only possible with a longitudinal study.…”

A Twin-Sibling Study on Early Growth and Hormone Levels in Adolescents

“…The results from studies relating birth weight to DHEAS or IGF-I levels in late adolescence and adulthood were not consistent (Beck Jensen et al 2011;Jaquet et al 1999;Poole et al 2011;Ruder et al 2011;Szathmári et al 2001;Tworoger et al 2006). Here, we investigate this association in late adolescence.…”