A Cross-Sectional Study of Dehydroepiandrosterone Sulfate in Prepubertal Children with Myelomeningocele

Abstract

Objective: To assess biochemical characteristics of adrenarche in patients with myelomeningocele (MMC), we examined serum levels of dehydroepiandrosterone sulfate (DHEAS) in prepubertal MMC patients. Patients and Methods: The study included a total of 54 prepubertal patients with MMC and shunted hydrocephalus: 13 patients (2 m, 11 f; aged 4.6–10.1 years, mean 8.1 ± 0.4) with isolated pubarche (Tanner stage PH 2–4, B1 or testes volume ≤3 ml) and 41 prepubertal MMC patients without pubarche (17 m, 24 f; aged 2.0–11.9 years; mean 6.8 ± 2.5). DHEAS levels were measured directly by chemiluminescence immunoassay (Nichols, USA). Auxological data (supine length, body mass index (BMI), arm span) and bone age (BA) were recorded. Results(mean ± SD): Basal DHEAS levels correlated with chronological age (CA) (r = 0.32, p < 0.05), BA (r = 0.65, p < 0.01; n = 23), BMI (r = 0.54, p < 0.01) and pubic hair stage (PH1 vs. PH2–4, r = 0.49, p < 0.01). 10/11 patients aged 2–4 years had DHEAS levels in the normal range, whereas 18/40 (45.0%) of the 5- to 9-year-old patients showed elevated levels (>+2 SDS). Ten patients with isolated pubarche (10/13; 2 m, 8 f; CA 8.3 ± 1.5 years) and 9 patients without pubarche (9/41; 6 m, 3 f; CA 6.9 ± 2.1 years) had elevated DHEAS levels (+6.34 and +4.05 SDS, respectively). The values correlated with BA/CA ratio (p < 0.05, n = 23). There was a trend to higher BMI SDS levels in patients with elevated DHEAS levels. Conclusion: Our data show an early and increased activation of adrenal androgen secretion in MMC patients.

Strain‐specific modifier genes governing craniofacial phenotypes

“…Steroid hormones perform a key role in neural development, and the effects of some of these hormones (e.g., androgens, estrogens, glucocorticoids, progesterone) on the developing brain are well established (Jelks et al,2007; Quadros et al,2007). Moreover, an association between the development of NTDs and corticosteroids has been reported (Hendrickx and Tarara,1990; Dindar et al,1999; Trollmann et al,2001). Ingenuity pathway analysis revealed that C21 steroid hormone metabolism is the most enriched pathway in genes demonstrating enhanced expression in B6 NT, but is not enriched in those displaying increased expression in 129 NTs (Supplemental Tables 2 and 3).…”

“…The effect of genetic background on acoustic startle response in fragile X knockout mice has also been reported, highlighting the influence of modifier genes on the fragile X phenotype (Errijgers et al,2008). In transgenic and gene‐targeted animals, a host of other physiologic endpoints including organ structure, locomotor activity, cardiovascular physiology, behavior, sepsis, ethanol tolerance, and autoimmune susceptibility are influenced by genetic background (Aziz et al,2007; Choi and Klingensmith,2009; de Mooij‐van Malsen et al,2009; Linsenbardt et al,2009; Shah et al,2010; Boross et al,2011; Painsipp et al,2011).…”