Precursor-to-product ratios in steroid hormone metabolism may accurately reflect enzymatic activity and production of metabolites relative to their disappearance. The purpose of this study was to explore the use of direct precursor-to-product steroid ratios to discriminate between infants with congenital adrenal hyperplasia (CAH) due to 21- α -hydroxylase deficiency and infants with no disorder, thus characterizing the biochemical phenotype in CAH. Deidentified dried blood spot samples from confirmed CAH cases identified by newborn screen (CAH-positive, N = 8) and from cases with no disorder (CAH-negative, N = 10) were obtained from the California State Newborn Screening Program. Samples (∼6.25 mm circular spots) underwent methanol and water extraction (9:1 ratio). Deuterated steroids served as isotope internal standards. 17-α-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), androstenedione (A4) and cortisol (F) concentrations were determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS), and the 17-OHP/S, 17-OHP/A4, and S/F ratios were calculated. The mean 17-OHP and A4 concentrations in samples from CAH cases were significantly increased when compared to cases with no disorder (p = 0.003 for both). 17-OHP/S and 17-OHP/A4 ratios were also significantly elevated in CAH cases (p = 0.007 and p < 0.001, respectively). In contrast, S and F concentrations and the S/F ratio were similar between the two groups. In CAH, the elevated 17-OHP/S ratio is a biomarker of diminished 21-α-hydroxylase activity, and the elevated 17-OHP/A4 ratio is a biomarker of adrenal androgen excess via increased 17,20-lyase activity. The similar S/F ratio indicates that the rate of production via 11-β-hydroxylase and disappearance of F is maintained in CAH.

ObjectiveEnhanced fatty acid desaturation by stearoyl-CoA desaturase enzyme-1 (SCD1) is associated with obesity. This study determined desaturation in cord plasma of newborns of mothers with and without gestational diabetes (GDM).Study designNewborns of mothers with GDM (n=21) and without (Control, n=22) were recruited. Cord plasma fatty acid desaturation indices (palmitoleic/palmitic, oleic/stearic ratios) were compared, and correlated with anthropometrics and biochemical measures. A subset of VLDL desaturation indices were determined to approximate liver SCD1 activity.ResultsThe total oleic/stearic index was higher in GDM, despite adjustment for cord glucose concentrations. Among GDM and Controls, the oleic/stearic index correlated with cord glucose concentrations (rs=0.36, p=0.02). Both palmitoleic/palmitic and oleic/stearic indices correlated with waist circumference (r=0.47, p=0.001; r=0.37, p=0.01). The VLDL oleic/stearic index was higher in GDM.ConclusionThe elevated total oleic/stearic index suggests increased lipogenesis in GDM newborns. Factors in addition to glucose supply may influence fetal SCD1 activity.