medwireNews: Plasma concentrations of the adrenal-derived 11-oxygenated-C19 androgen 11-ketotestosterone strongly correlate with salivary levels in children with congenital adrenal hyperplasia (CAH), UK researchers report.
The team, led by Nils Krone from the University of Sheffield, also found a high degree of correlation between the two sample types for both 17-hydroxyprogesterone and androstenedione.
They say that combining these two commonly used treatment markers with 11-ketotestosterone could “serve as a non-invasive monitoring tool in CAH, which will provide a significant amount of additional information and will ultimately improve management and outcomes in CAH.”
The multicentre study included 78 children (median age 12.8 years) with CAH due to 21-hydroxylase deficiency and 62 healthy age-, sex- and BMI-matched controls recruited in the UK between 2015 and 2018.
Paired blood and saliva samples were analysed for five androgens using liquid-chromatography tandem mass spectrometry, with significant associations observed between the two sample types for all five.
As reported in The Journal of Clinical Endocrinology & Metabolism, the strongest correlation between the two measurements was found for 11-ketotestosterone (rs=0.944), followed by androstenedione (rs=0.931), 11-hydroxyandrostenedione (rs=0.876), 17-hydroxyprogesterone (rs=0.871) and testosterone (rs=0.867).
The results were consistent when analysed by age and gender, and also when controlling for glucocorticoid dose and time elapsed from last treatment, the researchers note.
The team also examined the correlations according to 17-hydroxyprogesterone concentration. They found that in both plasma and saliva, concentrations of 11-ketotestosterone and 11-hydroxyandrostenedione were significantly higher in patients with high 17-hydroxyprogesterone levels (>36 nmol/L) and significantly lower in patients with low levels (<12 nmol/L) relative to those within target range (12–36 nmol/L).
Compared with controls, the patients with CAH had significantly higher plasma and saliva concentrations of all five hormones, but Krone and co-investigators note that there was consistent overlap between the two groups in plasma levels of the two 11-oxygenated androgens and, to a lesser degree, 17-hydroxyprogesterone.
Further analysis revealed that “in the majority of cases the overlap with control values corresponded to patients identified to have the plasma 17-hydroxyprogesterone either in the target or the suppressed range,” Krone et al remark.
They add: “This finding supports the potential clinical usefulness of 11-oxygenated androgens in defining undertreatment in patients with CAH [and] further highlights a need to employ hormonal profiles of several steroid hormones as reliable biochemical monitoring for assessing disease control.”
However, the team also accepts that the clinical relevance of their findings is limited by the fact that they did not measure salivary hormonal variations throughout the day and that hormonal measurements were not timed in relation to medication.
By Laura Cowen
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J Clin Endocrinol Metab 2019; doi:10.1210/jc.2019-00031