ArticleThe Journal of clinical endocrinology and metabolism2025
Free Cortisol and Free 21-Deoxycortisol in the Clinical Evaluation of Congenital Adrenal Hyperplasia.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Current insights into monitoring of congenital adrenal hyperplasia.Frontiers in endocrinology · 2026Review
- Free Cortisol and Free 21-Deoxycortisol in the Clinical Evaluation of Congenital Adrenal Hyperplasia.The Journal of clinical endocrinology and metabolism · 2025Article
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10 authors.
Funding
Abstract
contextSome patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF) may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some patients with untreated classic CAH.
objectiveDevelop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for free cortisol and free 21DF to quantify these steroids in patients with untreated classic CAH before and after Synacthen administration, and compare these concentrations to concentrations measured in patients with nonclassic CAH (NCCAH), other forms of adrenal insufficiency (AI), and controls.
methodsAn LC-MS/MS method to measure free cortisol and free 21DF was developed and validated. Total and free serum concentrations of both cortisol and 21DF were measured in patients with untreated classic CAH (n = 29), NCCAH (n = 5), AI (n = 3), and controls (n = 11) before and 60 minutes after stimulation with Synacthen.
resultsUnstimulated total cortisol concentrations of patients with untreated classic CAH (median 109 nmol/L) were lower than in patients with untreated NCCAH (249 nmol/L, P = .010) and controls (202 nmol/L, P = .016), but free cortisol concentrations were similar. Basal free 21DF concentrations were high in patients with 21OHD (median 5.32 nmol/L) and undetectable in patients with AI and controls (<0.19 nmol/L). After Synacthen administration, free 21DF concentrations increased in patients with 21OHD, while free cortisol concentrations did not change.
conclusionFree cortisol concentrations in patients with classic CAH were similar to those in controls and patients with NCCAH, indicating comparable cortisol availability. Additionally, patients with 21OHD produce high concentrations of 21DF, possibly explaining the low occurrence of symptoms in some patients with classic 21OHD. Free cortisol and 21DF levels should be considered in evaluating adrenal insufficiency in patients with CAH.
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