Survival without treatment of patients with classic and non-classic 21-hydroxylase deficiency.

21-hydroxylase deficiency, caused by biallelic CYP21A2 variants, results in cortisol and aldosterone deficiency with hyperandrogenism.

21-hydroxylase deficiency combines cortisol and aldosterone deficiency with hyperandrogenism, and standard treatment of classic forms relies on glucocorticoid, sometimes mineralocorticoid, replacement to prevent adrenal crises. This multicentre retrospective open cohort study describes 52 patients with classic disease (29 salt-wasting, 23 simple-virilizing) and 24 with non-classic disease who survived without glucocorticoid treatment for 8.7 years (IQR 4.7-14.3) and 28.1 years (IQR 12.2-39.0), respectively (p < 0.001). Among classic patients, 48% never received glucocorticoid treatment and 71% of these experienced no adrenal crisis during the untreated period, including during illness or surgical interventions. In the non-classic group, 21% were never treated and two patients (8.3%) had an adrenal crisis, both carrying an I2 splice/P31L genotype; all crises but one occurred before the age of 7 years.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

These data are no licence to stop treatment, but they document wider variability in glucocorticoid dependence than is usually taught and are a reminder that CYP21A2 genotype-phenotype correlation leaves real room for variation. Interpretation must stay cautious, with an obvious survival bias in a retrospective cohort: patients who died of an undiagnosed adrenal crisis are absent from it. The usable message lies elsewhere, in the concentration of crisis risk before age 7, which argues for maximal therapeutic education in early childhood.

Analysis by Dr Thibaut Benquey