Insulin Resistance Emerges Early After Glucocorticoid Treatment in Adult Patients With 21‐Hydroxylase Deficiency

ABSTRACT Background Metabolic disorders, particularly insulin resistance (IR), represent important complications in adults with 21‐hydroxylase deficiency (21OHD). Glucocorticoid (GC) therapy is a known risk factor, yet evidence from longitudinal analyses remains scarce. Methods In this study, based on a large, genetically characterized, single‐center cohort of Chinese adults with 21OHD, we performed both cross‐sectional and longitudinal analyses to investigate the risk factors for IR. Results We found that nearly one‐third of young adult 21OHD patients had IR. Current GC use remained independently associated with IR (OR 13.30, 95% CI 2.54–69.55; p = 0.002), whereas neither genotype nor androgen levels showed an association. We followed 52 patients without IR at baseline; incident IR occurred in 57.1% (4/7) of GC‐naive patients and 68.9% (31/45) of previously GC‐exposed patients, with median times to IR onset of 14.7 and 13.1 months, respectively. Importantly, dexamethasone use was independently associated with incident IR (HR 7.04, 95% CI 1.81–27.34; p = 0.005). Daily 1000 mg metformin therapy for 6 months did not significantly improve IR (median HOMA‐IR, 2.50–2.82; p = 0.460) and only provided a modest benefit in body weight (median BMI, 23.6–22.5 kg/m 2 ; p = 0.046). Conclusion These findings suggest that ongoing GC therapy, particularly dexamethasone, is a risk factor for IR in adults with 21OHD, and new onset IR generally emerged within approximately 1 year after regular treatment.