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

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.

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.

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/m²; p = 0.046).

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.