Silent Adrenal Insufficiency Persists in most Children After stopping Steroid Therapy for Nephrotic Syndrome: Study

Therefore, the cross-sectional study evaluated 73 children (ages 1–12) with steroid-sensitive nephrotic syndrome who were in remission and had been off steroids for 4 to 12 weeks. Excluding patients with steroid-resistant disease or ongoing steroid use, researchers diagnosed adrenal insufficiency based on two endpoints: an 8 AM baseline serum cortisol of <5 mcg/dL or a 30-minute post-stimulation cortisol of <18 mcg/dL following a 1 mcg intravenous low-dose ACTH test.

Key Clinical Findings of he Study Includes:

• High Post-Therapy Prevalence: Investigators found that an overwhelming 52 out of 73 pediatric participants (71.2%) met the strict criteria for AI weeks after completing their prescribed alternate-day steroid regimens.

• Superior Diagnostic Sensitivity: Researchers demonstrated that the Low-Dose Adrenocorticotropin Stimulation Test (LDST) profoundly outperformed standard baseline morning evaluations, successfully capturing 16 cases of profound adrenal dysfunction that presented with deceptively normal 8 AM cortisol metrics.

• Physical Toxicity Predictors: Scientists revealed that young patients physically manifesting cushingoid facies or a distinct moon face carried 4.96 times higher clinical odds of harboring underlying adrenal suppression compared to those devoid of structural steroid toxicity signs.

• Disease Relapse Correlation: Authors uncovered that children saddled with confirmed AI experienced a statistically significant increase in cumulative disease relapses, averaging 2.13 episodes compared to a mere 0.76 episodes among their unaffected counterparts.

The results suggest a remarkably high and sustained persistence of subclinical AI (71.2%) extending long after the complete withdrawal of glucocorticoids, emphasizing that diagnostic reliance solely on baseline morning cortisol levels will inevitably miss a significant proportion of compromised patients.

Thus, the study concludes that it could be highly beneficial for treating clinicians to maintain a heightened index of suspicion by utilizing clinical markers like cushingoid features to proactively guide diagnostic LDST, ultimately ensuring that vulnerable children promptly receive appropriate stress-dose corticosteroid coverage during subsequent periods of physiological illness.

Although the inclusion of both first-episode patients and frequent relapsers introduced an element of population heterogeneity into the dataset without the benefit of longitudinal tracking, it gently underscores a valuable opportunity for future prospective research to singularly focus on monitoring homogenous first-episode cohorts to map the true natural history and resolution timeline of this drug-induced suppression.

Reference

Kapila A, Singh A, Raizada N, Aggarwal A. Adrenal insufficiency after steroid therapy in children with steroid‑sensitive nephrotic syndrome: A cross‑sectional study. Indian J Endocr Metab 2025;29:423‑8.