Optimal functioning of hypothalamic-pituitary-adrenal axis after cessation of prednisolone therapy: a cross-sectional study in children with nephrotic syndrome

Background: Hypothalamic-pituitary-adrenal (HPA) axis recovery after cessation of steroid therapy in children with nephrotic syndrome (NS) has hardly been studied in the literature.

Methods: This 22-month cross-sectional study recruited children (2-14 years) with NS, having received a minimum 3 months of prednisolone, now in remission, and off steroids for 1, 3, or 6 months. Serum cortisol-basal and stimulated (with long-acting intramuscular adrenocorticotropic hormone), and factors affecting them, were assessed. Low basal and stimulated cortisol were taken as < 138 nmol/L and < 500 nmol/L, respectively.

Results: Of 80 (60 males) children, median (IQR) age 64 (43, 91.7) months, most were infrequently relapsing (34; 42.5%) or had a single episode of NS (35; 43.8%). As per duration since discontinuation, 23 (28.8%), 35 (43.8%), and 22 (27.4%) children were off steroids for 1, 3, and 6 months, respectively. Overall, 8 (10%) and 26 (32.5%) had low basal and stimulated cortisol levels, respectively. Proportions of children with HPA axis suppression (low peak cortisol) were 9/23 (39%), 12/35 (34%), and 5/22 (23%) in the groups off steroids for 1, 3, and 6 months, respectively. Optimal peak cortisol level, indicating adrenal recovery, was independently associated with duration since cessation of prednisolone [odds ratio (6 months vs. 1 month) was 10.07 (95%CI 1.46 to 69.51); P = 0.019] and basal cortisol levels > 138 nmol/L (odds ratio 25.0 (95%CI 2.94 to 200); P = 0.03).

Conclusions: Nearly two-thirds of children with mild courses of NS demonstrate optimal HPA axis function between 1 and 6 months post cessation of steroids. Duration since cessation and basal cortisol independently predict optimal adrenal response.