Background
Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder that leads to muscle wasting, loss of function, and premature death. Steroidal anti-inflammatories like prednisone are known to cause secondary adrenal insufficiency (AI). A recent randomized placebo- and prednisone-controlled trial of vamorolone, a dissociative steroidal anti-inflammatory, provided well-controlled/annotated data on morning and ACTH-stimulated cortisol levels in 121 young boys with DMD, previously steroid-naïve (4 to <7 years at baseline).
Objective
To examine the relationship between morning and ACTH-stimulated cortisol levels in both steroid-treated and steroid-naïve boys with DMD, and to investigate commonly used thresholds for screening AI.
Methods
Correlation and regression analyses were conducted. For investigating commonly used thresholds, “rule in” and “rule out” cutoff analyses were also conducted.
Results
In steroid-naïve participants, the correlation between morning and peak ACTH-stimulated cortisol levels was poor (Spearman r = 0.2). Upon steroid-treatment (prednisone or vamorolone) peak ACTH-stimulated cortisol was strongly positively associated with morning cortisol (Spearman r = 0.84). ACTH-stimulated cortisol taken at 30 min was lower than at 60 min in ~97% of samples. In steroid-treated participants, the 30-minute measurement strongly predicts the 60-minute measurement (R-squared = 0.99), but less so in steroid-naïve boys (R-squared = 0.72).
Conclusions
In steroid-treated boys, morning cortisol was a strong predictor of adrenal insufficiency as defined by the more invasive ACTH-stimulated cortisol (Synacthen) test. The strong correlation between 30- and 60-min ACTH stimulated cortisol levels suggested that a 30-min sample can predict 60-min cortisol level quite well. Different relationships between morning and ACTH stimulated cortisol levels were observed between steroid-naïve and steroid-treated boys, which should be studied further.