Correlations of morning and ACTH stimulated cortisol in steroid-naïve vs steroid-treated boys with Duchenne muscular dystrophy in the vamorolone trial


Clinical Trials

Poster Number: M178


Rebecca Tobin, Carleton University, ON, Canada, Alex Ahmet, Children's Hospital of Eastern Ontario, Canada, Leanne Ward, MD, Children's Hospital of Eastern Ontario, Canada, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Paula Clemens, MD, University of Pittsburgh, VBP15-004 Investigators, CINRG, Eric Hoffman, PhD, Binghamton University, Binghamton, NY, USA, Utkarsh Dang, PhD, Carleton University

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.