Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy

Dysfunction of the hypothalamic-pituitary-adrenal axis might contribute to metabolic disturbances frequently encountered in myotonic dystrophy. We hyp othesized that abnormal adrenocortical sensitivity to ACTH and/or glucocort icoid metabolism could be important in myotonic dystrophy. We assessed diurnal rhythmicity of saliva cortisol, adrenocortical reactivi ty by a low-dose (1 mug) Synacthen test, and glucocorticoid metabolism in b lood and urine in 42 myotonic dystrophy patients (22 males) and 50 controls (27 males). CTG triplet repeat expansions were quantified by Southern blot . Diurnal rhythmicity of saliva cortisol was flattened in both men and women with myotonic dystrophy, with significantly increased afternoon/evening lev els (P<0.013). The cortisol response to ACTH was associated with increased (CTG)(n) expansions in myotonic dystrophy men and women (P<0.01). Male myot onic dystrophy patients also had increased activation of cortisol from cort isone by 11 beta -hydroxysteroid dehydrogenase type 1. Both men and women w ith myotonic dystrophy had an increased 5 alpha /5 beta -reductase ratio (P <0.05 and P<0.01, respectively). Cortisol metabolites were related to the g enetic defect in myotonic dystrophy men (P<0.05), whereas ratios reflecting 11<beta>-hydroxysteroid dehydrogenase type I activity in myotonic dystroph y women were positively associated with obesity (P<0.05). Increased 11<beta>-hydroxysteroid dehydrogenase type I activity and adrenoc ortical reactivity to ACTH are related to the genetic defect in myotonic dy strophy men, whereas abnormal glucocorticoid metabolism is associated with alterations in body composition in female myotonic dystrophy patients. Thes e disturbances may explain altered circulating cortisol levels and contribu te to features of the metabolic syndrome in myotonic dystrophy.