INHIBITION OF NALOXONE-STIMULATED ADRENOCORTICOTROPIN RELEASE BY ALPRAZOLAM IN MYOTONIC-DYSTROPHY PATIENTS

Myotonic dystrophy (DM) is an autosomal dominant disorder causing myot onia, progressive muscle weakness, and endocrine abnormalities includi ng hypothalamic-pituitary-adrenal (HPA) axis hyperresponsiveness to CR H-mediated stimuli. This ACTH hyperresponsiveness appears directly rel ated to the underlying genetic abnormality, Naloxone (Nal)-mediated CR H release causes ACTH release in normal humans and an ACTH hyperrespon se in DM. Alprazolam (APZ) attenuates the ACTH release in response to Nal in normal individuals, probably by inhibiting CRH release, This st udy investigates the effects of APZ on Nal-induced HPA axis stimulatio n in DM, The ACTH response to Nal in DM subjects was significantly red uced by APZ, Despite this DM patients have a relative resistance to AP Z inhibition of Nal-induced ACTH/cortisol release. APZ caused a smalle r percentage reduction in AUC for ACTH in DM compared with controls. T hese findings provide further insight into the mechanism(s) of the HPA axis abnormalities in DM, In DM, there may be an increase in tonic op ioid inhibition to CRH release with compensatory increases in stimulat ory pathways, Alternatively, these patients may have a basal increase in pituitary vasopressin levels or an enhanced AVP/CRH synergistic mec hanism at the level of the corticotroph.