Premium
Inhibition of Naloxone‐Stimulated Adrenocorticotropin Release by Alprazolam in Myotonic Dystrophy Patients
Author(s) -
Joyner Julie M.,
Grice Jeffrey E.,
Hockings Gregory I.,
Torpy David J.,
Crosbie Georgina V.,
Walters Margaret M.,
Jackson Richard V.
Publication year - 1998
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1998.00220.x
Subject(s) - endocrinology , medicine , (+) naloxone , myotonic dystrophy , adrenocorticotropic hormone , hypothalamic–pituitary–adrenal axis , vasopressin , corticotropin releasing hormone , alprazolam , opioid , hormone , receptor , anxiety , psychiatry
Myotonic dystrophy (DM) is an autosomal dominant disorder causing myotonia, progressive muscle weakness, and endocrine abnormalities including hypothalamic‐pituitary‐adrenal (HPA) axis hyperresponsiveness to CRH‐mediated stimuli. This ACTH hyperresponsiveness appears directly related to the underlying genetic abnormality. Naloxone (Nal)‐mediated CRH release causes ACTH release in normal humans and an ACTH hyperresponse in DM. Alprazolam (APZ) attenuates the ACTH release in response to Nal in normal individuals, probably by inhibiting CRH release. This study investigates the effects of APZ on Nal‐induced HPA axis stimulation in DM. The ACTH response to Nal in DM subjects was significantly reduced by APZ. Despite this DM patients have a relative resistance to APZ inhibition of Nal‐induced ACTH/cortisol release. APZ caused a smaller percentage reduction in AUC for ACTH in DM compared with controls. These findings provide further insight into the mechanism(s) of the HPA axis abnormalities in DM. In DM, there may be an increase in tonic opioid inhibition to CRH release with compensatory increases in stimulatory pathways. Alternatively, these patients may have a basal increase in pituitary vasopressin levels or an enhanced AVP/CRH synergistic mechanism at the level of the corticotroph.