PARADOXICAL INHIBITION BY ASPIRIN OF NALOXONE-INDUCED ADRENOCORTICOTROPIN SECRETION IN MYOTONIC-DYSTROPHY

The ACTH response to endogenous or exogenous CRH is increased in patie nts with myotonic dystrophy (DM), possibly because of abnormal functio n of cAMP-dependent protein kinases in this condition. Arachidonic aci d (AA) metabolites are believed to interact with the cAMP-dependent se cond messenger system activated by CRH; therefore, drugs that interfer e with AA metabolism may alter ACTH secretion in DM. In this study, se ven DM patients were given naloxone, which stimulates endogenous CRH r elease, and aspirin, which inhibits the synthesis of prostaglandins fr om AA via the cyclooxygenase metabolic pathway. Pretreatment with aspi rin reduced the mean integrated ACTH response to naloxone by 33% (P < 0.05). However, the corresponding 18% reduction in cortisol levels was not statistically significant (P > 0.10). These findings are in contr ast to those of a previous study using an identical protocol, in which aspirin increased the ACTH response to naloxone in six normal volunte ers. This difference between DM and control subjects is consistent wit h the hypothesis that the interaction between AA metabolites and the c AMP-dependent protein kinase-A second messenger system is abnormal in the corticotrophs of persons with DM.