DISCORDANT CHANGES IN PLASMA ACTH AND BETA-LIPOTROPIN BETA-ENDORPHIN LEVELS IN CUSHINGS-DISEASE PATIENTS WITH DEPRESSION

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/-SD] depressed mood score = 0.17+/-0.4; modified Hamilton Depression scale score = 7.6+/-4.5) and five as severely depressed (mean depressed mood score = 2.4+/-0.5; modified Hamilton Depression scale score = 15+/-5.6) (p<0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0+/-16.7; severely depressed = 34.6+/-8.7 (p<0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration. These initial findings, taken together with data in related areas, suggest that greater diversity in regulation and cosecretion of ACTH and beta-LPH/beta-E may occur than is currently suspected. Such diversity may play a role in the relationship between HPA axis dysregulation and mood disorders.