Background. Dysregulation of corticotropin (ACTH) and cortisol response after corticotropin-releasing hormone (CRH) stimulation has been reported in bipolar patients. Most findings involve the pathophysiology of the depressive phase of the illness and its prediction. However, the possible predictive value of the CRH challenge test with respect to manic episodes remains unknown.

Methods. The ACTH and free cortisol response to the injection of 100 μg of synthetic human CRH and plasma cortisol-binding globulin levels were measured in 42 lithium-treated patients suffering from Research Diagnostic Criteria bipolar I disorder in remission, and 21 age- and sex-matched normal controls. A 1-year follow-up was conducted to assess any possible relationship between outcome and the hormonal response.

Results. Bipolar patients showed higher baseline and peak ACTH concentrations than control subjects. A higher area under ACTH concentration curve after CRH stimulation predicted manic/hypomanic relapse within 6 months by multiple regression analysis.

Conclusion. Bipolar patients in remission show mild abnormalities in ACTH levels before and after CRH stimulation. CRH challenge may be a potentially good predictor of manic or hypomanic relapse in remitted bipolar patients.