Late-onset congenital adrenal hyperplasia: A treatable cause of anxiety

Background: Some intermediaries of cortisol synthesis, especially the sulfa ted ester of dehydroepiandrosterone (DHEAS), are picrotoxin-like antagonist s of the gamma-aminobutyric acid A (GABA-A) receptor and exert potent anxio genic effects. We report 5 men and 7 women with refractory anxiety disorder s, who had late-onset congenital adrenal hyperplasia (CAH), and in whom int eractions between neuroactive steroids and anomalous brain substrates may h ave participated in the pathophysiology and treatment of anxiety. Methods: Twelve patients with refractory anxiety disorders as defined by DS M-IV had elevated DHEAS and specific enzyme deficiencies diagnostic of CAH. All were treated with adrenal suppressive therapy using ketoconatole or lo w (physiologic) dose glucocorticoids, Anxiety was rated by the Tension Scal e of the Profile of Mood States (POMS Tension) questionnaire before and dur ing hormonal treatment. Results: Reduction of DHEAS was associated with lower anxiety scores in all twelve cases. POMS Tension scares decreased by 55%, Hormonal treatment, wh ich failed to lower DHEAS, was ineffective. Conclusions: These findings suggest that late onset CAH can contribute to a nxiety disorders and that adrenal suppressive therapy or inhibition of ster oidogenesis with ketoconazole may be efficacious as adjuvant therapy. (C) 1 999 Society of Biological Psychiatry.