Late-onset congenital adrenal hyperplasia: a treatable cause of anxiety.

BACKGROUND Some intermediaries of cortisol synthesis, especially the sulfated ester of dehydroepiandrosterone (DHEAS), are picrotoxin-like antagonists of the gamma-aminobutyric acid A (GABA-A) receptor and exert potent anxiogenic effects. We report 5 men and 7 women with refractory anxiety disorders, who had late-onset congenital adrenal hyperplasia (CAH), and in whom interactions between neuroactive steroids and anomalous brain substrates may have participated in the pathophysiology and treatment of anxiety. METHODS Twelve patients with refractory anxiety disorders as defined by DSM-IV had elevated DHEAS and specific enzyme deficiencies diagnostic of CAH. All were treated with adrenal suppressive therapy using ketoconazole or low (physiologic) dose glucocorticoids. Anxiety was rated by the Tension Scale of the Profile of Mood States (POMS Tension) questionnaire before and during hormonal treatment. RESULTS Reduction of DHEAS was associated with lower anxiety scores in all twelve cases. POMS Tension scores decreased by 55%. Hormonal treatment, which failed to lower DHEAS, was ineffective. CONCLUSIONS These findings suggest that late onset CAH can contribute to anxiety disorders and that adrenal suppressive therapy or inhibition of steroidogenesis with ketoconazole may be efficacious as adjuvant therapy.