The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism

Endogenous Cushing's syndrome (CS) is associated with significant psychopathology during the course of the disease. The purpose of this study was to evaluate the psychological and endocrine status of patients with CS after correction of their hypercortisolism. Thirty-three patients with active CS were examined before and at 3 months (28 patients), 6 months (25 patients), and 12 months (29 patients) after correction of hypercortisolism. Before cure, 66.7% of the patients had significant psychopathology, with the predominant diagnosis of atypical depressive disorder (AD) in 51.5% and/or major affective disorder in 12%. After cure, overall psychopathology decreased significantly to 53.6% at 3 months, 36% at 6 months, and 24.1% at 12 months, when there was a parallel recovery of the hypothalamic-pituitary-adrenal axis assessed by serial morning ACTH stimulation tests. There was an inverse correlation between psychological recovery and baseline morning cortisol, but no correlation with ACTH-stimulated cortisol values at 60 min. AD continued to be the prevailing diagnosis after correction of hypercortisolism, whereas the frequency of suicidal ideation and panic increased. The presence of AD before and after correction of hypercortisolism might be due to glucocorticoid-induced suppression of hypothalamic CRH secretion. The slight increase in the incidence of panic after correction of hypercortisolism might be due to a decreased glucocorticoid restraint at the central arousal/sympathetic catecholaminergic system. We conclude that GS is associated with AD symptomatology, which gradually improves with time after correction of hypercortisolism. Health care providers should be aware of changes in symptomatology, including suicidal ideation and panic attacks, that occur in a subgroup of patients.