Increased Prevalence of Psychopathology and Maladaptive Personality Traits after Long-Term Cure of Cushing's Disease

Context and Objective: Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. Design: Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). Patients and Control Subjects: We included 51 patients cured of CD (16% men, 53 +/- 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 +/- 10 yr), and 55 matched controls. Results: Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). Conclusions: Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids. (J Clin Endocrinol Metab 95: E129-E141, 2010)Diabetes mellitus: pathophysiological changes and therap