Previous studies showed that in patients with active Cushing’s disease, psychopathology is often observed with major depression being the most common comorbid disorder, although mania and anxiety disorders have also been reported (1). Following successful treatment of Cushing’s disease, both physical and psychiatric signs and symptoms improve substantially (2;3). Furthermore, maladaptive personality traits were documented after treatment for Cushing’s disease in some, but not all, studies (3-6). At present, it is not clear whether, and to what extent, psychopathology and maladaptive personality traits persist after long-term cure of Cushing’s disease. We therefore aimed to explore the prevalence of psychopathology and maladaptive personality traits in patients after long-term remission of Cushing’s disease.

To assess psychopathology and personality traits in Cushing’s disease, the following groups of subjects were studied:

• 51 patients after long-term remission of Cushing’s disease (mean duration of remission 11 yrs) and 51 gender-, age-, and education-matched controls
• 55 patients previously treated for a non-functioning pituitary macroadenoma (NFMA) and 55 gender-, age-, and education-matched controls

First, we compared patients after remission of Cushing’s disease with their matched controls. Secondly, we compared them to patients previously treated for NFMA. Patients with NFMA also suffer from a pituitary tumor, which is treated via transsphenoidal surgery (surgery through the nose) as in Cushing’s disease. The only difference between the two patient groups is the excessive overexposure to cortisol in Cushing’s disease. Therefore, this comparison enables us to distinguish whether the impairments result from the tumor and its treatment, or from the cortisol overexposure.

We asked all patients and matched controls to complete questionnaires that measured apathy, irritability, anxiety, depression, affect (i.e. experiencing emotions), somatic/physical arousal, and personality traits. The questionnaires are all validated and are widely used.

The results of this study demonstrate that patients after long-term remission of Cushing’s disease scored worse on, and thus displayed more, apathy, irritability, anxiety, depression, affect, and arousal compared to their matched controls. In addition, patients after long-term remission had a significant higher prevalence (clinically relevant higher scores) of apathy, irritability, anxiety, and depression. Compared to NFMA patients, patients after remission of Cushing’s disease scored worse on, and thus higher, apathy, irritability, anxiety, affect, and arousal. There were no differences in depression scores between both patient groups.

On the personality traits questionnaire, patients after long-term remission of Cushing’s disease scored higher on (and thus worse and showed more) maladaptive personality traits ‘submissiveness’, ‘cognitive distortion’, ‘identity problems’, ‘affective lability’, ‘compulsivity’, ‘restricted expression’, ‘oppositionality’, ‘anxiousness’, ‘social avoidance’, and ‘insecure attachment’ compared to matched controls. When patients after remission of Cushing’s disease were compared to NFMA patients, patients with Cushing’s disease scored worse on ‘submissiveness’, ‘cognitive distortion’, ‘identity problems’, ‘affective lability’, ‘compulsivity’, ‘oppositionality’, ‘anxiousness’, ‘conduct problems’, ‘suspiciousness’, ‘social avoidance’, and ‘insecure attachment’. The personality traits are explained in Box 1 below.

The present study demonstrates that patients after long-term remission of Cushing’s disease suffer from more psychopathology and maladaptive personality traits compared to matched controls. In addition, patients after long-term remission of Cushing’s disease had significantly more psychopathology and maladaptive personality traits than patients previously treated for NFMA, indicating that the presence of psychopathology and maladaptive personality traits was not merely related to pituitary tumors and/or their treatment in general. Therefore, the long-term effects of Cushing’s disease on psychopathology and personality traits are more likely to be the consequence of previous cortisol excess. These observations point to irreversible effects of previous cortisol excess on the central nervous system.

Tiemensma J, Biermasz NR, Middelkoop HAM, van der Mast RC, Romijn JA, Pereira AM. 2010 Increased Prevalence of Psychopathology and Maladaptive Personality Traits after Long-Term Cure of Cushing’s disease. J Clin Endocrinol Metab 95(10):E129-E141.

Box 1. Personality traits

Submissiveness: always agreeing with others, hesitate to express your own views, difficulty in providing resistance

Cognitive distortion: difficulty distinguishing fantasy from reality

Identity problems: uncertainty about your own identity, often feeling like there are few things to look forward to

Affective lability: many emotional ups and downs, unpredictable moods, upset by little things, hypersensitive

Compulsivity: irresistible compulsions, doing everything very thoroughly, carefully planning everything

Restricted expression: problems with emotional expression (positive and negative)

Oppositionality: offering indirect resistance in performing tasks

Anxiousness: tendency to worry about everything, always feeling guilty about something

Social avoidance: tendency to avoid other people, feeling insecure

Insecure attachment: only feeling safe when your beloved one is close by

Conduct problems: inappropriate behavior, for example drinking too much, threatening other people, being in multiple fights

Suspiciousness: always being on guard, feeling like everybody is hostile towards you

Authors: J. Tiemensma, MSc., N.R. Biermasz, MD PhD, A.M. Pereira, MD PhD, J.A. Romijn, MD PhD (Summer, 2011)

Editor’s note: All authors are associated with the Department of Endocrinology and Metabolism of the Leiden University Medical Center, Leiden, The Netherlands Jitske Tiemensma is a neuroscientist/psychologist and PhD-student with a special interest in the long-term psychological effects of pituitary diseases.

References

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