In the fall issue of the newsletter, we addressed depression in Cushing’s syndrome (CS). The focus was on subtypes of depression, how different subtypes might be expressed symptomatically, how they might be biochemically different, and what treatment may be effective for depression in CS. This column will focus on our research findings on the course of depression following the treatment of CS.

Although for patients with Cushing’s syndrome, a “cure” can be obtained immediately through surgery, we know that the process of returning to a healthy state takes some time. For example, the return of functioning of the hypothalamic pituitary adrenal (HPA) axis, may take up to a year and patients remain on glucocorticoid replacement until that time. Resuming normal psychologic functioning after correction of hypercortisolism also appears to be a lengthy process. In our longitudinal study of 33 patients with CS, 54.6% met diagnostic criteria for a psychiatric illness before their treatment. The majority of those had atypical depression but there also were a few cases of hypomania, panic anxiety, or drug and alcohol abuse. At 3-months post- treatment, 53.6 % of the 28 returning patients met criteria for a psychiatric illness. Most were diagnosed with major depression (MDD) (32.1%) but some had atypical depression or anxiety disorders. Importantly, three patients reported being suicidal. At 6-monthspost-treatment, there were fewer psychiatric diagnoses (36%). Of the 25 returning, 32% had atypical depression. Three patients met criteria for MDD and one of these reported being suicidal. One year following treatment for CS, 7 (24%) of the 29 returning subjects still met criteria for a psychiatric illness. Again, atypical depression was the most common. One patient continued to report being suicidal. Thus, the general picture of the psychological profile of CS patients after correction of hypercortisolism is one of improvement. Across the year, there was an improvement in moods and feelings by self-report checklists and also a significant decrease in the number of patients with atypical depression. Interestingly, across the study, 4 patients who reported no psychiatric disorders before or during CS, developed a psychiatric condition after treatment for CS and during their recovery phase.

To look for recovery of the HPA axis, an ACTH stimulation test often is done during the convalescence. The ACTH test shows if the axis is returning to its normal state with the goal being discontinuation of glucocorticoid replacement therapy. A normal cortisol response was obtained by 13.6% at 3 months, by 21.7% at 6 months, and by over 50% at 12 months post-treatment. We thought that whether one had a normal cortisol response might be related to better psychological functioning. This, however, was not the case. There was no significant relationship between recovery of the HPA axis by ACTH testing and better psychological functioning. We do think that having more patients in the study may provide more information about this relation.

To look at the relation of recovery of the HPA axis and psychopathology in another way, we asked the following question: Is the actual spontaneous morning cortisol level of the patient related to psychological symptoms? Using standardized checklists, we found that at 3 months post-correction, there was no relation between cortisol level and psychological symptoms. However, at 6 and 12 months, having a lower morning baseline cortisol (before the ACTH stimulation tests) was strongly related to having more psychological symptoms. Also, 6 months and 12 months after correction of hypercortisolism, patients with higher cortisol levels felt more vigorous. It is important to remember that just because there is a relation (correlation) does not mean that cortisol is causing this relation.

Why might psychopathology remain even after correction of hypercortisolism and why might new psychopathology appear? To answer this, we can only speculate. Further research can provide more conclusive evidence. It may be that the CRH neuron is the last part of the axis to recover and CRH, rather than cortisol, may be responsible for mood disturbances. Also, it is too simplistic to think that only one biological factor contributes to a behavior. Most likely it is multiple factors such as several hormone systems acting in concert and factors such as social support or stressful life circumstances.

What can be done about new or continued psychological problems after correction of hypercortisolism? We would reiterate our suggestions from the previous column stressing the importance of being evaluated and followed by someone in the psychological profession. Your therapist and endocrinologist should have continued contact with each other (as well as with you), in order to adjust therapy as necessary. Helpful therapy may include both supportive psychotherapy and appropriate medications. We would like to stress to patients and family members, the importance of recognizing psychological problems in patients with CS, not only before treatment but after correction of hypercortisolism as well. The fact that some of our patients developed new psychological problems such as panic attacks or being suicidal is worrisome, if not identified and monitored.

Author: Lorah Dorn PhD, RN, CPNP & George Chrousos, MD (Spring, 1998)

Editor’s Note: Further information on this study can be obtained in: Dorn, L.D., Burgess, E., Friedman, T., Dubbert, B., Gold, P.W., & Chrousos, G.P. (1997). The longitudinal course of psychopathology in Cushing syndrome after correction of hypercortisolism. Journal of Clinical Endocrinology and Metabolism, 82:912-919.