On hospital Day 20, Mr. A is discharged back to his outpatient psychiatrist and receives quetiapine, 500 mg every night at bedtime, and bupropion XL, 300 mg/d. Although Mr. A’s depression and anxiety continue to be well controlled, his insomnia persists. Sleep hygiene is addressed, and alprazolam, 0.5 mg every night at bedtime, is added to his regimen, which proves to be effective.
OUTCOME A slow remission
After a year of treatment, Mr. A is slowly tapered off of all medications. Two years later, he is in complete remission of all psychiatric symptoms and no longer requires any psychotropic medications.
The authors’ observations
Treatment for hypercortisolism in patients with psychiatric symptoms triggered by glucocorticoid imbalance has typically resulted in a decrease in the severity of their psychiatric symptoms.9,11 A prospective longitudinal study examining 33 patients found that correction of hypercortisolism in patients with Cushing’s syndrome often led to resolution of their psychiatric symptoms, with 87.9% of patients back to baseline within 1 year.14 However, to our knowledge, few reports have described the management of patients whose symptoms are resistant to treatment of hypercortisolism.
In our case, after transsphenoidal resection of an adenoma, Mr. A became suicidal and paranoid, and his anxiety and insomnia also persisted. A possible explanation for the worsening of Mr. A’s symptoms after surgery could be the slow recovery of the hypothalamic-pituitary-adrenal (HPA) axis and therefore a temporary deficiency in glucocorticoid, which caused an increase in catecholamines, leading to an increase in stress.14 This concept of a “slow recovery” is supported by the fact that Mr. A was successfully weaned off all medication after 1 year of treatment, and achieved complete remission of psychiatric symptoms for >2 years. Furthermore, the severity of Mr. A’s symptoms appeared to correlate with his 24-hour urine cortisol and am cortisol levels, which is also supported by the findings of Starkman et al.15 Mr. A’s psychiatric symptoms were most severe when his am cortisol levels peaked after his surgical resection, and his symptoms improved as his cortisol levels returned to normal. In the interim, while his psychiatric symptoms were exacerbated by the persistence of elevated cortisol levels, Mr. A was admitted psychiatrically and treated with psychotropic medications. Once his cortisol levels normalized and his psychiatric symptoms were well controlled with quetiapine, alprazolam, and bupropion for 1 year, he was titrated off all medications.
Future research should evaluate the utility of screening all patients with treatment-resistant anxiety and/or insomnia for hypercortisolism. Even without other clues to endocrinopathies, serum cortisol levels can be used as a screening tool for diagnosing underlying medical causes in patients with anxiety and depression.2 A greater understanding of the relationship between medical and psychiatric manifestations will allow clinicians to better care for patients. Further research is needed to elucidate the quantitative relationship between cortisol levels and anxiety to evaluate severity, guide treatment planning, and follow treatment response for patients with anxiety. It may be useful to determine the threshold between elevated cortisol levels due to anxiety vs elevated cortisol due to an underlying medical pathology such as Cushing’s disease. Additionally, little research has been conducted to compare how psychiatric symptoms respond to pituitary macroadenoma resection alone, pharmaceutical intervention alone, or a combination of these approaches. It would be beneficial to evaluate these treatment strategies to elucidate the most effective method to reduce psychiatric symptoms in patients with hypercortisolism, and perhaps to reduce the incidence of post-resection worsening of psychiatric symptoms.
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