Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing's disease in remission

Front Endocrinol (Lausanne). 2022 Aug 8;13:934347. doi: 10.3389/fendo.2022.934347. eCollection 2022.


Context: Impaired cognition and altered quality of life (QoL) may persist despite long-term remission of Cushing's disease (CD). Persistent comorbidities and treatment modalities may account for cognitive impairments. Therefore, the role of hypercortisolism per se on cognitive sequelae remains debatable.

Objective: To investigate whether memory and QoL are impaired after long-term remission of CD in patients with no confounding comorbidity.

Design and setting: Cross-sectional case-control study in two tertiary referral centers.

Patients: 25 patients (44.5 ± 2.4 years) in remission from CD for 102.7 ± 19.3 Mo and 25 well-matched controls, without comorbidity or treatment liable to impair cognition.

Main outcome measures: Hippocampus- and prefrontal cortex-dependent memory, including memory flexibility and working memory, were investigated using multiple tests including sensitive locally-developed computerized tasks. Depression and anxiety were evaluated with the MADRS and HADS questionnaires. QoL was evaluated with the SF-36 and CushingQoL questionnaires. The intensity of CD was assessed using mean urinary free cortisol and a score for clinical symptoms.

Results: CD patients displayed similar performance to controls in all cognitive tests. In contrast, despite the absence of depression and a minimal residual clinical Cushing score, patients had worse QoL. Most of the SF36 subscales and the CushingQoL score were negatively associated only with the duration of exposure to hypercortisolism (p≤ 0.01 to 0.001).

Conclusions: Persistent comorbidities can be a primary cause of long-lasting cognitive impairment and should be actively treated. Persistently altered QoL may reflect irreversible effects of hypercortisolism, highlighting the need to reduce its duration.

Clinical trial registration number:, identifier NCT02603653.

Keywords: Cushing’s disease; cognition; hypercortisolism; memory; quality of life.

Publication types

  • Clinical Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Cognition
  • Cross-Sectional Studies
  • Cushing Syndrome* / complications
  • Humans
  • Middle Aged
  • Pituitary ACTH Hypersecretion* / complications
  • Pituitary ACTH Hypersecretion* / drug therapy
  • Quality of Life

Associated data