Impact of cortisol circadian rhythm on psychological well-being in treated Cushing syndrome: a cross-sectional study

Jun 15, 2026The Journal of clinical endocrinology and metabolism

How Daily Cortisol Patterns Relate to Mental Well-Being in Treated Cushing Syndrome

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Abstract

In biochemically controlled Cushing syndrome, normal late-night salivary cortisol (LNSC) levels are linked to significantly better mood and quality of life outcomes.

Patients with normal LNSC reported lower anxiety (4 vs 7) and depression scores (2.5 vs 6 vs 9) compared to those with abnormal LNSC.
Quality of life was notably higher in patients with normal LNSC in both psychosocial (67.5 vs 39.5) and physical (63.9 vs 44.3) domains.
Better emotional reaction, energy levels, and sleep quality were observed in patients with normal LNSC compared to those with abnormal LNSC.
Normalization of LNSC was consistently associated with improved outcomes across various mood and quality of life measures.
The highest diabetes rate was found in patients with abnormal LNSC levels.
Among surgically remitted Cushing disease patients, 18.6% exhibited abnormal LNSC, indicating a previously unrecognized clinical phenotype.

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CONTEXT: Patients with Cushing syndrome (CS) often experience impaired quality of life (QoL) and mood despite biochemical control. The relationship between late-night salivary cortisol (LNSC) and psychological outcomes remains poorly characterized.

OBJECTIVE: Assess QoL and mood outcomes in biochemically controlled CS patients based on circadian rhythm restoration.

DESIGN: Cross-sectional.

SETTING: Tertiary-care center.

PARTICIPANTS: Ninety treated, biochemically controlled patients with CS (84 Cushing disease (CD); 6 adrenal CS), stratified into three groups: normal LNSC (Group A), abnormal LNSC (Group B), on long-term GC replacement (Group C).

MAIN OUTCOME MEASURES: Hospital Anxiety and Depression Scale (HADS), CushingQoL questionnaire, Nottingham Health Profile (NHP).

RESULTS: Group A had lower HADS-Anxiety (4 vs 7, A vs B; p=0.006) and (HADS-Depression 2.5 vs 6 vs 9, A vs B; p=0.006, A vs C; p<0.001). QoL was better in group A vs C in psychosocial (67.5 vs 39.5; p<0.001) and physical (63.9 vs 44.3; p=0.005) domains. Group A had better Emotional Reaction (0 vs 24; p=0.002), A vs B; Energy Level (0 vs 63; p=0.001) and Sleep (13 vs 56; p<0.001), A vs C. In multivariable analyses excluding group C, LNSC normalization was consistently associated with better outcomes in all HADS domains, CushingQoL psychosocial, NHP Emotional Reaction, Social Isolation, Physical Abilities and Home Relationships. Group B had the highest diabetes rate. Among patients with surgically remitted CD, 18.6% had abnormal LNSC, characterizing a previously unrecognized clinical phenotype.

CONCLUSIONS: In biochemically controlled CS, LNSC normalization correlates with QoL, mood, and metabolic outcomes, and could represent a therapeutic target.

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Impact of cortisol circadian rhythm on psychological well-being in treated Cushing syndrome: a cross-sectional study

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