Sleep Impairment Similar in Cushing Syndrome, Mild Autonomous Cortisol Secretion

Patients with mild autonomous cortisol secretion (MACS) have similar sleep disturbances as patients with Cushing syndrome, according to results of a study published in the Journal of Clinical Endocrinology & Metabolism.

In both Cushing syndrome and MACS, varying degrees of hypercortisolism can affect circadian cortisol secretion and sleep.

Patients diagnosed with MACS (n=194) or Cushing syndrome (n=154) at the Mayo Clinic in the United States between 2019 and 2025 and healthy control individuals (n=89) recruited between 2019 and 2023 were evaluated for sleep outcomes using the Pittsburgh Sleep Quality Index (PSQI).

The MACS, Cushing syndrome, and control cohorts, of whom 73%, 89%, and 67% were women and 92%, 89%, and 91% were White, respectively, had median ages of 60, 48, and 56 years and a median BMI of 32, 34, and 28 kg/m2, respectively.

For sleep outcomes, all PSQI outcomes were worse among patients with MACS than control individuals (all P <.001). Among patients, more with Cushing syndrome vs MACS had:

  • Bad sleep quality (75% vs 58%; P <.001);
  • Sleep duration of less than 5 hours (24% vs 15%; P =.031);
  • At least 3 days of dysfunction due to daytime sleepiness (70% vs 56%; P =.011); and,
  • Higher total PSQI scores (mean, 12 vs 11; P =.005).

All outcomes of the Short Form 36 (SF-36) were significantly worse among patients with MACS than control individuals (all P <.001) and worse among patients with Cushing syndrome than MACS (all P £.004), except for the emotional limitation score (P =.002).

Similarly, patients with Cushing syndrome had lower Cushing Quality of Life (CushingQoL) scores than patients with MACS for physical (mean, 23.4 vs 44.9; P <.001), psychosocial (mean, 29.8 vs 46.7; P <.001), and overall (mean, 28.2 vs 46.2; P <.001) scores, respectively.

In Cushing syndrome and MACS, the researchers observed significant correlations between PSQI total scores and SF36 mental (r range, -0.50 to -0.40; both P <.001) and physical (r range, -0.35 to -0.28; both P <.001) component scores and CushingQoL overall (r range, -0.56 to -0.43; both P <.001), physical (r range, -0.57 to -0.38; both P <.001), and psychosocial (r range, -0.49 to -0.38; both P <.001) scores. In only MACS, PSQI was correlated with clinical severity (r, 0.17; P =.020). Among control individuals, PSQI total scores were correlated with SF36 mental (r, -0.29; P =.008) and physical (r, -0.45; P <.001) component scores.

Worse sleep was associated with every 1-kg/m2 increase in BMI among control individuals (b, 0.21; P =.005), inversely related with every 1-year increase in age among patients with Cushing syndrome (b, -0.12; P <.001), and inversely related with every 1-year increase in age (b, -0.08; P =.009) and positively related with every 1-point increase in clinical severity (b, 0.14; P =.044) and with female gender (b, 2.35; P =.002) among patients with MACS.

The major limitation of this study was the lack of objectively measured sleep outcomes.

The study authors concluded, “[W]e found that patients with MACS and [Cushing syndrome] demonstrate similar sleep impairment. Younger age, female sex and higher clinical severity score were associated with worse sleep in patients with MACS, while younger age was the only factor associated with poor sleep in patients with [Cushing syndrome].”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Sleep Disturbances in Patients With Cushing Syndrome and Mild Autonomous Cortisol Secretion

The Journal of Clinical Endocrinology & Metabolism, dgaf553, https://doi.org/10.1210/clinem/dgaf553

Abstract

Context

The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep.

Objectives

To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS versus referent subjects.

Methods

We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using 1) Short Form-36 in all participants, and 2) Cushing QoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI.

Results

PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <0.001 for all). Age-, sex, and BMI adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P >0.05 for all). In a multivariable analysis of patients with MACS, younger age, female sex and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep.

Conclusions

Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.