Research AppraisalSystematic Review

Cushing's syndrome: a systematic review of psychiatric and cognitive symptoms in case studies

Archives of endocrinology and metabolismLhul, Roni Vian da Silva, Nunes, Katiúscia Gomes, Almeida, Tobias Skrebsky de et al.7 Apr 2026DOI

Clinical Snapshot

75CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationPatients with Cushing's syndrome (chronic hypercortisolism), 74 cases, 81% female, mean age 35.7 years (range 13-81)
I — InterventionNot applicable - observational systematic review
C — ComparatorNot applicable - descriptive analysis of case studies
O — OutcomesPsychiatric symptoms (depression, psychosis, suicidal ideation, anxiety) and cognitive symptoms (memory impairment, attentional deficits, general cognitive complaints)

Bottom Line

This systematic review of 74 Cushing's syndrome cases reveals a broader spectrum of neuropsychiatric manifestations than traditionally recognised. While 93% presented psychiatric symptoms, the high prevalence of psychosis (35.1%) and suicidal ideation (20.3%) alongside depression (39.2%) challenges the conventional focus on mood and memory symptoms alone. Cognitive complaints affected one-third of patients, with significant symptom overlap in 26%. For Australian clinicians, this evidence supports systematic psychiatric screening in all Cushing's patients and highlights the need for multidisciplinary management involving endocrinology, psychiatry, and neuropsychology services. However, the case study methodology provides descriptive rather than definitive evidence, requiring cautious interpretation alongside clinical judgment. The findings emphasise that comprehensive neuropsychiatric assessment should be standard care, potentially preventing missed diagnoses of serious psychiatric complications including psychosis and suicide risk.

Evidence: Moderate

Key Findings

  • P Value: Not applicable - descriptive analysis

  • Effect Size: Depression 39.2%, psychosis 35.1%, suicidal ideation 20.3%

  • Primary Outcome: Psychiatric symptoms present in 93% of Cushing's syndrome cases

  • Nnt Or Sensitivity: Cognitive complaints in 32% of cases, with 26% showing overlapping psychiatric and cognitive symptoms

  • Confidence Interval: Not reported

Clinical Application

High feasibility - requires clinical awareness and systematic psychiatric/cognitive screening rather than new interventions Relevant to Australian endocrinologists and psychiatrists; supports need for multidisciplinary care pathways. May inform PBS-subsidised psychiatric medications and specialist referral patterns under Medicare Australian patients with confirmed or suspected Cushing's syndrome across endocrinology, psychiatry, and general practice settings

Abstract

OBJECTIVE: Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. MATERIALS AND METHODS: We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). RESULTS: revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. CONCLUSION: This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.

References

  1. 1.Lhul, R. V., Nunes, K. G., Almeida, T. S., Czepielewski, M. A., & Czepielewski, L. S. (2026). Cushing's syndrome: a systematic review of psychiatric and cognitive symptoms in case studies. Archives of Endocrinology and Metabolism. https://doi.org/10.20945/2359-4292-2026-0029
Share:XLinkedIn

This content is for educational purposes for healthcare professionals only and does not constitute clinical advice. Clinical decisions should be based on individual patient assessment, current guidelines, and appropriate specialist consultation. Editorial Standards · Privacy Policy · Terms of Service