ArticleFrontiers in endocrinology2026
Steroid alterations in Cushing's disease persist after remission: ACTH-driven steroid changes dissociate from mood-regulatory neurosteroids.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Cushing's disease (CD) is associated with high rates of depression and anxiety that often persist despite biochemical remission, yet the underlying mechanisms remain unclear. This study aims to characterize circulating neurosteroid (NS) profiles in CD and examine their associations with psychological symptoms. Design and methods: This is a cross-sectional study of 37 patients with CD (22 active, 15 remission) and 21 nonfunctioning pituitary adenoma (NFA) controls. NS levels were quantified by mass spectrometry; psychological symptoms were assessed using the 21-item Depression Anxiety Stress Scale (DASS-21). Discriminatory NS were identified by partial least squares discriminant analysis (PLS-DA), with a variable importance in projection (VIP) score > 1.0 used as the selection threshold. Results: Patients with CD exhibited higher depression (14 vs. 7.5, Conclusions: CD is characterized by a distinct and persistent steroid signature that persists beyond biochemical remission, reflecting hypercortisolism-driven epigenetic remodeling of steroidogenic pathways. The dissociation between ACTH-driven steroid alterations and mood-associated NS suggests that cortisol reduction alone may inadequately address psychiatric symptoms, warranting investigation of NS-targeted therapies.
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