クッシング病

OBJECTIVE: Cushing syndrome (CS) is associated with depression and anxiety. This study compared treated mood and anxiety disorders between patients with CS and controls, assessing differences by etiology and remission status. METHODS: A retrospective matched cohort study of patients with endogenous CS (2000-2024) from the Clalit Health Services database. Each patient was matched with five controls by age, sex, socioeconomic status, and BMI. Mood and anxiety disorders were identified through affective drug dispensations (ADD). Drug discontinuation was defined as ≥1 month without dispensations. RESULTS: The cohort included 540 patients with CS (mean age 47.79±17.01 years;64.44% women) and 2517 controls, with a median follow-up of 13.20 years (IQR 8.41-18.42). At baseline, patients with CS had nearly twice the odds of receiving ADD than controls (OR=1.93, 95% CI:1.39-2.66), with a significant excess in women (12.93% vs. 6.93%, OR=1.99, 95% CI: 1.38-2.87). During the entire follow up, drug discontinuation rates did not differ (HR=0.72, 95% CI: 0.50-1.04), whereas the risk of new-onset ADD was twofold higher in CS (HR=2.23, 95% CI: 1.89-2.62). This increased risk was observed in both Cushing disease (HR=2.44, 95% CI: 1.90-3.13) and adrenal CS (HR=2.17, 95% CI: 1.64-2.88). Using a 2-year landmark analysis initiated two years after diagnosis, the increased risk persisted in patients who achieved remission (HR=2.10, 95% CI: 1.59-2.78) and in those who did not (HR=2.38, 95% CI: 1.60-3.55). CONCLUSION: Endogenous CS is associated with a persistently increased risk of treated affective disorders at diagnosis and throughout long-term follow-up, underscoring the need for ongoing psychological care.

BACKGROUND: Accurate localization of adrenocorticotropic hormone (ACTH) secretion is crucial for the surgical management of ACTH-dependent Cushing's syndrome. While magnetic resonance imaging (MRI) and biochemical testing aid diagnosis, bilateral inferior petrosal sinus sampling (BIPSS) remains a reference standard in diagnostically challenging cases. In the absence of corticotropin-releasing hormone (CRH), vasopressin may serve as an effective alternative corticotroph stimulant during BIPSS; however, its additional benefit in lateralizing corticotroph adenomas remains uncertain. OBJECTIVE: To evaluate the diagnostic utility of BIPSS using vasopressin in selected patients with ACTH-dependent Cushing's syndrome and compare its accuracy with the high-dose dexamethasone suppression test (HDDST) and MRI in localization and lateralization. METHODS: Fourteen patients with biochemically confirmed ACTH-dependent Cushing's syndrome underwent HDDST, pituitary MRI, and BIPSS with Vasopressin as a corticotroph stimulant. BIPSS was performed to confirm a central source of ACTH secretion and assess lateralization. Transsphenoidal surgery (TSS) was performed in selected patients based primarily on MRI findings. RESULTS: Of 14 patients, 13 were diagnosed with Cushing's disease (CD) and one with ectopic ACTH secretion. BIPSS correctly identified a pituitary source in all Cushing's disease cases, while HDDST yielded false negatives in three cases (sensitivity 76.9%). Concordance lateralization between BIPSS and MRI was observed in eight of 13 CD cases (61.5%). Among nine patients who underwent TSS, five achieved remissions; four of these had concordant BIPSS and MRI lateralization. CONCLUSION: BIPSS is a valuable adjunct and remains a diagnostic tool for confirming pituitary origin in ACTH-dependent Cushing's syndrome, particularly when MRI and HDDST findings are inconclusive. Although vasopressin-stimulated BIPSS did not improve lateralization in this cohort, a higher proportion of patients achieving remission demonstrated concordant MRI and BIPSS findings; however, this observation should be interpreted cautiously due to the small sample size. BIPSS should not be used routinely but should be reserved for carefully selected cases with persistent diagnostic uncertainty.

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, p = 0.03) and stress scores (17 vs. 8.5, p = 0.03) than NFA. PLS-DA identified five discriminatory NS: 4-androstenedione (VIP = 2.0), 11-deoxycorticosterone (DOC) (VIP = 1.8), 7-OH-pregnenolone (VIP = 1.8), corticosterone (VIP = 1.7), and androsterone (VIP = 1.1); the first four were elevated, and androsterone decreased in CD. Despite biochemical remission, most NS alterations persisted, with 7-OH-pregnenolone paradoxically increasing further (121 vs. 22.5 ng/mL, p = 0.008). Mood symptoms did not correlate with cortisol, adrenocorticotropic hormone (ACTH), or urinary free cortisol (UFC). However, dehydroepiandrosterone (DHEA) correlated positively with depression (r = 0.4, p = 0.02) and stress (r = 0.4, p = 0.02), whereas allopregnanolone correlated negatively with depression (r = -0.4, p = 0.03) and stress (r = -0.4, p = 0.04). Among discriminatory NS, only 7-OH-pregnenolone correlated with stress (r = 0.3, p = 0.04). These NS-mood associations were absent in NFA. 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.

BACKGROUND: McCune-Albright Syndrome (MAS) is a rare, mosaic genetic disorder characterized by fibrous dysplasia of bone, endocrine hyperfunction, and skin pigmentation. Despite increasing clinical recognition, real-world data on diagnostic timelines, disease burden, and psychosocial impact among MAS patients-particularly in China-remain scarce. METHODS: We conducted a national, cross-sectional survey of Chinese MAS patients between November 2024 to June 2025 using a structured 95-item online questionnaire disseminated via the McCune-Albright Syndrome Clinical Research Consortium (MASCRC) database and the Bone Care Center patient community. Responses were de-duplicated and managed within the MASCRC data platform. Data were collected on demographics, initial symptoms, diagnostic delay, treatment history, quality of life, psychological distress, and support needs. Descriptive statistics, chi-square tests, and Mann-Whitney U tests were performed. RESULTS: A total of 152 valid responses were analyzed from MAS patients across 28 of 34 provincial-level regions, including 94 females (61.84%) and 58 males (38.16%), with a median age of 10.10 years (IQR: 7.80-15.00). The most common first symptoms were bone involvement (61.18%), peripheral precocious puberty (36.84%), and café-au-lait pigmentation (37.50%). Initial hyperthyroidism and Cushing syndrome were reported in 3.95% and 1.32% of cases, respectively. Median age at symptom onset was 5.50 years; median age at diagnosis was 6.00 years. Although the majority of patients were diagnosed within 1 year (median delay: 0 months, IQR: 0-6), 21.05% experienced a diagnostic delay of ≥ 1 year, and 27.63% reported prior misdiagnosis. GNAS mutation testing was performed in 48.68% of patients, with a detection rate of 36.49%. Long-term consistent treatment was reported by 37.00% of respondents, with regular follow-up (62.50%), medication (38.82%), and surgery (36.18%) being the most common strategies. Impact on daily life was substantial: 46.05% of patients reported moderate to severe disruption in education or employment, and family/economic burden was rated most severe (mean score 3.21/5). Self-reported psychological distress was common, with 78.29% reporting anxiety-related symptoms and 37.50% reporting depressive symptoms, yet only 15.79% accessed professional support. Over 90% expressed unmet needs for expert medical resources, while 79.61% desired improved insurance reimbursement, and 46.05% wished for peer-support platforms. CONCLUSIONS: MAS patients in China report substantial clinical and psychosocial burdens, with a subset experiencing prolonged diagnostic journeys and misdiagnoses. These findings highlight a need for earlier recognition, integrated multidisciplinary care, and structured patient support.