Adrenalectomy and conservative management are therapeutic approaches for mild autonomous cortisol secretion; however, their comparative clinical impact in routine practice remains uncertain. We aimed to evaluate real-world hormonal, clinical, and metabolic outcomes according to the treatment strategy in patients with mild autonomous cortisol secretion. This single-center retrospective observational study included consecutive patients with adrenal incidentaloma fulfilling guideline-based diagnostic criteria for mild autonomous cortisol secretion between January 2015 and December 2024. Sixty-five patients with complete hormonal evaluation and follow-up data were analyzed and classified into surgery (n=23) and conservative (n=42) groups. Demographic characteristics, adenoma features, comorbidities, hormonal parameters, and metabolic outcomes were assessed at baseline and at the final follow-up. The median follow-up duration was approximately 3 years and similar between groups (p>0.05). At baseline, the body mass index, adenoma size, and cortisol levels after the 1-mg dexamethasone suppression test were significantly higher, while adrenocorticotropic hormone levels were lower in the surgery group (p=0.02, p=0.02, p=0.036, and p<0.01, respectively). During the follow-up, adrenocorticotropic hormone levels increased and post-dexamethasone suppression test cortisol levels significantly decreased after adrenalectomy (p=0.001 and p=0.036, respectively), whereas metabolic parameters and comorbidity profiles remained largely unchanged. In the conservative group, total cholesterol increased modestly over time (p=0.048), with no significant changes in other clinical outcomes. No significant difference in comorbidity progression was observed between treatment strategies. In this real-world cohort, adrenalectomy resulted in clear hormonal improvement without parallel short-term metabolic or clinical benefits compared with conservative management. These findings highlight the heterogeneous clinical expression of mild autonomous cortisol secretion and underscore the importance of individualized patient selection for surgery.

Background/Objectives: Mild autonomous cortisol secretion (MACS) is associated with increased cardiometabolic morbidity, but its relationship with the retinal microcirculation is unknown. We compared retinal and peripapillary microvascular parameters between MACS and nonfunctioning adrenal adenoma (NFA) and, secondarily, examined their associations with continuously modeled post-dexamethasone cortisol. Methods: In this single-center, retrospective, cross-sectional study, 98 patients (45 NFA, 53 MACS) were included, and optical coherence tomography angiography (OCTA) and structural OCT data from one eye per patient were analyzed. The primary outcome was whole-image deep capillary plexus (DCP) vessel density. Multivariable models were adjusted for age, sex, body mass index, and cardiometabolic comorbidities; secondary analyses were corrected using the Benjamini–Hochberg false discovery rate (q values). Results: OCTA was evaluable in 89 patients. The primary outcome did not differ significantly between groups in the main analysis (NFA vs. MACS, 48.64 ± 5.71% vs. 47.31 ± 5.77%; adjusted difference −1.29 percentage points, 95% CI −3.97 to 1.38; p = 0.339) or in any sensitivity analysis. In secondary analyses, superior retinal nerve fiber layer (RNFL) thickness was greater in MACS (β = 17.38 µm; q < 0.001) and increased with ln(post-dexamethasone cortisol) (β = 13.74 µm; q = 0.010). Higher ln(post-dexamethasone cortisol) was also associated with lower parafoveal DCP (β = −2.72 percentage points; p = 0.013) and inside-disc radial peripapillary capillary vessel density (β = −3.13 percentage points; p = 0.026), which did not survive multiplicity correction; no superficial capillary plexus sector was associated with either exposure (all p ≥ 0.37). Conclusions: MACS was not significantly associated with whole-image DCP vessel density. The secondary associations with continuous cortisol are cross-sectional and hypothesis-generating and require prospective confirmation.

The potential association between mild autonomous cortisol secretion and psychopathological symptoms remains inadequately studied. This study aimed to investigate whether women with mild autonomous cortisol secretion exhibit greater psychological symptom severity and distress compared with patients with nonfunctional adrenal adenomas, as assessed by multidimensional self-report scales including the Beck Depression Inventory-II, Beck Anxiety Inventory, and Symptom Checklist‑90. A cross-sectional study was conducted at the endocrinology department of a tertiary-care hospital in Turkey between June 2022 and 2025. The study cohort included 91 women with adrenal adenomas, comprising 50 patients with mild autonomous cortisol secretion and 41 patients with nonfunctional adrenal adenoma. Questionnaire-derived scores from the 10 subscales and Global Severity Index of the Symptom Checklist-90, as well as the Beck Anxiety Inventory and Beck Depression Inventory-II, along with hormonal parameters, including morning cortisol, adrenocorticotropic hormone, dehydroepiandrosterone sulfate, 1-mg dexamethasone-suppressed cortisol, 24-hour urinary free cortisol, the dehydroepiandrosterone sulfate ratio, and the cortisol/dehydroepiandrosterone sulfate ratio, were compared between the groups. Women with mild autonomous cortisol secretion exhibited higher overall psychological distress, as measured by the Global Severity Index of the Symptom Checklist-90. Depressive (Beck Depression Inventory-II) and anxiety (Beck Anxiety Inventory) symptoms did not differ significantly between groups, although a non-significant pattern suggested that depressive symptom severity may increase with higher basal cortisol levels. No significant associations were found between hormonal parameters and psychological scores. These findings indicate that patients with mild autonomous cortisol secretion may experience increased general psychological distress, highlighting the importance of considering mental health in their clinical evaluation and warranting further research into the relationship between mild cortisol excess and specific psychiatric symptoms.