Prinzi Antonio, Lombardo Ausilia Maria, Finocchiaro Salvatore, Galvano Antonio, Vella Veronica, Frasca Francesco, Malandrino Pasqualino
Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy; Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy.
Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy.
Endocr Pract. 2025 Sep 17. doi: 10.1016/j.eprac.2025.09.009.
Mild autonomous cortisol secretion (MACS) is a frequent finding in adrenal incidentalomas (AI), yet its diagnosis remains challenging. We aimed to compare clinical and biochemical profiles between MACS and non-functioning AIs and to identify reliable biomarkers, alternative to the 1 mg dexamethasone suppression test (DST), that can support the diagnosis of MACS.
We retrospectively analyzed 171 patients with AIs (70 MACS, 101 non-functioning AI) evaluated between 2005 and 2025. MACS was defined by DST cortisol >1.8 μg/dL without overt Cushing's syndrome.
Patients with MACS showed a higher prevalence of dyslipidemia (68.1% vs 52.0%; P = .037) and anxiety-depressive disorders (25.0% vs 11.0%; P = .018). Biochemically, they showed lower adrenocorticotropic hormone (11.1 pg/mL vs 16.8 pg/mL; P = .014), dehydroepiandrosterone-sulfate (0.3 μg/mL vs 0.9 μg/mL; P < .001), and testosterone levels in male (3.56 ng/ml vs 5.41 ng/ml, P = .04), with higher post-DST cortisol (2.8 μg/dL vs 1.2 μg/dL; P < .001), 24-hour urinary-free cortisol (67.2 μg/24h vs 44.8 μg/24h; P < .001), and late-night serum cortisol (8.2 μg/dL vs 3.6 μg/dL, P < .001). Adrenocorticotropic hormone <15 pg/mL (P = .029) and dehydroepiandrosterone-sulfate <0.5 μg/mL (P = .009) independently predicted MACS (area under the curve: 0.78) and were combined into a 2-point diagnostic score with 89.5% sensitivity and 97.5% negative predictive value. Late-night cortisol ≥5.1 μg/dL showed good accuracy (area under the curve: 0.83) for identifying patients with MACS and correlated with the number of MACS-related comorbidities (P = .0178).
MACS is associated with neuropsychiatric and gonadal dysfunction. A simple and easily applicable biochemical score, together with late-night cortisol, may support diagnosis, particularly when the DST is inconclusive or in hospitalized patients.
轻度自主性皮质醇分泌（MACS）在肾上腺偶发瘤（AI）中很常见，但其诊断仍具有挑战性。我们旨在比较MACS与无功能AI的临床和生化特征，并确定可替代1毫克地塞米松抑制试验（DST）的可靠生物标志物，以支持MACS的诊断。
我们回顾性分析了2005年至2025年间评估的171例AI患者（70例MACS，101例无功能AI）。MACS由DST皮质醇>1.8μg/dL且无明显库欣综合征定义。
MACS患者血脂异常（68.1%对52.0%；P = 0.037）和焦虑抑郁障碍（25.0%对11.0%；P = 0.018）的患病率更高。生化方面，他们的促肾上腺皮质激素水平较低（11.1 pg/mL对16.8 pg/mL；P = 0.014）、硫酸脱氢表雄酮水平较低（0.3μg/mL对0.9μg/mL；P < 0.001），男性睾酮水平较低（3.56 ng/ml对5.41 ng/ml，P = 0.04），而DST后皮质醇水平较高（2.8μg/dL对1.2μg/dL；P < 0.001）、24小时尿游离皮质醇水平较高（67.2μg/24h对44.8μg/24h；P < 0.001）以及午夜血清皮质醇水平较高（8.2μg/dL对3.6μg/dL，P < 0.001）。促肾上腺皮质激素<15 pg/mL（P = 0.029）和硫酸脱氢表雄酮<0.5μg/mL（P = 0.009）可独立预测MACS（曲线下面积：0.78），并合并为一个2分诊断评分，敏感性为89.5%，阴性预测值为97.5%。午夜皮质醇≥5.1μg/dL在识别MACS患者方面具有良好的准确性（曲线下面积：0.83），且与MACS相关合并症的数量相关（P = 0.0178）。
MACS与神经精神和性腺功能障碍有关。一个简单且易于应用的生化评分，连同午夜皮质醇，可能有助于诊断，特别是在DST结果不确定或在住院患者中。
