Vogg Nora, Kurlbaum Max, Deutschbein Timo, Gräsl Benedict, Fassnacht Martin, Kroiss Matthias
Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Würzburg, Germany.
Central Laboratory, Core Unit Clinical Mass Spectrometry, University Hospital Würzburg, Würzburg, German.
Clin Chem. 2021 Jul 6;67(7):998-1007. doi: 10.1093/clinchem/hvab056.
The dexamethasone suppression test (DST) is the recommended first-tier test for suspected Cushing syndrome (CS). Missed dexamethasone intake or insufficient dexamethasone serum exposure may yield false positive results. Quantification of serum dexamethasone in DST samples may therefore improve test performance.
Simultaneous quantification of dexamethasone and cortisol by liquid chromatography-tandem mass spectrometry in 400 DST serum samples (100 overt CS, 200 excluded CS, 100 adrenal incidentalomas with (possible) autonomous cortisol secretion, AI-ACS) randomly selected within the indication groups. The 2.5th percentile of dexamethasone in patients with excluded CS was considered the lower limit of normal (LLN).
Serum dexamethasone varied from undetectable to 20.2 ng/mL with a median of 4.8 ng/mL (95% CI 4.5-5.1 ng/mL). Dexamethasone was undetectable in only 16 patients (4%), suggesting non-compliance. The dexamethasone LLN was 1.8 ng/mL (4.6 nmol/L). Decreased glomerular filtration rate and diabetes mellitus were associated with higher serum dexamethasone concentration, while body mass index, sex, age, nicotine, and oral contraceptives had no significant effect. By excluding the 27 samples with dexamethasone <LLN and applying the method-specific cortisol cutoff of 2.4 µg/dL (66 nmol/L) to samples with suspected CS, the clinical specificity for CS increased from 67.5% to 92.4% while preserving 100% clinical sensitivity. Among 100 AI-ACS samples (defined by immunoassay), 4 samples had dexamethasone <1.8 ng/mL and 14 samples had cortisol <2.4 µg/dL, which excluded autonomous cortisol secretion.
Quantification of dexamethasone and method-specific cortisol cutoffs in DST samples may reduce the false positive rate and lower the proportion of patients requiring further workup.
地塞米松抑制试验（DST）是疑似库欣综合征（CS）的推荐一线检查。地塞米松摄入遗漏或血清暴露不足可能产生假阳性结果。因此，对DST样本中的血清地塞米松进行定量分析可能会提高检测性能。
在各适应症组中随机选择400份DST血清样本（100例显性CS、200例排除CS、100例肾上腺偶发瘤伴（可能）自主性皮质醇分泌，AI-ACS），采用液相色谱-串联质谱法同时对地塞米松和皮质醇进行定量分析。排除CS患者中地塞米松的第2.5百分位数被视为正常下限（LLN）。
血清地塞米松水平从不可检测到20.2 ng/mL不等，中位数为4.8 ng/mL（95%CI 4.5-5.1 ng/mL）。仅16例患者（4%）的地塞米松不可检测，提示未遵医嘱。地塞米松的LLN为1.8 ng/mL（4.6 nmol/L）。肾小球滤过率降低和糖尿病与血清地塞米松浓度升高相关，而体重指数、性别、年龄、尼古丁和口服避孕药无显著影响。通过排除27份地塞米松<LLN的样本，并将疑似CS样本的方法特异性皮质醇临界值设为2.4 μg/dL（66 nmol/L），CS的临床特异性从67.5%提高到92.4%，同时保持100%的临床敏感性。在100份AI-ACS样本（通过免疫测定定义）中，4份样本的地塞米松<1.8 ng/mL，14份样本的皮质醇<2.4 μg/dL，排除了自主性皮质醇分泌。
对DST样本中的地塞米松进行定量分析以及采用方法特异性皮质醇临界值可能会降低假阳性率，并减少需要进一步检查的患者比例。
