Nakano Yui, Yokomoto-Umakoshi Maki, Nakatani Kohta, Umakoshi Hironobu, Nakao Hiroshi, Fujita Masamichi, Kaneko Hiroki, Iwahashi Norifusa, Ogasawara Tatsuki, Fukumoto Tazuru, Matsuda Yayoi, Sakamoto Ryuichi, Izumi Yoshihiro, Bamba Takeshi, Ogawa Yoshihiro
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Division of Metabolomics, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
J Endocr Soc. 2024 Jul 31;8(9):bvae140. doi: 10.1210/jendso/bvae140. eCollection 2024 Jul 26.
Adrenal incidentalomas, including nonfunctioning adrenal incidentalomas (NFAI), are associated with a high prevalence of diabetes mellitus (DM). While NFAI is diagnosed by exclusion when no hormone excess exists, subtle cortisol secretion may exist and contribute to DM development. However, it alone cannot explain the increased risk, and whether other steroid metabolites are involved remains unclear.
To investigate steroid metabolites associated with DM in patients with NFAI using plasma steroid profiles.
Using liquid chromatography-tandem mass spectrometry, 22 plasma steroid metabolites were measured in 68 patients with NFAI (31 men and 37 women). Data were adjusted for age before normalization.
Discriminant analysis showed that plasma steroid profiles discriminated between patients with and without DM in men (n = 10 and = 21, respectively) but not women: 11β-hydroxytestosterone, an adrenal-derived 11-oxygenated androgen, contributed most to this discrimination and was higher in patients with DM than in those without DM (false discovery rate = .002). 11β-hydroxytestosterone was correlated positively with fasting plasma glucose (r = .507) and hemoglobin A1c (HbA1c) (r = .553) but negatively with homeostatic model assessment of β-cell function (HOMA2-B) (r = -.410). These correlations remained significant after adjusting for confounders, including serum cortisol after the 1-mg dexamethasone suppression test. Bayesian kernel machine regression analysis verified the association of 11β-hydroxytestosterone with HbA1c and HOMA2-B in men.
Plasma steroid profiles differed between those with and without DM in men with NFAI. 11β-hydroxytestosterone was associated with hyperglycemia and indicators related to pancreatic β-cell dysfunction, independently of cortisol.
肾上腺偶发瘤，包括无功能肾上腺偶发瘤（NFAI），与糖尿病（DM）的高患病率相关。虽然当不存在激素过量时通过排除法诊断NFAI，但可能存在细微的皮质醇分泌并促进DM的发展。然而，其本身并不能解释风险增加的原因，其他类固醇代谢物是否参与其中仍不清楚。
使用血浆类固醇谱研究NFAI患者中与DM相关的类固醇代谢物。
使用液相色谱 - 串联质谱法，测量了68例NFAI患者（31例男性和37例女性）的22种血浆类固醇代谢物。在标准化之前对数据进行年龄校正。
判别分析表明，血浆类固醇谱在男性DM患者和非DM患者之间有区分能力（分别为n = 10和21），但在女性中无区分能力：11β-羟基睾酮，一种肾上腺衍生的11-氧化雄激素，对这种区分贡献最大，DM患者中的水平高于非DM患者（错误发现率= 0.002）。11β-羟基睾酮与空腹血糖（r = 0.507）和糖化血红蛋白（HbA1c）（r = 0.553）呈正相关，但与β细胞功能的稳态模型评估（HOMA2-B）呈负相关（r = -0.410）。在调整包括1毫克地塞米松抑制试验后的血清皮质醇等混杂因素后，这些相关性仍然显著。贝叶斯核机器回归分析证实了男性中11β-羟基睾酮与HbA1c和HOMA2-B的关联。
NFAI男性中，有DM和无DM者的血浆类固醇谱不同。11β-羟基睾酮与高血糖症以及与胰腺β细胞功能障碍相关的指标有关，且独立于皮质醇。
