Budzen Karolina, Mukai Kosuke, Mitsui Yuto, Otsuki Michio, Fukuhara Atsunori, Oshino Satoru, Saitoh Youichi, Kohara Masaharu, Morii Eiichi, Shimomura Iichiro
Departments of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Department of Endocrinology, Tokyo Women's Medical University Graduate School of Medical Science, Tokyo 162-8666, Japan.
Endocr J. 2025 Jan 6;72(1):93-102. doi: 10.1507/endocrj.EJ24-0344. Epub 2024 Oct 24.
There are differences in the responsiveness to differential diagnostic tests for Cushing's disease (CD), corticotroph tumor size, and the somatostatin receptor (SSTR) 5 expression in corticotroph tumors between CD patients. The differences in SSTR5 expression are particularly significant for identifying therapeutic targets for CD. However, prospective predictors of SSTR5 expression remain unclear. Thus, our objective was to elucidate the relationships among these clinical characteristics of CD, including SSTR5 expression. In 27 hospitalized patients with CD at Osaka University Hospital, Osaka, Japan, associations between corticotroph tumor diameter, the response of ACTH and cortisol to differential diagnostic tests for CD (CRH, desmopressin [DDAVP], and high-dose dexamethasone suppression test [HDDST]), the ACTH/cortisol index, and the SSTR5 immunoreactive score were retrospectively investigated. The response to differential diagnostic tests, ACTH/cortisol index, tumor diameter, and SSTR5 expression were significantly related (vs. tumor diameter [CRH: r = -0.54; DDAVP: r = -0.54; HDDST r = -0.67; ACTH/cortisol index: r = 0.76; SSTR5: r = -0.61], vs. CRH [DDAVP: r = 0.63, HDDST: r = 0.72, ACTH/cortisol index: r = -0.45; SSTR5: r = 0.56], vs. DDAVP [HDDST: r = 0.66; ACTH/cortisol index: r = -0.46; SSTR5: r = 0.76], vs. HDDST [ACTH/cortisol index: r = -0.62; SSTR5: r = 0.77], ACTH/cortisol index vs. SSTR5: r = -0.67). The areas under the receiver operating characteristic curve for the prediction of high SSTR5 expression via the CRH test, DDAVP test, HDDST, ACTH/cortisol index, and tumor diameter were 0.79, 0.87, 0.80, 0.71, and 0.71, respectively. Tests for differential diagnosis of CD, the ACTH/cortisol index, and the corticotroph tumor diameter have the potential for identifying SSTR5 expression in corticotroph tumors. These parameters may reflect the biological characteristics of corticotroph tumors.
库欣病(CD)患者在对库欣病的鉴别诊断测试的反应性、促肾上腺皮质激素肿瘤大小以及促肾上腺皮质激素肿瘤中生长抑素受体(SSTR)5表达方面存在差异。SSTR5表达的差异对于确定CD的治疗靶点尤为重要。然而,SSTR5表达的前瞻性预测指标仍不明确。因此,我们的目标是阐明CD的这些临床特征之间的关系,包括SSTR5表达。在日本大阪大学医院住院的27例CD患者中,回顾性研究了促肾上腺皮质激素肿瘤直径、促肾上腺皮质激素(ACTH)和皮质醇对CD鉴别诊断测试(促肾上腺皮质激素释放激素[CRH]、去氨加压素[DDAVP]和高剂量地塞米松抑制试验[HDDST])的反应、ACTH/皮质醇指数与SSTR5免疫反应评分之间的关联。鉴别诊断测试的反应、ACTH/皮质醇指数、肿瘤直径和SSTR5表达之间存在显著相关性(与肿瘤直径相比[CRH:r = -0.54;DDAVP:r = -0.54;HDDST:r = -0.67;ACTH/皮质醇指数:r = 0.76;SSTR5:r = -0.61],与CRH相比[DDAVP:r = 0.63,HDDST:r = 0.72,ACTH/皮质醇指数:r = -0.45;SSTR5:r = 0.56],与DDAVP相比[HDDST:r = 0.66;ACTH/皮质醇指数:r = -0.46;SSTR5:r = 0.76],与HDDST相比[ACTH/皮质醇指数:r = -0.62;SSTR5:r = 0.77],ACTH/皮质醇指数与SSTR5相比:r = -0.67)。通过CRH试验、DDAVP试验、HDDST、ACTH/皮质醇指数和肿瘤直径预测高SSTR5表达的受试者工作特征曲线下面积分别为0.79、0.87、0.80、0.71和0.71。CD的鉴别诊断测试、ACTH/皮质醇指数和促肾上腺皮质激素肿瘤直径有可能识别促肾上腺皮质激素肿瘤中的SSTR5表达。这些参数可能反映促肾上腺皮质激素肿瘤的生物学特征。