Sprenkeler Vera E, van Herwaarden Antonius E, van de Ven Annenienke C, Kusters Benno, Jenniskens Sjoerd F M, Netea-Maier Romana T, de Laat Joanne M
Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
J Neuroendocrinol. 2025 Sep;37(9):e70066. doi: 10.1111/jne.70066. Epub 2025 Aug 5.
Inferior petrosal sinus sampling (IPSS) is a diagnostic procedure used to differentiate between ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (EAS) and pituitary ACTH-dependent Cushing syndrome (CD). This study investigated the diagnostic value of IPSS, focusing on the use of prolactin adjustments and different calculation methods. We retrospectively analyzed data from patients with ACTH-dependent Cushing syndrome and inconclusive pituitary-MRI who underwent IPSS with corticotropin-releasing hormone (CRH) stimulation between 2015 and 2025. The cohort included 19 patients (16 CD, 3 EAS), with diagnoses confirmed by pathology examination and/or biochemical remission 1 year post-surgery. A pituitary source was confirmed in all patients with CD (n = 16) through pathology and/or biochemical remission. An ectopic source was confirmed by pathology in two of three patients with EAS. Using unadjusted ACTH ratios and previously established cut-off values resulted in three incorrect diagnoses out of 20 procedures. In contrast, prolactin-adjusted peak ACTH ratios provided a more distinct separation between CD and EAS, enabling correct diagnosis in all cases. Optimal cut-off values determined by receiver operating characteristic curve analysis were 1.0 for basal and 1.7 for concurrent prolactin-adjusted peak ACTH ratios, yielding 100% sensitivity and specificity. Basal prolactin-adjusted peak ACTH ratios were >1.5 in all patients with CD and <0.6 in all patients with EAS, while concurrent ratios were >1.1 in all patients with CD and <0.3 in all patients with EAS. Prolactin-adjusted peak ACTH ratios improve the diagnostic accuracy of IPSS and can effectively differentiate between ectopic and pituitary sources of ACTH. This study enhances the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) for differentiating pituitary from ectopic ACTH-dependent Cushing syndrome by incorporating prolactin measurements and exploring various calculation methods. The findings contribute to advancing diagnostic techniques and improving clinical management of endocrine disorders. By enabling more accurate identification of the underlying cause of ACTH-dependent Cushing syndrome, this work supports clinicians in selecting optimal treatment strategies.
岩下窦采血（IPSS）是一种用于区分异位促肾上腺皮质激素（ACTH）依赖性库欣综合征（EAS）和垂体ACTH依赖性库欣综合征（CD）的诊断方法。本研究调查了IPSS的诊断价值，重点关注催乳素调整的应用和不同的计算方法。我们回顾性分析了2015年至2025年间接受促肾上腺皮质激素释放激素（CRH）刺激的IPSS检查、患有ACTH依赖性库欣综合征且垂体MRI检查结果不明确的患者的数据。该队列包括19名患者（16例CD，3例EAS），诊断通过病理检查和/或术后1年的生化缓解得以证实。通过病理和/或生化缓解，所有CD患者（n = 16）均确诊为垂体来源。3例EAS患者中有2例经病理证实为异位来源。使用未经调整的ACTH比值和先前确定的临界值，在20次检查中有3次诊断错误。相比之下，催乳素调整后的ACTH峰值比值在CD和EAS之间提供了更明显的区分，在所有病例中均能做出正确诊断。通过受试者操作特征曲线分析确定的最佳临界值，基础值为1.0，同时期催乳素调整后的ACTH峰值比值为1.7，敏感性和特异性均为100%。所有CD患者的基础催乳素调整后的ACTH峰值比值>1.5，所有EAS患者的该比值<0.6，同时期比值在所有CD患者中>1.1，在所有EAS患者中<0.3。催乳素调整后的ACTH峰值比值提高了IPSS的诊断准确性，能够有效区分ACTH的异位和垂体来源。本研究通过纳入催乳素测量并探索各种计算方法，提高了岩下窦采血（IPSS）区分垂体性与异位ACTH依赖性库欣综合征的诊断准确性。这些发现有助于推进诊断技术，改善内分泌疾病的临床管理。通过能够更准确地识别ACTH依赖性库欣综合征的潜在病因，这项工作支持临床医生选择最佳治疗策略。
