Li Ding1, Baoping Wang1, Tingting Chen1, Ping Li1, Weihong Guo1, Yuxin Fan1, Fang Fang1, Jingqiu Cui1, Zuoliang Dong2, Qing He3, Ming Liu4. 1. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China. 2. Department of Clinical Laboratory, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China. 3. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China. hech69@163.com. 4. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154, Anshan, Road, Heping District, Tianjin, 300052, China. mingliu@tmu.edu.cn.
Abstract
PURPOSE: To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS). METHODS: The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis. RESULTS: In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort. CONCLUSIONS: ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.
PURPOSE: To develop an index for the differential diagnosis of corticotropin-dependent Cushing syndrome (CS). METHODS: The development cohort included 112 consecutive patients with clinicopathologically confirmed corticotropin-dependent CS at the Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, from December 2004 to May 2020, and data of 126 patients from studies published from 2016 to August 2020, identified through search in PubMed, Embase and the Cochrane Library, was extracted for external validation. The index was calculated as the product of plasma adrenocorticotropic hormone (ACTH, pmol/L) and urinary free cortisol (UFC, nmol/24 h) divided by 10,000. The discriminative ability was tested using receiver operating characteristics (ROC) curve analysis. RESULTS: In development cohort, area under curve of ROC analysis of the ACTH-UFC index in identifying Cushing disease (CD) was 0.977. The diagnostic accuracy of ACTH-UFC index ≤ 11 was comparable to that of 48 h 8 mg/d high-dose dexamethasone test (HDDST) in identifying CD, with sensitivity, specificity, positive and negative likelihood ratios of 96.6%, 87.5%, 7.73, and 0.04, respectively. The sensitivity of ACTH-UFC index ≤ 11 in parallel combination with pituitary magnetic resonance imaging (MRI) was 100% for identifying CD. The performance of the ACTH-UFC index in parallel or serial combination with pituitary MRI was similar in the validation cohort. CONCLUSIONS: ACTH-UFC index provides a rapid, convenient and non-invasive adjunctive approach for the differential diagnosis of corticotropin-dependent CS, with no risk of aggravating metabolic disturbances. Investigations for ectopic causes of corticotropin-dependent CS should be performed with ACTH-UFC index > 11 and negative contrasted pituitary MRI.
Authors: Patrick M Bossuyt; Johannes B Reitsma; David E Bruns; Constantine A Gatsonis; Paul P Glasziou; Les Irwig; Jeroen G Lijmer; David Moher; Drummond Rennie; Henrica C W de Vet; Herbert Y Kressel; Nader Rifai; Robert M Golub; Douglas G Altman; Lotty Hooft; Daniël A Korevaar; Jérémie F Cohen Journal: BMJ Date: 2015-10-28