Non-invasive Diagnostic Strategy in ACTH-dependent Cushing’s Syndrome

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 10; pp. 3273 - 3284
• Main Authors: Frete, Caroline, Corcuff, Jean-Benoît, Kuhn, Emmanuelle, Salenave, Sylvie, Gaye, Delphine, Young, Jacques, Chanson, Philippe, Tabarin, Antoine
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2020; Endocrine Society
• Subjects: ACTH Syndrome, Ectopic - blood; ACTH Syndrome, Ectopic - diagnosis; ACTH Syndrome, Ectopic - etiology; ACTH Syndrome, Ectopic - surgery; Adolescent; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - metabolism; Adult; Aged; Aged, 80 and over; Algorithms; Computed tomography; Cortisol; Cushing syndrome; Cushing's disease; Deamino Arginine Vasopressin - administration & dosage; Decision Support Techniques; Desmopressin; Dexamethasone; Diagnosis; Diagnosis, Differential; Diagnosis, Noninvasive; Female; Humans; Hydrocortisone - blood; Life Sciences; Magnetic Resonance Imaging; Male; Medical imaging; Methods; Middle Aged; Nervous system diseases; Neuroendocrine Tumors - blood; Neuroendocrine Tumors - complications; Neuroendocrine Tumors - pathology; Neurons and Cognition; Petrosal Sinus Sampling - adverse effects; Pituitary; Pituitary ACTH Hypersecretion - blood; Pituitary ACTH Hypersecretion - diagnosis; Pituitary ACTH Hypersecretion - pathology; Pituitary ACTH Hypersecretion - surgery; Pituitary Function Tests - methods; Pituitary Gland - diagnostic imaging; Pituitary Gland - drug effects; Pituitary Gland - pathology; Pituitary Gland - surgery; Predictive Value of Tests; Retrospective Studies; Tomography, X-Ray Computed; Young Adult; France; CT scanning; CRH test; Cushing’s disease; ectopic ACTH-syndrome; bilateral inferior petrosal sinus sampling; desmopressin test; Desmopressin test; Bilateral inferior petrosal sinus sampling; Ectopic ACTH-syndrome
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa409

Abstract Context Inferior petrosal sinus sampling (IPSS) is used to diagnose Cushing’s disease (CD) when dexamethasone-suppression and CRH tests, and pituitary magnetic resonance imaging (MRI), are negative or give discordant results. However, IPSS is an invasive procedure and its availability is limited. Objective To test a noninvasive diagnostic strategy associated with 100% positive predictive value (PPV) for CD. Design Retrospective study. Setting Two university hospitals. Patients A total of 167 patients with CD and 27 patients with ectopic ACTH-syndrome investigated between 2001 and 2016. Main Outcome Measure(s) Performance of a strategy involving the CRH and desmopressin tests with pituitary MRI followed by thin-slice whole-body computed tomography (CT) scan in patients with inconclusive results. Results Using thresholds of a cortisol increase > 17% with an ACTH increase > 37% during the CRH test and a cortisol increase > 18% with an ACTH increase > 33% during the desmopressin test, the combination of both tests gave 73% sensitivity and 98% PPV of CD. The sensitivity and PPV for pituitary MRI were 71% and 99%, respectively. CT scan identified 67% EAS at presentation with no false-positives. The PPV for CD was 100% in patients with positive responses to both tests, with negative pituitary MRI and CT scan. The Negative Predictive Value was 100% in patients with negative responses to both tests, with negative pituitary MRI and positive CT scan. Using this strategy, IPPS could have been avoided in 47% of patients in whom it is currently recommended. Conclusions In conjunction with expert radiologic interpretation, the non-invasive algorithm studied significantly reduces the need for IPSS in the investigation of ACTH-dependent Cushing’s syndrome.