Objective Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing’s disease (CD) vs ectopic ­ACTH secretion (EAS) is difficult to interpret. The present study aimed to identify and evaluate the diagnostic accuracy of corticotropin-releasing hormone (CRH) test, desmopressin test, and high-dose dexamethasone suppression test (HDDST) when used to establish a CD or EAS diagnosis. Design This study is a systematic review of the literature and meta-analysis. Methods MEDLINE, OVID, and Web of Science databases were searched for articles published between the years 1990-2021. Articles included described at least one test(s) (CRH, desmopressin, or HDDST) and the diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) used to establish a CD or EAS diagnosis. Results Sixty-two studies were included: 43 reported the use of HDDST, 32 CRH test, and 21 desmopressin test. CRH test was found to have the highest sensitivity in detecting CD (ACTH 86.9%, 95% confidence interval [CI] 82.1-90.6, cortisol 86.2%, 95%CI 78.3-91.5) and the highest specificity in detecting EAS (ACTH 93.9%, 95%CI 87-98.3, cortisol 89.4%, 95%CI 82.8-93.7). This resulted in a high diagnostic odds ratio (58, 95%CI 43.25-77.47), large area under the curve, and a receiver-operating characteristic (ROC) of 0.934. The diagnostic accuracy of HDDST and desmopressin test(s) was lower than that of the CRH test. Conclusion The meta-analysis indicates that a patient with a positive ACTH response after a CRH test is highly likely to have CD. Further studies analysing role of dynamic testing in addition to imaging are needed.

IntroductionPasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing’s Disease (CD). In previous studies and meta-analysis, first-generation SRLs were reported to be able to induce significant tumor shrinkage only in somatotroph adenomas. This systematic review and meta-analysis aim to summarize the effect of PAS on the shrinkage of the pituitary adenomas in patients with acromegaly or CD.Materials and methodsWe searched the Medline database for original studies in patients with acromegaly or CD receiving PAS as monotherapy, that assessed the proportion of significant tumor shrinkage in their series. After data extraction and analysis, a random-effect model was used to estimate pooled effects. Quality assessment was performed with a modified Joanna Briggs’s Institute tool and the risk of publication bias was addressed through Egger’s regression and the three-parameter selection model.ResultsThe electronic search identified 179 and 122 articles respectively for acromegaly and CD. After study selection, six studies considering patients with acromegaly and three with CD fulfilled the eligibility criteria. Overall, 37.7% (95%CI: [18.7%; 61.5%]) of acromegalic patients and 41.2% (95%CI: [22.9%; 62.3%]) of CD patients achieved significant tumor shrinkage. We identified high heterogeneity, especially in acromegaly (I2 of 90% for acromegaly and 47% for CD), according to the low number of studies included.DiscussionPAS treatment is effective in reducing tumor size, especially in acromegalic patients. This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022328152, identifier CRD42022328152

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