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      Hypercortisolemia Recurrence in Cushing's Disease; a Diagnostic Challenge

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          Abstract

          Cushing's disease recurrence following successful pituitary surgery is common and merits prompt and careful diagnosis, as untreated hypercortisolism leads to increased morbidity and mortality. However, an established recurrence definition has not been forthcoming. This poses a diagnostic challenge especially early in the course of returning hypercortisolemia and/or in the presence of non-neoplastic hypercortisolemia. A late-night salivary cortisol (LNSC) test is the first test to reveal abnormal results, however, has limitations related to assay performance as well as individual patient variability. Dexamethasone suppression tests and 24-h urinary free cortisol (UFC) results are next to reveal abnormal results. Other tests including, corticotropin-releasing hormone (CRH) stimulation test and combined CRH-dexamethasone test, as well as desmopressin stimulation test with/without dexamethasone are also used, although, none have proven to be the preeminent diagnostic test for recurrence determination. There is a possible role for these tests in predicting recurrence in patients who have experienced remission, though, this also remains challenging due to lack of established cutoff values. This article details and summarizes evidence about different diagnostic tests currently used to diagnose and predict Cushing's disease recurrence.

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          Most cited references72

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          Multisystem morbidity and mortality in Cushing's syndrome: a cohort study.

          Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS.
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            Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement

            Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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              Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume.

              Larger surgical caseload is associated with better patient outcome for many complex procedures. We examined the volume-outcome relationship for transsphenoidal pituitary tumor surgery using the Nationwide Inpatient Sample, 1996-2000. Multivariate regression adjusted for patient demographics, acuity measures, medical comorbidities, and endocrine status. A total of 5497 operations were performed at 538 hospitals by 825 surgeons. Outcome measured at hospital discharge was: death (0.6%), discharge to long-term care (0.9%), to short-term rehabilitation (2.1%), or directly home (96.2%). Outcomes were better after surgery at higher-volume hospitals (OR 0.74 for 5-fold-larger caseload, P = 0.007) or by higher-volume surgeons (OR 0.62, P = 0.02). A total of 5.4% of patients were not discharged directly home from lowest-volume-quartile hospitals, compared with 2.6% at highest-volume-quartile hospitals. In-hospital mortality was lower with higher-volume hospitals (P = 0.03) and surgeons (P = 0.09). Mortality rates were 0.9% at lowest-caseload-quartile hospitals and 0.4% at highest-volume-quartile hospitals. Postoperative complications (26.5% of admissions) were less frequent with higher-volume hospitals (P = 0.03) or surgeons (P = 0.005). Length of stay was shorter with high-volume hospitals (P = 0.02) and surgeons (P < 0.001). Hospital charges were lower for high-volume hospitals, but not significantly. This analysis suggests that higher-volume hospitals and surgeons provide superior short-term outcomes after transsphenoidal pituitary tumor surgery with shorter lengths of stay and a trend toward lower charges.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                08 November 2019
                2019
                : 10
                : 740
                Affiliations
                [1] 1Departments of Medicine (Endocrinology), Oregon Health & Science University , Portland, OR, United States
                [2] 2Endocrinology Division, Department of Medicine, Hospital Universitario “Dr. José E. González”, Universidad Autónoma de Nuevo León , Monterrey, Mexico
                [3] 3Neurological Surgery, Oregon Health & Science University , Portland, OR, United States
                [4] 4Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, United States
                Author notes

                Edited by: Marco Losa, Vita-Salute San Raffaele University, Italy

                Reviewed by: Nicholas A. Tritos, Harvard Medical School, United States; Mauro Antonio Czepielewski, Federal University of Rio Grande do Sul, Brazil

                *Correspondence: Maria Fleseriu fleseriu@ 123456ohsu.edu

                This article was submitted to Pituitary Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2019.00740
                6856050
                31787930
                a7d7b074-c6d2-46e5-af36-b455b10464e8
                Copyright © 2019 Hinojosa-Amaya, Varlamov, McCartney and Fleseriu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 August 2019
                : 14 October 2019
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 78, Pages: 11, Words: 7977
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                hypercortisolemia,recurrence,cushing's disease,cushing's syndrome,cushing,diagnostic testing,remission

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