F Ceccato1,2, C Artusi3, M Barbot4, L Lizzul4, S Pinelli4, G Costantini4, S Niero4, G Antonelli3, M Plebani3, C Scaroni4. 1. Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile, 105-35128, Padua, Italy. filippo.ceccato@unipd.it. 2. Department of Neurosciences DNS, University of Padova, Padua, Italy. filippo.ceccato@unipd.it. 3. Laboratory Medicine Unit, Department of Medicine DIMED, University-Hospital of Padova, Padua, Italy. 4. Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile, 105-35128, Padua, Italy.
Abstract
BACKGROUND AND AIM: Dexamethasone Suppression Test (DST), recommended for Cushing's Syndrome (CS) diagnosis, explores the pituitary feedback to glucocorticoids. Its diagnostic accuracy could be affected by dexamethasone bioavailability, and therefore, we have developed and validated a dexamethasone threshold after 1-mg DST. MATERIALS AND METHODS: We studied 200 subjects: 125 patients were considered retrospectively and 75 were enrolled prospectively as the validation cohort. Serum dexamethasone, Late Night Salivary Cortisol (LNSC), and Urinary Free Cortisol (UFC) were measured with LC-MS/MS. Normal LNSC and UFC levels were used to exclude CS. The lower 2.5th percentile of dexamethasone distribution in non-CS patients with cortisol ≤ 50 nmol/L after 1-mg DST was used as threshold. RESULTS: 16 patients were CS and 184 non-CS (108 adrenal incidentaloma and 76 excluded CS); 4.5 nmol/L resulted the calculated threshold. Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate-low specificity (63%, increased to 91% at 138 nmol/L) to diagnose CS in the whole cohort of patients. We could reduce the number of false-positive results (from 10 to 6 and from 7 to 4 in AI and excluded CS) considering adequate dexamethasone levels. Dexamethasone levels were not affected by hypercortisolism, age, gender, smoke, weight, and creatinine. 6% of non-CS patients did not achieve adequate dexamethasone levels (40% of tests with serum cortisol > 138 nmol/L after 1-mg DST). CONCLUSIONS: We developed and validated the routine dexamethasone measurement during 1-mg DST: it is independent from patient's clinical presentation, and it should be used to increase the specificity of serum cortisol levels.
BACKGROUND AND AIM: Dexamethasone Suppression Test (DST), recommended for Cushing's Syndrome (CS) diagnosis, explores the pituitary feedback to glucocorticoids. Its diagnostic accuracy could be affected by dexamethasone bioavailability, and therefore, we have developed and validated a dexamethasone threshold after 1-mg DST. MATERIALS AND METHODS: We studied 200 subjects: 125 patients were considered retrospectively and 75 were enrolled prospectively as the validation cohort. Serum dexamethasone, Late Night Salivary Cortisol (LNSC), and Urinary Free Cortisol (UFC) were measured with LC-MS/MS. Normal LNSC and UFC levels were used to exclude CS. The lower 2.5th percentile of dexamethasone distribution in non-CSpatients with cortisol ≤ 50 nmol/L after 1-mg DST was used as threshold. RESULTS: 16 patients were CS and 184 non-CS (108 adrenal incidentaloma and 76 excluded CS); 4.5 nmol/L resulted the calculated threshold. Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate-low specificity (63%, increased to 91% at 138 nmol/L) to diagnose CS in the whole cohort of patients. We could reduce the number of false-positive results (from 10 to 6 and from 7 to 4 in AI and excluded CS) considering adequate dexamethasone levels. Dexamethasone levels were not affected by hypercortisolism, age, gender, smoke, weight, and creatinine. 6% of non-CSpatients did not achieve adequate dexamethasone levels (40% of tests with serum cortisol > 138 nmol/L after 1-mg DST). CONCLUSIONS: We developed and validated the routine dexamethasone measurement during 1-mg DST: it is independent from patient's clinical presentation, and it should be used to increase the specificity of serum cortisol levels.
Entities:
Keywords:
Cushing’s syndrome; Dexamethasone; Diagnostic accuracy; Liquid chromatography–tandem mass spectrometry
Authors: A T T Leão; L Vieira Neto; M O Rodrigues; A B Moraes; M P de Paula; V A Pereira Journal: J Endocrinol Invest Date: 2021-03-31 Impact factor: 4.256
Authors: Maria Fleseriu; Richard Auchus; Irina Bancos; Anat Ben-Shlomo; Jerome Bertherat; Nienke R Biermasz; Cesar L Boguszewski; Marcello D Bronstein; Michael Buchfelder; John D Carmichael; Felipe F Casanueva; Frederic Castinetti; Philippe Chanson; James Findling; Mônica Gadelha; Eliza B Geer; Andrea Giustina; Ashley Grossman; Mark Gurnell; Ken Ho; Adriana G Ioachimescu; Ursula B Kaiser; Niki Karavitaki; Laurence Katznelson; Daniel F Kelly; André Lacroix; Ann McCormack; Shlomo Melmed; Mark Molitch; Pietro Mortini; John Newell-Price; Lynnette Nieman; Alberto M Pereira; Stephan Petersenn; Rosario Pivonello; Hershel Raff; Martin Reincke; Roberto Salvatori; Carla Scaroni; Ilan Shimon; Constantine A Stratakis; Brooke Swearingen; Antoine Tabarin; Yutaka Takahashi; Marily Theodoropoulou; Stylianos Tsagarakis; Elena Valassi; Elena V Varlamov; Greisa Vila; John Wass; Susan M Webb; Maria C Zatelli; Beverly M K Biller Journal: Lancet Diabetes Endocrinol Date: 2021-10-20 Impact factor: 32.069
Authors: Marta Araujo-Castro; Ana García Cano; Lucía Jiménez Mendiguchía; Héctor F Escobar-Morreale; Pablo Valderrábano Journal: Sci Rep Date: 2021-10-15 Impact factor: 4.379