Plasma Free Cortisol in States of Normal and Altered Binding Globulins: Implications for Adrenal Insufficiency Diagnosis.

Autor: Dichtel LE; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Schorr M; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Loures de Assis C; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts., Rao EM; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts., Sims JK; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts., Corey KE; Harvard Medical School, Boston, Massachusetts.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts., Kohli P; Harvard Medical School, Boston, Massachusetts.; Division of Pulmonology and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts., Sluss PM; Harvard Medical School, Boston, Massachusetts.; Clinical Pathology, Massachusetts General Hospital, Boston, Massachusetts., McPhaul MJ; Endocrinology, Quest Diagnostics Nichols Institute, San Juan Capistrano, California., Miller KK; Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.
Jazyk: angličtina
Zdroj: The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2019 Oct 01; Vol. 104 (10), pp. 4827-4836.
DOI: 10.1210/jc.2019-00022
Abstrakt: Context: Accurate diagnosis of adrenal insufficiency is critical because there are risks associated with overdiagnosis and underdiagnosis. Data using liquid chromatography tandem mass spectrometry (LC/MS/MS) free cortisol (FC) assays in states of high or low cortisol-binding globulin (CBG) levels, including cirrhosis, critical illness, and oral estrogen use, are needed.
Design: Cross-sectional.
Objective: Determine the relationship between CBG and albumin as well as total cortisol (TC) and FC in states of normal and abnormal CBG. Establish the FC level by LC/MS/MS that best predicts TC of <18 μg/dL (497 nmol/L) (standard adrenal insufficiency diagnostic cutoff) in healthy individuals.
Subjects: This study included a total of 338 subjects in four groups: healthy control (HC) subjects (n = 243), patients with cirrhosis (n = 38), intensive care unit patients (ICU) (n = 26), and oral contraceptive (OCP) users (n = 31).
Main Outcome Measure(s): FC and TC by LC/MS/MS, albumin by spectrophotometry, and CBG by ELISA.
Results: TC correlated with FC in the ICU (R = 0.91), HC (R = 0.90), cirrhosis (R = 0.86), and OCP (R = 0.70) groups (all P < 0.0001). In receiver operator curve analysis in the HC group, FC of 0.9 μg/dL (24.8 nmol/L) predicted TC of <18 μg/dL (497 nmol/L; 98% sensitivity, 91% specificity; AUC, 0.98; P < 0.0001). Decreasing the cutoff to 0.7 μg/dL led to a small decrease in sensitivity (92%) with similar specificity (91%).
Conclusions: A cutoff FC of <0.9 μg/dL (25 nmol/L) in this LC/MS/MS assay predicts TC of <18 μg/dL (497 nmol/L) with excellent sensitivity and specificity. This FC cutoff may be helpful in ruling out adrenal insufficiency in patients with binding globulin derangements.
(Copyright © 2019 Endocrine Society.)
Databáze: MEDLINE