RESUMEN
BACKGROUND: Serum thyroid-stimulating hormone (TSH) reference intervals are dependent on population characteristics, including prevalent thyroid disease and iodine status. Studies in the US have demonstrated increasing TSH levels with age, and the American Thyroid Association recommends higher TSH goals for older patients taking thyroid supplementation, but few laboratories offer age-specific reference intervals for TSH. Our objective was to establish TSH reference ranges in our racially diverse population in northern California. METHODS: Data mining of electronic medical records was used with the a posteriori approach to select a euthyroid reference population for TSH reference intervals. A report gathered all TSH results from 2 weeks from >1 year in the past, excluding results from patients with thyroid-related disease or medication use at any time before or after the TSH test. RESULTS: The reference population numbered 33038 and consisted of approximately 44% of the total TSH results reported in the selected time periods. The population identified as 46.5% white, 18.3% Asian, 17.0% Hispanic/Latino, 8.0% black/African American, and 10.3% other or unknown. These data demonstrate an increase in the median and 97.5 percentile of TSH levels with increasing age in adults. No clinically significant difference was seen between female and male individuals or between the self-identified races, except for lower TSH levels in the black/African American population. CONCLUSIONS: The a posteriori approach using data mining for disease-specific criteria proved to be an efficient method for obtaining a large healthy reference population. Age-specific TSH reference ranges could prevent inappropriate diagnoses of subclinical hypothyroidism in older patients.
RESUMEN
BACKGROUND: Efficient tools are needed to stage liver disease before treatment of patients infected with hepatitis C virus (HCV). Compared to biopsy, several studies demonstrated favorable performance of noninvasive multianalyte serum fibrosis marker panels [fibrosis-4 (FIB-4) index] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI), but suggested cutoffs vary widely. Our objective was to evaluate FIB-4 index and APRI and their component tests for staging fibrosis in our HCV-infected population and to determine practical cutoffs to help triage an influx of patients requiring treatment. METHODS: Transient elastography (TE) results from 1731 HCV-infected patients were mapped to an F0-F4 equivalent scale. Each patient's APRI and FIB-4 index were calculated. Areas under the receiver operator curve (AUROCs) and false-positive and false-negative rates were calculated to retrospectively compare the performance of the indices and their component tests. RESULTS: The highest AUROCs for distinguishing severe (F3-F4) from mild-to-moderate (F0-F2) fibrosis had overlapping 95% CIs: APRI (0.77; 0.74-0.79), FIB-4 index (0.76; 0.73-0.78), and AST (0.74; 0.72-0.77). Cutoffs had false-negative rates of 2.7%-2.8% and false-positive rates of 6.4%-7.4% for all 3 markers. CONCLUSIONS: AST was as effective as FIB-4 index and APRI at predicting fibrosis. Published cutoffs for APRI and FIB-4 index would have been inappropriate in our population, with false-negative rates as high as 11%. For our purposes, no serum fibrosis marker was sufficiently sensitive to rule-out significant fibrosis, but cutoffs developed for AST, FIB-4 index, and APRI all had specificities of 79.2%-80.3% for ruling-in severe fibrosis and could be used to triage 1/3 of our population for treatment without waiting for TE or liver biopsy.
RESUMEN
CONTEXT: An index case of a clinically euthyroid woman of South Asian descent was identified with discordant TSH results: undetectable TSH on our routine assay and normal TSH on an alternate assay. Low TSH concentrations due to functionally compromising TSH mutations have been reported. Here we describe a new phenomenon of functional TSH that is undetectable by 4 widely used US Food and Drug Administration (FDA)-approved TSH immunoassays marketed by a single vendor. OBJECTIVE: The purpose of this study was to identify additional cases and investigate the cause of the falsely undetectable TSH. DESIGN: All samples with TSH results of <0.01 µIU/mL were retested with a second TSH assay. Discordant samples were evaluated on up to 8 FDA-approved TSH immunoassays and the TSHß gene was sequenced. Retrospectively, thyroid function tests, diagnoses, and medications from 1.6 million individuals were analyzed. RESULTS: Out of approximately 2 million individuals, we have identified a cohort of 20 hypothyroid and euthyroid patients of shared ethnicity with falsely undetectable TSH (<0.01 µIU/mL) in 4 of 8 commercially available TSH assays. Half of these individuals were initially treated based on repeated falsely undetectable TSH values (7 euthyroid patients were treated with methimazole and 2 hypothyroid patients had doses of levothyroxine decreased). In all cases, a retrospective chart review revealed that clinical assessments and free T4 and total T3 results were inconsistent with the undetectable TSH results. Specific antibodies failing to detect TSH in these cases were identified in the 4 affected assays. A novel TSHß point mutation was identified. CONCLUSIONS: Our data suggest that these individuals have a previously unrecognized, functionally normal, TSH variant to which some monoclonal antibodies fail to bind. To assure appropriate patient management, clinicians and laboratorians need to be aware that certain TSH variants may be undetectable in some hyperselective TSH assays.
