Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Risk Factors for Recurrence of Benign Paroxysmal Positional Vertigo: A Prospective Study.

OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) can be treated successfully in most cases. However, recurrences are common. We aimed to prospectively investigate demographic and clinical risk factors for BPPV recurrence. Our second aim was to investigate whether seasonality affects recurrences. METHODS: We recruited adult Dutch patients presenting at our dizziness clinic with a diagnosis of definite or possible BPPV for a prospective observational study with 1-year follow-up. Factors collected from patient history and questionnaires were age, sex, ethnicity, previous treatment for BPPV, duration of BPPV symptoms, number of treatment sessions for the initial BPPV episode, the affected canal, recent head trauma, and a history of vestibular neuritis, Menière's disease, (vestibular) migraine, gout, diabetes mellitus, and chronic renal failure. Factors derived from blood samples were uric acid, glycated hemoglobin, and 25-hydroxyvitamin D. RESULTS: We included 139 subjects with a mean age of 65 (SD, 13) years, of whom 70% was female. A total of 48 subjects (34.5%) suffered from at least one recurrence during the 1-year follow-up. Independent risk factors for recurrence of BPPV were "multiple treatment sessions for the initial BPPV episode" (incidence rate ratio, 1.74; 95% confidence interval 1.06-2.85; p = 0.027) and history of gout (incidence rate ratio, 1.90; 95% confidence interval, 1.01-3.57; p = 0.045). CONCLUSION: One-third of patients presenting in a tertiary dizziness clinic develop at least one recurrence of BPPV within 1 year. Multiple treatment sessions and a history of gout are independent risk factors for recurrence.