Intra- and interindividual biological variation of five analytes used in assessing thyroid function: implications for necessary standards of performance and the interpretation of results.

Abstract

Intra- and interindividual components of biological variation have been determined for total thyroxin (TT4), free thyroxin (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyrotropin (TSH). Calculated analytical goals (CV, %) for the precision required for optimal patient care are: TT4 less than or equal to 2.5, FT4 less than or equal to 4.7, TT3 less than or equal to 5.2, FT3 less than or equal to 3.9, and TSH less than or equal to 8.1. The marked degree of individuality demonstrated for all hormones indicates that, if conventional population-based reference ranges are used uncritically, major changes in hormone concentration may not be correctly identified for some patients because observed values continue to lie within the reference range. At analyte concentrations approximating the mean values found in this study, and for analytical performance meeting the appropriate analytical goal, the differences required for consecutive results to be significantly different (p less than or equal to 0.5) have been calculated as: TT4, 14.7 nmol/L; FT4, 5.7 pmol/L; TT3, 0.6 nmol/L; FT3, 1.3 pmol/L, and TSH, 0.7 milli-int. unit/L.

Components of biological variation, including seasonality, in blood concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers

“…1%/9 . 1%) is also comparable to that obtained by Browning et al (1986) over a 5-week study span, i.e. 9 .…”

“…26 and 0 . 60 (Holzel & Deschner, 1988;Costongs et al, 1985;Browning et al, 1986). Our I-indices computed for cortisol (21 .…”

“…Moreover, it was generally found that the intraindividual variability in plasma TSH (Costongs et al, 1985;Feldt-Rasmussen et al, 1985;Browning et al 1986;Holzel & Deschner, 1988;Juan-Pereira et al, 1991) and plasma T3 (Costongs et al, 1985;Browning et al, 1986;Holzel & Deschner, 1988;Ricos & Arbos, 1990;Juan-Pereira et al, 1991) was small compared to the interindividual variability. Browning et al (1986) concluded that if conventional population-based reference intervals are used uncritically, major changes in hormone levels may not be detected since individuals may have values that are unusual for them but that still fall within the reference limits. Ricos & Arbos (1990) have examined the components of biological variation in serum cortisol, PRL, and testosterone and they reported low ratios of the intra-/interindividual variability for these three hormones.…”

Renal Function and Electrolyte Levels in Hyperthyroidism: Urinary Protein Excretion and the Plasma Concentrations of Urea, Creatinine, Uric Acid, Hydrogen Ion and Electrolytes

“…This is probably one reason why these changes have been reported inconsistently or not at all by previous investigators who compared hyperthyroid patients with a control group of other healthy individuals rather than having each patient serve as his or her own control. It has recently been reemphasized that if conventional population-based reference ranges are used uncritically, major changes in analyte concentration or activity may not be appreciated because the values continue to be within the reference range (Browning et al, 1986).…”

Low Serum TSH With Normal Total Thyroid Hormone Levels: An Indicator of Free T4 Excess

“…Alternatively, free T4 levels may have been inappropriately high for these particular individuals. Browning et al (1986) have pointed out that major changes in hormone concentrations may not be correctly identified in some patients because the observed values lie within their respective reference ranges. In our study, even in those subjects in whom an elevated value was not recorded, free T4 levels clustered towards the upper end of the reference range.…”