Interpretation of TSH results can be improved by reference values fluctuating in time

The secretion of thyroid stimulating hormone (thyrotropin, TSH), is characterized by a marked circadian rhythm. Plasma or serum TSH values are significantly lower in the afternoon and in the evening as compared to the early morning. As in clinical practice, blood sampling time shows an important variation, a reliable assessment of thyroid status is often not an easy task for the clinician. The biological variation of TSH plays a major role in the intra-individual variability of TSH results in serum or plasma. The observed intra-day variation largely exceeds the reported inter-vendor variation and the coefficient of variation of clinical TSH assays. Therefore, a mathematical solution was sought for correcting interpretation of TSH results for sampling time.

We have developed a cosinor model which allows to compensate TSH decision values for the fluctuating serum or plasma TSH concentrations throughout the day.

The following mathematical function could be derived: corrected TSH cutoff_value (mIU/L)=0.40 + 0.24*cos(((π/12) *T) + 6) in which T represents the time (hours). This mathematical function can be easily implemented into a laboratory's informatics system and furthermore allows a better tailored diagnosis of (subclinical) hyperthyroidism, regardless the blood sampling time.

Implementing the corrected cut-off values result in a marked reduction of apparent (false positive) hyperthyroidism diagnosis, in particular in the afternoon.