Diurnal fluctuations in thyroid hormones - the Bispebjerg study of diurnal variations

Misinterpretation of diurnal variation in thyroid hormones and thyroid stimulating hormone (TSH) could have a significant impact on diagnostic interpretation. However, the circadian rhythm of plasma thyroxine (T4) and triiodothyronine (T3) is unclarified. The aim of this study was to assess the clinical relevance of diurnal variation in thyroid hormones and TSH.

Blood samples from 24 healthy Caucasian males were drawn every third hour for 24 h in a controlled environment. Diurnal variation of TSH and total/free peripheral thyroid hormones was evaluated by cosinor rhythmometry. Data was fitted with both ordinary least squares regression and mixed-effects models.

Cosinor analysis showed statistically significant diurnal variation of TSH (p < 0.001), which displayed the lowest levels in the early afternoon and peaked at 2 am. During 24 h, the average within subject coefficient of variation of TSH was 31%, whereas for the peripheral thyroid hormones it was between 4-7%. All thyroid parameters exhibited large between-participant differences in individual mesor values. Extending the model to account for these individual differences in biological set-point - a mixed-effects cosinor analysis - all thyroid parameters showed statistically significant diurnal variation (p < 0.001), except free T3 (p = 0.056). Total T3 displayed a diurnal profile almost synchronized with TSH, albeit with a small temporal lag, while free/total T4 oscillated opposite to TSH with a peak around mid-day and nadir at night.

In conclusion, thyroid parameters in this study exhibited significant diurnal variation, particularly TSH. These physiological fluctuations should be considered when diagnosing thyroid diseases.