Figure 3.

Graphical summary of 1) the potential underlying biological mechanisms of within-person variation in thyroid-stimulating hormone (TSH) levels over time, 2) the main sources, and 3) the clinical implications. The main topics discussed in this review are illustrated. The main sources of within-person variation in TSH levels over time are pulsatile secretion, circadian rhythm, seasonality, and ageing, as illustrated in 3.2. The main hypotheses for the underlying mechanisms of within-person variations are illustrated in 3.1. The pituitary needs to respond quickly to changes in the environment to maintain homeostasis, which is one of the potential underlying biological mechanisms of pulsatile secretion of TSH. The biological clock regulates the circadian rhythm of many physiological processes including pituitary hormones and energy metabolism. The seasonality in TSH levels are possibly caused by changes in environmental temperature, with studies indicating generally highest levels during winter season. Multiple studies showed that on a population level, TSH levels generally increase with age. However, the size and rate of the increase within an individual is not completely clear. Finally, the implications of within-person variation in TSH levels over time for clinical practice and scientific research are illustrated in 3.3. Within-person variation in TSH levels is not only present in healthy euthyroid individuals, but also seen in patients with (un)treated thyroid disease. It occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention and the season of thyroid testing plays a role in the transition of patients between subclinical hypothyroidism and the euthyroid status. We recommend regular monitoring of an individual’s TSH levels by obtaining repeated measurements so different sources of within-person variations can be considered.