Within-Person Variation in Serum Thyrotropin Concentrations: Main Sources, Potential Underlying Biological Mechanisms, and Clinical Implications

Abstract

BackgroundIndividuals exhibit fluctuations in the concentration of serum thyroid-stimulating hormone (TSH) over time. The scale of these variations ranges from minutes to hours, and from months to years. The main factors contributing to the observed within-person fluctuations in serum TSH comprise pulsatile secretion, circadian rhythm, seasonality, and ageing. In clinical practice and clinical research however, such within-person biological variation in serum TSH concentrations is often not considered. The aim of this review is to present an overview of the main sources of within-person variation in TSH levels, as well as the potential underlying biological mechanisms, and the clinical implications.SummaryIn euthyroid individuals, the circadian rhythm, with a nocturnal surge around 02:00–04:00 h and a nadir during daytime has the greatest impact on variations in serum TSH concentrations. Another source of within-person variation in TSH levels is seasonality, with generally higher levels during the cold winter months. Since TSH is secreted in a pulsatile manner, TSH levels also fluctuate over minutes. Furthermore, elevated TSH levels have been observed with ageing. Other factors that affect TSH levels include thyroid peroxidase (TPO)-antibody positivity, BMI, obesity, smoking, critical illness, and many xenobiotics, including environmental pollutants and drugs. Potential underlying biological mechanisms of within-person variation in TSH levels can be safely concluded from the ability of TSH to respond quickly to changes in cues from the internal or external environment in order to maintain homeostasis. Such cues include the biological clock, environmental temperature, and length of day. The observed increase in TSH level with ageing can be explained at a population level and at an organism level. In clinical practice, the season for thyroid testing can influence a patient’s test result and it occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention.ConclusionsSerum TSH concentrations vary over time within an individual, which is caused by multiple different internal and external factors. It is important to take the within-person variations in serum TSH concentrations into account when testing a patient in clinical practice, but also in performing clinical research.

Establishment of Reference Intervals for Thyroid-Associated Hormones Using refineR Algorithm in Chinese Population at High-Altitude Areas

“…The present study found little effects of altitude on serum TSH among Tibetans, which is consistent with the results of an observation study (11). Relatively short half-life of TSH (17 to 93 min) (15), pulsatile secretion manners (15,22) and feedback regulation of the HPT axis may roughly explain the phenomenon, although the exact mechanism is unclear. In euthyroid people, synthetic TSH is released in a manner combining a basal (non-pulsatile) and a pulsatile form and can be promptly cleared after action on the thyroid gland.…”

“…This long-term adaptation may lead to thyroid-related hormone levels in Tibetans different from those in the plain (9)(10)(11). Even if the effects of sex, age (12)(13)(14), region, sampling time (15), and pregnancy status (16) on thyroid-related hormones are well discussed, however, only few articles (10,11,17) have assessed the influence of altitude on thyroid-associated hormones, let alone establishing altitudespecific RIs.…”

Physiological linkage of thyroid and pituitary sensitivities

“…2) [1]. Though there are many potential sources of intraindividual variation in thyroid function [14], FT4 and TSH levels tend to be relatively stable for each healthy individual in the population such that inter-individual variation, as manifest as the population range, is greater than intra-individual variation [15]. This stability in turns implies intra-individual stability of thyroid and pituitary sensitivity.…”

An exploratory study of short-term camping in Antarctica: Hormonal and mood states changes

“…Cortisol is a catabolic (Brillon et al 1995, Simmons et al 1984 and stress-related hormone (Russell and Lightman 2019) that inhibits testosterone secretion (Cumming et al 1983); thus, changes in cortisol concentration alter the body anabolic-catabolic balance. Also, cortisol presents an inhibitory effect on TSH secretion (Van der Spoel et al 2021, Re et al 1976). The stress of moderate and intense physical exertion is an additional stimulus for cortisol secretion (Hill et al 2008).…”