Independent of time, within-person variation in TSH is also caused by effects of among others medication, illness, TPO antibody positivity, and iodine intake. Furthermore, TSH levels change with age, with in general higher levels with increasing age ( 5). Within-person variation in TSH levels is caused by rhythms ranging from minutes to years, including pulsatile secretion, circadian rhythm, monthly changes, and seasonality ( 3, 4).

In the current review we focus on biological variation, in particular on within-person biological variation. Variation in TSH levels can be caused by biological and non-biological variation, the latter includes pre-analytical and analytical variations, and has been reviewed by others ( 3). In this review, we discuss the magnitude of the variation in TSH levels and the potential sources (internal and external) that may contribute. Consequently, the influence of variation in TSH levels on diagnosis and study outcomes might be underestimated. However, the magnitude and the importance of variation in TSH levels within a person over time are not completely clear yet. Indeed, it is known that TSH levels can vary over time within a person.Īmong other, TSH levels are influenced by drugs, acute and chronic illness, undernutrition, the biological clock, seasonality, pregnancy, and by other hormones, e.g., cortisol. By adapting the level of TSH, circulating levels of thyroxine (T4) and partly triiodothyronine (T3) are controlled and kept within a normal range ( 1, 2). Thyroid stimulating hormone (TSH) is a key player in this system, which is designed to respond quickly to changes in the environment aiming to maintain homeostasis in the human body. Hormones of the hypothalamus-pituitary-thyroid (HPT) axis are part of a feedforward and feedback system. 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. 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.Ĭonclusions: Serum TSH concentrations vary over time within an individual, which is caused by multiple different internal and external factors. The observed increase in TSH level with ageing can be explained at a population level and at an organism level.

Such cues include the biological clock, environmental temperature, and length of day. 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. 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. Furthermore, elevated TSH levels have been observed with ageing. Since TSH is secreted in a pulsatile manner, TSH levels also fluctuate over minutes. Another source of within-person variation in TSH levels is seasonality, with generally higher levels during the cold winter months. Summary: In 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.

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. In clinical practice and clinical research however, such within-person biological variation in serum TSH concentrations is often not considered. The main factors contributing to the observed within-person fluctuations in serum TSH comprise pulsatile secretion, circadian rhythm, seasonality, and ageing. The scale of these variations ranges from minutes to hours, and from months to years. 2Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlandsīackground: Individuals exhibit fluctuations in the concentration of serum thyroid-stimulating hormone (TSH) over time.1Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.Evie van der Spoel 1* Ferdinand Roelfsema 2 Diana van Heemst 1

Diurnal vs nocturnal concentration tsh