Interconnection between circadian clocks and thyroid function

Ikegami, K., Refetoff, S., Van Cauter, E. et al. Interconnection between circadian clocks and thyroid function. Nat Rev Endocrinol 15, 590–600 (2019).


Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription–translation feedback loops of specific genes, which are referred to as ‘circadian clock genes’. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep–wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic–pituitary–thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer.

Key points

  • The hypothalamic–pituitary–thyroid axis is controlled by the central circadian pacemaker located in the suprachiasmatic nucleus.
  • Daily TSH secretion profiles are often disrupted in patients with hypothyroidism or hyperthyroidism.
  • Circadian dysfunction caused by shift work, travel across time zones or irregular sleep–wake cycles might be a novel lifestyle risk factor for disturbances in thyroid homeostasis in modern societies.
  • Disruption of circadian clock genes in vivo and in vitro disturbs cell cycle progression.
  • The circadian clock is thought to be disrupted in well-differentiated thyroid cancer.

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