Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

Bellastella G, Maiorino M, Scappaticcio L, et al. Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases Life (Basel, Switzerland). 2021 May;11(5).


Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.



From ancient hourglasses to sophisticated modern clocks, the measurement of time has been considered indispensable by man for the verification of the flow of natural and human phenomena. The earliest recorded recognition of the importance of biological rhythms in plants and animal dates back to at least 5000 BC. Light/darkness-correlated variations in leaf movements in some plants had been already observed by Androstene during the Empire of Alexander the Great, and the importance of temporal factors was even recognized in biblical times as stated in Ecclesiastes: “To everything there is a season and a time to every purpose under Heaven: a time to be born and a time to die; a time to plant and a time to harvest”. Moreover, as reported in Genesis, the light was created by God first of all, and this is of particular significance, since, as we will see later on, the alternation of light/darkness is the main synchronizing factor in the circadian rhythm [1]

Bellastella G, Maiorino M, Scappaticcio L, et al. Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases Life (Basel, Switzerland). 2021 May; 11(5). Figure 2: Synchronization by light input of the rhythmic variations in hypothalamic–pituitary–thyroid secretions: It acts directly, through the retino-hypothalmic tract (RHT), by exciting the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which then outputs the circadian signal via neural projection, exciting the rhythmic secretion of thyrotropin-releasing hormone (TRH) and consequently of thyrotropin (TSH) and thyroid hormones(T4:thyroxine; T3:triiodotyronine). Light acts also indirectly, by modulating with an inhibiting effect the variations in melatonin secretion at retina and pineal gland levels, thus further stimulating the secretions of the hypothalamic–pituitary–thyroid axis.

5. Conclusions

Knowledge and respect of biological rhythms and of their endogenous and environmental synchronizing factors is mandatory not only for physicians but also for patients, to ensure the best conditions for the lives of human beings. This is particularly important for the HPT axis, as the knowledge and respect of the reciprocal relationship between the secretions of this axis and the circadian machinery may avoid, on the one hand, the disruption of the circadian rhythmic organization of the subjects and, on the other hand, the consequences of this disruption, which can cause not only thyroid dysfunction but also thyroid cancer. Further studies have to be encouraged to better clarify physiological and pathophysiological aspects of this issue and to search for more appropriate preventive choices to avoid circadian but also ultradian and infradian rhythm disruption of the HPT axis and to search for more effective therapeutic options to promptly correct these alterations, when they have already occurred.

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