Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

Abstract

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.

The Relationship and Gender Disparity Between Thyroid Nodules and Metabolic Syndrome Components Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis

“…Therefore, metabolic diseases may occur through circadian machinery, causing thyroid diseases. Thyroid dysfunction may alter, in a mirror-like manner, circadian clocks, causing metabolic disorders ( 49 ). This may provide a new research direction for studying the relationship between TNs and MetS and its components.…”

A Review of Evidence for the Involvement of the Circadian Clock Genes into Malignant Transformation of Thyroid Tissue

“…In oncological diseases, patient prognosis might be potentially improved by normalization of circadian rhythms [ 18 ]. Therefore, chronobiotic therapeutic factors were recommended to be used for prevention and/or treatment of these diseases (e.g., [ 17 ]). Two major treatment approaches were suggested for avoiding the pathological consequences of circadian clock dysfunction.…”

“…As stressed in several (nonsystematic) reviews of such findings [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], the examination of the pattern of expression of circadian clock genes might be of practical importance for the establishment of an adequate presurgical diagnosis of thyroid tumors [ 19 ]. Although the frequency of thyroid nodules (i.e., discrete masses in the gland) is very high (they are detected in up to 65% of general populations), most of them are benign.…”

“…[ 50 ] gave rise to hypotheses that the abnormal functioning of circadian clock genes may have various pathological consequences, including tumorigenesis [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. In particular, it was assumed that the characteristics of clock genes signaling their abnormal functioning can serve as specific molecular markers of malignant transformation of thyroid tissue [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Physiological Rhythms and Biological Variation of Biomolecules: The Road to Personalized Laboratory Medicine

“…Moreover, infradian variations have been observed in various measurands including TSH and thyroid hormones [ 85 , 112 ], sperm physiology [ 113 ], urinary excretion of growth hormone [ 114 ], enzymes [ 115 , 116 ], etc.…”