Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects

Abstract

This review was aimed at collecting the knowledge on the pathophysiological and clinical aspects of endocrine rhythms and their implications in clinical practice, derived from the published literature and from some personal experiences on this topic. We chose to review, according to the PRISMA guidelines, the results of original and observational studies, reviews, meta-analyses and case reports published up to March 2024. Thus, after summarizing the general aspects of biological rhythms, we will describe the characteristics of several endocrine rhythms and the consequences of their disruption, paying particular attention to the implications in clinical practice. Rhythmic endocrine secretions, like other physiological rhythms, are genetically determined and regulated by a central hypothalamic CLOCK located in the suprachiasmatic nucleus, which links the timing of the rhythms to independent clocks, in a hierarchical organization for the regulation of physiology and behavior. However, some environmental factors, such as daily cycles of light/darkness, sleep/wake, and timing of food intake, may influence the rhythm characteristics. Endocrine rhythms are involved in important physiological processes and their disruption may cause several disorders and also cancer. Thus, it is very important to prevent disruptions of endocrine rhythms and to restore a previously altered rhythm by an early corrective chronotherapy.

Keywords: chronotherapy; circadian clocks; endocrine rhythms; rhythm disruption.

Figure 1

Circadian and ultradian variations in ACTH and cortisol concentrations obtained by subsequent samples in a young man. The black band indicates the sleep period, the arrows the mealtimes (personal observation).

Figure 2

Daily variations in plasma GH levels obtained by samples taken at defined intervals in a young man. The black band indicates the sleep period, the arrows the mealtime (personal observation).

Figure 3

Daily variations in prolactin secretion in a young healthy woman: secretory peaks during nocturnal sleep and an afternoon nap indicated by the empty bands. The arrows indicate the time of meals (personal observation).

Figure 4

Infradian circatrigintan rhythms of plasma LH and FSH concentrations in healthy women (A) and in five women with hypogonadotropic amenorrhea (B,C): occurrence of the ovulatory gonadotropin peak in women with normal menstrual cycle (A) and its absence from patients with amenorrhea (B,C) (personal observation).