ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Endocrinol. 2020:JOE-20-0066.R2. PMID: 32380472.

Human physiology and behavior are adapted to daily environmental cycles by means of endogenous circadian clocks. Biological tasks, including cell proliferation, differentiation, energy storage and immune regulation, are preferentially confined to specific periods of the 24-h cycle. This circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle (1). Of interest, the fluctuations of cortisol and the expression of its receptor are crucial in modulating endogenous and exogenous signals and preparing the transition to activities confined to periods of light or darkness, acting (along with the autonomous nervous system) as a bridge between the suprachiasmatic master clock and almost all peripheral clocks (2).

In this narrative review, the authors describe and summarize the hierarchical control of the hypothalamic–pituitary–adrenal (HPA) axis circadian rhythm, the importance of peripheral mediators (nutrient intake, metabolism, inflammation and the autonomous nervous system) and discuss if the glucocorticoid effector system is the key component of this system as well as the interplay with other circadian systems (3). Relevant paradigms are taken from adrenal disorders that are considered models of HPA circadian rhythm disruption, particularly conditions of corticosteroid excess (hypercortisolism and adrenocortical tumors) and of corticosteroid insufficiency. These conditions, while seemingly opposite in their clinical presentation, share two common pathophysiological pathways that are described as sensitive to clock regulation: impaired immune function and increased atherosclerotic risk (4, 5, 6, 7). Of interest to Pediatric Endocrinology is the discussion on glucocorticoid-correcting medications, both replacement and reduction therapies, and the benefits of mimicking the normal daily peaks and troughs of cortisol in order to avoid exposure to glucocorticoids late in the evening and at night and to act in phase with the endogenous clock (8, 9).

References:

1. Asher G, Sassone-Corsi P. Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock. Cell, 2015: 161, 84-92.

2. Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schutz, G. & Schibler, U. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science, 2000; 289, 2344-7.

3. Nader, N., Chrousos, G. P. & Kino, T. Interactions of the circadian CLOCK system and the HPA axis. Trends Endocrinol Metab, 2010; 21, 277-86.

4. Alexandraki, K. I. & Grossman, A. B. Novel insights in the diagnosis of Cushing’s syndrome. Neuroendocrinology, 2010; 92 Suppl 1, 35-43.

5. Moreira, A. C., Antonini, S. R. & De Castro, M. MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing’s syndrome. Eur J Endocrinol, 2018; 179, R1-r18.

6. Graziadio, C., Hasenmajer, V., Venneri, M. A., Gianfrilli, D., Isidori, A. M. & Sbardella, E. Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role? Front Endocrinol (Lausanne), 2018; 9, 434.

7. Bancos, I., Hazeldine, J., Chortis, V., Hampson, P., Taylor, A. E., Lord, J. M. & Arlt, W. Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality. Eur J Endocrinol, 2017; 176, 471-480.

8. Venneri, M. A., Hasenmajer, V., Fiore, D., Sbardella, E., Pofi, R., Graziadio, C., Gianfrilli, D., Pivonello, C., Negri, M., Naro, F., et al. Circadian Rhythm of Glucocorticoid Administration Entrains Clock Genes in Immune Cells: A DREAM Trial Ancillary Study. J Clin Endocrinol Metab, 2018; 103, 2998-3009.

9. Debono, M., Harrison, R. F., Chadarevian, R., Gueroult, C., Abitbol, J. L. & Newell-Price, J. Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion. J Clin Endocrinol Metab, 2017; 102, 3461-3469.