Endocrine Abstracts

Background: Immune function and responses are tightly regulated by the circadian clock system and hypothalamic-pituitary-adrenal (HPA) axis. Accumulating evidence supports that there is a strong mutual relationship between these two regulatory systems at multiple levels. Recent publications suggest that the clock system may also regulate glucocorticoid release from adrenal glands by altering the sensitivity of the adrenal cortex to adrenocorticotropic hormone (ACTH).

Aim: To investigate the influence of a polymorphism in clock gene Period3 on adrenal cortisol response to ACTH in patients with autoimmune thyroid disease (AITD).

Methods: A total of 72 unrelated patients with AITD [Graves’ disease (GD), 37; Hashimoto’s thyroiditis (HT), 35] who were genotyped for Period3 rs2797685 (G/A) polymorphism in a previous study were included. A standard dose (250 μg) ACTH (1-24) stimulation test was performed. Basal serum ACTH levels and serum cortisol concentrations before and 30 and 60 minutes after intravenous injection of ACTH (1-24) were measured by ELISA.

Results: Free thyroid hormone levels were normal in all participants at the time of the ACTH (1-24) stimulation test. The mean basal serum ACTH levels and serum cortisol measurements before and after ACTH (1-24) stimulation test were not significantly different between GD and HT groups. No association was observed between genotypes of the studied polymorphism and serum levels of these parameters in GD, HT and overall AITD groups.

Conclusion: Period3 rs2797685 (G/A) polymorphism was not determinative for ACTH-stimulated cortisol release in patients with AITD. Although linkages between circadian clock system and the HPA axis has been identified, further studies with different clock genes are needed to elucidate the physiologic as well as pathologic inter-communications between these two systems.