Endocrine Abstracts

Introduction: Alteration in the expression of clock-related genes has been observed in various diseases. Adrenal sensitivity to adrenocorticotropic hormone (ACTH) apart from the hypothalamo-pituitary-adrenal axis is also regulated by the intrinsic adrenal clock. A link between clock genes and glucocorticoid adrenal production has been suggested by in vitro and animal studies. In the present study we investigated clock genes expression in human benign tumors of the adrenal cortex. Methods: Sixteen fresh frozen adrenal tissues were collected from November 2016 to December 2017. All patients (13 females/3 males) had adrenalectomy either because of tumor size (n=7) or secretory syndrome (n=9). CLOCK, BMAL1, CRY1 and PER1 genes expression were analysed with qRT-PCR in benign adrenal tissues (13 adenomas and 3 hyperplasias) and in the peritumoral normal tissue. Protein expression of the aforementioned genes was evaluated by Western Blot analysis. Clinical, biochemical and histological data of the operated patients were also collected retrospectively.

Results: Patients’ mean age was 50±13 years old. Four out of 16 patients had overt Cushing syndrome, 2 had subclinical Cushing, 3 had Conn adenomas, and the remaining 7 patients had non functional adenomas (NF). Mean tumor size was 3.7±1.2 cm, Ki-67 was 1–2% and Weiss score 0-1. All clock-related genes exhibited lower expression in adrenal tumors compared to the peritumoral tissue, in the t test paired analysis. However only CLOCK and BMAL1 were significantly down-regulated (P<0.05). Moreover, PER1 showed significant lower expression in NF adenomas compared to cortisol-secreting adenomas, in the Mann-Whitney test (non-parametric analysis).

Conclusion: Our in vivo preliminary data demonstrated for the first time that the core clock genes CLOCK, BMAL1, CRY1 and PER1 are differently expressed in adrenal adenomas compared to peritumoral normal tissues, suggesting that dysregulation of the local circadian clock system may play a role in either the development or evolution of adrenal adenomas.