Fibroblast growth factor 21 in patients with mild autonomic cortisol secretion and non-functioning adrenal...

Epidemiological studies have reported a link between adrenocortical adenomas (ACA), obesity, and cardiometabolic risk. Fibroblast growth factor 21 (FGF21) is a stress-induced protein synthesised predominantly in the liver, which regulates metabolism. The aim of the current study was to evaluate the concentration of FGF21 in patients with ACA and its relationship with hypothalamic-pituitary- adrenal function, obesity, markers of cardiometabolic health, and adenoma size.

A total of 197 patients with ACA were included in the analysis, 82 diagnosed with mild autonomous cortisol secretion (MACS) and 115 with non-functioning adrenal adenoma incidentaloma (NFAI). MACS was defined as serum cortisol concentration post 1 mg dexamethasone test (DST) ≥ 1.8 μg/dL. In each patient weight, height, and waist circumference were measured, and body mass index (BMI) was calculated. Serum concentrations of FGF21, cortisol, dehydroepiandrosterone sulphate, adrenocorticotropic hormone (ACTH), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, glucose, and insulin were measured. The cortisol-to ACTH ratio, homeostatic model assessment for insulin resistance index (HOMA-IR), lipid accumulation product (LAP), and cardiometabolic index (CMI) were calculated. Adrenal tumour size was evaluated from imaging procedures.

Serum FGF21 concentrations were significantly higher in patients with MACS than in NFAI, which was independent of BMI. There were no differences between MACS and NFAI groups regarding HOMA-IR, LAP, and CMI. We observed a positive correlation between serum FGF21 concentration and cortisol level after DST, as well as the cortisol-to-ACTH ratio. FGF21 was negatively correlated with dehydroepiandrosterone sulphate (DHEAS). There were no significant correlations between serum FGF21 concentration and BMI, waist circumference, and HOMA-IR, but serum FGF21 levels were positively correlated with TG, LAP, and CMI. Positive relationships between adenoma size and serum FGF21 concentration were found.

Higher levels of FGF21 in adrenal tumours with MACS when compared with NFAI represent another pathophysiological link related to chronic glucocorticoid excess.