Endocrine Abstracts

Background

Agouti related peptide (AgRP) is a neuropeptide, produced by the hypothalamus and by the adrenal glands. AgRP is an antagonist of proopiomelanocortin (POMC) and its principal role is to stimulate appetite. Although current evidences suggest that AgRP levels are influenced by glucocorticoids, it is still not clear, whether they depend on adrenocorticotropic hormone (ACTH) or cortisol. One of the aims of this study was to address this issue. Furthermore an analysis of AgRP in the differentiation of Cushing´s disease (CD), ectopic Cushing syndrome (ECS), adrenocortical adenoma (ACA), and adrenocortical carcinoma (ACC) was performed.

Methods

We performed a retrospective analysis of AgRP levels in blood samples of 103 patients with proven Cushing syndrome (CS), including 44 with ACTH-dependent CS (n = 33 CD, n = 11 ECS) and 59 ACTH-independent CS (n = 21 ACA, n = 38 ACC). Levels of AgRP were measured with ELISA. Considering the AgRP fluctuating levels throughout the day, the analysis was performed on midnight serum samples for all patients. Correlation with midnight cortisol levels, basal ACTH, and in ACC with tumor burden and overall survival (OS) were investigated.

Results

Considering the entire cohort, a negative AgRP-ACTH correlation (rs = –0.60, P < 0.001) and a moderate positive AgRP-cortisol correlation (rs = 0.25, P = 0.02) was identified. Levels of AgRP did not differ between CD and ECS [median 0.39 (0.23–0.57). ng/ml vs 0.43 (0.34–0.65) ng/ml, respectively, P = 0.99]. Concerning the ACTH-independent CS, ACC were characterized by significant higher levels of AgRP compared to ACA [median 1.38 (0.22–8.71) ng/ml vs 0.45 (0.25–0.79) ng/ml, respectively, P = 0.035] with a mean ACC/ACA fold change of 4.7. Furthermore, AgRP levels were significantly higher in ACC in comparison to both CD (P < 0.0001) and ECS (P = 0.014). Among ACC, AgRP levels were higher in patients with a higher tumor burden (considered as two or more site of metastasis) compared to those with a lower tumor burden (P = 0.025). No difference in terms of OS was observed between patients with low AgRP levels (considered as <1.38 ng/ml) in comparison to those with high AgRP levels (≥1.38 ng/ml) (median survival 14 vs 15 months, respectively, P = 0.47).

Conclusions

AgRP seems to play an intriguing role in the pathophysiology of cortisol-secreting ACC and could be an interesting marker in the differentiation of the ACTH-independent CS. On the other hand, the analysis of AgRP seems not to be beneficial in the differentiation of ACTH-independent CS. Further analyses on a larger population are necessary to confirm our results.