Elevated Plasma Agouti-Related Protein May Be a Marker for Cushing Disease

Plasma levels of the orexigenic neuropeptide agouti-related protein (AgRP) are elevated in Cushing disease, and it may be a marker of hypothalamic AgRP.

Plasma levels of the orexigenic neuropeptide agouti-related proftein (AgRP) are elevated in Cushing disease (CD) and are a marker of hypothalamic AgRP, according to study findings published in the Journal of Clinical Endocrinology & Metabolism.

Previous research has shown a correlation between plasma AgRP and adiposity in individuals who are weight stable, and that plasma AgRP levels increase with fasting and then decline with eating. In this study, the relationship between plasma AgRP and hypothalamic AgRP was examined in rats, and then the relationship between cortisol and plasma AgRP was also evaluated in humans with CD.

Researchers conducted a retrospective analysis that evaluated plasma AgRP levels in 31 patients with CD before undergoing transsphenoidal surgery, as well as in matched control patients who had participated in a separate study. In addition, plasma AgRP was prospectively measured in a subgroup of 13 patients with CD before surgery and then 6 to 12 months postoperatively. Plasma and hypothalamic AgRP were also measured in rodents that had been adrenalectomized, with and without corticosterone replacement.

Plasma AgRP levels were higher in patients with CD compared with control patients (139±12.3 vs 54.2±3.1 pg/mL; P <.0001), and in the CD cohort, mean 24-hour urine free cortisol levels were 257±39 μg/24 hours. Strong positive correlations were also observed between plasma AgRP and urine free cortisol (r=0.76; P <.0001), and in 11 of 13 patients who achieved a surgical cure, AgRP levels declined from 126±20.6 to 62.5±8.0 pg/mL (P <.05) postoperatively. This decrease paralleled a similar decline in urine free cortisol. In the rat study, plasma AgRP was stimulated by corticosterone and correlated with the expression of hypothalamic AgRP.

“While further study is needed, these data establish plasma AgRP as a potential biomarker in Cushing’s disease that could prove clinically useful both diagnostically and in long-term monitoring for tumor recurrence,” wrote the researchers.

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Page-Wilson G, Peters JB, Panigrahi SK, et al. Plasma AgRP and cortisol levels in cushing’s disease: evidence for the regulation of AgRP by glucocorticoids in humans [published online December 28, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01909