Objective: The insufficient diagnostic accuracy for differentiation between benign and malignant adrenocortical disease and lack of sensitive markers reflecting tumor load emphasize the need for novel biomarkers for diagnosis and follow-up of adrenocortical carcinoma (ACC). Design: Since the inhibin α-subunit is expressed within the adrenal cortex, the role of serum inhibin pro-αC as a tumor marker for ACC was studied in patients. Methods: Regulation of adrenal pro-αC secretion was investigated by adrenocortical function tests. Serum inhibin pro-αC levels were measured in controls (n=181) and patients with adrenocortical hyperplasia (n=45), adrenocortical adenoma (ADA, n=32), ACC (n=32), or non-cortical tumors (n=12). Steroid hormone, ACTH, and inhibin A and B levels were also estimated in patient subsets. Results: Serum inhibin pro-αC levels increased by 16% after stimulation with ACTH (P=0.043). ACC patients had higher serum inhibin pro-αC levels than controls (medians 733 vs 307 ng/l, P<0.0001) and patients with adrenocortical hyperplasia, ADA, or non-adrenocortical adrenal tumors (148, 208, and 131 ng/l, respectively, P=0.0003). Inhibin pro-αC measurement in ACC patients had a sensitivity of 59% and specificity of 84% for differentiation from ADA patients. Receiver operating characteristic analysis displayed areas under the curve of 0.87 for ACC vs controls and 0.81 for ACC vs ADA (P<0.0001). Surgery or mitotane therapy was followed by a decrease of inhibin pro-αC levels in 10/10 ACC patients tested during follow-up (P=0.0065). Conclusions: Inhibin pro-αC is produced by the adrenal gland. Differentiation between ADA and ACC by serum inhibin pro-αC is limited, but its levels may constitute a novel tumor marker for ACC.

dx.doi.org/10.1530/EJE-11-0693, hdl.handle.net/1765/65617
European Journal of Endocrinology
Department of Internal Medicine

Hofland, J, Feelders, R.A, van der Wal, R, Kerstens, M.N, Haak, H.R, de Herder, W.W, & de Jong, F.H. (2012). Serum inhibin pro-αC is a tumor marker for adrenocortical carcinomas. European Journal of Endocrinology, 166(2), 281–289. doi:10.1530/EJE-11-0693