title: Serum inhibin pro-αC is a tumor marker for adrenocortical carcinomas.
abstract: 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).
  
  
  METHODS
  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.
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Room Ee 532, PO Box 1738, 3000 DR Rotterdam, The Netherlands. j.hofland@erasmusmc.nl
authors: Johannes
authors: J
authors: Hofland
authors: Richard A
authors: RA
authors: Feelders
authors: Ronald
authors: R
authors: van der Wal
authors: Michiel N
authors: MN
authors: Kerstens
authors: Harm R
authors: HR
authors: Haak
authors: Wouter W
authors: WW
authors: de Herder
authors: Frank H
authors: FH
authors: de Jong
mesh_terms: D000304:Adrenal Cortex Function Tests / Q000592:standards; D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000097:blood / Q000175:diagnosis; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D003937:Diagnosis, Differential; D003940:Diagnostic Techniques, Endocrine / Q000592:standards; D018450:Disease Progression; D005260:Female; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011498:Protein Precursors / Q000097:blood / Q000502:physiology*; D012016:Reference Values; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011498:Protein Precursors; C095971:inhibin-alpha subunit precursor; D007265:Inhibins