• Arman Jahangiri, Jeffrey R Wagner, Melike Pekmezci, Anne Hiniker, Edward F Chang, Sandeep Kunwar, Lewis Blevins, and Manish K Aghi.
• 1University of California at San Francisco (UCSF) Department of Neurosurgery and The California Center for Pituitary Disorders (CCPD); 2Department of Neuropathology; and 3Division of Endocrinology and Metabolism.
• Neurosurgery. 2013 Mar 5.

BackgroundSilent corticotrophic adenomas (SCAs) stain adrenocorticotropic hormone (ACTH)+ without causing Cushing's disease. SCAs are reportedly more aggressive, but information comes from small series. ObjectiveTo determine whether SCAs behave more aggressively than Hormone-Negative Adenomas (HNAs), and characterize SCA ACTH production alterations. MethodsSCAs (n=75) and HNAs (n=1726) diagnosed at our institution from 1990-2011 were retrospectively reviewed. RT-PCR was used to compare expression of ACTH-producing factors. ResultsSCA patients exhibited comparable gender and age as HNA patients (P=0.7-0.9). SCAs exhibited comparable size as HNAs (2.2 vs. 2.0 cm, P=0.2), with cavernous sinus invasion in 30% of SCAs versus 18% of HNAs (P=0.03). SCA patients had higher mean preoperative serum ACTH (46 versus 19 ng/L; P=0.005; normal=5-27 ng/L), but comparable serum cortisol (13 versus 12 ≥g/dL; normal=4-22 ≥g/dL; P<0.05) as HNA patients. SCAs were gross totally resected 59% of the time, versus 53% for HNAs (P=0.8). Kaplan-Meier 3-year progression/recurrence rates were 34% for strongly ACTH-positive Type I SCAs, 10% for weakly ACTH-positive Type II SCAs, and 6% for HNAs (P<0.0001 SCA vs. HNA; P<0.0001 Type I vs HNA; and P=0.08 Type II vs HNA). Expression of ACTH precursor pro-opiomelanocortin was 900-fold elevated in SCAs and 1300-fold elevated in Cushing's disease-causing adenomas (CDCAs) versus HNAs (P<0.001). Transcription of PC1/3, which cleaves pro-opiomelanocortin into ACTH, was 30-fold higher in CDCAs than SCAs (P=0.02). ConclusionIn the largest series to date, SCAs exhibited comparable size, but increased cavernous sinus invasion and progression/recurrence versus HNAs. SCAs exhibit deficient pro-opiomelanocortin to ACTH conversion. Close follow-up is warranted for SCAs.

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