A Comprehensive Long-Term Retrospective Analysis of Silent Corticotrophic Adenomas versus Non-Horomone Expressing Adenomas





Keywords: pituitary adenoma, outcome, Cushing's disease, cortisol, hormone dysfunction

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Abstract

      
     Silent corticotrophic adenomas (SCAs) which stain for ACTH but do not cause Cushing’s disease are reported to be more aggressive and sometimes recur with Cushing’s disease but these reports are based on small series.
     We identified 88 SCAs and 97 NHAs. SCA patients were younger (mean age 48 versus 56; P<0.001) and more female (52% versus 36%; P<0.001).
     SCAs diagnosed at our institution 1990-2011 were retrospectively reviewed, with Non-Horomone Expressing Adenomas (NHAs) resected and followed during the same intervalas controls.
     NHAs were larger(2.7 vs. 1.9 cm; P<0.001), and more frequently experienced visual abnormalities (96% versus 42%; P<0.001) or apoplexy (10% versus 6%; P<0.01). NHAs and SCAs had similar (P<0.05) rates of hypopituitarism (59%/60%) and headache (32%/24%). Mean preoperative serum cortisol was higher in SCAs than NHAs (18 versus 10 ug/dL; P<0.05). Gross total resection rates were 53% (SCAs) and 66% (NHAs) (P<0.05). Both groups had comparable MIB-1 labeling (2%; P=0.8). Kaplan-Meier analysis revealed 3-year recurrence rates of 3% (NHA), 15% (Type-II SCA=strongly ACTH+, n=43), and 46% (Type-I SCA=weakly ACTH+, n=45) (P<0.001). Three Type-I SCA patients developed Cushing’s disease an average of 7 years (range 4-9) after SCA diagnosis.
     This is a retrospective study.
     In the largest series to date, we found SCAs to exhibit smaller size, but increased recurrence compared to NHAs, particularly in Type-I SCAs. SCA patients exhibited elevated (but still normal) cortisol compared to NHA patients, and some Type-II SCAs eventually developed Cushing’s disease.
     These findings suggest aggressive surgery and radiosurgery for residual SCAs is warranted, along with close postoperative follow-up.


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