Silent Corticotroph Adenomas: An Aggressive Tumor Type That Merits Appropriate Pre-operative Characterization

Introduction: Silent corticotroph adenomas (SCAs) are a non-functional type of pituitary adenomas that stain positive for ACTH but do not cause hypercortisolemia or Cushing’s Disease (CD). It is estimated that SCAs represent 6% of all non-functioning adenomas (NFA) and the WHO has classified them as a high-risk type of adenoma due to their aggressive characteristics. The objective of this study is to analyze a pituitary center experience on the surgical treatment of SCAs and how it compares to other corticotroph adenomas causing CD and other NFA.

Methods: Data from a pituitary center was searched for patients with SCAs, CD, and NFA who underwent resection by three neurosurgeons in 2017-2022. SCA was defined as histopathologic confirmation of corticotroph adenoma in the absence of hypercortisolemia. All samples were reviewed by a neuro-pathologist. Demographic, clinical, laboratorial, radiographic, surgical, and post-operative variables were collected.

Results: One-hundred-and-eighty-eight patients were identified for analysis: 144 NFAs, 28 CD, and 16 SCAs. All patients underwent endoscopic endonasal transsphenoidal resection. Preoperatively, SCAs had comparable age at presentation (p=0.29), BMI (p=0.36), female proportion (p=0.11), and tumor diameter (p=0.68) with NFA; while age at presentation (p=0.051) and BMI (p=0.08) were trending towards significance when compared to CD, and a lower female proportion (SCA:68.75% vs CD:96.43%,p=0.01) and larger tumor size (SCA:23.25 vs CD:10.79,p=0.0002) were found. SCAs had comparable CSF leak rates, length of stay, and readmission events among cohorts (p>0.05). A higher rate of diabetes insipidus was found in SCA cases (SCA:25% vs NFA:6.25%,p=0.02). Notably, pre-operative ACTH levels were significantly higher in SCA (p < 0.0001) but not significantly different than CD (p=0.86).

Conclusion : SCAs represent a unique tumor subtype that impose a treatment challenge on neurosurgeons and endocrinologists. Surgical outcomes were equivalent between tumor subtypes, except for a higher risk of diabetes insipidus in SCAs. Even though SCAs are considered non-functional tumors, pre-operative ACTH levels were significantly higher than NFA, and comparable to CD’s in the absence of hypercortisolemia. Careful consideration of these findings would aid at better pre-operative characterization of this patient population.