Silent Corticotroph Adenomas: An Aggressive Tumor Type That Merits Appropriate Preoperative Characterization

Introduction: Silent corticotroph adenomas (SCAs) are a nonfunctional type of pituitary adenomas that stain positive for ACTH but do not directly cause hypercortisolemia or Cushing’s disease (CD). It is estimated that SCAs represent 6% of all nonfunctioning adenomas and the WHO has recently classified them as a high-risk type of adenoma due to their aggressive characteristics. Recent studies have shown lower progression-free survival in patients with SCAs but have lacked objective clinical, chemical, and demographic characterization of these tumors when compared to other subtypes of adenomas. 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 nonfunctioning adenomas (NFA).

Methods: Data from a pituitary center was searched for patients with SCAs, CD, and NFA who underwent resection by three neurosurgeons in 2017 to 2022. SCA was defined as histopathologic confirmation of corticotroph adenoma in the absence of hypercortisolemia; CD was diagnosed based on clinical-laboratory criteria in the presence of a corticotroph adenoma; NFA was diagnosed based on negative immunoreactivity to ACTH, GH, and prolactin without evidence of hormone hypersecretion. All samples were reviewed by a neuro-pathologist. Patient demographic, clinical, laboratorial, radiographic, surgical, and postoperative variables were collected for each of the subjects. The three group cohorts were compared in regard to the previously mentioned variables.

Results: A total of 188 patients were identified for analysis: 144 NFAS, 28 CD cases, and 16 SCAs. All patients underwent endoscopic endonasal resection of the adenoma. Preoperatively, SCAs had comparable age at presentation (SCA 55.81 vs. NFA 59.91, p = 0.29), BMI (SCA 33.38 vs. NFA 31.37, p = 0.36), female proportion (SCA 68.75% vs. NFA 44.78%, p = 0.11), and tumor diameter (SCA 23.25 vs. NFA 24.25, p = 0.68) with NFA tumors; while age at presentation (SCA 55.81 vs. CD 46.43, p = 0.051) and BMI (SCA 33.38 vs. CD 39.80, 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, preoperative ACTH levels were statistically significant higher in SCA when compared to NFA (SCA 94.71 vs. NFA 27.45, p < 0.0001) but not significantly different than CD (SCA 94.71 vs. CD 88.67, p = 0.86).

Conclusion: SCAs represent a unique tumor subtype that imposes a challenge on neurosurgeons and endocrinologists. They appear to draw characteristics from both CD and NFA; in this study, patients with SCAs were more commonly older compared to CD onset, with a remarkably larger adenoma size at presentation. Surgical outcomes were equivalent between tumor subtypes, except for a higher risk of diabetes insipidus in SCAs. Even though SCAs are considered nonfunctional, preoperative ACTH levels were significantly higher than NFA’s serum levels, and comparable to CDs in the absence of hypercortisolemia. Careful consideration of these findings would aid at better preoperative characterization of this patient population ([Fig. 1]).

Fig. 1

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
05 February 2024