Silent Corticotroph Pituitary Adenomas: Clinical Characteristics, Long-Term Outcomes, and Management of Disease Recurrence

Objective: Silent corticotroph adenomas (SCA) are a distinct subtype of nonfunctioning pituitary adenomas (NFA) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing's disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. We aim to analyze our institution's surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence/progression. Secondary objectives are to define best treatment strategies in the event of tumor recurrence/progression.

Method: A retrospective analysis of our institutional experience identified 100 patients with SCAs and 841 other NFAs treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuro-imaging data, rates of endocrinopathy, and neurologic outcomes were recorded. SCA and standard NFA cohorts were compared with regard to these characteristics and outcomes.

Results: The SCA cohort more commonly presented with cranial neuropathy (13 vs. 5.7%, p = 0.0051) and headache (53 vs. 42.3%, p = 0.042) compared with the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs. NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs. NFA 54.6 ± 14.9, p = 0.0082). Reoperations were comparable between cohorts (SCA 16% vs. NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between cohorts with the exception of higher rates of preoperative pan-hypopituitarism in NFA patients (2 vs. 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 mm (±10.8 mm) compared with 26 mm (±11.3 mm) in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56 vs. 49.7%), although this did not reach statistical significance. There were no significant differences in extent of resection, intraoperative cerebrospinal fluid (CSF) leak rates, endocrine or neurologic outcomes, or postoperative complications. K_i-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared with the NFA (1.94 ± 1.99; p = 0.015). Although no difference in overall rates of progression or recurrence was noted, SCAs had a significantly lower progression-free survival (24.5 vs. 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections.

Conclusion: In the largest surgical series to assess outcomes in SCAs to date, our findings suggest that SCAs are more biologically aggressive tumors compared with standard NFA. Progression-free survival in SCAs is nearly half the duration compared with other NFAs. Close neuroimaging and clinical follow-up is warranted. Residual disease should be considered for early post-operative adjuvant radiosurgery, especially in younger patients with SCAs.

Publication History

Article published online:
12 February 2021