Background:
According to the 2022 WHO classification, silent corticotroph adenomas (SCAs) are T-PIT-lineage pituitary neuroendocrine tumours without clinical and biochemical evidence of cortisol excess at diagnosis (WHO Classification of Tumours Editorial Board, 2022). SCAs without adrenocorticotropic hormone (ACTH) immunohistochemistry (IHC) expression can commonly be misclassified as non-functioning pituitary adenomas (NFPA). However, T-PIT transcription factors IHC enables accurate identification. This reclassification is critical, as SCAs exhibit a more aggressive clinical course than true NFPA, with higher rates of cavernous sinus invasion and recurrence (Ben-Shlomo & Cooper, 2018; Himstead et al., 2024) . Furthermore, although rare, SCAs can evolve into functional corticotroph adenomas (Zoli et al., 2015).
Case Series:
We present two cases illustrating the diagnostic refinement and clinical relevance of T-PIT IHC.
Patient A, a 74-year-old female, was initially diagnosed with a null cell adenoma after resection of a non-enhancing 30×27×30mm lesion in the right sphenoid sinus, radiologically suspicious for a mucocele. Routine IHC was ACTH-negative, suggesting a null cell adenoma. However, retrospective additional transcription factor staining revealed T-PIT positivity, prompting reclassification to SCA.
Patient B, a 46-year-old male, had an initial diagnosis of a NFPA resected in 2008, complicated by panhypopituitarism. He received radiotherapy for disease progression in 2013. In 2023, re-operation revealed a T-PIT-positive, ACTH-positive SCA, despite no prior clinical or biochemical evidence of cortisol excess. Interpretation of disease activity was confounded by chronic hydrocortisone replacement therapy, highlighting the challenge of assessing subclinical disease burden in such contexts.
Conclusion:
These cases highlight the diagnostic and prognostic value of T-PIT transcription factor IHC in accurately identifying SCAs. Given their risk of recurrence, invasiveness, and potential progression to Cushing’s syndrome, failure to recognise SCAs risks suboptimal surveillance. A lower threshold to perform a screening test for Cushing’s syndrome appears to be required for patients with NFPA and routine incorporation of T-PIT, SF1 and PIT1 IHC into pituitary tumour evaluation is critical for accurate lineage classification, and to guide appropriate surveillance and long-term management.