A late awakening: delayed functional transformation of a silent corticotroph adenoma into Cushing disease

Silent corticotroph adenomas (SCAs) are a biologically distinct subset of nonfunctioning pituitary adenomas (NFPAs) characterized by corticotroph lineage without clinical or biochemical evidence of hypercortisolism. Although SCAs exhibit more aggressive growth behavior than other NFPAs, delayed transformation into overt adrenocorticotropic hormone (ACTH)-dependent hypercortisolism is rare. We describe a woman in her early 30s who presented with headaches and visual field deficits and was found to have a pituitary macroadenoma. Initial endocrine evaluation revealed mild hyperprolactinemia attributed to stalk effect, without evidence of hormonal hypersecretion. She underwent transsphenoidal surgery, and pathology was interpreted as an NFPA based on negative immunostaining. Transcription factor analysis was not performed. Postoperative imaging demonstrated a stable 5-mm residual lesion. More than 2 decades after surgery, progressive ACTH elevation emerged despite continued radiographic stability and preceded the development of clinical hypercortisolism by several years. Biochemical testing confirmed ACTH-dependent Cushing disease. Repeat surgery was performed and surgical pathology showed a T-box transcription factor-positive corticotroph adenoma with sparsely granulated ACTH expression. This case highlights the potential for very late functional transformation of SCAs and underscores the importance of long-term clinical and biochemical surveillance even in asymptomatic patients with stable residual disease on imaging.