SAT-020 - The Calm before the Cortisol Storm: Delayed Functional Conversion of A Corticotroph Adenoma

Introduction
Silent corticotroph adenomas (SCAs) are nonfunctioning pituitary adenomas characterized by ACTH and/or T-Pit immunopositivity without biochemical hypercortisolism. Although most remain clinically silent, a subset undergoes phenotypic conversion into active corticotroph adenomas, resulting in Cushing disease. Transformation from silent to functioning adenoma has been reported in up to 9% of SCAs, with conversion occurring months to years after diagnosis. We report a case of a recurrent SCA with late transformation into overt ACTH-dependent Cushing disease, highlighting the unpredictable and dynamic biology of these tumors.
Case Presentation
A man in his 60s presented with acute headache, ptosis, and visual disturbance and was found to have a 1.9×2.3×1.8 cm hemorrhagic sellar mass with cavernous sinus invasion and mild optic chiasm compression, consistent with pituitary apoplexy. He underwent transsphenoidal resection with symptomatic improvement; pathology showed hemorrhage and necrosis without viable tumor. Surveillance MRI at 6 months showed no residual disease.
Three and a half years postoperatively, he developed progressive cranial neuropathies and weight gain. MRI demonstrated a 1.2×2.7×3.2 cm sellar mass with cavernous sinus and clivus involvement. Initial endocrine evaluation suggested a nonfunctional adenoma with preserved adrenal reserve. He underwent repeat transsphenoidal surgery; pathology confirmed a T-Pit–positive corticotroph adenoma.
Three months later, he developed rapid-onset metabolic and electrolyte abnormalities. Biochemical evaluation revealed markedly elevated ACTH (131–172 pg/mL), cortisol (34.9–53.6 µg/dL), abnormal late-night salivary cortisol, and increased 24-hour urinary free cortisol, consistent with ACTH-dependent Cushing disease. He was treated with fractionated radiation therapy with subsequent biochemical suppression and is currently under surveillance for hypopituitarism.
Discussion
Transformation from silent to functional corticotroph adenoma is uncommon but well described and is typically associated with invasive macroadenomas and recurrent disease. Phenotypic conversion is linked to increased expression of prohormone convertase 1/3 (PC1/3), enabling active POMC processing and ACTH secretion. PC1/3 immunohistochemistry remains the most practical marker for assessing transformation potential, while proliferative indices, tumor size, invasiveness, and emerging molecular features such as USP8/TP53 mutations provide complementary prognostic information. No single feature reliably predicts transformation, underscoring the need for long-term biochemical and radiologic surveillance. This case underscores the dynamic behavior of SCAs and the risk of late functional conversion with significant clinical consequences.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*