EP1814 - LBA_ECE_1433 - Multimodal management of silent corticotroph tumors with Crooke's cell features transforming into severe Cushing's disease—the ERCUSYN Kraków cohort

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Abstract Background Silent corticotroph tumors (SCTs) are pituitary neuroendocrine tumors of corticotroph lineage characterized by T-PIT positivity without clinical or biochemical hypercortisolism at diagnosis. Transforming into overt ACTH-dependent Cushing's disease (CD) has been reported in approximately 4% of cases, representing a rare but clinically significant phenomenon. Methods We report three patients from the ERCUSYN Kraków cohort with initially silent corticotroph PitNETs with Crooke's cell features who subsequently developed overt CD during long-term follow-up. Results A 53-year-old woman underwent resection of a nonfunctioning pituitary macroadenoma measuring up to 40 mm. Histopathology demonstrated a densely granulated corticotroph tumor with scattered Crooke's cells (Ki-67 approximately 3%). Proton radiotherapy was subsequently performed. Six years later, rapid tumor progression involving the sella and left cavernous sinus was observed together with biochemical ACTH-dependent hypercortisolism (loss of circadian rhythm, late-night cortisol 19.3 µg/dL, urinary free cortisol 308-445 µg/24 h, ACTH 97.7 pg/mL), despite only mild clinical manifestations. The progression was accompanied by severe mass-effect symptoms, including visual field impairment, ptosis, and convergent strabismus. Combination therapy with pasireotide LAR and temozolomide was initiated. Temozolomide was discontinued after the first cycle due to bone marrow aplasia, while continued pasireotide therapy resulted in radiological stabilization and normalization of cortisol levels. An 80-year-old man underwent incomplete transsphenoidal resection of a 35 mm nonfunctioning macroadenoma (Knosp grade 2). Histopathology confirmed a corticotroph PitNET with Crooke's cell features, followed by adjuvant radiotherapy. Approximately nine years later, the patient developed clinically overt ACTH-dependent CS without significant radiological tumor progression. Initial treatment with pasireotide was insufficient. Due to severe hypercortisolism, osilodrostat was initiated directly in a block-and-replace regimen (up to 30 mg/d) with hydrocortisone supplementation, resulting in biochemical remission and clinical improvement. A 71-year-old woman underwent four transsphenoidal resections of a corticotroph macroadenoma within two years followed by radiotherapy. Five years later, marked tumor progression (Knosp grade 4) occurred with severe mass-effect symptoms including convergent strabismus and impaired ocular motility. Treatment with pasireotide and temozolomide was initiated; however, overt CD developed during therapy. Osilodrostat was introduced and administered for six months, achieving biochemical control of hypercortisolism. Subsequently, temozolomide therapy was continued, and after seven cycles the patient remains clinically stable with radiological tumor regression. Conclusions SCTs with Crooke's cell features may transform into severe CD many years after the initial diagnosis, sometimes even without marked radiological progression. These observations highlight the importance of long-term endocrine surveillance and often necessitate multimodal therapeutic strategies including surgery, radiotherapy, and targeted medical therapy.

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