SAT-019 - Expanding the Spectrum of Nelson Syndrome: Corticotroph Tumor Progression and Subsequent Infarction While on Osilodrostat

Background:
Corticotroph tumor progression (CTP), also known as Nelson Syndrome, is a recognized condition traditionally identified following bilateral adrenalectomy (BLA) for Cushing’s Disease. Emerging evidence suggests CTP can also occur during medical therapy with steroidogenesis inhibitors and glucocorticoid receptor antagonists, including osilodrostat and mifepristone. However, few cases have been reported to provide enough data on incidence, risk factors, and management. This unique case serves to broaden further data on such cases.

Case Presentation:
A 33-year-old female presented with a two-year history of hirsutism, weight gain, and mood changes. Biochemical evaluation confirmed hypercortisolism, demonstrated by increased 24‑hour urinary free cortisol (172 mcg/24 h; N= 4–50 mcg/24 h), elevated late‑night salivary cortisol (1.7 mcg; ULN < 0.09 mcg), and 1‑mg dexamethasone suppression testing (DST) (serum cortisol 23.2 mcg/dL; N < 1.8 mcg/dL). An elevated ACTH level (77 pg/mL; N = 7.2–63.6 pg/mL) confirmed ACTH-dependence. The initial MRI did not identify an adenoma; however, dynamic testing (desmopressin stimulation, high-dose DST) along with inferior petrosal sinus sampling, confirmed a pituitary source. She underwent endonasal transsphenoidal surgery; however, postoperative remission was not achieved. The patient declined further surgery and radiotherapy. Osilodrostat was initiated, resulting in biochemical and clinical improvement. Over a two‑year period, serial MRIs demonstrated progressive tumor growth. An MRI in August 2025 showed a 1.7 cm pituitary lesion enlarging to 2.8 cm by October 2025 when the patient presented with acute left abducens nerve palsy. By November 2025, the lesion was no longer visualized on MRI, consistent with tumor infarction or hemorrhage, with labs showing evolving panhypopituitarism, including central hypogonadism and new-onset hypothyroidism.

Discussion
This case demonstrates CTP development with subsequent pituitary infarction during osilodrostat therapy, a rare phenomenon that, to our knowledge, has not been previously reported. Increasing evidence suggests that Nelson’s syndrome/CTP is not limited to post‑BLA patients and can also occur during medical therapy for Cushing’s disease. The pathophysiology of CTP remains unclear but likely involves loss of cortisol-mediated negative feedback along with tumor-intrinsic characteristics. Rapid CTP growth may predispose to pituitary apoplexy and subsequent infarction. Management is challenging when surgery and radiotherapy are declined. Potential subsequent medical therapies in these cases include somatostatin analogs, dopaminergic agents, and temozolomide, but evidence for optimal management is negligible. Further research is warranted to identify risk factors, optimize monitoring, and guide medical therapy in this complex patient population.

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