SUN-058 From Cushing's to Nelson: A Case of Aggressive Pituitary Adenoma

Abstract Disclosure: A. Deswal: None. A. Dwarakanathan: None. Introduction: Patients with treatment-resistant Cushing's disease infrequently undergo bilateral adrenalectomy (BLA) to manage their hypercortisolemia. However, a rare complication known as Nelson Syndrome (NS) can develop, characterized by new or worsening pituitary adenomas along with excessive ACTH production and skin hyperpigmentation. Prophylactic radiotherapy post-BLA can reduce incidence of NS, but some patients may still require further surgical intervention, such as endoscopic endonasal transsphenoidal surgery (ETSS).Case Presentation:A 31-year-old man had been suffering from fatigue, back pain, and chronic diarrhea for 2 years when he initially presented to our office. He had a plethoric face, buffalo hump, abdominal obesity and purple striae on skin. Laboratory investigations revealed : 8 AM cortisol 25 μg/dL (6.7-22.6 μg/dL), 8 AM cortisol after 8 mg dexamethasone suppression test 22, and ACTH 115 (7-69 pg/mL). MRI brain revealed two lesions within the pituitary gland, each about 3 mm. Elevated ACTH was noted in the left inferior petrosal sinus vein. He was diagnosed with pituitary-dependent Cushing's disease. He underwent ETSS twice for tumor resection. Despite this, his cortisol levels remained elevated. The biopsy of the extracted mass from both the surgeries, did not reveal any adenomatous ACTH-secreting cells. He was also treated with ketoconazole and cabergoline for a short time with no improvement in his symptoms. He ultimately underwent BLA to manage persistent hypercortisolemia. Six months later, ACTH levels continued to rise, peaking at 1024 pg/mL. A 0.6 x 0.9 x 0.6 cm pituitary mass was seen on brain MRI. It continued to grow in size, leading to bitemporal hemianopsia. He again underwent ETSS, but one month post-op, MRI still revealed the presence of a pituitary mass. Ultimately, radiotherapy was done, which was successful in preventing further growth of the pituitary mass as well as stabilizing ACTH levels.Discussion:Our patient had a uniquely aggressive pituitary adenoma to begin with. His tumor continued to increase in size after the first ETSS, prompting a second resection. The biopsy of the tissue did not reveal any ACTH-staining cells, hence precluding chances of it arising from residual tumor. Despite having undergone three surgical resections, he continued to produce ACTH with resultant hypercortisolemia. It’s suspected that this ACTH was coming not only from the pituitary mass but also from a source different than the masses visible on MRI. Cases of ACTH-producing extrasellar pituitary adenomas have been reported in the literature. Negative histopathology of the resected pituitary mass or persistence of elevated ACTH levels post-surgical resection should prompt a search for parasellar lesions. Regardless of their origin, such lesions can be managed by radiotherapy, which would decrease the tumor burden and also target the hidden masses. Presentation: Sunday, July 13, 2025