SUN-055 Treading the Unknown Path: Tackling a Rare Form of Cushing Disease

Abstract Disclosure: N. Bang: None. M. Diab: None. J. Lim: None. Introduction: Crooke cell adenoma (CCA) is an uncommon but aggressive form of corticotroph adenoma comprised of Crooke cells that secrete ACTH that contribute to Cushing disease. There have been 106 documented cases of this condition (1). Crooke cells are comprised of cytoplasmic granules containing hyaline. CCA is diagnosed when over half of the cells exhibit these cytological changes. Crooke cells are immunopositive for the transcription factors T-PIT and CK8/18, as well as for ACTH. Case Description: A 57 y/o woman with a history of primary hypothyroidism presented to the emergency department for impaired peripheral vision, fatigue, facial swelling, and weight gain. Her brain MRI revealed a pituitary macroadenoma that was 2.8 cm x 3.7 cm x 4.1 cm in size with encasement of the left internal carotid artery. The endocrinology team evaluated the patient for pituitary hormonal disorders. The morning cortisol and ACTH levels were both elevated at 19.1 mcg/dL (6.2 to 19.4 mcg/dL) and 209 mcg/dL (7.2 to 63.3 mcg/dL), respectively. The 24-hour urine cortisol level was high at 362 mcg (6 to 42 mcg/24 hr). These findings were concerning for Cushing disease. The patient subsequently underwent transsphenoidal resection of her pituitary mass. The tumor pathology revealed a corticotroph adenoma with positive staining for ACTH, CK8/18, and T-PIT. After surgery, the patient developed partial hypopituitarism leading to arginine vasopressor deficiency and secondary adrenal insufficiency. The patient is being closely monitored for either persistence versus recurrence of Cushing disease. Discussion: This case shows that it is important to consider CCA in the differential when treating patients with Cushing disease. CCA can be challenging to treat, as the recurrence rate can be greater than 60 percent (2). CCA can transform into Crooke cell carcinoma, which can contribute to dural metastases. Complications of hypercortisolism impair quality of life and increase patient’s mortality. It is crucial to understand how to identify patients who are at considerable risk of developing Crooke cell changes. However, there are currently no clinical recommendations available to guide this. Findings from this study (3) can be used to understand the management of CCA. This will make it easier for clinicians to recognize and to manage CCA in their practices. 1 Taiwo A, Kamalumpundi V, Becker N, et al. Pituitary crooke cell adenoma: Two cases of an aggressive pituitary adenoma. JCEM Case Rep. 2023;1(6): luad114. 2 Olivera CB. The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors. Brain Pathol. 2025;35(1): e13302. 3 Heaney AP. Clinical review: Pituitary carcinoma: Difficult diagnosis and treatment. J Clin Endocrinol Metab. 2011;96(12): 1064. Presentation: Sunday, July 13, 2025