MON-084 A Forgotten Eye-Opener: Cushing Disease Initially Presenting as Exophthalmos

Abstract Disclosure: D. Tran: None. C. Urnes: None. P. Sequeira: None. C. Hurtado: None. Background: Exophthalmos is a rarely recognized sign of Cushing’s syndrome (CS). Though included in initial descriptions of the disease by Harvey Cushing in 1932 and its presence in as many as 30-45% of patients with active CS, endocrine exophthalmos is now more typically associated with Graves’ disease. Evaluation of CS requires careful application and interpretation of biochemical testing, imaging, and invasive measures such as bilateral inferior petrosal sinus sampling (BIPSS) to establish a diagnosis. We present a case of Cushing syndrome initially presenting as exophthalmos and blurry vision that was ultimately diagnosed as Cushing disease following BIPSS with desmopressin. Clinical case: A 51-year-old female with a primary complaint of three months of blurry vision, eye swelling, and proptosis was referred to Endocrinology for evaluation of Cushing syndrome. Upon presentation she also reported weakness standing from chair, easy bruising, and facial redness. Her past medical history included hypertension, hyperlipidemia, multiple pancreatic cysts under surveillance, and uncontrolled insulin-dependent type 2 diabetes mellitus. She denied exogenous glucocorticoid use. Physical exam revealed facial rounding, bilateral proptosis, facial plethora, purple abdominal striae, and proximal muscle weakness. Initial labs demonstrated 24-hour urine cortisol of 299.4 mcg/dL (4.0 to 50.0 mcg/dL) and a low-dose dexamethasone suppression test with AM cortisol of 8.5 mcg/dL (<1.8 mcg/dL), establishing a diagnosis of Cushing syndrome. Thyroid function was normal. High-dose dexamethasone testing revealed suppression of ACTH (68 to 18 pg/mL) and AM cortisol (23.4 to 4.5 mcg/dL) suggesting Cushing disease, although MRI did not identify a pituitary lesion. The patient was referred to neurosurgery for BIPSS which revealed a central-to-peripheral plasma ACTH gradient of 8.5 pg/mL before desmopressin administration and 33.5 pg/mL 2 minutes following desmopressin administration. A diagnosis of Cushing disease was made and the patient was scheduled for pituitary resection with neurosurgery. Conclusion: This case highlights an unusual case of Cushing disease initially presenting as exophthalmos. It also demonstrates the importance of confirmatory testing with BIPSS with desmopressin in cases of Cushing disease without evidence of a pituitary lesion on MRI. Presentation: Monday, July 14, 2025