MON-085 Pituitary Cushing Syndrome Masquerading as Ectopic ACTH syndrome: IPSS Ambiguous Results

Abstract Disclosure: E. Rogal: None. E. Przhiyalkovskaya: None. S. Deunezhewa: None. I. Sitkin: None. V. Azizyan: None. L. Nikankina: None. A. Lapshina: None. Most patients with ACTH-dependent hypercortisolism have an ACTH-secreting pituitary tumor. Approximately 10-15% of patients have an ectopic source of ACTH-production. Severe clinical course, spontaneous hypokalemia, 24-hour urine free cortisol (UFC) >1000 mcg favor an ACTH-ectopic syndrome. However, there is a subset of patients with pituitary Cushing Syndrome (CS) whose clinical presentation can overlap with that of ectopic ACTH-secretion.53-year old woman developed severe signs of glucocorticoid excess in 3 months: full plethoric face, hirsutism, generalized weakness, elevated blood pressure (BP)160/90 mmHg, hyperglycemia up to 20 mmol/l. The patient was put on insulin therapy, 5 antihypertensive drugs and potassium supplements 3-5 g per day. Initial diagnostic work-up – Potassium 1,8 mEq/L, HbA1c 10,2%, Serum cortisol post 1 mg Dex 1500 nmol/l, 11 pm serum cortisol 1272 nmol/l, 24-Hour UFC 6573 nmol/l, 11 pm Cortisol saliva 264 nmol/l, 8 am ACTH 149 ng/ml, 11 pm ACTH 223 ng/ml, Prolactin 484 IU/l. Head MRI showed 5,5 5,3 7 mm pituitary adenoma. Chest CT revealed a 5 mm clear-cut single subpleural focus in the left lung. No remarkable findings on abdominal and pelvic CT. Considering hypokalemia, severe hypercortisolism, markedly elevated ACTH, chest CT and MRI results petrosal sinus sampling (IPSS) was performed.Due to lack of desmopressin, IPSS without stimulation was conducted. Despite successful central-to-peripheral Prolactin gradient 1,8 (Right Sinus (RS) 955,6; Left Sinus (LS); Peripheral vein (PV) 522,3), ACTH central-to-peripheral gradient could not be calculated as absolute RS ACTH values were >2000 ng/ml, whereas PV ACTH were >2000, >2000, 1921, 1802 and 1623 respectively. One sample was diluted 10 times with the following results – RS ACTH 4572 ng/ml, LS ACTH 2678 ng/ml and PV ACTH 1921 ng/ml. As ACTH gradient was 2,38, pituitary CS was confirmed. The patient underwent transsphenoidal surgery. Histological examination – Crooke’s cell adenoma. Immunohistochemistry - corticotroph adenoma; strong expression of ACTH, CAM.5, T-box and II type somatostatin receptors, Ki-67%<1%. Lab tests 5-th day post-surgery – cortisol 429 nmol/l, ACTH 27,6 pg/ml, potassium normalized. The patient was dismissed from the hospital on dynamic follow-up.Three months follow-up showed considerable muscle function improvement, BP normalized, HbA1c had improved 6,2%, insulin and antihypertensive therapy had been discontinued. Lab work-up – midnight cortisol saliva 2,6 nmol/l, UFC 70,3 nmol/l, midnight serum cortisol 269 nmol/l, morning serum cortisol 269,5 nmol/l, morning ACTH 51,9 pg/ml. Key learning points: 1.Severe phenotype can be misleading in suspected pituitary CS 2.Dilution sample technique is a reasonable approach in terms of ACTH values ambiguity 3. Crooke’s cell pituitary adenoma may exhibit aggressive clinical behavior mimicking ACTH-ectopic syndrome Presentation: Monday, July 14, 2025