Endocrine Abstracts

JOINT2626

Introduction: The differential diagnosis between Cushing’s disease (CD) and ectopic (paraneoplastic) Cushing’s syndrome (ECS) is frequently difficult, notably when bilateral inferior petrosal sinus sampling is unavailable or a pituitary incidentaloma is visualized. We present a comparison between patients diagnosed with CD and ECS and our experience in their diagnosis in a tertiary center of Endocrinology.

Patients and Methods: This retrospective study identified 27 patients diagnosed with CD [78% females, mean age 37. 5 years (10-65)] and 21patients with ECS [67% females, mean age 50 years (18-74)] evaluated in our department between 1997-2024. Data on clinical presentation and hormonal workup were analyzed; 85% of CD and 90% of ECS patients were confirmed histologically.

Results: CD patients had 16 (59%) microadenomas and 11 (41%) macroadenomas. Causes of ECS: neuroendocrine tumors in 12 patients (57%); medullary thyroid cancer in 5 patients (24%); lymphoma in 1 patient; thalamic tumor 1 patient, unknown primary tumor in 2 cases (10%). Almost all the ECS and only 63% of CD patients presented with typical cushingoid appearance. In ECS more frequent were hypertension (81% vs 67%, P < 0. 05) and hypokalemia (range 1. 65-3. 2 mmol/l) in 72% vs 0%, while in CD patients more frequently were found overweight/obesity (78% vs 50%, P < 0. 001) and osteoporosis/osteopenia (40. 7% vs 24%, P < 0. 05), while dyslipidemia (81% in ECS vs 74%) and prediabetes/diabetes (52% in ECS vs 48%) were non-significantly different. ECS patients had higher median morning cortisol level 46 vs 22 µg/dL, P < 0. 001, higher late night serum cortisol 18. 7 vs 15 mg/dL, P < 0. 05, higher ACTH [141 pg/mL (range 35-1221) vs 77 pg/mL (range 21-201), P < 0. 05], higher UFC levels (5. 97 vs 1. 59 xULN, P < 0. 05). Levels in ECS patients overlapped with those in CD in 57% of cases for morning cortisol, 50% for late night cortisol, 72% for ACTH. Inadequate cortisol suppression (<50% reduction) after high dose dexamethasone (DST, 8mg/day for 2 days) was recorded in 93% of ECS patients, but also in 47. 6% of 21 CD patients (in 44. 5% of those with macroadenomas and in 41% of those with microadenomas). Extensive imaging identified the primary tumor in 71. 4% of ECS patients.

Conclusion: Patients with ECS had higher prevalence of hypertension and hypokalemia and lower prevalence of obesity and osteoporosis compared with patients with CD. ECS patients had significantly higher morning and late-night serum cortisol, ACTH and UFC levels. High dose DST had 93% sensitivity but only 52% specificity for ECS. Management of ACTH-dependent CS needs a multidisciplinary approach.