Endocrine Abstracts

JOINT593

Introduction: Ectopic ACTH Cushing syndrome (EAS) is a rare yet significant cause of endogenous hypercortisolism. Differentiating EAS from pituitary Cushing syndrome (CD) poses a diagnostic challenge due to overlapping clinical and biochemical features. While inferior petrosal sinus sampling (BIPSS) is the gold standard and newer nuclear imaging modalities hold promise, these are not widely available. This study presents 2 decades of experience with EAS from a tertiary care center in India; comparing it’s clinical, biochemical and radiological characteristics with those of CD. Additionally, it evaluates the diagnostic utility of the overnight high-dose dexamethasone suppression test (ONHDST) in this population.

Methods: This retrospective study analyzed 113 adults (30% male, age 18-72 years) diagnosed with ACTH-dependent Cushing syndrome (CS) (plasma ACTH>20.0 pg/ml). The diagnosis of EAS was made by histologic confirmation of tumor on histopathology, finding an ectopic tumor on radiology/imaging, or a central: peripheral gradient of <2 on BIPSS. Parameters differentiating EAS and CD were analyzed, and the diagnostic performance of ONHDST was evaluated.

Results: Among 113 patients with ACTH-dependent CS, 27(24%) had EAS while 86(76%) had CD. The most common source of EAS was the lung in 14(52%) patients [10 pathologically confirmed pulmonary neuroendocrine tumors (NET), 4 did not undergo surgery]. 4 patients had thymic NET, 2 had medullary thyroid carcinoma, 1 had a gall bladder NET and 6 had occult EAS. Multivariable logistic regression identified male gender, hypokalemia, and <50% suppression on ONHDST as significant predictors of EAS. In a receiver-operating characteristic (ROC) curve analysis, <50% suppression following ONHDST had 77% sensitivity, 62% specificity, 40% positive predictive value (PPV) and 89% negative predictive value (NPV) in diagnosing EAS vs CD (AUC 0.70; 95% CI 0.59-0.81; P = 0.002). The major diagnostic dilemma usually occurs when the MRI is normal or shows a small microadenoma. In this situation the ONHDST using the same cut-off performed better (sensitivity 77%, specificity 71%, PPV 54% and NPV 87%) (AUC 0.77; 95% CI 0.66-0.88; P = 0.00009). Among 10 patients with histopathologically confirmed pulmonary NET, 9 were in remission at last contact, while one patient was lost to follow-up. Other forms of EAS (n = 17) had poorer outcomes: 9 lost to follow-up, 7 died, and 1 in remission after bilateral adrenalectomy.

Conclusion: EAS accounted for 24% of ACTH-dependent CS in our institution and was mostly due to pulmonary NETs, which had good prognosis. The ONHDST is a valuable test in differentiating CD from EAS, especially in resource limited settings.