Diagnostic Strategy and Prognostic Factors for Ectopic Adrenocorticotropic Hormone Syndrome: A Retrospective Study of 64 Cases

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a serious life-threatening disease. Tumor localization is crucial in EAS management. This underscores the importance of evaluating imaging methods and prognostic factors to provide a clear basis for patient diagnosis and management.

The aim of this study was to investigate imaging methods and analyze the relevant prognostic factors for EAS.

The retrospective study followed 64 cases of EAS diagnosed between 1992 and 2020. Clinical features, biochemical analysis, and imaging studies were collected, and survival data were followed up and analyzed.

Of 64 patients, 41% were female with a mean (±SD) age at diagnosis of 47 ± 16 years. Computed tomography (CT), 18-F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-CT, and octreotide scintigraphy had similar sensitivity in localizing ectopic ACTH-secreting tumors. However, in cases with negative imaging on CT, both of 18F-FDG PET-CT and octreotide scintigraphy further localized 25% tumors. The combination of all three modalities failed to further increase the sensitivity. Patients with thymic tumors survived longer than those with pulmonary or pancreatic tumors (p = 0.013 and 0.047, respectively). Multivariate analyses showed that hypokalemia (p = 0.004) and treatment modality (p = 0.048) were independent prognostic factors. The optimal serum potassium cutoff based on maximum log-rank statistics (p = 0.012) was 2.90 mmol/L.

CT is the first choice for tumor localization in EAS. CT in combination with a nuclear medicine or molecular imaging modality is necessary for further identification of an ectopic source. Serum potassium <2.90 mmol/L is associated with shorter overall survival, and tumor resection plays the most important role in the survival improvement.