Root cause analysis of diagnostic and surgical failures in the treatment of suspected Cushing's disease

Cushing's disease (CD) is a condition characterized by excess glucocorticoid from an ACTH pituitary adenoma. Identifying surgical candidates represents a major diagnostic challenge. We performed a root cause analysis (RCA) of treatment failures for patients with suspected CD. The present study aims to categorize failures in treatment. Medical records were reviewed from 2008 to 2017 for all patients treated surgically for suspected CD. Demographics, past medical history, endocrine outcomes, imaging findings, laboratory studies and clinical features were collected. Eighty-five patients were identified with pre-operative suspicion for CD. Thirty-four (40.0%) had undergone prior surgery confirming ACTH adenoma, leaving 51 (60.0%) for analysis. The average length of follow-up was 18.3 ± 24.1 months, 42 (82.4%) patients had postoperative biochemical remission of hypercortisolism. Forty-three (84.3%) had histologically confirmed CD, two (3.9%) were diagnosed with extracranial ACTH-secreting tumors, four (7.8%) had no obvious tumor upon intraoperative exploration, one (1.9%) had suspected pituitary ACTH hyperplasia, and one (1.9%) had no identifiable pathologic tissue despite apparent gross tumor observed during surgery. Thirty-four (66.7%) patients had remission following surgery alone, four (7.8%) after reoperation, and four (7.81%) after radiosurgery. One patient (1.9%) was found to have an ectopic source of ACTH, and one (1.9%) had immunohistochemically confirmed adrenal tumors. On RCA, we identified six categories of treatment failures. CD is a diagnostic challenge that can be difficult to distinguish from other forms of hypercortisolism. Surgical efficacy can be improved with more accurate patient selection, and perhaps with improved imaging methods.