Corticotropin-independent macronodular adrenal hyperplasia: A clinicopathologic correlation

Objectives: To investigate the clinical presentation, laboratory findings, and pathologic characteristics of patients with corticotropin (ACTH)-independent macronodular adrenal hyperplasia. Design: Retrospective review. Setting: Academic medical center. Patients: All patients with bilateral adrenocortical nodules associated with ACTH-independent hypercortisolism without clinicopathologic features of primary pigmented nodular adrenocortical disease with atrophic internodular adrenal cortex. Main Outcome Measures: Compare and contrast our findings with those previously reported; assess response to adrenalectomy. Results: Nine patients met the criteria for corticotropin-independent macronodular adrenal hyperplasia. All patients had biochemical evidence of Cushing syndrome, although repetitive testing was frequently required. As a result, the diagnosis was delayed from 1 to 20 years. In all patients, both the low- and highdose dexamethasone suppression tests failed to suppress cortisol secretion. No patient had elevated ACTH levels, and following curative bilateral adrenalectomy, no patient subsequently developed Nelson syndrome, with follow-up ranging from 1 to 8.5 years. Unique histologic features were identified in all cases. Conclusion: Amalgamating this series with other clinical reports plus basic research information, corticotropin-independent macronodular adrenal hyperplasia must be considered a separate and legitimate cause of Cushing syndrome.