SAT-350 Comparative Proteomic Analysis of Various Forms of Bilateral Adrenocortical Hyperplasia

Bilateral Adrenal Hyperplasias (BAH) are responsible for approximately 10% of ACTH-independent Cushing syndrome and are classified as either micronodular or macronodular. Whereas Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) are subtypes of micronodular hyperplasia, Primary Macronodular Adrenal Hyperplasia (PMAH) is the most common form of macronodular BAH. These tumors are classified differently based on clinical, histological and genetic features but they all share a dysregulation of the cyclic AMP/protein kinase (PKA) pathway, a molecular signaling system that is essential for the synthesis and secretion of glucocorticoids. In this project, we investigated the molecular differences between the various types of BAHs using a proteomic approach on normal tissue, iMAD, PPNAD and PMAH. In total, we identified 37 proteins differentially expressed between these diagnostic groups. Most of these proteins were involved in metabolism and mitochondrial function, which is consistent with prior transcriptomic data as well as the secretory status of BAH. We are currently comparing all "-omics" for consistency and/or important differences. Interestingly, each BAH (iMAD, PPNAD and PMAH) has its own proteomic signature and can be separated by primary component analysis highlighting differences in molecular pathways. We propose that the 37 proteins identified herein may provide new clues for the formation of these neoplasms, how they link to the PKA pathway, and importantly assist in their clinical diagnosis.