QCT showed the highest adrenal toxic effect among QdNOs in H295R cells.
PKC, ERK, JNK, p38MAPK and Nrf2 pathways were involved in adrenal toxicity of QCT.
CYP17A1, NR4A2 and G6PD were molecular targets in adrenal toxicity of QCT.
CYP17A1 was the key switch to reduce the aldosterone production induced by QCT.
Genomic and proteomic analysis provided new insight into adrenal toxicity of QdNOs.