Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome.

This review reports the main molecular alterations leading to development of benign cortisol- and/or aldosterone-secreting adrenal tumors. Causes of adrenal Cushing syndrome can be divided in 2 groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly primary pigmented nodular adrenocortical disease, most of the time due to germline-inactivating mutations, and primary bilateral macronodular adrenal hyperplasia that can be caused in some rare syndromic cases by germline-inactivating mutations of , , and and of in isolated forms. somatic-activating mutations are the main alterations in unilateral cortisol-producing adenomas. In primary hyperaldosteronism (PA), familial forms were identified in 1% to 5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric hybrid gene, FH-II due to germline mutations, FH-III due to germline mutations, FH-IV due to germline mutations and PA, and seizures and neurological abnormalities syndrome due to germline mutations. Several somatic mutations have been found in aldosterone-producing adenomas in , , , , and genes. In addition to these genetic alterations, genome-wide approaches identified several new alterations in transcriptome, methylome, and miRnome studies, highlighting new pathways involved in steroid dysregulation.