Molecular genetics of adrenocortical tumor formation and potential pharmacologic targets

Minerva Endocrinol. 2012 Jun;37(2):133-9.


Abnormalities in the cAMP/PKA signaling pathway have been linked to the formation of benign adrenal tumors, as well as a possible predisposition to adrenocortical cancer. Mutations in the G-protein coupled receptor are associated with McCune-Albright syndrome and ACTH-independent macronodular adrenal hyperplasia, while defects in cAMP-dependent protein kinase A can lead to the development of Carney's complex, as well as primary pigmented nodular adrenocortical disease (PPNAD), and micronodular adrenocortical hyperplasia (MAH). Defects in phosphodiesterases, which regulate cAMP levels, have also been demonstrated in PPNAD and MAH. The Wnt signaling pathway, which is involved in oncogenesis in a variety of tumors, has also been implicated in adrenocortical tumorigenesis. MicroRNA profiling has added to our understanding of the signaling pathways involved in tumor formation in the adrenal cortex. Will this all lead to the development of specific targets for pharmacologic therapies? In this article, we review the molecular genetics of adrenocortical tumors and refer to potential targets for pharmacologic therapy.

Publication types

  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / physiology
  • Adrenal Cortex Neoplasms / drug therapy
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenocorticotropic Hormone / physiology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Chromogranins
  • Cyclic AMP / physiology
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • GTP-Binding Protein alpha Subunits, Gs / deficiency
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / physiology
  • Humans
  • MicroRNAs / physiology
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology
  • Receptors, Corticotropin / deficiency
  • Receptors, Corticotropin / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Wnt Proteins / physiology


  • Antineoplastic Agents
  • Chromogranins
  • MicroRNAs
  • Neoplasm Proteins
  • Receptors, Corticotropin
  • Wnt Proteins
  • Adrenocorticotropic Hormone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs