title: Protein kinase A defects and cortisol-producing adrenal tumors.
abstract: OBJECTIVE
  Cushing syndrome caused by cortisol-producing adrenal adenomas is a rare condition, associated with high morbidity due to weight gain, diabetes mellitus, osteoporosis, hypertension, muscle weakness, mood disturbance and others. The first gene to be identified as causative of Cushing syndrome was PRKAR1A. We present an update on protein kinase A (PKA) defects and Cushing syndrome.
  
  
  RESULTS
  The cyclic AMP-dependent PKA catalytic subunit alpha (PRKACA) hotspot point mutation (c.617A > C [p.Leu206Arg]), leading to an increase of basal PKA activity, and formation of cortisol-producing adenoma has been frequently shown to cause the most common form of adrenocorticotropic hormone-independent Cushing syndrome.
  
  
  CONCLUSIONS
  Somatic PRKACA mutations have been found in up to 50% of patients with adrenal adenomas. Germline PRKACA amplification was also seen in bilateral adrenal hyperplasias. PRKACA activation was associated with higher cortisol levels, smaller tumor size and overt Cushing syndrome. This breakthrough is expected to improve our understanding of how PKA defects lead to Cushing syndrome and may spearhead the development of new, molecularly designed therapies.
authors: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors: Mihail
authors: M
authors: Zilbermint
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000235:genetics*; D003480:Cushing Syndrome / Q000235:genetics*; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics*; D006801:Humans
chemical_list: D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human