Abstract
Untargeted, next generation sequencing approaches have provided deep insights
into genetic events that result in unopposed steroidogenesis from the adrenal
cortex. In particular, somatic mutations in the gene encoding the catalytic
subunit α of protein kinase A (PKA) (PRKACA) were identified
independently by several groups as the most frequently altered gene in
cortisol-producing adenomas. Detailed functional studies could explore the
molecular consequences of these hot-spot mutations and large international
cohorts have provided the basis to explore the clinical characteristics
associated with this mutation. Thereby, PRKACA mutations are highly
specific for cortisol over-secretion, while they are absent or very rare in the
context of other adrenal diseases. Patients carrying these somatic mutations are
affected by a more severe phenotype and are identified at a younger age. Thus,
these genotype/phenotype correlations provide further evidence for the
importance of PKA-dependent pathways for adrenal physiology and disease.
Key words
adrenal tumor - adrenal cortex - cortisol - Cushing’s syndrome
