Protein kinase A defects and cortisol-producing adrenal tumors

We present an update on protein kinase A (PKA) defects and Cushing syndrome. Recent findings: 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. Summary: 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.
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya Source Type: research