Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond.

Bilateral adrenal hyperplasia currently accounts for up to 2 thirds of cases of primary aldosteronism. As such, it represents a major opportunity for targeted medical management as opposed to unilateral surgically correctable forms of the disease. Although the majority of cases of primary aldosteronism are sporadic, bilateral adrenal hyperplasia may occur in the context of familial hyperaldosteronism where it is associated with specific germline mutations. Over the past 5 years, impressive progress has been made in our understanding of the genetic basis underlying primary aldosteronism, allowing us to identify and characterize new familial forms of the disease and to understand the mechanisms involved in the formation of aldosterone producing adenoma. In contrast, our knowledge of the genetic contribution to the development of bilateral adrenal hyperplasia, and in a larger context, to renin and aldosterone levels in the general population, is still poor. This review summarizes our current knowledge on the genetics of bilateral adrenal hyperplasia and addresses some open questions to be addressed by future research. In particular, genome-wide association studies in large populations may provide clues to understanding the genetic susceptibility underlying the development of primary aldosteronism.

Long-term effects of vasopressin on the subcellular localization of ENaC in the renal collecting system.

Previous studies revealed that chronic (days) vasopressin treatment stimulates amiloride-sensitive sodium transport in isolated renal cortical collecting ducts and increases the abundance of beta- and gamma-subunits of the epithelial sodium channel (ENaC) in the kidney. The aim of the present work was to investigate in vivo the cellular basis of these effects. The long-term effect of V2 vasopressin agonist (1-deamino-8-D-arginine vasopressin (dDAVP)) on the abundance and subcellular localization of ENaC along the rat renal collecting system was determined by immunohistochemistry and laser confocal microscopy. Moreover, we studied by real-time reverse transcriptase-polymerase chain reaction the effect of vasopressin on proteins implicated in the regulation of ENaC (Nedd4-2, prostasin, Sgk1). After 5 days of administration, dDAVP markedly increased the intracellular pool of the beta- and gamma-ENaC subunits in the principal cells, with an increasing gradient from connecting tubule to the outer medullary collecting duct, but did not increase any subunit at the cell surface. The apical immunostaining of ENaC increased in response to sodium restriction, as expected, but dDAVP did not further enhance this apical labelling. dDAVP increased the gene expression of prostasin in the cortex but not that of Nedd4-2 and Sgk1. These findings suggest that the previously reported increase in sodium transport induced by sustained stimulation of vasopressin V2 receptor is probably mediated by other mechanism than an increase in the apical density of ENaC.