Adverse cardiovascular outcomes of corticosteroid excess.

Corticosteroid excess is associated with adverse cardiovascular outcomes. Patients with Cushings's syndrome, either caused by endogenous or exogenous glucocorticoid excess, and patients with primary aldosteronism have increased cardiovascular risk. The increase in risk is mediated partly by traditional cardiovascular risk factors including hypertension and metabolic syndrome but also by other, less well-characterized mechanisms.

Salt, aldosterone and hypertension.

Clinical studies have shown that aldosterone and salt are independently related to hypertension, cardiovascular morbidity and mortality. More recently, studies in humans have demonstrated that, similarly to animals, endogenous aldosterone and dietary salt intake have not only separate, but also combined effects to accelerate target-organ deterioration. The aldosterone-salt interaction has important clinical implications, because combined effects of both can be minimized, if not avoided, by reducing salt intake.

Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma.

Experimental and human data suggest that adverse cardiovascular (CV) and renal effects of aldosterone excess are dependent on concomitant dietary salt intake. Increased urinary protein (Uprot) is an early sign of nephropathy independently associated with CV risk. We have previously reported a positive association between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but not in patients with normal aldosterone levels.

Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: no evidence for mutations in familial hyperaldosteronism type II in a large affected kindred.

Objective: Familial hyperaldosteronism type II (FH-II) is characterized by inheritance of primary aldosteronism (PAL) but, unlike FH-I, is not glucocorticoid remediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. Analysis of two pedigrees previously demonstrated linkage of FH-II with a locus at chromosome 7p22. We sought to determine whether mutations in the exons or intron/exon boundaries in PRKAR1B (encoding protein kinase A regulatory subunit R1-beta), which resides within the linked locus, are associated with FH-II.