These findings expand on the clinical spectrum of phenotypes associated with KCNJ5 mutations and implicate these mutations in the pathogenesis of hypertension associated with increased aldosterone response to ACTH stimulation.
Adrenocorticotropic hormone (ACTH)-secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity.
Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended.
However, when RAP is not allowed to rise, ACTH is associated with sodium retention and severe systemic hypertension, suggesting that the natriuretic effects of ACTH are caused by increased RAP and that the natriuresis blunts the chronic hypertensive effects of ACTH.
PNAH was associated with cushingoid features, virilization and hypertension with a lack of cortisol suppression on high DST, undetectable plasma ACTH and absent cortisol and ACTH responses to CRH.
The correlation between excretion of aldosterone and cortisol metabolites and suggests that, in TT subjects, ACTH exerts an important common regulatory influence on adrenal corticosteroid production in subjects with hypertension.
Influence of somatostatin analogue (SMS 201-995, octreotide) on blood pressure in adrenocorticotrophin (ACTH) treated rats: role of hyperinsulinaemia in ACTH hypertension.