Overproduction of sodium-retaining steroids by the zona glomerulosa is adrenocorticotropin-dependent and mediates hypertension in dexamethasone-suppressible aldosteronism.
Dexamethasone suppressed urinary aldosterone to less than 1.5 micrograms/day in 1-2 days and lowered blood pressure in a woman and in her 2 1/2-yr-old daughter, both of whom have hypertension and hyporeninemia and are members of a kindred with dexamethasone-suppressible aldosteronism. ACTH given for 7 days produced a sustained increase in aldosterone production and a rise in blood pressure in both patients. The abnormal suppression with dexamethasone and further stimulation with ACTH indicate that the aldosteronism is ACTH-dependent in this disorder. The cause of the ACTH-dependence of aldosterone production in this disorder is unknown but may represent continued stimulation rather than the usual (secondary) inhibition by ACTH of 11-hydroxylation and 18-hydroxylation in zone glomerulosa cells. Blood pressure was normal during treatment with spironolactone and during pregnancy, when the action of aldosterone and other similar steroids was presumably blocked by an increased production of progesterone; this suggests that the hypertension is dependent upon sodium-retaining steroids such as aldosterone. Aminoglutethimide given during treatment with ACTH decreased urinary aldosterone and blood pressure and increased PRA, with minimal effects on plasma cortisol or urinary 17-hydroxycorticosteroids. These results provide additional evidence that aldosterone, acting alone or in conjunction with other steroids synthesized by the zona glomerulosa, mediates the hypertension and hyporeninemia of dexamethasone-suppressible aldosteronism.
D000302:Adrenal Cortex / Q000378:metabolism; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D000616:Aminoglutethimide; D002675:Child, Preschool; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology*; D007700:Kinetics; D011247:Pregnancy; D012083:Renin / Q000097:blood; D013148:Spironolactone
D000616:Aminoglutethimide; D013148:Spironolactone; D000450:Aldosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D012083:Renin