Which hypertension syndrome features unusual steroid metabolites in the urine that typically do not exist?
GRA, familial hyperaldosteronism type 1, is an autosomal-dominant hypertensive disorder resulting from a hybrid gene located on chromosome 8. The defective gene consists of the regulatory gene of 11β-hydroxylase gene and the structural region of the aldosterone synthase gene. Normally, angiotensin-II (Ang-II) induces the production of aldosterone by stimulating the aldosterone gene, CYP11B2, whereas adrenocorticotropic hormone (ACTH) stimulation of the 11β-hydroxylase gene, CYP11B1, leads to cortisol production. A highly similar DNA sequence of these two genes and an unequal crossing over are the causes for GRA etiology. The ACTH-stimulated chimeric gene produces aldosterone in the zona fasciculata instead of the zona glomerulosa, and thus mineralocorticoid production is unresponsive to its traditional regulators Ang-II and potassium. Steroid analysis of urine in affected individuals shows the presence of unusual steroid metabolites of a chimeric protein normally not seen, 18-oxocortisol and 18-hydroxycortisol, which can be helpful to diagnose this condition.
In GRA, plasma renin is reduced, whereas aldosterone level can be increased. Hypokalemia is commonly seen. Given the severity of hypertension at presentation, patients suffer hemorrhagic strokes from ruptured aneurysms. Hence cerebral magnetic resonance angiography is a requisite in these patients at the time of diagnosis; repeat imaging every 5 years should be considered. Low-dose glucocorticoid therapy suppresses ACTH and aldosterone production, thereby serving an important therapeutic role. Both amiloride and spironolactone are also effective.