Treatment of familial hyperaldosteronism type I: Only partial suppression of adrenocorticotropin required to correct hypertension

In familial hyperaldosteronism type I, inheritance of a hybrid 11 beta-hydr oxylase/aldosterone synthase gene leads to ACTH-regulated overproduction of aldosterone (causing hypertension) and of "hybrid" steroids, 18-hydroxy- a nd 18-oxo-cortisol. To determine whether complete suppression of the hybrid gene is necessary to normalize blood pressure, we sought evidence of persi sting expression in eight patients who were rendered normotensive for 1.3-4 .5 yr by glucocorticoid treatment. At the time of the study, six patients w ere receiving dexamethasone (0.125-0.25 mg/day) and two patients were takin g prednisolone (2.5 or 5 mg/day). Urinary 18-oxo-cortisol levels during tre atment demonstrated close correlation with mean "day curve" (blood collecte d every 2 h for 24 h) cortisol (r = 0.74), consistent with regulation by AC TH. Although urinary 18-oxo-cortisol levels were lower during than before t reatment (mean 12.6 +/- 2.4 SEM vs. 35.0 +/- 5.6 nmol/mmol creatinine; P < 0.01), they remained above normal (0.8-5.2 nmol/mmol creatinine) in all eig ht patients. Although mean upright plasma potassium levels during treatment were higher, aldosterone levels lower, PRA levels higher, and aldosterone to PRA. ratios lower than before treatment, PRA levels were uncorrected (<1 3 pmol/l min) and aldosterone to PRA ratios were uncorrected (>65) during t reatment in four patients. For each of the eight patients, day curve aldost erone levels during treatment correlated more tightly with cortisol(mean r for the eight patients, 0.87 +/- 0.05 SEM) than with PRA (mean r = 0.36 +/- 0.10 SEM). Hence, control of hypertension by glucocorticoid treatment was associated, in all patients, with only partial suppression of ACTH-regulate d hybrid steroid and aldosterone production. Normalization of urinary hybri d steroid levels and abolition of ACTH-regulated aldosterone production is not a requisite for hypertension control and, if used as a treatment goal, may unnecessarily increase the risk of Cushingoid side effects.