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Severity of Hypertension in Familial Hyperaldosteronism Type I: Relationship to Gender and Degree of Biochemical Disturbance¹

Hypertension Unit, University Department of Medicine, Greenslopes Hospital, Brisbane 4120, Australia

Address all correspondence and requests for reprints to: Prof. Richard D. Gordon, Hypertension Unit, University Department of Medicine, Greenslopes Hospital, Brisbane 4120, Australia. E-mail: med.gslopes{at}mailbox.uq.edu.au

In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid 11ß-hydroxylase/aldosterone synthase gene causes ACTH-regulated aldosterone overproduction. In an attempt to understand the marked variability in hypertension severity in FH-I, we compared clinical and biochemical characteristics of 9 affected individuals with mild hypertension (normotensive or onset of hypertension after 15 yr, blood pressure never >160/100 mm Hg, 1 medication required to control hypertension, no history of stroke, age >18 yr when studied) with those of 17 subjects with severe hypertension (onset before 15 yr, or systolic blood pressure >180 mm Hg or diastolic blood pressure >120 mm Hg at least once, or 2 medications, or history of stroke). Severe hypertension was more frequent in males (11 of 13 males vs. 6 of 13 females; P < 0.05). All 4 subjects still normotensive after age 18 yr were females. Of 10 other affected, deceased individuals (7 males and 3 females) from a single family, all six who died before 60 yr of age (4 by stroke) were males. Biochemical studies were conducted in 6 mild and 16 severe subjects. The 2 groups were similar in terms of urinary sodium excretion. Mild subjects tended, although not significantly, to have lower urinary 18-oxo-cortisol (mean ± SD, 27.4 ± 9.0 vs. 35.2 ± 12.9 nmol/mmol creatinine·day), higher plasma potassium (4.0 ± 0.3 vs. 3.6 ± 0.4 mmol/L), and lower recumbent (0800 h after overnight recumbency) plasma aldosterone levels (498 ± 279 vs. 744 ± 290 pmol/L). Upright (midmorning after 2–3 h of upright posture) plasma aldosterone levels were similar (mild, 485 ± 150; severe, 474 ± 188 pmol/L). In 1 normotensive female, upright PRA was much higher, and the upright aldosterone/PRA ratio was much lower than that in the other subjects. The remaining mild subjects had similar upright PRA levels (mild, 2.8 ± 1.4; severe, 3.7 ± 3.2 pmol/L·min) and aldosterone/PRA ratios (mild, 199.5 ± 133.4; severe, 200.6 ± 150.9) as severe subjects. During angiotensin II (AII) infusion studies (n = 6 mild and 10 severe), performed during recumbency, aldosterone levels were lower in the mild group both basally (404 ± 144 vs. 843 ± 498 pmol/L; P < 0.05) and after 60 min AII (2 ng/kg·min; 261 ± 130 vs. 520 ± 330 pmol/L; P < 0.05). Aldosterone was unresponsive (rose by <50%) to AII in all subjects. Day curve studies (blood collected every 2 h for 24 h; n = 2 mild and 7 severe) demonstrated abnormal regulation of aldosterone by ACTH rather than by AII in both groups. In conclusion, in this series of patients with FH-I, males had more severe hypertension, and the degree of hybrid gene-induced aldosterone overproduction may have contributed to the severity of hypertension.

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