M. Stowasser et al., Severity of hypertension in familial hyperaldosteronism type I: Relationship to gender and degree of biochemical disturbance, J CLIN END, 85(6), 2000, pp. 2160
In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid 11 be
ta-hydroxylase/aldosterone synthase gene causes ACTH-regulated aldosterone
overproduction. In an attempt to understand the marked variability in hyper
tension severity in FH-I, we compared clinical and biochemical characterist
ics of 9 affected individuals with mild hypertension (normotensive or onset
of hypertension after 15 yr, blood pressure never >160/100 mm Hg, less tha
n or equal to 1 medication required to control hypertension, no history of
stroke, age >18 yr when studied) with those of 17 subjects with severe hype
rtension (onset before 15 yr, or systolic blood pressure >180 mm Hg or dias
tolic blood pressure >120 mm Hg at least once, or greater than or equal to
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 stil
l 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 con
ducted in 6 mild and 16 severe subjects. The 2 groups were similar in terms
of urinary sodium excretion. Mild subjects tended, although not significan
tly, to have lower urinary 18-oxo-cortisol (mean +/- SD, 27.4 +/- 9.0 vs. 3
5.2 +/- 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 recu
mbency) plasma aldosterone levels (498 +/- 279 us. 744 +/- 290 pmol/L). Upr
ight (midmorning after 2-3 h of upright posture) plasma aldosterone levels
were similar (mild, 485 +/- 150; severe, 474 +/- 188 pmol/L). In 1 normoten
sive female, upright PRA was much higher, and the upright aldosterone/PRA r
atio was much lower than that in the other subjects. The remaining mild sub
jects had similar upright PRA levels (mild, 2.8 +/- 1.4; severe, 3.1 +/- 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, aldosteron
e 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 us. 5
20 +/- 330 pmol/L; P < 0.05). Aldosterone was unresponsive (rose by <50%) t
o 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 AC:TK 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 o
f hybrid gene-induced aldosterone overproduction may have contributed to th
e severity of hypertension.