Severity of hypertension in familial hyperaldosteronism type I: relationship to gender and degree of biochemical disturbance.
In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid 11beta-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, < or = 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 > 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 x 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 x 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 x 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.
Stowasser
M
M
University Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
Bachmann
A W
AW
Huggard
P R
PR
Rossetti
T R
TR
Gordon
R D
RD
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis / Q000097:blood; D002940:Circadian Rhythm; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D006929:Hyperaldosteronism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011187:Posture; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012727:Sex Characteristics; D012964:Sodium / Q000652:urine
C038135:18-oxocortisol; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone