Primary aldosteronism, a common entity? the myth persists

Padfield, P. L.

doi:10.1038/sj.jhh.1001321

Cited by 39 publications

(31 citation statements)

References 21 publications

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“…However, an exquisite differential sensitivity in aldosterone secretory responses to changes in circulating Ang II and [desaspartyl 1 ]-Ang II (Ang III) is observed after peptide infusion or postural changes in patients with IHA but not APA (39)(40)(41). Taken together, the findings in this work provide proof of principle that an intrinsic alteration in the membrane properties of ZG cells can induce autonomous aldosterone production with clinical features typical of IHA, including increase responsiveness to Ang II (42).…”

Section: Discussionmentioning

confidence: 52%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

171

166

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When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK −/− ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK −/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK −/− mice. Thus, TASK −/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.

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Section: Discussionmentioning

confidence: 52%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

171

166

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“…20,21 Concerns have been raised about the potential overdiagnosis of PA in various hypertensive populations. [22][23][24][25][26] The major concern has been about relying on the ARR to diagnose PA or to preselect patients for suppression testing. The current protocol was specifically designed to overcome this deficiency by conducting suppression testing in all evaluated subjects.…”

Section: Discussionmentioning

confidence: 99%

Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension

Calhoun

Nishizaka²,

Zaman³

et al. 2002

Hypertension

651

327

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Abstract-Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was Ͻ1.0 ng/mL per hour and urinary aldosterone was Ͼ12 g/24-hour during high urinary sodium excretion (Ͼ200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (Ͼ20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. Key Words: hyperaldosteronism Ⅲ hypertension, essential Ⅲ blacks Ⅲ diuretics Ⅲ renin P rimary hyperaldosteronism (PA) has historically been thought to be an uncommon cause of hypertension, with an estimated prevalence of Ͻ2% among the general hypertensive population. Recent studies, however, have suggested that the prevalence of PA may be as high as 8% to 30% in selected hypertensive populations. 1-10 These reports have been based on either a high plasma aldosterone/plasma renin activity ratio (ARR) or a lack of suppression of plasma or urinary aldosterone in patients identified by an elevated ARR. As PA is generally remediable by treatment with an aldosterone antagonist or, in the case of adrenal adenoma, by adrenalectomy, knowing the true prevalence of PA in selected hypertension populations is clinically important for maximizing diagnosis and treatment.Prior studies determining the prevalence of PA have been based on an elevated ARR or confirmatory suppression testing in subjects preselected for a high ARR. The former approach would tend to overestimate the prevalence of PA, because patients with a falsely elevated ARR would be included, whereas the latter approach would underestimate the prevalence of PA because of the exclusion of patients with a falsely low ARR. Diagnosis of PA by confirmatory suppression testing of all evaluated patients would be necessary to overcome these limitations.The prevalence of PA has not been systematically determined in a population that has included a large proportion of African American subject...

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“…14 ARR has been proposed as the most sensitive screening test, 3,5,[11][12][13]15 but it has been criticized because it predominantly depends on low PRA values 5,9,16,17 and because of its low specificity. 18 For this reason combined criteria including also an aldosterone level above a minimal threshold have been proposed.…”

Section: -13mentioning

confidence: 99%

“…5,6 A low-renin profile represents a hallmark of this condition but it is not clear to what extent it overlaps with the so-called 'low-renin (essential) hypertension' which is thought to affect about onethird of the hypertensive population and indicate a sodium volume-dependent hypertension deserving appropriate treatment. [7][8][9][10] There is general agreement that the diagnostic protocol for primary aldosteronism requires a multi-step evaluation and should begin with a first-step laboratory screening, followed, when appropriate, by confirmation tests and further functional and anatomical evaluation.…”

Section: Introductionmentioning

confidence: 99%

The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women

et al. 2008

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Primary aldosteronism is increasingly investigated in hypertension being associated with an elevated cardiovascular risk. Aldosterone has been reported to increase in the luteal phase in normal women but to our knowledge the influence of the ovarian cycle on the first screening for primary aldosteronism (that is, on the levels of plasma aldosterone and its relationship to PRA levels) was never investigated. We measured hormonal levels during one cycle in 26 low-renin mild hypertensive outpatients. LH, FSH, 17 b-estradiol, progesterone, aldosterone and PRA were assayed at the seventh, fourteenth, twenty-first and twenty-eighth days of the cycle after 30 min of recumbency. Aldosterone and PRA increased from the seventh (follicular phase) to twentyfirst day (luteal phase) from 11.2 to 17.8 ng 100 ml À1 and from 0.23 to 0.35 ng ml À1 h À1 , respectively (both P ¼ 0.004) The proportion of patients with aldosterone 415 ng 100 ml À1 significantly increased from the follicular to the luteal phase, (8/26 vs 19/25, P ¼ 0.018); a similar increase was found for Aldosterone-PRA Ratio 430 combined with either a minimum PRA value of 0.5 ng ml À1 h À1 or aldosterone 415 ng 100 ml À1 (7/26 vs 16/25 and 7/26 vs 17/25 respectively, Po0.05).Aldosterone was positively related to PRA and progesterone. Higher aldosterone levels may be frequently encountered in the second part of the ovarian cycle in low-renin hypertensive women. This variability appears to be an important factor to be taken into account in the first-step laboratory screening for primary aldosteronism and should be considered in the process of standardization of the diagnostic work-up for this disease.

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Primary aldosteronism, a common entity? the myth persists

Cited by 39 publications

References 21 publications

TASK channel deletion in mice causes primary hyperaldosteronism

TASK channel deletion in mice causes primary hyperaldosteronism

Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension

The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women

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