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Pathophysiology and clinical features of primary aldosteronism

Pathophysiology and clinical features of primary aldosteronism
Literature review current through: Jan 2024.
This topic last updated: May 05, 2022.

INTRODUCTION — Nonsuppressible (primary) hypersecretion of aldosterone is an underdiagnosed cause of hypertension. The classic presenting signs of primary aldosteronism are hypertension and hypokalemia, but potassium levels are often normal in modern-day series of aldosteronomas.

The pathophysiology and clinical features of primary aldosteronism will be reviewed here. The treatment of this disorder and an approach to the diagnosis of hypertension and hypokalemia are discussed separately. (See "Treatment of primary aldosteronism" and "Diagnosis of primary aldosteronism".)

TYPES OF PRIMARY ALDOSTERONISM — Renin-independent, incompletely suppressible (primary) hypersecretion of aldosterone is an increasingly recognized but still underdiagnosed cause of hypertension [1-4]; it is estimated to be responsible for 5 to 20 percent of hypertension in humans [4-6]. Many subtypes of primary aldosteronism have been described since Conn's original report of the aldosterone-producing adenoma (APA) in 1954 [7-10].

The most frequent causes of primary aldosteronism include:

Bilateral idiopathic hyperaldosteronism (or idiopathic hyperplasia [IHA], 60 to 70 percent)

Unilateral APAs (≥10 mm) or aldosterone-producing micronodules (<10 mm; 30 to 40 percent)

Less common forms include:

Unilateral hyperplasia or primary adrenal hyperplasia (caused by micronodular or macronodular hyperplasia of the zona glomerulosa of one adrenal gland). The clinical presentation and outcome of these patients is similar to those with APAs [11,12]. (See "Treatment of primary aldosteronism", section on 'Patients with unilateral adenoma or hyperplasia'.)

Familial hyperaldosteronism (FH) type I (glucocorticoid-remediable aldosteronism [GRA]) due to a CYP11B1/CYP11B2 chimeric gene, type II (the familial occurrence of APA or bilateral IHA or both) caused by germline CLCN2 pathogenic variants), type III caused by germline KCNJ5 pathogenic variants, type IV caused by germline CACNA1H pathogenic variants, and primary aldosteronism with seizures and neurologic abnormalities (PASNA) caused by germline CACNA1D pathogenic variants. (See "Familial hyperaldosteronism".)

Pure aldosterone-producing adrenocortical carcinomas and ectopic aldosterone-secreting tumors (eg, neoplasms in the ovary or kidney). (See "Clinical presentation and evaluation of adrenocortical tumors", section on 'Adrenocortical carcinoma'.)

PATHOPHYSIOLOGY

Renal actions of aldosterone — The clinical features of primary aldosteronism are, in part, determined by the renal actions of aldosterone. The primary effect of aldosterone is to increase the number of open sodium channels in the luminal membrane of the principal cells in the cortical collecting tubule, leading to increased sodium reabsorption [13]. The ensuing loss of cationic sodium makes the lumen electronegative, thereby creating an electrical gradient that favors the secretion of cellular potassium into the lumen through potassium channels in the luminal membrane (figure 1) [14].

Although aldosterone initially induces sodium and water retention, this is followed within a few days by a spontaneous diuresis (called aldosterone escape) that returns excretion to the level of intake and partially lowers the extracellular fluid volume toward normal (figure 2) [15-17]. This response is induced by the volume expansion as escape typically occurs in humans after a weight gain of approximately 3 kg [15]. The mechanisms responsible for the escape phenomenon are incompletely understood, but at least three factors may be important: increased secretion of atrial natriuretic peptide (ANP) induced by the hypervolemia [18], decreased abundance of the thiazide-sensitive sodium-chloride cotransporter that mediates sodium reabsorption in the distal tubule [19], and pressure natriuresis [17,20]. In contrast, there appears to be no change in the abundance of the aldosterone-sensitive collecting tubule sodium channel [19].

Similar considerations apply to hypokalemia. The potassium-wasting effect of excess aldosterone is counterbalanced by the potassium-retaining effect of hypokalemia itself. As a result, the plasma potassium concentration stabilizes at a lower level, but progressive hypokalemia does not occur unless some other factor is added, such as increased aldosterone production or the use of diuretic therapy. The mechanisms by which hypokalemia limits further potassium wasting are discussed elsewhere. (See "Causes of hypokalemia in adults", section on 'Increased urinary losses'.)

With both sodium and potassium handling, a new steady state is established in which the extracellular fluid volume and plasma potassium concentration are stable, although respectively increased and decreased because of the initial effects of aldosterone. In the steady state, both urinary sodium and potassium excretion are roughly equal to dietary intake, similar to that in normal subjects. Similar principles apply to the administration of diuretics as a new steady state is achieved within two to three weeks. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'The steady state' and "Time course of loop and thiazide diuretic-induced electrolyte complications".)

Mutations in aldosterone-producing adenomas — An aldosterone-producing adenoma (APA) is a solitary neoplasm (≥10 mm) composed of clear cells, compact eosinophilic cells, or a mixture of both [21]. Somatic mutations appear to be the cause of aldosterone hypersecretion in more than 90 percent of patients with APAs [22]. Some of these mutations are associated with specific clinical features. Of note, identification of a mutation in an APA does not currently affect management.

Ion channel mutations

KCNJ5 mutations — Somatic mutations in KCNJ5 appear to be present in approximately 40 percent of patients with APAs [22-29]. Point mutations in and near the selectivity filter of the potassium channel KCNJ5 produce increased sodium conductance and cell depolarization, triggering calcium entry into glomerulosa cells, the signal for aldosterone production and cell proliferation.

In a multicenter study of 351 aldosterone-producing lesions from patients with primary aldosteronism and 130 other adrenocortical lesions, two somatic mutations in KCNJ5 (G151R or L168R) were identified in 47 percent of APAs [23]. Somatic KCNJ5 mutations were absent in patients with primary aldosteronism due to unilateral hyperplasia and in 130 non-aldosterone-secreting adrenal lesions. KCNJ5 mutations were overrepresented in APAs from women compared with men (63 versus 24 percent), and APAs with KCNJ5 mutations were larger than those without (27.1 versus 17.1 mm) [23].

In a separate multicenter study, KCNJ5 sequencing was performed on somatic (APA, n = 380) and peripheral (APA, n = 344; bilateral adrenal hyperplasia, n = 174) DNA of patients with primary aldosteronism [24]. Somatic KCNJ5 mutations (G151R or L168R) were found in 34 percent (129 of 380) of APAs. They were significantly more prevalent in women (49 percent) than men (19 percent, p<0.001) and were associated with higher preoperative aldosterone levels but not with therapeutic outcome after surgery [24]. Germline KCNJ5 mutations were not found in patients with bilateral adrenal hyperplasia [24].

Other — Other less common somatic mutations in ATP1A1, ATP2B3, CACNA1D, and CTNNB1 genes have also been identified. In APAs that did not have KCNJ5 mutations, somatic mutations of ATP1A1 (encoding an Na+/K+ ATPase alpha subunit) were found in 16 (5.2 percent) and of ATP2B3 (encoding a Ca2+ ATPase) in five (1.6 percent) [30]. Similar results were noted in a second study [31]. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations, and lower potassium concentrations compared with mutation-negative cases [30].

Additional somatic APA mutations have been identified in CACNA1D, encoding a voltage-gated calcium channel [32]. In one study, CACNA1D mutations were identified in 11 percent of aldosteronomas and were exclusive of KCNJ5 mutations [33]; patients carrying these mutations had smaller tumors and were older than those with KCNJ5 mutations. In two cases with early onset of primary aldosteronism, de novo germline mutations of CACNA1D were identified and associated with complex, severe neurologic and neuromuscular abnormalities (cerebral palsy, seizures, athetosis, spastic quadriplegia). The distribution of somatic mutations may vary by racial background. In a study of 75 patients with APAs, 66 (88 percent) of whom were White, the most frequently mutated genes were KCNJ5 (28 patients; 43 percent), CACNA1D (14; 21 percent), ATP1A1 (11; 17 percent), ATP2B3 (3; 4 percent), and CTNNB1 (2; 3 percent) [22]. In contrast, among 73 African American patients with APAs, somatic driver mutations were found in 65 (89 percent): CACNA1D (27 patients; 42 percent), KCNJ5 (22; 34 percent), ATP1A1 (5; 8 percent), and ATP2B3 mutations (3; 4 percent) [29].

Activating mutations of CTNNB1 (beta-catenin) — Activating mutations of exon 3 of the CTNNB1 gene (beta-catenin) in the Wnt signaling pathway have been identified in benign adrenocortical tumors (typically in larger and nonsecreting adenomas), in APAs, and in adrenocortical carcinomas. (See "Clinical presentation and evaluation of adrenocortical tumors".)

In primary aldosteronism, aldosterone secretion is relatively independent from the suppressed renin-angiotensin system but can be regulated by several hormones activating variable levels of eutopic or aberrant hormone receptors, including those for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) [34-37]. The role of aberrant hormone receptors in adrenal disease is reviewed separately. (See "Cushing's syndrome due to primary bilateral macronodular adrenal hyperplasia", section on 'Aberrant hormone receptors' and "Clinical presentation and evaluation of adrenocortical tumors".)

Activating somatic CTNNB1 mutations have been identified in tumors of three women with APAs, two of whom presented during pregnancy and one after menopause [38]. All three had heterozygous activating mutations of CTNNB1 and large overexpression of aberrant LH/hCG and GnRH receptors (100-fold higher than in other APAs). This suggests that CTNNB1 mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. It is thought that the high levels of endogenous hCG during pregnancy and of GnRH and LH after menopause led to the identification of APAs in these patients.

Idiopathic hyperplasia — The underlying pathophysiology of increased secretion of aldosterone by the zona glomerulosa in patients with bilateral idiopathic hyperaldosteronism (or idiopathic hyperplasia [IHA], occasionally unilateral [39]) is still incompletely understood. An aldosterone secretory factor has not been identified. Although angiotensin II adrenal hypersensitivity in patients with IHA has been recognized for many years [40], the hyperaldosteronism in patients with IHA is not reversed with angiotensin II inhibitors.

In a cohort of 15 IHA adrenals, CYP11B2 immunoreactivity in the non-nodular zona glomerulosa was only observed in 4 of the 15 adrenals, a finding that suggested that hyperplasia of CYP11B2-expressing cells may not be the major cause of IHA [41]. The adrenal cortex of all 15 IHA adrenals harbored at least one CYP11B2-positive aldosterone-producing micronodule (<10 mm in diameter) [21,41]. Somatic mutations in genes encoding CACNA1D were found in 58 percent of the micronodules. These data suggest that IHA may result from not only hyperplasia but also aldosterone-producing micronodules that harbor somatic aldosterone-driver gene mutations.

CLINICAL FEATURES — Primary and nonsuppressible hypersecretion of aldosterone is an increasingly recognized but still underdiagnosed cause of hypertension [4]. The classic presenting signs of primary aldosteronism are hypertension and hypokalemia, but potassium levels are frequently normal in modern-day series of primary aldosteronism. In general, when compared with patients with idiopathic hyperplasia (IHA), patients with an aldosterone-producing adenoma (APA) tend to have more severe hypertension and are more frequently recognized to be hypokalemic. However, these clinical findings do not reliably distinguish between APA and IHA.

Hyperaldosteronism exerts deleterious cardiovascular effects independent of the plasma potassium concentration. The overall treatment goal in patients with primary aldosteronism is to prevent the adverse outcomes associated with excess aldosterone, including hypertension, hypokalemia, renal toxicity, and cardiovascular damage. (See 'Renal effects' below and 'Cardiovascular risk' below.)

Hypertension — Hypertension is the major clinical finding in primary aldosteronism [7-10]. The elevation in blood pressure is dependent upon the mild volume expansion that occurs, being prevented in animals and effectively treated in humans by dietary sodium restriction [42,43]. Persistent hypervolemia also leads to an increase in systemic vascular resistance that helps to perpetuate the hypertension [42].

In addition to promoting the development of hypertension, hypervolemia is responsible for another characteristic finding in primary aldosteronism: marked suppression of renin release, leading to a very low plasma renin activity and plasma renin concentration [8-10]. The finding of suppressed renin measurements is of diagnostic importance in distinguishing primary from secondary hyperreninemic forms of hyperaldosteronism, as occur with renovascular hypertension, coarctation of the aorta, renin-secreting neoplasms, or diuretic therapy. (See "Diagnosis of primary aldosteronism".)

The blood pressure in primary aldosteronism is often substantially elevated. In one series, as an example, the mean blood pressure was 184/112 and 161/105 mmHg in patients with an adrenal adenoma and hyperplasia, respectively [44]. Despite these high blood pressure levels, malignant hypertension is a rare occurrence [45].

Primary aldosteronism may be associated with resistant hypertension, which is defined as failure to achieve goal blood pressure despite adherence to an appropriate, three-drug regimen including a diuretic. In a review of 1616 patients with resistant hypertension, 11 percent fulfilled criteria for primary aldosteronism; hypokalemia was seen in only 45 percent [46]. (See "Definition, risk factors, and evaluation of resistant hypertension", section on 'Primary aldosteronism'.)

Rarely, hypertension is absent in patients with primary aldosteronism [4,47,48]. In this setting, the blood pressure may become very low with relief of the aldosterone excess, suggesting that aldosterone excess produced the expected significant increase in blood pressure over baseline.

Even serum aldosterone levels in the high-normal range may be associated with increased blood pressure. This was illustrated in a report from the Framingham Offspring study in which baseline serum aldosterone levels were obtained among 1688 initially nonhypertensive participants (mean blood pressures of 121/75 and 117/71 mmHg for males and females, respectively) [49]. At follow-up at four years, an increase in blood pressure category or the development of hypertension had occurred in 34 and 15 percent of individuals, respectively. Compared with the lowest quartile of serum aldosterone (range of 2 to 7 ng/dL), the highest quartile (range of 14 to 60 and 72 ng/dL) was associated with an increased risk of elevated blood pressure (odds ratio [OR] 1.60, 95% CI 1.19-2.14) and hypertension (OR 1.61, 95% CI 1.05-2.46). Although these results are intriguing, interpretation of serum aldosterone levels requires knowledge of the exact level of salt and potassium intake and plasma renin values. These parameters were not available in enrolled individuals.

Hypokalemia: An inconsistent finding — Although hypokalemia has historically been considered to be one of the major clinical features of primary aldosteronism, it is now estimated that only 9 to 37 percent of patients with primary aldosteronism are hypokalemic [1,50].

In a retrospective, international report combining data from five centers (Italy, United States, Singapore, Chile, and Australia), less than 50 percent of patients diagnosed with primary aldosteronism were hypokalemic at presentation [50]. In a second series, hypokalemia was found in 50 percent of patients with APAs and 17 percent of patients with bilateral hyperplasia [51]. (See "Diagnosis of primary aldosteronism".)

Hypokalemia is more often present in patients with primary aldosteronism who are on an adequate sodium intake [9,10,44]. Two factors contribute to the urinary potassium wasting in this setting: the hypersecretion of aldosterone, which directly promotes potassium secretion in the cortical collecting tubule, and adequate delivery of sodium and water to the distal secretory site [52]. As an example, increasing sodium intake and therefore distal delivery will exacerbate the hypokalemia in this setting since aldosterone secretion will not be appropriately suppressed by the volume expansion [53].

The fall in the plasma potassium concentration in primary aldosteronism is accompanied by metabolic alkalosis. This disorder is largely due to increased urinary hydrogen excretion mediated both by hypokalemia and by the direct stimulatory effect of aldosterone on distal acidification. (See "Pathogenesis of metabolic alkalosis".)

For patients who do have hypokalemia, the plasma potassium tends to be relatively stable, at least over the short term, since the potassium-wasting effect of excess aldosterone is counterbalanced by the potassium-retaining effect of hypokalemia itself. Progressive hypokalemia does not occur unless some other factor is added, such as increased aldosterone production or the use of diuretic therapy (see 'Renal actions of aldosterone' above). The mechanisms by which hypokalemia limits further potassium wasting are discussed elsewhere. (See "Causes of hypokalemia in adults", section on 'Increased urinary losses'.)

Cardiovascular risk — Patients with primary aldosteronism have a higher rate of cardiovascular morbidity and mortality than age- and sex-matched patients with primary hypertension and the same degree of blood pressure elevation [54-58]. The cardiovascular effects of hyperaldosteronism are independent of the plasma potassium concentration.

Patients with primary aldosteronism have greater left ventricular (LV) mass measurements and decreased LV function when compared with age-, sex-, and blood pressure-matched patients with other types of hypertension [56,58]. Other cardiovascular risks include stroke, myocardial infarction, and atrial fibrillation.

The best evidence for excess cardiovascular morbidity comes from a meta-analysis of 31 studies, including 3838 patients with primary aldosteronism and 9284 patients with essential hypertension. Patients with APA and IHA had an increased risk of stroke (OR 2.58), coronary artery disease (OR 1.77), atrial fibrillation (OR 3.52), and heart failure (OR 2.05) [59]. In addition, the diagnosis of primary aldosteronism was associated with a higher risk of diabetes (OR 1.33), metabolic syndrome (OR 1.53), and left ventricular hypertrophy (OR 2.29).

Dietary salt may affect the impact of primary aldosteronism on cardiac damage. In a case-control study of 21 patients with primary aldosteronism and 21 control patients with primary hypertension, 24-hour urinary sodium excretion was an independent predictor for LV wall thickness and mass in patients with primary aldosteronism but not primary hypertension [60]. Although data are limited, dietary salt restriction may help reduce cardiovascular risk in these patients.

Additional evidence for the adverse cardiovascular effects of excess aldosterone comes from randomized, controlled trials that have demonstrated improved survival with the mineralocorticoid receptor antagonists spironolactone (in patients with advanced heart failure) and eplerenone (in patients with LV dysfunction after a myocardial infarction) [61,62]. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Primary components of therapy'.)

These observations are consistent with animal and human studies showing that hyperaldosteronism exerts deleterious cardiovascular effects independent of the plasma potassium concentration. These effects may be mediated at least in part by mineralocorticoid receptors in the heart and blood vessels (including coronary artery and aorta) [63-65]. Activation of the mineralocorticoid receptor may act in part by impairing endothelial function, an effect that may be mediated by reduced glucose 6-phosphate dehydrogenase activity [66]. These effects can be largely or completely abolished by the administration of a mineralocorticoid receptor antagonist or by reducing plasma aldosterone concentrations by adrenalectomy [64,66].

Metabolic syndrome — Type 2 diabetes and metabolic syndrome are more prevalent in patients with primary aldosteronism than in controls matched for sex, age, BMI, and blood pressure [67]. This may explain, at least in part, the increased cardiovascular disease morbidity and mortality in primary aldosteronism patients.

Renal effects — Aldosterone may raise the glomerular filtration rate (GFR) and renal perfusion pressure independent of systemic hypertension. In addition, increased urinary albumin excretion is common. These changes appear to be largely reversible with treatment, as illustrated by the following findings:

In a report of 25 patients with primary aldosteronism, the GFR and effective renal plasma flow decreased six months after surgery for removal of adrenal adenoma but did not change after blood pressure control in the comparison group with primary hypertension (formerly called "essential" hypertension) [68]. In addition, hyperaldosteronism was associated with tubular dysfunction, as assessed with urinary beta-2 microglobulin excretion, which improved six months after surgery. These changes cannot be explained by reductions in blood pressure alone, since the patients with adrenal adenoma and primary hypertension had similar blood pressure at baseline and blood pressure control at six months.

Similar findings were seen in a second series of 50 patients with primary aldosteronism treated with adrenalectomy or spironolactone and 100 patients with primary hypertension started on antihypertensive therapy [69]. At baseline, the GFR and albumin excretion were higher in the patients with primary aldosteronism. In the first six months of follow-up, the reductions in GFR and albuminuria were significantly greater in the patients with primary aldosteronism, who also were more likely to have restoration of normal albumin excretion. Blood pressure control was similar in the two groups.

In a third report of 408 patients with primary aldosteronism and a control group of 408 patients with primary hypertension, more patients in the primary aldosteronism group had a serum creatinine concentration above 1.25 mg/dL than controls (29 versus 10 percent in the primary aldosteronism and control groups, respectively) [70]. Age, male sex, low potassium, and high serum aldosterone concentrations were independent predictors of a lower GFR. In the primary aldosteronism group, adrenalectomy increased the serum creatinine and decreased the mean GFR from 71 to 64 mL/min. Treatment with spironolactone resulted in a similar decline in GFR. Thus, surgical cure or mineralocorticoid receptor blockage reverses the hyperfiltration state and unmasks the underlying renal insufficiency.

Quality of life — Several studies have demonstrated the negative impact of primary aldosteronism on quality of life [71-73]. In a systematic review of 15 studies, untreated patients with primary aldosteronism (APA and IHA) showed an impaired physical and mental quality of life compared with the general population [72]. Symptoms of anxiety, demoralization, stress, depression, and nervousness were more frequently reported in untreated patients with primary aldosteronism than in the general population and in patients with hypertension [72]. Surgical management often normalizes quality of life measures. Medical therapy improves quality of life, but not to the same extent as surgery [73].

Other

Mild hypernatremia — The persistent mild volume expansion resets the osmostat regulating antidiuretic hormone release and thirst upward by several mEq/L [74]. As a result, patients with primary aldosteronism usually have a stable plasma sodium concentration between 143 and 147 mEq/L.

Hypomagnesemia — Mild hypomagnesemia due to urinary magnesium wasting also may occur in patients with persistent mineralocorticoid excess. How this occurs is incompletely understood. The ascending limb of the loop of Henle, as an example, is the primary site of tubular magnesium reabsorption [75]; inhibition of sodium transport in this segment during aldosterone escape [16] may be associated with a parallel decline in magnesium reabsorption. (See "Regulation of magnesium balance".)

Muscle weakness — Muscle weakness can occur in patients with primary aldosteronism. It is primarily due to hypokalemia and is not typically prominent unless the plasma potassium concentration is below 2.5 mEq/L. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Severe muscle weakness or rhabdomyolysis'.)

Genotype-phenotype correlation — As noted above, somatic mutations are the cause of aldosterone hypersecretion in approximately 90 percent of patients with APAs. Some mutations have been associated with specific clinical features, but their identification does not currently affect management. Genotype-phenotype correlations include the following (see 'Mutations in aldosterone-producing adenomas' above):

APAs with KCNJ5 mutations are more common in females than males and appear to be larger than APAs without mutations [23,24].

APAs with ATP1A1 or ATP2B3 mutations appear to be more common in men and associated with higher plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases [30].

Patients with CACNA1D mutations appear to have smaller tumors and are older than patients with KCNJ5 mutations [33].

KCNJ5 mutations have the highest prevalence in Asian populations [76-78] followed by those of European [41] and African ancestries [79].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary aldosteronism".)

SUMMARY

Types of primary aldosteronism – Nonsuppressible (primary) hypersecretion of aldosterone is an underdiagnosed cause of hypertension. The classic presenting signs of primary aldosteronism are hypertension and hypokalemia. The most common subtypes are aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. (See 'Types of primary aldosteronism' above.)

Pathophysiology – Somatic mutations appear to be the cause of aldosterone hypersecretion in more than 90 percent of patients with APAs. (See 'Mutations in aldosterone-producing adenomas' above.)

Clinical features

Hypertension – Primary aldosteronism may be associated with resistant hypertension, which is defined as failure to achieve goal blood pressure despite adherence to an appropriate, three-drug regimen including a diuretic. (See 'Hypertension' above.)

Hypokalemia in some patients – Although hypokalemia is considered to be a "classic" sign of primary aldosteronism, many patients with primary aldosteronism due to an adrenal adenoma and, more commonly, those with adrenal hyperplasia, are not hypokalemic. (See 'Hypokalemia: An inconsistent finding' above.)

Kidney impairment – Aldosterone may raise the glomerular filtration rate (GFR) and renal perfusion pressure independent of systemic hypertension. In addition, increased urinary albumin excretion is common. These changes appear to be largely reversible with treatment. (See 'Renal effects' above.)

Cardiovascular risk – Patients with primary aldosteronism, when matched for age, blood pressure, and the duration of hypertension, have a greater risk of cardiovascular disease when compared with patients with other types of hypertension, including primary hypertension (formerly called "essential" hypertension), pheochromocytoma, and Cushing syndrome. The excess cardiovascular risk resolves after appropriate treatment of the mineralocorticoid excess. (See 'Cardiovascular risk' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Norman M Kaplan, MD, who contributed to earlier versions of this topic review.

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Topic 140 Version 32.0

References

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