Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism
© Amar et al; licensee BioMed Central Ltd. 2010
Received: 22 October 2009
Accepted: 19 May 2010
Published: 19 May 2010
Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension.
This review deals with the prevalence, presentation, diagnosis and management of surgically correctable forms of primary aldosteronism (PA).
Disease name and synonyms
Primary aldosteronism subtypes
Surgically correctable subtypes:
Aldosterone-producing adenoma (alias Conn's adenoma, aldosteronoma), including:
Renin- or angiotensin-unresponsive adenoma
Renin- or angiotensin-responsive adenoma
Primary unilateral adrenal hyperplasia
Adrenocortical carcinoma with aldosterone hypersecretion
Non surgically correctable subtypes:
Idiopathic adrenal hyperplasia
Familial hyperaldosteronism type I (alias glucocorticoid-remediable aldosteronism), OMIM # 103900
Familial hyperaldosteronism type II, OMIM # 605635
Hyperaldosteronism is a condition caused by the overproduction of aldosterone, and is characterized by sodium retention and potassium excretion with resultant hypertension and hypokalemia. The condition was first described by J Conn , who further distinguished primary and secondary hyperaldosteronism on the basis of plasma renin levels, PA being characterized by renin suppression . In a recent clinical practice guideline, PA was defined as "a group of disorders in which aldosterone production is inappropriately high, relatively autonomous from the renin-angiotensin system, and non-suppressible by sodium loading" .
Prevalence of a raised aldosterone to renin ratio and of aldosterone-producing adenomas in referral samples or samples from a large community
Source and first author
ARR threshold, ng/dL per ng/mL.h-1
Subjects tested, n
Raised ARR, %
Confirmed PA, %
Proven adenoma, %
Community sample of hypertensive and non-hypertensive subjects
Newton-Cheh C, 2007
Referral samples of >1000 hypertensive patients
Nishikawa T, 2000
Rossi E, 2002
Rossi GP, 2006
Fogari R, 2007
Douma S, 2008
Adrenalectomy for Conn's adenoma has been reported in childhood . The prevalence of surgically correctable PA in children and adolescents is not known but is probably very low.
Between 1977 and 1981, the incidence rate of aldosterone-producing adenomas for which the patient underwent surgery was estimated at 0.8 per million individuals per year in Denmark . This figure is a low estimate, as it was obtained at a time when the aldosterone to renin ratio was not in use and computed tomography was not widely available. A national epidemiological survey in Japan estimated that 1,450 patients had been diagnosed with PA of any form in 1997 . In 1997, there were about 70 million Japanese adults aged 60 or less; thus, the incidence rate of PA could be estimated to be 2 cases per 100,000 individuals per year in this age group.
Patients with PA present with various degrees of hypertension and/or hypokalemia.
Surgically correctable PA is usually diagnosed in the fourth or fifth decade. Mean age at PA diagnosis across 9 large series ranged between 45 and 55 years, with an overall average of 50 years [15–24]. Hypertension was generally detected 5 to 10 years before PA was diagnosed, indicating a significant delay between the onset of PA and its diagnosis. Grade III hypertension - with blood pressure (BP) levels of 180/110 mmHg or more - or resistant hypertension - with BP levels of 140/90 mmHg or more on triple antihypertensive treatment - are reported more frequently in patients with PA than in those with essential hypertension [7, 25]. The higher frequency of severe hypertension in patients with PA than in those with essential hypertension may be the consequence of an exploration bias, as current recommendations suggest screening for secondary causes, including PA, in patients with severe or difficult-to-treat hypertension . Left ventricular hypertrophy, microalbuminuria, and acute cardiovascular events are probably more frequent in patients with PA than in patients with essential hypertension and similar levels of BP (see Treatment objectives below).
Hypokalemia, usually defined as serum kalemia ≤ 3.5 mmol/l, is only present in a minority of patients with PA [5–9]. However, the frequency of hypokalemia is related to whether PA can be surgically cured. A study with a large series of patients reported that hypokalemia was present in 7%, 17% and 48% of patients with essential hypertension, idiopathic PA, and aldosterone-producing adenoma, respectively . Hypokalemia may be symptomatic and present as muscular weakness, cramps, paresthesia or palpitations with or without atrial fibrillation. There are rare cases in which PA is revealed by symptomatic hypokalemia without hypertension, with or without adenoma .
PA may also be documented in patients presenting with an incidentally detected adenoma. In a survey of 1096 patients with an adrenal 'incidentaloma', 16 patients were found to have PA, all of whom were moderately hypertensive .
Etiology of primary aldosteronism
The aldosterone to renin ratio is a heritable trait with a moderate degree of linkage to chromosome 11p . The etiology of aldosterone-producing adenoma and primary unilateral hyperplasia is not known.
Mechanism of hypertension in primary aldosteronism
The main effects of aldosterone are mediated by the mineralocorticoid receptor found in the cytosol of epithelial cells, particularly in the renal collecting duct. Aldosterone's major action on epithelial cells is to regulate the reabsorption of Na+, thereby also influencing the transport of water, K+, and H+ across the membrane. An electrochemical gradient permits the passage of sodium from the lumen into the epithelial cell through the amiloride-sensitive epithelial sodium channel. From there, active transport by the Na+/K+-ATPase carries the Na+ across the basolateral membrane, from the epithelial cell into the bloodstream, while simultaneously excreting K+; water follows the movement of the Na+. Aldosterone hypersecretion therefore increases exchangeable sodium, suppresses renin, increases the aldosterone to renin ratio, causes hypertension, and induces hypokalemia.
Diagnosis of primary aldosteronism
The aldosterone to renin ratio as a screening test
Aldosterone secretion increases when standing upright and with decreasing sodium intake. It decreases with decreasing plasma potassium concentrations and increasing age. Renin levels are also increased by decreases in sodium intake and the standing position, and they also decrease with increasing age. Therefore, using the aldosterone to renin ratio decreases the intra- and inter-patient variability in renin and aldosterone levels linked to sodium intake, body position and age[29, 30]. The aldosterone to renin ratio was introduced by K Hiramatsu and colleagues in 1981 as a screening tool to facilitate the diagnosis of PA among hypertensive patients .
Although logical and convenient, using the aldosterone to renin ratio has several limitations. First, renin levels can be determined as either plasma renin activity or active renin concentration, and aldosterone can be determined with iodinated or tritiated markers, with or without an extraction step. Consequently, reference values and diagnostic thresholds for renin, aldosterone and the aldosterone to renin ratio are laboratory-specific. Second, there is no agreement on the aldosterone to renin ratio cut-off value for diagnosing PA. In a systematic literature review, the aldosterone to plasma renin activity cut-off values suggested ranged from 7.2 to 100 ng/dl per ng/ml.h, corresponding to a 14-fold variation . The most frequently used cut-off values for aldosterone to plasma renin activity ratio are in the range of 20 to 50 ng/dl (554 to 1,385 pmol/l) per ng/ml.h; for aldosterone to active renin concentration, these values are in the range of 2.4 to 4.9 ng/dl (66 to 136 pmol/l) per mU/L (see  and Table 2). Third, the aldosterone to renin ratio is positively related to age, female sex, hypertensive status, and the use of beta-blockers or hormonal replacement therapy, and is negatively related to the use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and diuretics. The aldosterone to renin ratio may be abnormally high in patients with normal aldosterone levels and very low renin levels, specifically in some elderly patients, some patients with a high sodium intake or those taking beta-blockers, in whom renin is undetectable. Some experts have therefore suggested that renin values below an appropriate minimal value (2.5 to 5 mU/l) should not be used to calculate the aldosterone to renin ratio [7, 22].
Some authors suggest screening for PA without the discontinuation of medication . However, antihypertensive agents alter the aldosterone to renin ratio. For example, in the Framingham Offspring Cohort, an aldosterone to renin ratio exceeding the value suggestive of PA was present in 3.1% of normotensive men and 8.8% of normotensive women, in 7.9% and 23.1% of untreated hypertensive men and women, and was present in 31.1% of men or women on beta-blockers (Figure 1). Therefore, diuretics and antihypertensive agents should be discontinued for at least two weeks and spironolactone, eplerenone and aliskiren for at least six weeks before determining the aldosterone to renin ratio. In cases in which a complete therapeutic washout would not be safe, antihypertensive medication should be limited to non-dihydropyridine calcium channel-blockers and alpha-blockers, which interfere minimally with the measurements. Hypokalemic patients are given potassium chloride for two reasons: to prevent arrhythmia and because hypokalemia inhibits aldosterone secretion, thereby increasing the risk of false negative results. In addition to antihypertensive agents, drospirenone, a progestin with antimineralcorticoid activity, may interfere with laboratory screening and confirmatory testing for the diagnosis of PAL and should be withdrawn in hypertensive women investigated for aldosteronism.
Renin-aldosterone dissociation is a key element of all definitions of PA. A raised aldosterone to renin ratio is a sensitive but non-specific test ([2–9] and Table 2). Biochemical confirmatory tests are therefore necessary in patients with a positive aldosterone to renin ratio, to avoid costly and invasive imaging tests.
Suppression tests intended to confirm PA
Oral sodium loading test
Increase sodium intake to >200 mmol/d for 3 d, provide ClK to keep plasma K+
Urinary aldosterone determined from the morning of d 3 to the morning of d 4
PA unlikely if urinary aldosterone <10 μg/24 h
PA likely if urinary aldosterone >12 μg/24 h
Saline infusion test
Patient in recumbent position for at least 1 h, 2 liters of 0.9% saline iv over 4 h, starting at 0800-0930 h
Kalemia, aldosterone and cortisol at the beginning and the end of the test
PA unlikely if plasma aldosterone <5 ng/dl
PA likely if plasma aldosterone >10 ng/dl
Fludrocortisone suppression test
0.1 mg oral fludrocortisone every 6 h for 4 d. Provide slow-release KCl to keep plasma K+ and slow release NaCl to maintain urinary sodium excretion >3 mmol/kg body weight
Kalemia 4 times a day during the 4 days. On day 4
determine plasma cortisol, aldosterone and PRA in seated posture at 1000 h
PA likely if upright plasma aldosterone >6 ng/dl on day 4 at 1000 h
Captopril challenge test
25-50 mg captopril orally after sitting for at least 1 hour. Patient in seated position for 1 or 2 hours
Plasma aldosterone, PRA and cortisol before and 1 or 2 hours after captopril
PA likely if plasma aldosterone is not suppressed by captopril
Diagnosis of surgically correctable primary aldosteronism
As mentioned above, cases with unilateral aldosterone hypersecretion, including the classic aldosterone-producing Conn's adenoma, are surgically correctable forms of PA. Unilateral aldosterone hypersecretion should be confirmed by AVS in most or perhaps all cases (see  and Figure 2). Unfortunately, AVS is not widely available, and is an invasive test exposing patients to potential complications.
Non-secreting adenomas are present in about 2% of adult non-cancer patients and their prevalence increases with age . The presence of an adenoma in patients with PA suggests the presence of an aldosterone-producing adenoma, but it cannot exclude the combination of a non-secreting adenoma and idiopathic PA[3, 44]. The proportion of patients with a unilateral nodule on their computed tomography scan or magnetic resonance imaging, but a bilateral or contralateral secretion documented by AVS, was about 20% in a meta-analysis of 38 studies. Nonetheless, a non-secreting adenoma is unlikely in young patients with PA and the presence of an isolated characteristic adrenal adenoma > 1 cm in PA patients aged less than 40 [6, 50] or less than 55 is considered by some experts as an acceptable surrogate for diagnosing unilateral aldosterone hypersecretion.
Recent guidelines recommend computed tomography in all patients with confirmed PA to detect an adrenal carcinoma, even if an adrenalectomy is not otherwise considered. Adrenal carcinomas are very rare, with an annual incidence estimated at 1-2 per million population, and present as isolated PA in less than 5% of cases . Adrenal carcinomas presenting as PA are usually larger than 40 mm in diameter.
Adrenal vein sampling
AVS involves determining aldosterone and cortisol levels in the inferior vena cava and in the two adrenal veins. Considering the variability in ACTH secretion and the acute control of aldosterone secretion by ACTH, some experts advocate AVS during exogenous ACTH infusion. Other experts suggest AVS in the early morning, at the time of the spontaneous peak of ACTH secretion. A comparative study reported that exogenous ACTH infusion does not improve the detection of unilateral aldosterone hypersecretion if the two adrenal veins are catheterized simultaneously.
Proposed thresholds for interpreting results from adrenal vein sampling
Adrenal to IVC cortisol ratio
Dominant to non-dominant A/C ratio
Non-dominant to IVC A/C ratio
Adrenal venous sampling without ACTH stimulation
>4 or 5
Adrenal venous sampling with ACTH stimulation
AVS is a relatively complex procedure, with rates of failure (documented by a cortisol concentration in the cannulated vein(s) below two times higher than those in the inferior vena cava) between 3  and 22% . It is invasive, and carries a risk of complications of between 0.2  and 5% ; complications mainly include adrenal hematomas, groin hematomas and dissection of adrenal veins . However, AVS is superior to image-based techniques for therapeutic decisions, because the objective of surgery is to suppress unilateral hypersecretion, not a unilateral nodule. As mentioned above, a unilateral adenoma is compatible with an incidentaloma associated with idiopathic PA, particularly in elderly patients. Conversely, unilateral hypersecretion may be associated with primary unilateral adrenal hyperplasia undetectable on imaging. In a recent series, one in three patients undergoing adrenalectomy for PA had a lateralized aldosterone hypersecretion without a unilateral adenoma.
Hypertension with hypokalemia and suppressed renin is known as mineralocorticoid hypertension, the mineralocorticoid involved being aldosterone in the vast majority of cases . PA is easily excluded by the absence of aldosterone hypersecretion in cases of mineralocorticoid hypertension due to an excess secretion of cortisol or deoxycorticosterone, of which some can be corrected surgically; in apparent mineralocorticoid excess; during exposure to glycyrrhizic acid (liquorice); or in pseudo-hypermineralocorticoidism due to Liddle syndrome .
Management including treatment
Treatment objectives in patients with PA are to reduce BP, correct hypokalemia, and to prevent or reverse the eventual cardiovascular or renal alterations caused by aldosterone excess. In retrospective case-control studies, the cardiovascular and renal consequences of hypertension were reported to be more severe in patients with PA than in patients with essential hypertension and similar levels of office BP [63, 64]. Thus, correcting for aldosterone hypersecretion is a treatment objective per se . Whether PA is associated with an increased prevalence of glucose metabolism disorders is still disputed .
In patients with lateralized aldosterone hypersecretion, this goal can be achieved by adrenalectomy and probably by the long-term prescription of aldosterone antagonists. Patients' preferences should be taken into account. Candidates for surgery should be told that the presence of an aldosterone-producing adenoma poses no threat of cancer, that surgery may not cure their hypertension completely, and that the frequency of complications for laparoscopic adrenalectomy is about 8%.
With regard to the risk of hypokalemia-induced arrhythmia during anesthesia, hypokalemic patients should be provided potassium chloride or aldosterone antagonists before surgery.
A complete unilateral adrenalectomy is required in patients with primary unilateral adrenal hyperplasia. It is also preferable to adenoma enucleation in cases in which computed tomography has shown a Conn's adenoma, as multiple adenomas are frequent and are not necessarily identified by preoperative imaging. Besides, the adrenal gland is a small organ, and devascularizing an adenoma frequently results in the devascularization of the entire gland, making conservative surgery difficult. Laparoscopic surgery, using transperitoneal  or retroperitoneal approaches, is currently the procedure of choice. Mean operating time and length of hospitalization are typically 90 min and 4 days [22, 70], respectively. The mean complication rate is 8% [20, 70]. Complications of laparoscopic surgery include conversion to open surgery, hematoma due to intraoperative vascular injury, thromboembolism, pneumothorax or hemothorax, with most complications being benign.
The most common aspect is a unilateral, yellow, lipid-laden adenoma varying in diameter from 5 to 35 mm. Despite producing aldosterone, the tumor usually consists of zona fasciculata-type cells although zona glomerulosa- or mixed cell-type tumors have been described. Aldosterone-secreting adrenal carcinomas are extremely rare. These malignant tumors exceed 40 mm in size with involvement of local lymph nodes or invasion of adjacent organs .
Surgery abolishes aldosterone hypersecretion and hypokalemia in most patients with unilateral aldosterone hypersecretion [17, 20–22, 72]. It produces a large decrease in systolic BP (typically -20 to -40 mmHg), and in the number of antihypertensive medications prescribed (typically -1 therapeutic class) [19–22].
Prediction of blood-pressure outcome
A dominant aldosterone-dependant component of hypertension and a low probability of associated essential hypertension are predictive of a better BP outcome after adrenalectomy.
In univariate analysis, several patient characteristics that suggest aldosterone-dependent hypertension have been associated with a favorable outcome: they include the presence of a typical and large aldosterone-producing adenoma on imaging studies or at pathological examination [15, 17, 20, 24, 72]; high urinary aldosterone excretion, low plasma renin or low serum potassium levels[18, 22, 72]; the absence of an increase in the plasma aldosterone concentration after standing up and the preoperative normalization of BP on monotherapy with high-dose spironolactone[17, 75]. Conversely, non-specific characteristics usually present in essential and/or severe hypertension have been associated with a poor BP outcome of adrenalectomy: they include older age [15, 17–20, 72, 74–76] or longer duration of hypertension before surgery[17–19, 21, 22, 72]; higher body-mass index [21, 22, 72] male sex [15, 20, 72, 74]; a history of essential hypertension in first-degree relatives[17, 18]; preoperative BP[17, 21] and number of prescribed antihypertensive drugs [17–20, 72]; and the presence of remodeling of resistance arteries.
Various factors have each been associated with a less favorable BP outcome in at least one multivariate model: lower urinary aldosterone excretion; a small adenoma or the presence of contralateral morphological abnormalities; the absence of BP control in patients on spironolactone; a higher number of antihypertensive medications required to control BP; older age or a longer history of hypertension; higher body mass index; male sex; and the presence of a family history of hypertension[15, 17, 18, 20, 22, 72]. The validity of these multivariate analyses is threatened by small sample sizes; comparisons across studies are difficult because the various models did not include the same variables.
The relevance of these prognostic markers for selecting patients for surgery should not be overemphasized, as they do not take into account the invariable cure of hypokalemia and hyperaldosteronism by adrenalectomy and provide only a weak prediction of the BP benefit in individual patients. For example, according to the only prediction model validated to date, number of antihypertensive medication ≤ 2, a body mass index ≤ 25 kg/m2, a duration of hypertension ≤ 6 years and female sex are the best predictors of hypertension cure following adrenalectomy. However, even if none of these features was present in an individual patient, this patient still had a 25% probability of being completely cured by an adrenalectomy and if not cured, hypertension was almost always better controlled. In another study in which the mean systolic BP decrease was -25 mmHg after surgery, the clinical impact of statistically significant prognostic factors was limited: the mean systolic BP decrease was only 3 mmHg less (-22 instead of -25 mmHg) in patients with a 0.5 mmol/l higher level of serum potassium before surgery, the most powerful predictor of unfavorable outcomes.
Operated patients can expect to be completely or partially weaned from mineralocorticoid antagonists or non-specific antihypertensive medication. The alternative to surgery is lifelong medication intended to correct or prevent the deleterious direct or indirect effects of hyperaldosteronism. Younger patients have a longer life expectancy and therefore derive a greater benefit from surgery. They also carry the smallest anesthetic risk. Early diagnosis of lateralized PA is therefore of paramount importance. The benefit-risk ratio is more balanced in older patients, especially if their antihypertensive medication has compelling indications, such as beta-blockers for coronary artery disease or angiotensin-converting enzyme and spironolactone for heart failure.
Alternatives to adrenalectomy
Mineralocorticoid receptor antagonists - spironolactone and eplerenone - provide a specific treatment for PA in patients who are not candidates for surgery. Unfortunately, only a few of these patients show a good BP response to spironolactone monotherapy . Furthermore, long-term tolerance of spironolactone at doses exceeding 50 mg per day is poor. There is no published evidence to suggest that high doses of eplerenone are more effective and better tolerated than spironolactone in patients with PA. If necessary, lower doses of aldosterone receptor antagonists may be associated with non-specific antihypertensive agents.
The etiopathogenesis and genomics of PA and aldosterone-producing adenomas are currently being studied by several research groups. Collaborative prospective studies are needed to document and standardize critical steps in the diagnosis of PA and the confirmation of lateralized PA in relation to surgically correctable PA. This specifically applies to studying the advantages that post-suppression plasma aldosterone concentrations have over basal concentrations, and the cut-off values that are used to detect a clinically relevant lateralizing ratio at AVS. As the rate of cure of hypertension following adrenalectomy is only 50%, there is also a need for randomized trials comparing the safety, acceptability and efficacy of surgery and aldosterone antagonists, regarding BP and target organ damage.
Surgically correctable PA is sought in patients with hypokalemic or difficult-to-treat hypertension, and is diagnosed by the presence of unilateral aldosterone hypersecretion at AVS. Surgery is particularly useful for young PA patients, who can be completely cured, and for PA patients with resistant hypertension, whose BP control can be markedly improved.
This study was supported in part by PHRC grant AOM 06 179 and by grants from INSERM and Ministère Délégué à la Recherche et des Nouvelles Technologies for the COMETE Network.
- Conn JW: Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med. 1955, 45: 3-17.PubMedGoogle Scholar
- Conn JW, Cohen EL, Rovner DR: Suppression of Plasma Renin Activity in Primary Aldosteronism. Jama. 1964, 190: 213-21.PubMedGoogle Scholar
- Funder JW, Carey RM, Fardella C, et al: Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008, 93: 3266-81. 10.1210/jc.2008-0104.View ArticlePubMedGoogle Scholar
- Newton-Cheh C, Guo CY, Gona P, et al: Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample. Hypertension. 2007, 49: 846-56. 10.1161/01.HYP.0000258554.87444.91.View ArticlePubMedGoogle Scholar
- Nishikawa T, Omura M: Clinical characteristics of primary aldosteronism: its prevalence and comparative studies on various causes of primary aldosteronism in Yokohama Rosai Hospital. Biomed Pharmacother. 2000, 54 (Suppl 1): 83s-5s. 10.1016/S0753-3322(00)80019-0.View ArticlePubMedGoogle Scholar
- Mulatero P, Stowasser M, Loh KC, et al: Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004, 89: 1045-50. 10.1210/jc.2003-031337.View ArticlePubMedGoogle Scholar
- Rossi GP, Bernini G, Caliumi C, et al: A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006, 48: 2293-300. 10.1016/j.jacc.2006.07.059.View ArticlePubMedGoogle Scholar
- Fogari R, Preti P, Zoppi A, Rinaldi A, Fogari E, Mugellini A: Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test. Hypertens Res. 2007, 30: 111-7. 10.1291/hypres.30.111.View ArticlePubMedGoogle Scholar
- Douma S, Petidis K, Doumas M, et al: Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet. 2008, 371: 1921-6. 10.1016/S0140-6736(08)60834-X.View ArticlePubMedGoogle Scholar
- Rossi E, Regolisti G, Negro A, Sani C, Davoli S, Perazzoli F: High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among Italian hypertensives. Am J Hypertens. 2002, 15: 896-902. 10.1016/S0895-7061(02)02969-2.View ArticlePubMedGoogle Scholar
- Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J: Global burden of hypertension: analysis of worldwide data. Lancet. 2005, 365: 217-23.View ArticlePubMedGoogle Scholar
- Abasiyanik A, Oran B, Kaymakci A, Yasar C, Caliskan U, Erkul I: Conn syndrome in a child, caused by adrenal adenoma. J Pediatr Surg. 1996, 31: 430-2. 10.1016/S0022-3468(96)90753-8.View ArticlePubMedGoogle Scholar
- Andersen GS, Toftdahl DB, Lund JO, Strandgaard S, Nielsen PE: The incidence rate of phaeochromocytoma and Conn's syndrome in Denmark, 1977-1981. J Hum Hypertens. 1988, 2: 187-9.PubMedGoogle Scholar
- Takayanagi R, Miura K, Nakagawa H, Nawata H: Epidemiologic study of adrenal gland disorders in Japan. Biomed Pharmacother. 2000, 54 (Suppl 1): 164s-8s. 10.1016/S0753-3322(00)80036-0.View ArticlePubMedGoogle Scholar
- Obara T, Ito Y, Okamoto T, et al: Risk factors associated with postoperative persistent hypertension in patients with primary aldosteronism. Surgery. 1992, 112: 987-93.PubMedGoogle Scholar
- Gleason PE, Weinberger MH, Pratt JH, et al: Evaluation of diagnostic tests in the differential diagnosis of primary aldosteronism: unilateral adenoma versus bilateral micronodular hyperplasia. J Urol. 1993, 150: 1365-8.PubMedGoogle Scholar
- Proye CA, Mulliez EA, Carnaille BM, et al: Essential hypertension: first reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism?. Surgery. 1998, 124: 1128-33. 10.1067/msy.1998.93108.View ArticlePubMedGoogle Scholar
- Sawka AM, Young WF, Thompson GB, et al: Primary aldosteronism: factors associated with normalization of blood pressure after surgery. Ann Intern Med. 2001, 135: 258-61.View ArticlePubMedGoogle Scholar
- Lumachi F, Ermani M, Basso SM, Armanini D, Iacobone M, Favia G: Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature. Am Surg. 2005, 71: 864-9.PubMedGoogle Scholar
- Pang TC, Bambach C, Monaghan JC, et al: Outcomes of laparoscopic adrenalectomy for hyperaldosteronism. ANZ J Surg. 2007, 77: 768-73. 10.1111/j.1445-2197.2007.04225.x.View ArticlePubMedGoogle Scholar
- Rossi GP, Bolognesi M, Rizzoni D, et al: Vascular remodeling and duration of hypertension predict outcome of adrenalectomy in primary aldosteronism patients. Hypertension. 2008, 51: 1366-71. 10.1161/HYPERTENSIONAHA.108.111369.View ArticlePubMedGoogle Scholar
- Letavernier E, Peyrard S, Amar L, Zinzindohoue F, Fiquet B, Plouin PF: Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J Hypertens. 2008, 26: 1816-23. 10.1097/HJH.0b013e3283060f0c.View ArticlePubMedGoogle Scholar
- Zarnegar R, Bloom AI, Lee J, et al: Is adrenal venous sampling necessary in all patients with hyperaldosteronism before adrenalectomy?. J Vasc Interv Radiol. 2008, 19: 66-71. 10.1016/j.jvir.2007.08.022.View ArticlePubMedGoogle Scholar
- Zarnegar R, Young WF, Lee J, et al: The aldosteronoma resolution score: predicting complete resolution of hypertension after adrenalectomy for aldosteronoma. Ann Surg. 2008, 247: 511-8. 10.1097/SLA.0b013e318165c075.View ArticlePubMedGoogle Scholar
- Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P: Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002, 40: 892-6. 10.1161/01.HYP.0000040261.30455.B6.View ArticlePubMedGoogle Scholar
- Mancia G, De Backer G, Dominiczak A, et al: 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens. 2007, 25: 1751-62. 10.1097/HJH.0b013e3282f0580f.View ArticlePubMedGoogle Scholar
- Medeau V, Moreau F, Trinquart L, et al: Clinical and biochemical characteristics of normotensive patients with primary aldosteronism: a comparison with hypertensive cases. Clin Endocrinol (Oxf). 2008, 69: 20-8. 10.1111/j.1365-2265.2008.03213.x.View ArticleGoogle Scholar
- Mantero F, Terzolo M, Arnaldi G, et al: A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000, 85: 637-44. 10.1210/jc.85.2.637.PubMedGoogle Scholar
- Rossi GP, Seccia TM, Palumbo G, et al: Within-patient reproducibility of the aldosterone: renin ratio in primary aldosteronism. Hypertension. 2009, 55: 83-9. 10.1161/HYPERTENSIONAHA.109.139832.View ArticlePubMedGoogle Scholar
- Tanabe A, Naruse M, Takagi S, Tsuchiya K, Imaki T, Takano K: Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism. J Clin Endocrinol Metab. 2003, 88: 2489-94. 10.1210/jc.2002-021476.View ArticlePubMedGoogle Scholar
- Hiramatsu K, Yamada T, Yukimura Y, et al: A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med. 1981, 141: 1589-93. 10.1001/archinte.141.12.1589.View ArticlePubMedGoogle Scholar
- Campbell DJ, Nussberger J, Stowasser M, et al: Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009, 55: 867-77. 10.1373/clinchem.2008.118000.View ArticlePubMedGoogle Scholar
- Montori VM, Young WF: Use of plasma aldosterone concentration-to-plasma renin activity ratio as a screening test for primary aldosteronism. A systematic review of the literature. Endocrinol Metab Clin North Am. 2002, 31: 619-32. 10.1016/S0889-8529(02)00013-0. xi.View ArticlePubMedGoogle Scholar
- Gallay BJ, Ahmad S, Xu L, Toivola B, Davidson RC: Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio. Am J Kidney Dis. 2001, 37: 699-705. 10.1016/S0272-6386(01)80117-7.View ArticlePubMedGoogle Scholar
- Mulatero P, Rabbia F, Milan A, et al: Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002, 40: 897-902. 10.1161/01.HYP.0000038478.59760.41.View ArticlePubMedGoogle Scholar
- Willenberg HS, Schinner S, Ansurudeen I: New mechanisms to control aldosterone synthesis. Horm Metab Res. 2008, 40: 435-41. 10.1055/s-2008-1065336.View ArticlePubMedGoogle Scholar
- Pizzolo F, Pavan C, Corrocher R, Olivieri O: Laboratory diagnosis of primary aldosteronism, and drospirenone-ethinylestradiol therapy. Am J Hypertens. 2007, 20: 1334-7. 10.1016/j.amjhyper.2007.08.009.View ArticlePubMedGoogle Scholar
- Gordon RD, Gomez-Sanchez CE, Hamlet SM, Tunny TJ, Klemm SA: Angiotensin-responsive aldosterone-producing adenoma masquerades as idiopathic hyperaldosteronism (IHA: adrenal hyperplasia) or low-renin essential hypertension. J Hypertens Suppl. 1987, 5: S103-6.PubMedGoogle Scholar
- Irony I, Kater CE, Biglieri EG, Shackleton CH: Correctable subsets of primary aldosteronism. Primary adrenal hyperplasia and renin responsive adenoma. Am J Hypertens. 1990, 3: 576-82.PubMedGoogle Scholar
- Rossi GP, Belfiore A, Bernini G, et al: Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone-producing adenoma. J Hypertens. 2007, 25: 1433-42. 10.1097/HJH.0b013e328126856e.View ArticlePubMedGoogle Scholar
- Williams JS, Williams GH, Raji A, et al: Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. J Hum Hypertens. 2006, 20: 129-36. 10.1038/sj.jhh.1001948.View ArticlePubMedGoogle Scholar
- Young WF: Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf). 2007, 66: 607-18. 10.1111/j.1365-2265.2007.02775.x.View ArticleGoogle Scholar
- Hirohara D, Nomura K, Okamoto T, Ujihara M, Takano K: Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives. J Clin Endocrinol Metab. 2001, 86: 4292-8. 10.1210/jc.86.9.4292.View ArticlePubMedGoogle Scholar
- Stowasser M, Gordon RD: Primary aldosteronism--careful investigation is essential and rewarding. Mol Cell Endocrinol. 2004, 217: 33-9. 10.1016/j.mce.2003.10.006.View ArticlePubMedGoogle Scholar
- Lumachi F, Marzola MC, Zucchetta P, et al: Non-invasive adrenal imaging in primary aldosteronism. Sensitivity and positive predictive value of radiocholesterol scintigraphy, CT scan and MRI. Nucl Med Commun. 2003, 24: 683-8. 10.1097/00006231-200306000-00011.View ArticlePubMedGoogle Scholar
- Vincent JM, Morrison ID, Armstrong P, Reznek RH: The size of normal adrenal glands on computed tomography. Clin Radiol. 1994, 49: 453-5. 10.1016/S0009-9260(05)81739-8.View ArticlePubMedGoogle Scholar
- White ML, Gauger PG, Doherty GM, et al: The role of radiologic studies in the evaluation and management of primary hyperaldosteronism. Surgery. 2008, 144: 926-33. 10.1016/j.surg.2008.07.025. discussion 33.View ArticlePubMedGoogle Scholar
- Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR: The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004, 25: 309-40. 10.1210/er.2002-0031.View ArticlePubMedGoogle Scholar
- Kempers MJ, Lenders JW, van Outheusden L, et al: Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009, 151: 329-37.View ArticlePubMedGoogle Scholar
- Young WF, Stanson AW, Thompson GB, Grant CS, Farley DR, van Heerden JA: Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004, 136: 1227-35. 10.1016/j.surg.2004.06.051.View ArticlePubMedGoogle Scholar
- Gicquel C, Bertagna X, Gaston V, et al: Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res. 2001, 61: 6762-7.PubMedGoogle Scholar
- Rossi GP, Ganzaroli C, Miotto D, et al: Dynamic testing with high-dose adrenocorticotrophic hormone does not improve lateralization of aldosterone oversecretion in primary aldosteronism patients. J Hypertens. 2006, 24: 371-9. 10.1097/01.hjh.0000202818.10459.96.View ArticlePubMedGoogle Scholar
- Daunt N: Adrenal vein sampling: how to make it quick, easy, and successful. Radiographics. 2005, 25 (Suppl 1): S143-58. 10.1148/rg.25si055514.View ArticlePubMedGoogle Scholar
- Magill SB, Raff H, Shaker JL, et al: Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism. J Clin Endocrinol Metab. 2001, 86: 1066-71. 10.1210/jc.86.3.1066.PubMedGoogle Scholar
- Doppman JL, Gill JR: Hyperaldosteronism: sampling the adrenal veins. Radiology. 1996, 198: 309-12.View ArticlePubMedGoogle Scholar
- Young WF, Stanson AW: What are the keys to successful adrenal venous sampling (AVS) in patients with primary aldosteronism?. Clin Endocrinol (Oxf). 2009, 70: 14-7. 10.1111/j.1365-2265.2008.03450.x.View ArticleGoogle Scholar
- Omura M, Sasano H, Fujiwara T, Yamaguchi K, Nishikawa T: Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling. Metabolism. 2002, 51: 350-5. 10.1053/meta.2002.30498.View ArticlePubMedGoogle Scholar
- Stewart PM: Mineralocorticoid hypertension. Lancet. 1999, 353: 1341-7. 10.1016/S0140-6736(98)06102-9.View ArticlePubMedGoogle Scholar
- Biller BM, Grossman AB, Stewart PM, et al: Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2008, 93: 2454-62. 10.1210/jc.2007-2734.PubMed CentralView ArticlePubMedGoogle Scholar
- Vantyghem MC, Marcelli-Tourvieille S, Defrance F, Wemeau JL: [11beta-hydroxysteroide dehydrogenases. Recent advances]. Ann Endocrinol (Paris). 2007, 68: 349-56.View ArticleGoogle Scholar
- Warnock DG: Liddle syndrome: genetics and mechanisms of Na+ channel defects. Am J Med Sci. 2001, 322: 302-7. 10.1097/00000441-200112000-00002.View ArticlePubMedGoogle Scholar
- Pascoe L, Jeunemaitre X, Lebrethon MC, et al: Glucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree. J Clin Invest. 1995, 96: 2236-46. 10.1172/JCI118279.PubMed CentralView ArticlePubMedGoogle Scholar
- Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ: Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005, 45: 1243-8. 10.1016/j.jacc.2005.01.015.View ArticlePubMedGoogle Scholar
- Sechi LA, Novello M, Lapenna R, et al: Long-term renal outcomes in patients with primary aldosteronism. Jama. 2006, 295: 2638-45. 10.1001/jama.295.22.2638.View ArticlePubMedGoogle Scholar
- Connell JM, MacKenzie SM, Freel EM, Fraser R, Davies E: A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr Rev. 2008, 29: 133-54. 10.1210/er.2007-0030.View ArticlePubMedGoogle Scholar
- Matrozova J, Steichen O, Amar L, Zacharieva S, Jeunemaitre X, Plouin PF: Fasting plasma glucose and serum lipids in patients with primary aldosteronism: a controlled cross-sectional study. Hypertension. 2009, 53: 605-10. 10.1161/HYPERTENSIONAHA.108.122002.View ArticlePubMedGoogle Scholar
- Catena C, Colussi G, Nadalini E, et al: Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med. 2008, 168: 80-5. 10.1001/archinternmed.2007.33.View ArticlePubMedGoogle Scholar
- Novitsky YW, Kercher KW, Rosen MJ, Cobb WS, Jyothinagaram S, Heniford BT: Clinical outcomes of laparoscopic adrenalectomy for lateralizing nodular hyperplasia. Surgery. 2005, 138: 1009-16. 10.1016/j.surg.2005.09.027.View ArticlePubMedGoogle Scholar
- Ishidoya S, Ito A, Sakai K, et al: Laparoscopic partial versus total adrenalectomy for aldosterone producing adenoma. J Urol. 2005, 174: 40-3. 10.1097/01.ju.0000162045.68387.c3.View ArticlePubMedGoogle Scholar
- Assalia A, Gagner M: Laparoscopic adrenalectomy. Br J Surg. 2004, 91: 1259-74. 10.1002/bjs.4738.View ArticlePubMedGoogle Scholar
- Walz MK: [Adrenal tumors]. Chirurg. 2008, 79: 1087-94. 10.1007/s00104-008-1638-z.View ArticlePubMedGoogle Scholar
- Zarnegar R, Lee J, Brunaud L, et al: Good blood pressure control on antihypertensives, not only response to spironolactone, predicts improved outcome after adrenalectomy for aldosteronoma. Surgery. 2007, 142: 921-9. 10.1016/j.surg.2007.09.001. discussion -9.View ArticlePubMedGoogle Scholar
- Shen WT, Lim RC, Siperstein AE, et al: Laparoscopic vs open adrenalectomy for the treatment of primary hyperaldosteronism. Arch Surg. 1999, 134: 628-31. 10.1001/archsurg.134.6.628.View ArticlePubMedGoogle Scholar
- Stowasser M, Klemm SA, Tunny TJ, Storie WJ, Rutherford JC, Gordon RD: Response to unilateral adrenalectomy for aldosterone-producing adenoma: effect of potassium levels and angiotensin responsiveness. Clin Exp Pharmacol Physiol. 1994, 21: 319-22. 10.1111/j.1440-1681.1994.tb02520.x.View ArticlePubMedGoogle Scholar
- Nomura K, Toraya S, Horiba N, Ujihara M, Aiba M, Demura H: Plasma aldosterone response to upright posture and angiotensin II infusion in aldosterone-producing adenoma. J Clin Endocrinol Metab. 1992, 75: 323-7. 10.1210/jc.75.1.323.PubMedGoogle Scholar
- Blumenfeld JD, Sealey JE, Schlussel Y, et al: Diagnosis and treatment of primary hyperaldosteronism. Ann Intern Med. 1994, 121: 877-85.View ArticlePubMedGoogle Scholar
- Ghose RP, Hall PM, Bravo EL: Medical management of aldosterone-producing adenomas. Ann Intern Med. 1999, 131: 105-8.View ArticlePubMedGoogle Scholar
- Jeunemaitre X, Chatellier G, Kreft-Jais C, et al: Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol. 1987, 60: 820-5. 10.1016/0002-9149(87)91030-7.View ArticlePubMedGoogle Scholar
- Meria P, Kempf BF, Hermieu JF, Plouin PF, Duclos JM: Laparoscopic management of primary hyperaldosteronism: clinical experience with 212 cases. J Urol. 2003, 169: 32-5. 10.1016/S0022-5347(05)64028-1.View ArticlePubMedGoogle Scholar
- Mulatero P, Bertello C, Rossato D, et al: Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab. 2008, 93: 1366-71. 10.1210/jc.2007-2055.View ArticlePubMedGoogle Scholar
- Espiner EA, Ross DG, Yandle TG, Richards AM, Hunt PJ: Predicting surgically remedial primary aldosteronism: role of adrenal scanning, posture testing, and adrenal vein sampling. J Clin Endocrinol Metab. 2003, 88: 3637-44. 10.1210/jc.2002-022051.View ArticlePubMedGoogle Scholar
- Murashima M, Trerotola SO, Fraker DL, Han D, Townsend RR, Cohen DL: Change in the pattern of adrenal venous sampling over time in patients with primary aldosteronism. J Hum Hypertens. 2009, 23: 292-4. 10.1038/jhh.2008.108.View ArticlePubMedGoogle Scholar
- Auchus RJ, Michaelis C, Wians FH, et al: Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism. Ann Surg. 2009, 249: 318-21. 10.1097/SLA.0b013e3181961d77.View ArticlePubMedGoogle Scholar
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