A Prospective Observational Study of Factors Affecting the Change in Quality of Life in Patients With Primary Aldosteronism After Treatment.

OBJECTIVE: To explore the changes in the health-related quality of life (HRQoL) in patients with primary aldosteronism (PA) after standardized treatment and determine the effects of different variables on the change in the HRQoL of patients. METHODS: A total of 116 patients with PA were prospectively included from November 2020 to March 2022. Data were collected at their initial diagnosis and the follow-up after 12 months of treatment, including demographic and clinical data and the scores of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The scores of each dimension of SF-36 of patients before and after treatment were compared, and the factors affecting their change in the quality of life were analyzed using multiple linear regression. RESULTS: After standardized treatment, the aldosterone-to-renin ratio (Z = -4.967, P < .001), systolic blood pressure (t = 8.985, P < .001), and diastolic blood pressure (t = 7.233, P < .001) of patients with PA decreased compared with baseline, and hypokalemia was effectively corrected (χ2 = 69.014, P < .001). In terms of quality of life, 6 of 8 dimensions of SF-36 and the total score of SF-36 significantly improved at 1-year follow-up compared with baseline (all P < .05). The results of multiple linear regression showed that the improvement in the HRQoL in patients with PA after standardized treatment was correlated with the change in the blood potassium level (P = .007) and systolic blood pressure (P = .003). CONCLUSION: Correction of hypokalemia and control of diastolic blood pressure are essential factors contributing to the improvement in the HRQoL in patients with PA regardless of the standardized treatment received.

Follow-up care and assessment of comorbidities and complications in patients with primary aldosteronism: The clinical practice guideline of the Taiwan Society of aldosteronism.

Primary aldosteronism (PA) is the most common form of endocrine hypertension, characterized by excess aldosterone production that leads to an increased risk of cardiovascular events and target organ damage. Both adrenalectomy and medical treatment have shown efficacy in improving clinical outcomes and comorbidities associated with PA, including a specific subtype of PA with autonomous cortisol secretion (ACS). Understanding the comorbidities of PA and establishing appropriate follow-up protocols after treatment are crucial for physicians to enhance morbidity and mortality outcomes in patients with PA. Additionally, the screening for hypercortisolism prior to surgery is essential, as the prognosis of patients with coexisting PA and ACS differs from those with PA alone. In this review, we comprehensively summarize the comorbidities of PA, encompassing cardiovascular, renal, and metabolic complications. We also discuss various post-treatment outcomes and provide insights into the strategy for glucocorticoid replacement in patients with overt or subclinical hypercortisolism. This clinical practice guideline aims to equip medical professionals with up-to-date information on managing concurrent hypercortisolism, assessing treatment outcomes, and addressing comorbidities in patients with PA, thereby improving follow-up care.

Primary aldosteronism in pregnancy.

Primary aldosteronism (PA) is the most common form of secondary hypertension. Although hypertensive disorders seem to affect around 5-10% of pregnancies worldwide, literature counts less than 80 cases of PA diagnosed during the peri-partum period. In this review we discuss about current knowledge on pathophysiology, natural history, diagnosis and treatment of PA in pregnancy. Because of the physiologic changes in the renin-angiotensin-aldosterone system (RAAS) and the contraindication to both confirmatory test and subtype differentiation, diagnosis of PA during pregnancy is challenging and relies mostly on detection of low/suppressed renin and high aldosterone levels. The course of pregnancy in patients with PA is highly variable, ranging from progesterone-induced amelioration of blood pressure (BP) control to severe and resistant hypertension with potential maternal and fetal complications. Mineralcorticoid receptor antagonists (MRA) are the recommended and most effective drugs for treatment of PA. As the anti-androgenic effect of spironolactone can potentially interfere with sexual development, their prescription is not recommended during pregnancy. On the other side, eplerenone, has proven to be safe and effective in 6 pregnant women and may be added to conventional first line drug regimen in presence of resistant hypertension or persistent hypokalemia. Ideally, patients with unilateral forms of PA should undergo adrenalectomy prior to conception, however, when PA is diagnosed during pregnancy and medical therapy fails to adequately control hypertension or its complications, adrenalectomy can be considered during the second trimester in case of unilateral adrenal mass at MRI-scan.

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

PURPOSE OF REVIEW: Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. RECENT FINDINGS: Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

Personalized Treatment of Patients With Primary Aldosteronism.

Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Primary Aldosteronism.

Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with resistant hypertension. However, it is estimated that only about 2% of patients who have risk factors for primary aldosteronism have been formally tested or diagnosed. The first step in the diagnosis of primary aldosteronism is case detection and involves testing patients who are at risk, including individuals with resistant hypertension, as well as those with well-controlled hypertension and a first-degree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke (i.e., younger than 40 years). Initial case detection is performed by simultaneously measuring plasma aldosterone concentration and plasma renin activity; an elevated aldosterone-renin ratio (greater than 30) indicates independent aldosterone secretion (i.e., aldosteronism). After a positive case detection, confirmatory testing should be performed. Confirmatory tests include the captopril challenge, oral or intravenous salt loading, or fludrocortisone suppression. Results are positive if aldosterone levels remain high after interventions that suppress or interrupt physiologic production of aldosterone. If the confirmatory test is positive, adrenal computed tomography and adrenal vein sampling should be performed to differentiate unilateral from bilateral adrenal production of aldosterone. Patients with unilateral primary aldosteronism should undergo adrenalectomy, whereas those with bilateral production should be treated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone.

Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.

Diagnosis, treatment and genetic analysis of a case of familial aldosteronism type II with WFS1 gene mutation.

Primary aldosteronism (PA) is a disease characterized by hypertension and hypokalemia due to the excessive aldosterone secretion from the adrenal cortex, which leads to the retention of both water and sodium, and the inhibition of the renin-angiotensin system as well. Familial hyperaldosteronism type II (FH-II) is known as an autosomal dominant hereditary disease, which is a scarce cause of PA. In this report, we cllected the clinical data of a patient with repeated hypertension and hypokalemia of uncertain diagnosis since 2014. Nevertheless, we discovered by genetic sequencing in 2021 that the CLCN2 and WFS1 gene mutation of the patient, whose mother belongs to heterozygote genotype and father belongs to wild-type genotype. Combined with a series of endocrine function tests and imaging studies, the patient was finally certified her suffering from FH-II and WFS1 gene mutation. By summarizing and analyzing the characteristics and genetic test results of this case, we recommended gene sequencing for patients with PA whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.

[Conn's syndrome-Frequent and still too rarely diagnosed to underdiagnosed]. / Das Conn-Syndrom ­ häufig, und immer noch zu selten diagnostiziert.

Conn's syndrome represents the most common cause of endocrine hypertension and is associated with an increased cardiovascular risk, a series of comorbidities (including type 2 diabetes mellitus) and with their frequent occurrence. Therefore, a correct and rapid diagnosis is of essential importance. Measurement of the aldosterone-renin ratio is used as a first screening test for primary aldosteronism. This should ideally be evaluated under optimized conditions (e.g. at rest), after adjustment of the blood pressure medication and with an equilibrated potassium balance. In cases of elevated aldosterone to renin ratio, further confirmatory testing as well as imaging of the adrenal glands is needed. After confirmation of Conn's syndrome a differentiation between a unilateral and bilateral adrenal disease is necessary for further treatment planning. The current gold standard is still selective adrenal vein catheterization. Promising alternatives to an adrenal vein catheter, such as functional imaging techniques and measurement of steroid profiles are currently being investigated in clinical trials. In cases of lateralization of aldosterone production, unilateral laparoscopic adrenalectomy of the affected side is the treatment of choice. In contrast, patients with bilateral disease or patients with contraindications for adrenalectomy should receive life-long treatment with mineralocorticoid receptor antagonists.

How common is primary aldosteronism?

PURPOSE OF REVIEW: Primary aldosteronism, characterized by renin-independent aldosterone secretion from one or both adrenal glands, is the most common and modifiable form of secondary hypertension. The prevalence of primary aldosteronism is increasingly recognized to be much higher than previously thought with many cases still undetected. RECENT FINDINGS: Prior prevalence studies on primary aldosteronism have reported a wide range of estimates due to heterogeneity of both disease definitions and study populations such that it is difficult to claim a single point estimate. More recent evidence demonstrates that primary aldosteronism, as defined by conventional biochemical diagnostic criteria, is highly prevalent within populations where it is not typically considered such as mild-to-moderate hypertension, prehypertension, and even normotension. Yet, our current screening approach fails to capture many cases. Furthermore, there is mounting evidence that renin-independent aldosteronism exists as a continuum of disease that extends below the current biochemical diagnostic thresholds used to define primary aldosteronsim and has clinically relevant treatment and outcome implications for a much broader patient population. Indeed, much of what we current label as 'essential hypertension' is, in fact, renin-independent aldosterone-mediated hypertension. SUMMARY: Primary aldosteronism and milder forms of renin-independent aldosteronism are highly prevalent, yet vastly under-recognized, in the general population.

Quality of life in primary aldosteronism: A prospective observational study.

BACKGROUND: Previous studies suggested that patients affected by primary aldosteronism (PA) have impaired quality of life (QOL) compared to the general population, but a direct comparison with patients affected by essential hypertension (EH) has never been performed. The aim of the study was to compare the QOL of patients affected by PA to the QOL of patients affected by EH. MATERIAL AND METHODS: We designed a prospective observational study comparing the QOL of patients with PA and carefully matched patients with EH before and after treatment. We recruited 70 patients with PA and 70 patients with EH, matched for age, sex, blood pressure levels and intensity of antihypertensive treatment. We assessed QOL at baseline and after specific treatment for PA or after optimization of medical therapy for patients with EH. RESULTS: Patients with PA displayed impaired QOL compared with the general healthy population, but similar to patients with EH. Both laparoscopic adrenalectomy and treatment with mineralocorticoid receptor antagonist allowed an improvement of QOL in patients with PA, that was more pronounced after surgical treatment. Optimization of blood pressure control by implementation of antihypertensive treatment (without MR antagonists) allowed a minimal improvement in only one of eight domains in patients with EH. CONCLUSIONS: Patients with PA have impaired QOL, which is likely caused by uncontrolled hypertension and the effects of intensive antihypertensive treatment. Surgical and medical treatment of PA allows a significant improvement of QOL, by amelioration of blood pressure control and, after surgical treatment, by reduction of antihypertensive treatment.

Superselective adrenal arterial embolization for idiopathic hyperaldosteronism: 12-month results from a proof-of-principle trial.

OBJECTIVES: This study aimed to assess the safety, blood pressure changes, and biochemical responses of superselective adrenal artery embolization (SAAE) in hypertensive patients with idiopathic hyperaldosteronism (IHA). BACKGROUND: SAAE is a minimally invasive procedure that has been used to successfully treat aldosterone-producing adenoma. However, its effect for patients with IHA is unevaluated. METHODS: A total of 41 hypertensive patients who were diagnosed with IHA and underwent SAAE at the Fuwai Hospital between December 2010 and June 2016 were prospectively enrolled. The blood pressure, antihypertensive medications, plasma aldosterone and potassium levels, and adverse events were assessed. The primary endpoint was the change in home blood pressure at 12 months, compared with baseline. RESULTS: SAAE was technically successful in 39 patients. Postoperatively, home and 24-hr mean blood pressures were reduced by 14/9 and 10/7 mmHg at 1 month, respectively, and by 13/7 and 11/7 mmHg at 12 months, respectively. The number of antihypertensive agents used reduced by 1.0 and 1.1 at 1 month and 12 months, respectively (all p < .001). Compared with baseline (524.0 pmol/L), the standing plasma aldosterone reduced to 293.4 pmol/L at 12 months (p < .001). Serum potassium increased from 3.0 to 4.1 mmol/L while the rate of potassium supplement and mineralocorticoid receptor antagonist use reduced from 87.1 and 89.7%, respectively, to 28.2 and 17.9%, respectively, at 12 months (all p < .001). There were no serious complications in the perioperative and 12-month follow-up periods. CONCLUSIONS: SAAE was effective and feasible for IHA treatment, without serious complications, therefore, maybe a potential treatment.

Developing a research database of primary aldosteronism: rationale and baseline characteristics.

BACKGROUND: Management of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. METHODS: The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. RESULTS: Totally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 (21.7) mmHg, mean diastolic blood pressure (DBP) was 97.2 (14.5) mmHg. Among included patients, the mean serum potassium level was 2.85 (IQR, (2.47-3.36) mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 (IQR, 20.0-40.4) ng/dL. The characteristics of patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. CONCLUSION: Through integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.

Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China.

OBJECTIVE: To investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA. METHODS: A prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018. RESULTS: Of the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients' blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups. CONCLUSION: It is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.

Impact of Victoria's first dedicated endocrine hypertension service on the pattern of primary aldosteronism diagnoses.

BACKGROUND: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk. AIMS: To analyse the impact of Victoria's first dedicated endocrine hypertension service (EHS) on the pattern of PA diagnosis. METHODS: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (n = 267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2) and Year 3 (Y3), based on their first visit. RESULTS: The proportion of primary care referrals increased (20% in Y1, 47% in Y2, 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1, 14% in Y2, 19% in Y3). Among PA patients, the median duration of hypertension prior to their first visit decreased (11 years in Y1, 10 years in Y2, 7 years in Y3), and the prevalence of end-organ damage decreased (44% in Y1, 42% in Y2, 33% in Y3). Targeted management of PA improved clinical and biochemical outcomes. The average blood pressure reduction following targeted management increased from 16/12 mmHg in Y1 to 23/12 mmHg in Y3. CONCLUSION: The EHS, with its strong component of general practitioner engagement, led to increased primary care referrals and PA detection earlier in the course of hypertension. Referred patients were on fewer antihypertensives and had less end-organ damage which simplified the diagnostic process, allowing targeted treatment to be commenced earlier and patient outcomes optimised.

Primary Aldosteronism: a Continuum from Normotension to Hypertension.

PURPOSE OF REVIEW: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Emerging evidence suggests that PA is associated with cardiovascular, metabolic, and renal complications, that likely develop insidiously, due to prolonged inappropriate mineralocorticoid receptor activation. In this review, we discuss the expanding clinical and pathological spectrum of PA. RECENT FINDINGS: Clinical and molecular studies conducted over the recent years reveal that PA traverses a series of contiguous stages. Pre-clinical, but hormonally overt PA has been identified in patients with normal blood pressure, and such patients harbor an increased risk of developing hypertension. Similarly, genetic and histopathological advancements have exposed a spectrum of PA pathology that corresponds to a continuum that spans from pre-clinical stages to florid PA. PA evolves from pre-hypertensive stages to resistant hypertension, along with serious cardiovascular and renal consequences. Early recognition of PA and targeted therapy will be essential for cardiovascular morbidity and mortality prevention in a large number of patients.

Taiwan mini-frontier of primary aldosteronism: Updating treatment and comorbidities detection.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

[Hyperaldosteronism]. / Hyperaldosteronismus.

Aldosterone is produced in the adrenal cortex and governs volume and electrolyte homeostasis. Hyperaldosteronism can occur either as primary aldosteronism (renin-independent) or secondary aldosteronism (renin-dependent). As the commonest cause of secondary hypertension, primary aldosteronism is associated with increased cardiovascular risk. Its most prevalent subtypes are aldosterone-producing adenomas as the most frequent unilateral form and bilateral hyperaldosteronism. Unilateral hyperplasia, familial hyperaldosteronism and aldosterone-producing carcinoma are rare. The aldosterone/renin ratio serves as a screening parameter for primary aldosteronism. If this ratio is elevated, confirmatory testing and adrenal imaging are performed. Adrenal venous sampling is considered the gold standard for the distinction of unilateral from bilateral disease. Unilateral disease can potentially be cured by adrenalectomy, whereas patients that are not candidates for surgery or have bilateral disease are treated with mineralocorticoid receptor antagonists. Over the past 10 years, somatic mutations in ion channels or transporters have been identified as causes of aldosterone-producing adenomas and so-called aldosterone-producing cell clusters (potential precursors of adenomas and correlates of bilateral hyperplasia, but also of subclinical hyperaldosteronism). In addition, germline mutations in overlapping genes cause familial hyperaldosteronism. Secondary hyperaldosteronism can occur in patients with hypertension treated with diuretics or in renal artery stenosis.

Primary Aldosteronism: Where Are We Now? Where to from Here?

The past nine years have seen major advances in establishing the etiology of unilateral primary aldosteronism, and very possibly that of bilateral hyperaldosteronism, in response to somatic mutations in aldosterone synthase expressing cells. Though there have been important advances in the management of primary aldosteronism, in small but convincing studies, they represent minor changes to current guidelines. What has been totally absent is consideration of the public health issue that primary aldosterone represents, and the public policy issues that would be involved in addressing the disorder. In his introduction to PiPA 6, Martin Reincke calculated that only one in a thousand patients in Germany with primary aldosteronism were treated appropriately, an astounding figure for any disease in the 21st century. Towards remedying this totally unacceptable public health issue, the author proposes a radical simplification and streamlining of screening for primary aldosteronism, and the management of most patients by general practitioners. The second bottle-neck in current management is that of mandatory adrenal venous sampling for all but 1-2% of patients, a costly procedure requiring rare expertise. Ideally, it should be reserved - on the basis of likelihood, enhanced imaging, or peripheral steroid profiles - for a small minority of patients with clear evidence for unilateral disease. Only when costs are minimized and roadblocks removed will primary aldosteronism be properly treated as the public health issue that it is.