Primary aldosteronism with hypokalemic rhabdomyolysis: a case report and review of the literature.

BACKGROUND: Hypokalemic rhabdomyolysis is a rare clinical manifestation of primary aldosteronism, making its diagnosis challenging, particularly when it becomes the primary presenting symptom. Herein, we present a case of primary aldosteronism with hypokalemic rhabdomyolysis and conduct a related literature review. CASE PRESENTATION: We report the case of a 54-year-old Chinese male patient who presented with intermittent weakness over the past year and was admitted with sudden limb paralysis for 2 days. The final diagnosis was primary aldosteronism accompanied by hypokalemic rhabdomyolysis syndrome. By reviewing the related Chinese and English literature, we noticed that only a few cases were published since 1978. After excluding irrelevant literatures, we summarized and analyzed 43 patients of with primary aldosteronism accompanied by hypokalemic rhabdomyolysis syndrome. All patients showed good recovery, with normalized blood potassium levels, and a majority achieved normalized blood pressure. Some patients still required medication for blood pressure control. CONCLUSIONS: Primary aldosteronism rarely causes rhabdomyolysis; the occurrence of severe hypokalemia and rhabdomyolysis should prompt consideration of primary aldosteronism in the differential diagnosis. Early detection and treatment are crucial for determining patient prognosis.

The prevalence of metabolic syndrome in primary aldosteronism and essential hypertension: A systematic review and meta-analysis.

It remained debates on metabolic-related disorders in patients with primary aldosteronism (PA) and essential hypertension (EH). A systematic review and meta-analysis was conducted to explore the prevalence of metabolic syndrome (MS) and the related indicators in PA and EH. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their commencement to December 2023 were searched for eligible studies. The meta-analysis was performed by Review Manager 5.3 and STATA 15.1 software. A total of 12 studies were included, revealing that there was no significant difference between PA and EH in the prevalence of MS (1.27[0.92, 1.76], p = 0.14) with higher heterogeneity (I2 = 68%, p = 0.0002), while it became significant different (1.45[1.17, 1.81], p = 0.0008) and lower heterogeneity (I2 = 26%, p = 0.19) in patients who were overweight or obese by subgroup analysis. Higher systolic blood pressure (2.99[0.67, 5.31], p = 0.01; I2 = 43%, p = 0.06) and diastolic blood pressure (2.10[0.82, 3.38], p = 0.001; I2 = 36%, p = 0.11) with lower heterogeneity, and lower triglyceride in PA group with higher heterogeneity (-0.23[-0.37, -0.09], p = 0.001; I2 = 76%, p < 0.0001) were observed. No significant difference was found in other indicators. This study showed a higher prevalence of MS in patients who were overweight or obese with PA. However, it was not the same in these patients who were in normal weight. More researches were needed to explore the relationship between PA and metabolism of glucose and lipid.

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

Elderly men are underscreened for primary aldosteronism even in Hypertension Excellence Centre.

Purpose The Endocrine Society (ES) guidelines recommend screening for primary aldosteronism (PA) in high risk hypertensive patients presenting with at least one of seven criteria (resistant HTN, hypokalaemia, adrenal nodule, etc.) Although guidelines are clear and screening is simple, compliance rates among clinicians are extremely low. This results in underdiagnosis of early disease, leading to cadiovasculaer complications and the extra-burden of advanced chronic kidney disease. We aimed to evaluate the screening rates in our Nephrology and Hypertension clinics, as an example of a dedicated Hypertension Excellence Centre. Materials and methods Data on adult hypertensive patients was retrieved from January 2018 to December 2020. Included in the study were hypertensive patients who had at least one of the ES criteria for PA screening. Of all suitable patients, we compared those who were screened for PA to patients who were not screened. Univariate and multivariate cox regression analyses were used for comparison between groups. Results Of 661 patients with HTN, 218 patients (33%) met the ES guidelines for PA screening. Forty-six of them (21.1%) were referred for screening. Advanced age and male gender were associated with lower screening referral rates. Odds ratio for age was 0.945 for every year (95% CI 0.915 - 0.975). There was a trend towards decreased referral rate in advanced kidney disease. Conclusions A 21% screening rate, suggests that many cases of PA are likely missed, more often in older patients. We therefore advocate for PA screening of all hypertensive patients, especially elderly patients with CKD, in whom clinicians' awareness is low but the absolute risk is high.

Aldosterone is a hormone secreted from the adrenal gland.Oversecretion of aldosterone (Primary Aldosteronism [PA]) causes salt retention, urinary loss of potassium and difficult to control hypertension.Both hypertension and hyperaldosteronism act synergistically and cause, over time, severe cardiac, vascular and renal damage.Different guidelines support doctors' decision-making algorithm, suggesting who should be evaluated for aldosterone hypersecretion.Our study demonstrates that even in an expert hypertension centre, many candidates for screening are missed. Elderly men are specifically underscreened.Since PA is not as rare as once thought, and can have a devastating impact on patients' health, we suggest screening all hypertensive patients for autonomous hypersecretion of aldosterone.

Sparing confirmatory testing in primary aldosteronism (SCIPA): a multicenter retrospective diagnostic accuracy study.

BACKGROUND: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. METHODS: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. RESULTS: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 - 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) CONCLUSION: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing. PROTOCOL REGISTRATION NUMBER: SRCTN34186253.

68Ga-pentixafor PET/CT in the localization diagnosis of primary aldosteronism concurrent subclinical cushing's syndrsome: two case reports.

PURPOSE: Adrenal venous sampling (AVS) is recommended for subtyping primary aldosteronism (PA). However, in cases of PA, concurrent subclinical Cushing's syndrome (SCS) has the potential to confound AVS results. Pentixafor, a CXC chemokine receptor type 4-specific ligand, has been reported as a promising marker to evaluate functional nature of adrenal adenomas. This study aims to investigate the clinical value of Gallium-68 Pentixafor Positron Emission Tomography-Computed Tomography (68Ga-Pentixafor PET/CT) in the localization diagnosis of patients with PA plus SCS. METHODS: Two patients with a confirmed diagnosis of PA plus SCS underwent AVS and 68Ga-Pentixafor PET/CT. RESULTS: AVS results revealed no lateralization for both patients while 68Ga-Pentixafor PET/CT showed a unilateral adrenal nodule with increased uptake of 68Ga-Pentixafor. Unilateral adrenalectomy was performed based on the results of 68Ga-Pentixafor PET/CT. Subsequently, complete biochemical remission of autonomous aldosterone and cortisol secretion were achieved in both cases. CONCLUSIONS: 68Ga-Pentixafor PET/CT shows promising potential for the localization of aldosterone and cortisol co-secreting adrenal adenoma in patients with PA plus SCS.

[Surgical treatment for primary aldosteronism]. / Rôle de la chirurgie dans l'hyperaldostéronisme primaire.

Primary aldosteronism is the most common cause of secondary hypertension in the middle-aged population. A high level of suspicion is required, due to the higher morbidity and mortality associated with damage to target organs (heart, brain, vessels, kidneys) than with essential hypertension. Screening involves 3 phases: detection, confirmation and detection of lateralization if surgery is an option. The choice of treatment will depend on the cause and the patient's wishes and may be either medical (mineralocorticoid receptor antagonists) or surgical (unilateral adrenalectomy). Both treatment options reduce the risk of cardiovascular morbidity and mortality if blood pressure is well controlled.

L'hyperaldostéronisme primaire est la cause la plus fréquente d'hypertension artérielle secondaire dans la population d'âge moyen. Un haut niveau de suspicion doit être de mise en raison d'une morbimortalité liée aux atteintes d'organes cibles (cœur, cerveau, vaisseaux, reins) plus élevée que lors d'hypertension artérielle essentielle. Le dépistage se fait en 3 phases : détection, confirmation et recherche de latéralisation si une chirurgie est envisageable. Le choix du traitement va dépendre de la cause et des désirs du patient et peut être médicamenteux (antagonistes des récepteurs des minéralocorticoïdes) ou chirurgical (surrénalectomie unilatérale). Les deux options thérapeutiques diminuent le risque de morbimortalité cardiovasculaire si la tension artérielle est bien contrôlée.

Report on three cases of familial primary aldosteronism type IV.

Primary aldosteronism is the most common cause of secondary hypertension, which is caused by increased aldosterone secretion in the adrenal cortex and contains many subtypes, among which familial hyperaldosteronism is relatively rare. Familial hyperaldosteronism can be divided into four subtypes based on its clinical manifestations and mutated genes: FH-I , FH-II , FH-III , and FH-IV . This article reports on three patients with FH-IV: a mother and her two sons. They were diagnosed with hypertension in other hospitals, and hypokalemia was found during hospitalization in our department. Diltiazem and terazosin were used for elution for 1 month. Renin and aldosterone levels in standing or supine positions improved, and the aldosterone-to-renin ratio was positive. Primary aldosteronism was diagnosed based on improved saline and captopril inhibition tests. As the three patients were blood-related immediate family members, gene screening was performed, diagnosing them with FH-IV . This article reports the clinical characteristics of the three cases in combination with related literature to improve the understanding of FH-IV .

The association between blood pressure variability and renal damage in patients with primary aldosteronism.

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non-dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24-h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24-h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone-renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24-h wSD of systolic BP (ß = 0.383).The study also found significant correlations between the 24-h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24-h urinary microalbumin, underscoring the critical role of the 24-h wSD of systolic BP (ß = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Target organ damage in untreated hypertensive patients with primary aldosteronism.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

Temporal trends in clinical features of patients with primary aldosteronism over 20 years.

Primary aldosteronism (PA) accounts for approximately 5-10% of hypertension cases. Over the past 20 years, the reported incidence of PA has increased due to widespread screening for secondary hypertension and imaging studies. We aimed to evaluate the temporal trends in the clinical characteristics and subtypes of PA. A total of 1064 patients with PA in two tertiary hospitals between 2000 and 2021 were categorized into three groups according to the year of diagnosis: 2000-2009, 2010-2015, and 2016-2021. The clinical characteristics of the patients over the three time periods were compared using a trend analysis. The age at diagnosis and sex of patients with PA did not change over 20 years. The proportion of patients with bilateral hyperaldosteronism (BHA) increased (11%, 25%, and 40%, P for trend <0.001). The proportion of hypokalemia (87%, 61%, and 40%) and plasma aldosterone concentration (36.0, 30.8, and 26.6 ng/dL) decreased (all P for trend <0.001). There was a trend toward an increased proportion of incidentally detected patients compared to clinically symptomatic patients (36%, 55%, and 61%, P for trend <0.001). The concordance rate of imaging and adrenal venous sampling results decreased (91%, 70%, and 57% P for trend <0.001). However, the proportion of patients with resistant hypertension and comorbidities did not differ. In conclusion, among patients with PA, patients with BHA and incidental detection have increased over 20 years, and more patients are likely to present with milder clinical symptoms and biochemical profiles.

Update on Primary Aldosteronism: Time to Screen All Hypertensives.

Primary aldosteronism (PA), characterized by autonomous renin-independent aldosterone production, is the most common endocrine cause of hypertension.1 PA was initially considered a rare cause of secondary hypertension, as experts described 0.451% prevalence in mild to moderate hypertension when hypokalemia was an essential reason for screening.1 However, recent data suggests that PA may be present even in patients with normokalemia, and 515% of patients in the hypertensive cohort have underlying overt PA.2.

Resident-led improvement project to screen for primary hyperaldosteronism in patients with resistant hypertension in an outpatient clinic.

Clinical practice guidelines recommend screening for primary hyperaldosteronism (PH) in patients with resistant hypertension. However, screening rates are low in the outpatient setting. We sought to increase screening rates for PH in patients with resistant hypertension in our Veterans Affairs (VA) outpatient resident physician clinic, with the goal of improving blood pressure control. Patients with possible resistant hypertension were identified through a VA Primary Care Almanac Metric query, with subsequent chart review for resistant hypertension criteria. Three sequential patient-directed cycles were implemented using rapid cycle improvement methodology during a weekly dedicated resident quality improvement half-day. In the first cycle, patients with resistant hypertension had preclinic PH screening labs ordered and were scheduled in the clinic for hypertension follow-up. In the second cycle, patients without screening labs completed were called to confirm medication adherence and counselled to screen for PH. In the third cycle, patients with positive screening labs were called to discuss mineralocorticoid receptor antagonist (MRA) initiation and possible endocrinology referral. Of 97 patients initially identified, 58 (60%) were found to have resistant hypertension while 39 had pseudoresistant hypertension from medication non-adherence. Of the 58 with resistant hypertension, 44 had not previously been screened for PH while 14 (24%) had already been screened or were already taking an MRA. Our screening rate for PH in resistant hypertension patients increased from 24% at the start of the project to 84% (37/44) after two cycles. Of the 37 tested, 24% (9/37) screened positive for PH, and 5 patients were started on MRAs. This resident-led quality improvement project demonstrated that a focused intervention process can improve PH identification and treatment.

Evaluation of coagulation profile in dogs with ACTH-dependent hyperadrenocorticism compared to healthy dogs by rotational thromboelastometry (ROTEM).

Despite their low morbidity, thromboembolic events in hyperadrenocorticism are associated with high mortality. Identifying the main hemostatic abnormalities will improve the prophylactic approach of these canine patients. The aim of this study was to evaluate hemostatic alterations related with ACTH-dependent HAC and its association with hypercoagulable state. For this purpose, 25 dogs diagnosed with ACTH-dependent HAC were compared with 28 healthy dogs as a control group. The hemostatic variables included platelet count, antithrombin, fibrinogen, D-dimer, PT, aPTT, rotational thromboelastometry (ROTEM) and platelet aggregation. Results showed a hypercoagulable state in 32% (8/25) dogs by ROTEM, which had at least 2 of the next features: decreased coagulation time (CT) or clot formation time (CFT) on INTEM (5/25) or EXTEM (4/25); increased maximum clot firmness (MCF) on INTEM (9/25), EXTEM (6/25) and FIBTEM (9/25). These same variables had a significant difference (P≤ 0.05) compared with the control group, as well as the parameters of α-angle and CT. Median fibrinogen levels (310 vs.178 mg/dL), mean platelet aggregation (11.1 vs. 7.9 Ohms), median platelet count (360 vs. 225 ×103/µL) and mean antithrombin activity (140 vs. 119%) were increased in ACTH-dependent HAC dogs compared to control group. PT (7.1 vs. 8.0 seconds) and aPTT (11.6 vs. 15.2 seconds) were also shortened in ACTH-dependent HAC dogs. Our findings confirm the presence of a hypercoagulable tendency in dogs with HAC. Although multifactorial, fibrinogen concentration and MCF FIBTEM showed the relevance of this protein for hypercoagulability in HAC.

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.

PURPOSE: Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications. METHODS: Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated. RESULTS: 265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828-0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases. CONCLUSIONS: ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

Best Practice Alert to Promote Screening for Primary Aldosteronism Among People With Apparent Treatment-Resistant Hypertension.

OBJECTIVE: Guidelines recommend screening all individuals with resistant hypertension for primary aldosteronism (PA) but less than 2% are screened. We aimed to develop a noninterruptive Best Practice Alert (BPA) to assess if its implementation in the electronic health record improved PA screening rates among individuals with apparent treatment-resistant hypertension (aTRH). METHODS: We implemented a noninterruptive BPA on 9/17/2022 at our ambulatory primary care, endocrinology, nephrology, and cardiology clinics. We assessed clinical parameters of people with aTRH before (9/17/2021-9/16/2022) and after (9/17/2022-9/16/2023) the BPA was implemented. The noninterruptive BPA embedded with an order set identified people with aTRH and recommended screening for PA if it was not previously performed. RESULTS: There were 10 944 and 11 463 people with aTRH who attended office visits during the 12 months before and after the BPA implementation, respectively. There were no statistically significant differences in median age (P = .096), sex (P = .577), race (P = .753), and ethnicity (P = .472) between the pre- and post-BPA implementation groups. There was a significant increase in PA screening orders placed (227 [2.1%] vs 476 [4.2%], P < .001) and PA screening labs performed (169 [1.5%] vs 382 [3.3, P < .001) after BPA implementation. PA screening tests were positive in 26% (44/169) and 23% (88/382) of people in the pre- and post-BPA groups, respectively (P = .447). CONCLUSION: Implementation of a real-time electronic health record BPA doubled the screening rate for PA among people with aTRH; however, the overall screening rate was low.