Diagnosis Of Primary Aldosteronism Research Articles

Improvement in quality of life and psychological symptoms after treatment for primary aldosteronism: Asian Cohort Study.

BackgroundIn addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related quality of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy.MethodsThirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment.ResultsAt 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treatment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improvement in the affective domain of BDI-II at 1 year post-treatment.ConclusionBoth surgical and medical therapy improve HRQoL and psychological symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay for simultaneous quantification of aldosterone, renin activity, and angiotensin II in human plasma

Accurate quantification of plasma aldosterone (ALD) and renin activity (PRA)is critical for the diagnosis of primary aldosteronism (PA). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered the “gold standard” method for the determination of ALDand PRA. The aim of this study is to develop a new LC-MRM/MS assay for quantifying plasma ALD, PRA, and angiotensin II (Ang II) simultaneously and validate its effectiveness. To be more specific, plasmasamples were prepared by solid-phase extraction and separated in an ultra-performance reversed-phase column. MS detection was performed via a triple quadrupole mass spectrometer containing both positive and negative ion monitoring modes. The developed assay was then validated according to the standard guidelines and the influence of sample incubation on ALD and Ang II concentration was evaluated. In addition, the variation of endogenous Ang I was explored. The proposed LC-MRM/MS method was compared another LC-MS/MS method, which detects ALD, Ang I, and Ang II separately. Analyteswere separated and quantified within 5 min. The assay wasvalidated to be linear up to 5000 pg/ml for ALD and Ang II and 33.3 ng/ml/h for PRA.The lower limit of quantification (LLOQ) was 15 pg/ml, 15 pg/ml, and 0.1 ng/ml/hfor ALD, Ang II, and PRArespectively. Specificity, precision, accuracy, and stability were tested to meet the requirements of the guidelines. Significant changes were not found in ALD and Ang II concentrations over the 3 h-incubation. In addition, it was demonstratedthat the resultof PRA was not stronglyinfluenced by the endogenous Ang I. Comparison with another LC-MS/MS method was performed using the same apparatusand the proposed method was proved to be in good coincidence with the correlation coefficients rangingfrom 0.955to0.996. A sensitive and reliable method for simultaneousquantification of ALD, PRA, and Ang II has been developed and this study will significantly promote laboratory workflow efficiency and throughput.

Subtype-specific trends in the clinical picture of primary aldosteronism over a 13-year period.

Primary aldosteronism has two main clinically and biologically distinct subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). We aimed to evaluate the changes of each subtype's clinical characteristics over a 13-year period. This retrospective study involved time-trend analyses to identify changes in the clinical features of APA and BAH at diagnosis (2006-2018). A nationwide database from 41 Japanese referral centers was searched, which identified 2804 primary aldosteronism patients with complete baseline information and adrenal venous sampling (AVS) data. The proportion of patients with APA decreased from 51% in 2006-2009 to 22% in 2016-2018. Among the 1634 patients with BAH, trend analyses revealed decreases in hypertension duration (median 7--3 years; P < 0.01) and hypokalemia prevalence (18--11%; P < 0.01). However, among the 952 patients with APA, there were no significant changes in hypertension duration (median 8 years) and hypokalemia prevalence (overall 70%). Furthermore, the APA group had a trend towards increased use of multiple hypertensive drugs at diagnosis (30--43%; P < 0.01). When subtypes were reclassified according to the precosyntropin stimulation AVS data, APA patients tended to be diagnosed earlier and at milder forms, consistent with the trend in overall primary aldosteronism patients. During 2006-2018, we identified marked subtype-specific trends in the clinical findings at the diagnosis of primary aldosteronism. Our results suggested that the emphasis on the implementing cosyntropin stimulation during AVS might lead to under-identification of APA, especially in patients with mild or early cases.

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

BackgroundManagement 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.MethodsThe 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.ResultsTotally, 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.ConclusionThrough 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.

The Value of Different Single or Combined Indexes of the Captopril Challenge Test in the Diagnosis of Primary Aldosteronism.

ObjectiveThe result interpretation of the captopril challenge test (CCT) for the diagnosis of primary aldosteronism (PA) is not standardized. Superiorities of different indexes in the CCT have not been fully investigated. We aimed to comprehensively evaluate the value and influence factors of different CCT-associated indexes in the diagnosis of PA.MethodsWe enrolled 312, 85, 179 and 97 patients in the groups of PA, essential hypertension (EH), unilateral PA (UPA) and bilateral PA (BPA), respectively. For each single index investigated, we computed diagnostic estimates including the area under the receiver operating characteristic curve (AUC). We performed pre-specified subgroup analyses to explore influence factors. We assessed the diagnostic value of combined indexes in binary logistic regression models.ResultsPost-CCT aldosterone to renin ratio (ARR) (AUC = 0.8771) and plasma aldosterone concentration (PAC) (AUC = 0.8769) showed high value in distinguishing PA from EH, and their combination (AUC = 0.937) was even superior to either alone. The diagnostic efficacy was moderately high for post-CCT aldosterone to angiotensin II ratio (AA2R) (AUC = 0.834) or plasma renin activity (PRA) (AUC = 0.795) but low for the suppression percentage of PAC (AUC = 0.679). Post-CCT PAC had a significantly higher AUC in the UPA than BPA subgroup (AUC = 0.914 vs 0.827, P<0.05).ConclusionWe can take post-CCT ARR and PAC altogether into account to distinguish PA from EH, while caution should be taken to interpret CCT results with the suppression percentage of PAC. Post-CCT PAC may perform better to identify the unilateral than bilateral form of PA.

WITHDRAWN: Liddle syndrome: a case report

Liddle syndrome is an autosomal dominant hereditary disease caused by a single gene mutation. Typical clinical manifestations are early-onset hypertension and hypokalaemia and can be treated using ENaC blockers (amiloride and aminopterin). This report describes a 17-year-old male with hypertension and hypokalaemia. We performed a Captopril inhibition test and a postural stimulation test for the diagnosis and typing of primary aldosteronism. The serum renin was low, and aldosterone was high, so the patient was initially misdiagnosed as primary aldosteronism. After a genetic analysis, a diagnosis of Liddle syndrome was made due to the presence of an SCNN1B p.Pro617Ser mutation. After diagnosis, the patient was administered one tablet of amiloride twice a day (each tablet contains 2.5mg of amiloride hydrochloride and 25mg of hydrochlorothiazide 25mg). The patient's blood pressure (average of 120-135/70-80mmHg) and serum potassium levels (3.6-4.0mmol/L) returned to normal and were well-controlled after treatment. The patient is an atypical case of Liddle syndrome; genetic analysis is helpful and essential for diagnosis.

Abstract #1003305: Double Challenges in Clinical Endocrinology: Panhypopituitarism and delayed diagnosis of Primary Aldosteronism

Abstract #1003305: Double Challenges in Clinical Endocrinology: Panhypopituitarism and delayed diagnosis of Primary Aldosteronism

Repeated hormonal and radiological evaluation of hypertensive patients is necessary for correct primary aldosteronism diagnosis and treatment

Repeated hormonal and radiological evaluation of hypertensive patients is necessary for correct primary aldosteronism diagnosis and treatment

The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism.

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

Machine learning based models for prediction of subtype diagnosis of primary aldosteronism using blood test

Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.

Significance of Discordant Results: between Confirmatory Tests in Diagnosis of Primary Aldosteronism

Context: Current clinical guidelines recommend confirmation of positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results. Objective: The aim of the present study was to explore the role of two confirmatory tests in subtype diagnosis of PA. Design: Retrospective cross-sectional study. Setting: The study was conducted at two referral centers. Participants and Method: We identified 360 hypertensive patients who underwent both captopril challenge test (CCT) and saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS). Main Outcome Measure: The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests. Results: Of patients studied, 127 were positive for both CCT and SIT (double-positive), while 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs. 72/127 [56.7%], P < 0.01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients. Conclusion: Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.

Persistent Hyperkalemia Post-Adrenalectomy for Aldosterone-Producing Adenoma

Abstract Background:Post-operative hypoaldosteronism due to chronic suppression of the renin-aldosterone axis of the contralateral gland can be complicated with hyperkalemia. We describe a case of persistent hyperkalemia post adrenalectomy for aldosterone-producing adenoma. Clinical Case: A 47-year-old male was first diagnosed with hypertension in 2011. He was investigated for secondary hypertension after hospital admission in 2019 for hypertensive urgency and symptomatic hypokalemia (potassium, K 1.9–2.3 mmol/L, n = 3.5–5.0). Subsequent laboratory investigation revealed elevated serum aldosterone (3565 pmol/L, n &amp;lt; 103) with an aldosterone renin ratio of 115 (n &amp;lt; 35). A confirmatory test with saline loading showed an unsuppressed serum aldosterone level of 1840 pmol/L. Adrenal CT reported a 4.1-cm, heterogeneous left adrenal lesion. A diagnosis of primary aldosteronism was made, and he underwent laparoscopic left adrenalectomy in July 2020. Histopathology examination was consistent with adrenal cortical adenoma. Both potassium supplementation and spironolactone were stopped immediately postoperatively. Two weeks later, he developed symptomatic hyperkalemia (K 6.0 mmol/L), requiring hospital admission, and started on potassium binder. Throughout clinic follow-ups, potassium remained high (K 5.4–6.1 mmol/L), despite low potassium diet and potassium binder. His case was co-managed with the nephrology team and given a trial of frusemide and sodium bicarbonate to normalize his potassium. However, after 4 months, he remained hyperkalemic. Repeated serum aldosterone was not elevated (&amp;lt;103 pmol/L). He was then started on fludrocortisone and finally managed to achieve serum potassium normalisation (K 4.1–4.5 mmol/L). Conclusion: This case highlights the importance of monitoring potassium levels in all patients after adrenalectomy, particularly those with clinical risk factors. Retrospective studies by Park et al and Fischer et al reported that a long duration of hypertension, impaired preoperative renal function, older age, and large adenoma size represent risks for developing hyperkalemia postoperatively, whereas the use of mineralocorticoid receptor antagonists preoperatively does not prevent hyperkalemia. Treatment includes a low potassium diet, a high sodium diet, adequate hydration, potassium binder, frusemide, and fludrocortisone. In some cases, hyperkalemia may be prolonged, necessitating long-term fludrocortisone therapy, up to 11–46 months².

Primary Hyperaldosteronism in Pregnancy: A Case Report

Background: Primary aldosteronism (PA) is a renin-independent hypersecretion of aldosterone that remains an underdiagnosed etiology of hypertension. Less than 50 cases of primary hyperaldosteronism in pregnancy have been reported in literature that are associated with pregnancy complications including preeclampsia. Clinical Case: A 41-year-old female G9P4 at 32 weeks gestation was admitted for suspected preeclampsia due to elevated blood pressure during a routine prenatal visit. Her comorbidities include type 2 diabetes, uncontrolled hypertension, and preeclampsia in a previous pregnancy. Home medications included Lisinopril 10 mg once daily which was discontinued upon pregnancy and switched to Labetalol 400 mg twice daily and Nifedipine ER 30 mg daily. She was on a total of 220 units of insulin daily.On presentation, patient complained of anxiety but denied any headache, nausea, visual disturbances, chest pain, palpitations, muscle cramps, or fatigue. Her blood pressure was 180/100 mmHg with heat rate of 73. Laboratory values was notable for potassium: 2.8 mmol/L (n 3.5–5 mmol/L), bicarbonate: 28 mmol/L (n 24–31 mmol/L), and magnesium: 1.4 mEq/L (n 1.3–1.9 mEq/L). Liver function test and platelet count were normal. Spot protein-creatinine ratio was 0.3 (n 0–0.2). ECG was normal sinus rhythm with a heart rate of 82 without decreased T wave amplitude or U waves. She received three doses of oral 40 mEq potassium chloride over twelve hours and potassium level post repletion was 3.0 mmol/L.Initially, her hypokalemia was attributed to high insulin dose requirements. Despite down titration of insulin, patient continued to have hypokalemic episodes (nadir 2.7 mmol/L) refractory to oral and parenteral potassium supplementation. She remained hypertensive despite Labetalol 600 mg every 8 hours, Nifedipine ER 30 mg every 12 hours, with as needed hydralazine 10 mg IV pushes, and underwent urgent cesarean delivery. Uncontrolled hypertension persisted postpartum with recurrent episodes of hypokalemia. Further investigations revealed a plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels of 43.5 ng/dL (n <10 ng/dL) and 1.67 ng/mL/hr (n 0.17–5.38 ng/mL/hr) respectively, potassium at time of testing was 3.6 mmol/L. PAC to PRA ratio was greater than 20:1 with an absolute PAC greater than 15 ng/dL, which is highly suggestive of PA. Conclusion: We present a case of suspected PA with spontaneous hypokalemia potentially masked by the use of ACE inhibitors uncovered during pregnancy. Given the changes to the renin-angiotensin-aldosterone system (RAAS) during pregnancy, the diagnosis of PA is difficult to establish during gestation. Still, little is known on how to optimally treat these patients. Reference: Morton, A., 2015. Primary Aldosteronism and Pregnancy. Pregnancy and hypertension. An International Journal of Women’s Cardiovascular Health, Volume 5 Issue 4, 259–262.

Stable Serum Potassium After Intracerebral Hemorrhage Is Predictive of Primary Aldosteronism

Background: Primary aldosteronism (PA) is a well-known risk factor for cardiovascular complications including intracerebral hemorrhage (ICH). Still, there seem to be many PA patients who have been missing the opportunities for the diagnosis of PA even after stroke. PA screening tests in all stroke patients are, however, inefficient. Here we focused on ICH, where hypertension has a great contribution, and searched for the indications of performing PA screening tests in ICH patients. Methods: 1) Out of 181 ICH patients admitted to our hospital between June 2016 and February 2017, 126 patients of hypertensive ICH were enrolled in this study. Plasma aldosterone concentration (PAC), plasma renin activity (PRA) and other hormones were measured in the morning two days after admission. 2) 1,242 hypertensive ICH patients admitted to our hospital after January 2013 were retrospectively reviewed Results: 1) After excluding those who had been taking medications which could intervene with PAC or PRA on admission, nine patients were positive for PA screening (PAC/PRA ratio >200 and PAC >120 pg/mL) and 46 were negative. Age (68.6 vs 67.1 y), sex (male 66.7 vs 67.3 %) and blood pressure (172/97 vs 177/100 mmHg) were similar between these two groups. Serum potassium was slightly lower in positive group on admission (3.6 vs 3.9 mmol/L; P=0.108), and the difference became more evident two days later (3.7 vs 4.0 mmol/L; P=0.042). There were no differences in other hormones including cortisol and catecholamine on day 2. PA positive patients had more severe motor or cognitive impairments (Functional independence measure 58 vs 95; P=0.015). 2) After collecting 25 clinical parameters in 1,242 hypertensive ICH patients, dimension reduction procedure using t-SNE certainly divided these patients into clusters compatible with PA screening tests. Only 4% of PA positive group showed serum potassium lower than 3.5 mmol/L on admission (sensitivity 97%), and the increase in serum potassium during the first 2 days were milder in PA positive group (P=0.001). Discussion: This is the largest study ever that investigated the clinical features of PA in ICH patients. We uncovered that transitional changes of serum potassium after the onset of ICH were efficient markers to decide who should go on to PA screening tests. ICH increases sympathetic activity and subsequent renin secretion, resulting in low serum potassium even in PA negative group. But about two days later, when its activity peaked out, serum potassium in PA negative group restores to their original states while that in PA positive group are stable due to constitutive secretion of aldosterone. Since ICH patients with PA are at higher risk for recurrent hemorrhage and other complications, diagnosis of PA is important even after the occurrence of ICH. PA screening should not be awaited just because they have developed ICH.

The Spatial Epidemiology of Patients Who Were Screened for and Diagnosed With Primary Aldosteronism in Southern Thailand

Background: In Thailand where biochemical testing for detection of primary aldosteronism (PA) is only available in a few tertiary centers, which may contribute to a delay in case detection. This study aimed to identify the geographic distribution of PA screening and diagnosis and its contributing epidemiologic and geographic factors in Southern Thailand. Method: Data of 688 patients who underwent PA screening between 2011–2017 were reviewed from the electronic database. The patients’ residences were extracted from the identification cards or the address recorded in the hospital system. The presence of an endocrinologist and the dominant religion in each province were recorded. The province, district and subdistrict of each patient were transformed to a 6-digit administrative area code corresponding with the global one (GADM©). A generalized log-linear model was used to identify predictors for individuals being screened. Results: Overall, the prevalence and crude incidence rates of PA in Southern Thailand were 15.6% and 1.66/1,000,000 person-years, respectively. The provinces located adjacent to the Andaman Sea had the highest incidences of PA (3.62–5.17 patients/1,000,000 person-years). Areas with the highest screening rates were located at and near Songkhla where the major tertiary medical center is located. A multivariate log-linear model demonstrated that the distance from the major tertiary center was the only predictive factor for screening while the availability of an endocrinologist and cultural differences were not. The chances of patients who lived in Songkhla, lived less than or more than 200 km from Songkhla to receive PA screening were 100% (reference), 82% (95% CI:0.69–0.97, p-value 0.03), and 66% (95% CI:0.55–0.78, p-value < 0.001), respectively. Conclusion: Geographic location was the main factor contributing to a delay in case detection for PA. A public health policy should be developed to mitigate the geographic barrier thus improving the ability of patients to access healthcare services. Further research relating to the underlying risk of the disease such as genetic transmission in populations with a high incidence of PA should be performed.

A Case of Primary Hyperaldosteronism Presenting as Hemorrhagic Stroke

Background: Primary aldosteronism (PA) is the most common form of secondary hypertension. Patients with PA are more likely to suffer from end-organ damage compared to matched controls with essential hypertension. We present a case of PA identified in a patient who presented with hypertensive emergency and hemorrhagic stroke. Clinical Case: A 52-year-old man with hypertension and chronic kidney disease presented with sudden onset left-sided weakness. He had a ten year history of hypertension and was taking carvedilol, losartan, and hydralazine prior to presentation. On arrival, his blood pressure was 263/142 mmHg. He had 3/5 grade weakness in the left upper and lower extremities. Laboratory analysis showed a potassium level of 2.8 mmol/L (n = 3.5–5 mmol/L) and a bicarbonate level of 33 mmol/L (n = 21–29 mmol/L). Screening labs for PA were drawn after potassium repletion. CT Head without contrast revealed an acute 2.5-centimeter intracerebral hemorrhage of the right basal ganglia. He was admitted to the intensive care unit and was started on a nicardipine drip with an improvement of blood pressure. His weakness improved and he was discharged home on carvedilol, hydralazine, nifedipine, and losartan.Screening for PA revealed a plasma aldosterone concentration (PAC) of 22.8 ng/dL (n < 16 ng/dL) and a plasma renin activity (PRA) of 0.1 ng/ml/hr (n = 0.2–1.6 ng/ml/hr). The PAC/PRA ratio was therefore extremely elevated at 228. The presence of spontaneous hypokalemia, very low renin, and PAC >20 ng/dL confirmed the diagnosis of primary aldosteronism. He underwent an adrenal MRI which revealed two left adrenal nodules, the largest measuring 10 mm, and a 7.3 mm right adrenal nodule, consistent with bilateral adrenal adenomas. The patient did not desire surgery, therefore adrenal vein sampling was deferred. His hypertension improved with the addition of a mineralocorticoid receptor antagonist. Eight weeks after his stroke the patient was readmitted due to chest pain. He was found to have severe multi-vessel coronary artery disease and underwent a four vessel coronary artery bypass. Conclusion: Patients with PA have higher rates of adverse cardiovascular events compared to age-, sex-, and blood pressure-matched controls with essential hypertension. Studies demonstrate that aldosterone excess has blood pressure independent proinflammatory and profibrotic effects on the vessel wall which leads to endothelial dysfunction and thus accelerated atherosclerosis. Appropriate treatment can eliminate the excess cardiovascular risk associated with PA. This case highlights the importance of including PA in the differential diagnosis of secondary hypertension, particularly among patients presenting with spontaneous hypokalemia, severe uncontrolled hypertension and early onset cardiovascular or cerebrovascular disease.

Primary Aldosteronism as the Initial Presentation of Adrenocortical Multiple Hormone Producing Tumor

Introduction: Primary aldosteronism (PA) accounts for ∼10% of cases of hypertension in adults, however it’s a rare disease in children. We present a rare pediatric case with PA as the initial presentation of adrenocortical multiple hormone producing tumor. Case: A 7-year-old Japanese girl, who had right-sided hypoplastic leg and foot syndactyly, presented to our hospital due to abnormal ECG of ST depression at V6 on school health check-up. She showed normal growth, no signs of virilization nor Cushingoid appearance. She had elevated blood pressure (164/98 mmHg), low potassium (2.6–3.0 mEq/L) and low cardiac ejection fraction (30–40%). Her plasma aldosterone concentration (PAC) was 441 pg/mL and aldosterone/renin ratio (ARR) was 1470. Contrast-enhanced CT and MRI showed a right adrenal mass (34×22×30 mm) with high lipid content, which led to the diagnosis of primary aldosteronism by the right adrenal adenoma. Adrenal venous sampling failed to identify localization of aldosterone production. Since the possibility of bilateral production of aldosterone remained, the girl was treated with multiple anti-hypertensive medicine including spironolactone and potassium supplementation. Although the serum potassium levels were maintained within normal range, exercise-induced PVCs occurred 6 months after first visit. Abdominal US showed no changes in size of the tumor. Ten months later, she showed gradual weight gain without growth deceleration. Twelve months later, abdominal US revealed apparent enlargement of the right adrenal mass, and MRI scan showed a 156% increase in size of the right adrenal mass (32×50×53 mm). She showed further weight gain with moon face, hirsutism and acne. Hormonal analysis revealed elevated serum and urine cortisol levels (30–40μg/dL and 269–337 μg/m2/day, respectively), and suppressed ACTH levels with no diurnal variation. Serum testosterone levels elevated to 1.00 ng/mL and serum DHEA-S to 273 μg/dL. Retrospective analysis of serum testosterone at the first visit was already mildly elevated to 0.47 ng/mL. Although no distant metastases were detected before surgery, direct liver invasion was found at right adrenal tumor rejection. Clinical Lessons: Primary aldosterone producing adenoma is extremely rare in childhood. In our case, initially the adrenal tumor produced aldosterone predominantly, and it revealed to produce glucocorticoid and androgen later on. Androgen producing adrenal tumor in children tends to have malignant nature. Although initial presentation was compatible with the primary aldosteronism, intense follow-up with detailed monitoring of various hormone levels and images, and early surgical intervention should be considered.

Machine Learning-Based Models for Prediction of Subtype Diagnosis of Primary Aldosteronism Using Blood Test

Abstract Context: Primary aldosteronism (PA) is a common cause of secondary hypertension and is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who can be cured by unilateral adrenalectomy and should be referred to specialized centers. The use of machine learning has been introduced in some fields of clinical prediction. Combining machine learning with clinical data could lead to the development of new models for predicting unilateral subtype of PA. Objective: The aim of this study was to develop a predictive model of subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Design and setting: This was a retrospective cross-sectional study in referral centers. Patients: We retrospectively analyzed 91 patients with unilateral and 138 patients with bilateral subtype of PA diagnosed according to adrenal venous sampling findings, and stratified randomly split to the training (80%) and test cohorts (20%). Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop prediction models from 21 clinical variables. Classifiers were trained using stratified 10 fold cross-validation of the training cohort and hyperparameters of each classifier were adjusted using grid search to optimize the accuracy in the training cohort. Main Outcome Measures: The accuracy and the area under the receiver operating characteristic curve (AUC) for subtype prediction in the test cohort were compared among the optimized classifiers. Results: Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium levels, plasma aldosterone concentrations, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF. Conclusions: Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.

ABDOMINAL AORTIC CALCIFICATION IN ALDOSTERONE PRODUCING ADENOMA AND IDIOPATHIC HYPERALDOSTERONISM

Objective: Aldosterone promotes vascular calcification, which leads to atherosclerosis and eventually cardiovascular disease via enhancing vascular osteoinductive signaling, oxidative stress, inflammation and apoptosis. As an independent prediction of coronary artery disease (CAD), abdominal aortic calcification has been useful as well as coronary artery calcification. It has been shown that patients with aldosterone producing adenoma (APA) have higher rate of CAD comparing patients with idiopathic hyperaldosteronism (IHA) at the diagnosis of primary aldosteronism (PA). However, no data have shown whether the degree of abdominal aortic calcification is different between APA and IHA. We aimed to clarify the degree of abdominal aortic calcification in each subtype of PA. Design and method: This retrospective observational study comprised 170 patients diagnosed with PA. We divided participants into APA (n = 48) and IHA (n = 132), according to the results of adrenal venous sampling (AVS) and pathological findings. Aortic calcification index (ACI) was evaluated by unenhanced abdominal computed tomography, focusing around the left renal artery and scanning 10 times at 10-mm intervals. Results: Age was not different between the two subtypes (p = 0.47). Duration of hypertension and plasma aldosterone concentration were significantly higher in APA than IHA (p &lt; 0.001, p &lt; 0.001, respectively). Neither smoking ratio, HbA1c, LDL-cholesterol, nor eGFR was different between the two subtypes (p = 0.86, p = 0.49, p = 0.20, p = 0.47, respectively). The percentage of patients with ACI &gt; 1 was significantly higher in APA than IHA (APA vs. IHA; 17/48 (35.4%) vs. 25/132 (18.9%), p = 0.03). In patients with ACI &gt; 1, ACI was correlated with duration of hypertension in both subtypes of PA (APA; r = 0.62, p = 0.01, IHA; r = 0.49, p = 0.02). Conclusions: Abdominal aortic calcification was progressed in APA than IHA. This result was concordant with higher rate of CAD in APA than IHA. In both subtypes of PA, patients with longer duration of hypertension tended to coexist abdominal aortic calcification, demonstrating an importance of early diagnosis and treatment before developing to aortic calcification in either subtype of PA.

EVALUATION OF A NEW DIAGNOSTIC TEST FOR PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is the most common form of endocrine hypertension. Currently, diagnosis comprises a screening test based on the aldosterone –to-renin ratio (ARR), followed by a confirmatory test to verify autonomous aldosterone secretion. However, available confirmatory tests (fludrocortisone, saline infusion) are laborious or relatively expensive. For this reason, the non-invasive Captopril test has been widely used despite its lower specificity. Recently, a new overnight screening test (DCVT) has been proposed, using oral administration of combined blockers of RAAS (renin–angiotensin–aldosterone system). The aim of the study was to assess the performance of DCTV in the diagnosis of PA in patients in whom the diagnosis was confirmed by the established Captopril test. Design and method: A total of 94 subjects with hypertension were investigated over a 2-year period. To confirm PA diagnosis all the patients underwent the Captoptil challenge test, as previously described. In addition, in all participants the DCVT was performed (patients received 2 mg Dexamethasone, 50 mg Captopril and 320 mg Valsartan at midnight and an extra dose of 50 mg Captopril 1 h before blood sampling in the next morning). Results: In the whole group of patients, 37 were diagnosed with PA on the basis of Captopril test cut-offs. The remaining 57 patients were considered to have essential hypertension. There was no significant difference in the main characteristics (age, sex, BMI, blood pressure, fasting blood glucose, lipids) between the two groups, except for potassium which was lower in patients with PA (p &lt; 0.001). The areas under the receiver–operator characteristics curves for the post DCTV-aldosterone and post-DCVT ARR were 0.88 and 0.82, respectively. The optimal cutoff value for post DCTV- aldosterone was 262 pmol/l, which yielded a sensitivity and specificity of 83% and 75% respectively. Conclusions: In conclusion, DCVT is an reasonable alternative to the more complex invasive confirmatory tests in the PA diagnosis. Similarly to Captopril test, DCVT is safe and much easier to perform, so it may serve as a feasible alternative, despite slightly lower performance indices. When interpreting the results of DCVT, post- DCTVT aldosterone is recommended compared to post-DCVT ARR.