FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Hypertension Editors' Picks: Hyperaldosteronism.

Disclosure: M.A. Grytaas: None. P. Methlie: None. I. Marinelli: None. E. Zavala: None. M. Øksnes: None. T. Upton: None. K. Simunkova: None. D.A. Vassiliadi: None. K. Løvås: None. S. Bensing: None. I. Botusan: None. K. Berinder: None. G.M. Russell: None. G. Ueland: None. O. Kampe: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension but is grossly underdiagnosed. Early detection, accurate discrimination between unilateral and bilateral PA and appropriate treatment are vital to prevent cardiovascular and renal complications. The current workup however is a cumbersome, multistep process that may not detect dynamic aldosterone variability or nocturnal hypersecretion. Furthermore, subtype determination with adrenal venous sampling is invasive and technically challenging. Novel dynamic 24-hour steroid profiling may represent a major step forward in the diagnostics and subtyping of PA. Aim: To assess 24-hour rhythmicity of aldosterone and metabolites in PA, and to develop a novel dynamic diagnostic tool to discriminate PA from healthy subjects (HS), using tissue microdialysis. Material and methods: Twenty-minute frequency microdialysis fractions were collected over 24 hours from 64 ambulatory patients with PA (26 bilateral, 24 unilateral, 14 with undetermined subtype) using the U-Rhythm sampler followed by multiplex hormone assay liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixteen patients subsequently treated with adrenalectomy for unilateral PA had additional postoperative samplings. Microdialysis samplings from 214 HS were used as controls. We calculated statistical distributions of dynamic biomarkers of abnormality, and developed a machine learning classifier that discriminates PA from HS. Results: Although there were large interindividual variations, PA patients did show a disturbed circadian rhythmicity of aldosterone compared with HS, including some with multiple very high ultradian spikes. Unilateral PA had higher aldosterone spikes and more disturbed rhythmicity compared with bilateral PA. A profound reduction of aldosterone levels and normalisation of rhythmicity was seen post adrenalectomy. Applying a Random Forest classifier in a subgroup of 20 PA patients, 82% specificity and 85% sensibility were achieved to discriminate PA from HS. Our analysis also suggests 18-hydroxycortisol as the most discriminative dynamic biomarker. Conclusions: We demonstrate for the first time circadian and ultradian rhythms of aldosterone in a large cohort of PA compared with HS. Based on our preliminary results, dynamic 24-hour samplings may provide a novel method for diagnosing and subtyping PA, and assess biochemical cure after adrenalectomy. Presentation: Thursday, June 15, 2023

Context: Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. PA consists of two subtypes: the unilateral and bilateral subtype. Patients with unilateral PA, who usually have a higher plasma aldosterone concentration than those with bilateral PA, exhibit a more severe clinical phenotype. We hypothesized that PA subtype affects the prevalence of VF.Objective: To evaluate whether unilateral PA is associated with the prevalence of VF.Design: Cross-sectional study in a single referral center.Patients: We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests.Measurements: The prevalence of VF according to PA subtype.Results: We included 113 patients with PA who were subtype classified according to adrenal vein sampling, of whom 37 patients had unilateral PA and 76 patients had bilateral PA, whereas 58 patients had non-PA. We excluded 39 patients with PA who were not subtype classified. Patients with PA had a higher prevalence of VF (28% [32/113]) than those with non-PA (12% [7/58]; p = 0.020). Moreover, unilateral PA had a higher prevalence of VF (46% [17/37]) than bilateral PA (20% [15/76]; p = 0.021). There was no significant difference between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (odds ratio, 3.16; 95% confidence interval, 1.12-8.92; p = 0.017). Among patients with unilateral PA, serum cortisol concentrations after 1 mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dl) than those without (0.96 ± 0.33 g/dl; p = 0.048).Conclusions: Unilateral PA is an independent risk factor for VF, which is associated with autonomous cortisol secretion. Thus, careful management is required to prevent the development of VF in patients with unilateral PA.

Objective Primary aldosteronism (PA) is a major cause of secondary hypertension. The association between PA and other hormone disorders is unclear. The present study aimed to evaluate whether the parathyroid hormone (PTH) value is associated with PA subtypes or specific treatments. Methods We enrolled 135 patients with PA who had their PTH value measured before undergoing a specific treatment. We evaluated whether PTH value is associated with PA subtypes or with specific treatments. The present study is a single-center retrospective study (2011-2018). Results Our study showed that, among the patients with PA, the proportion of those with PTH elevation was >30%. The PTH value was significantly correlated with both the basal plasma aldosterone concentration (PAC) and PAC after a captopril challenge test. However, the PTH value was not significantly different between the patients with unilateral and bilateral PA. We observed that the serum PTH value decreased after treatment of PA with unilateral adrenalectomy or mineralocorticoid receptor antagonists. Conclusion Our findings suggest that the PTH value in PA patients might be associated with the autonomous production of aldosterone. However, there was no correlation between the PTH value and PA subtypes in our study. Additionally, our study showed that targeted treatment for PA may lead to a decrease in the serum PTH levels. Hence, the PTH value could potentially be used as an index for measuring the suitability for PA treatment.

INTRODUCTION: Primary aldosteronism (PA) is characterized by the autonomous production of aldosterone, usually from an aldosterone producing adenoma in one adrenal gland or idiopathic hyperaldosteronism, with bilateral adrenal lesions. It has been suggested that aldosterone overproduction, hypokalemia, or the complication of subclinical hypercortisolism (SH) in patients with PA, are related to impaired glucose homeostasis and insulin resistance. However, the true contributions of these factors to disturbances of carbohydrate metabolism in PA have not been investigated thoroughly from a large-scale epidemiologic viewpoint. In the present study, the true prevalence of glucose intolerance in more than 2000 patients with PA and its association with aldosterone concentration, hypokalemia, and SH were studied in a multicenter collaborative study. METHODS: The prevalence of diabetes was determined in 2210 patients with PA (diagnosed or HbA1c ≥6.5%, NGSP) and compared with that of the Japanese general population from the National Survey of the Ministry of Health, Labour and Welfare in 2016, according to age and sex. In 1386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected SH (serum cortisol ≥1.8 μg/dL after 1-mg dexamethasone suppression test) and PA laterality on the prevalence of diabetes or prediabetes (5.7%≤HbA1c<6.5%) were examined. RESULTS: Of the 2210 patients with PA, 477 (21.6%) had diabetes, this prevalence of being higher than that of the general population (12.1%) or in 10 year cohorts aged 30 to 69 years. According to the χ2 test, diabetes was present significantly more frequently in PA patients with suspected SH (26.8%) than in those with F-1mgDST <1.8 μg/dL (16.9%; p=0.001). When using logistic regression analysis, it was found that age, sex, BMI, and F-1mgDST ≥1.8 μg/dL were significant contributing factors to the presence of diabetes, whereas laterality of PA was not a significant factor. Despite more active PA profiles (e.g. higher PAC, lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on prevalence of diabetes; however, prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA. SUPPORT: This research was supported by the Japan Agency for Medical Research and Development (AMED) for the Practical Research Project for Rare/Intractable Disease.

Primary aldosteronism (PA) is associated with a higher prevalence of abdominal aortic calcification (AAC). Unilateral and bilateral PA are the most common subtypes of PA. However, no studies have addressed the difference in the prevalence of AAC between the two subtypes. In addition to aldosterone, parathyroid hormone (PTH), an important regulator of calcium metabolism, was also reported to be elevated in individuals with unilateral PA. Therefore, we hypothesized that the prevalence of AAC may be higher in individuals with unilateral PA, which may be related to the plasma aldosterone concentration (PAC) and PTH levels. We included 156 PA patients who underwent adrenal venous sampling and 156 with essential hypertension (EH) matched by age and sex. Of the former, 76 were diagnosed with unilateral PA, and 80 were diagnosed with bilateral PA. The aortic calcification index (ACI) presented the severity of AAC and was measured by adrenal computed tomography scan. Our results showed that compared with the EH group, the prevalence and severity of AAC were higher in PA patients (32.7 vs. 19.6%; 4.32 ± 3.61% vs. 2.53 ± 2.42%, respectively). In the PA subgroup analysis, unilateral PA was associated with a higher and more severe AAC than bilateral PA (40.7 vs. 25.0%; 5.12 ± 4.07% vs. 3.08 ± 2.34%, respectively). Moreover, PAC and PTH levels were higher in individuals with unilateral PA than in those with bilateral PA (P < 0.05). After risk adjustment, multivariate regression analysis revealed that PAC and PTH were positively-associated with AAC in patients with PA (P < 0.05). In conclusion, unilateral PA patients exhibited a higher prevalence of AAC and more severe AAC due to elevated PAC and PTH levels.

The Potential Clinical Application of a Lower Bilateral Adrenal LIMB Width Ratio (L/RW) in Patients with Bilateral Primary Hyperaldosteronism

Aldosterone and Primary Aldosteronism: Star Performers in Hypertension Research

Adrenal venous sampling is recommended as the golden standard for subtyping primary aldosteronism (PA). However, it is invasive and inconvenient, and seeking a better way to make differential diagnosis of PA is necessary. The objective of the study was to evaluate the diagnostic value of ACTH stimulation test under 1 mg dexamethasone suppression test (DST) in determining the subtypes of PA. Ninety-five patients with PA confirmed by saline infusion test were included in this study. According to adrenal venous sampling and histopathology, 39 patients were diagnosed as bilateral adrenal hyperplasia (BAH), 37 as aldosterone-producing adenoma (APA), and 19 as unilateral adrenal hyperplasia (UAH). An ACTH stimulation test under 1 mg DST was performed in all patients. Plasma aldosterone and cortisol levels were measured every 30 minutes until 120 minutes after the iv injection of 50 IU ACTH. During the ACTH stimulation test, aldosterone levels in APA and UAH were similar (P > .05) but higher than those in BAH (P < .001). Furthermore, stimulated aldosterone levels of unilateral PA (APA and UAH) were significantly higher than bilateral PA (BAH) (P < .001). Receiver-operated characteristics curve analyses showed the aldosterone after ACTH stimulation was effective for distinguishing between unilateral PA and bilateral PA. The diagnostic accuracy was highest at 120 minutes after ACTH stimulation, and the optimal cutoff value of the aldosterone was 77.90 ng/dL, with a sensitivity of 76.8%, a specificity of 87.2%, a positive predictive value of 89.6%, and a negative predictive value of 72.3%. The ACTH stimulation test under 1 mg DST is useful to determine the subtypes of PA, especially in unilateral and bilateral PA, and may guide further treatment in PA patients.

Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF. To evaluate whether unilateral PA is associated with the prevalence of VF. This was a retrospective cross-sectional study in a single referral centre. We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests. We measured the prevalence of VF, according to PA subtype. One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non-PA; 39 patients with PA were not subtype-classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non-PA (12%, 7/58; P=.011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P=.021). There was no significant difference in the prevalence of VF between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12-8.92; P=.017). Among patients with unilateral PA, serum cortisol concentrations after 1-mg dexamethasone suppression test were higher in those with VF (1.32±0.67g/dL) than those without (0.96±0.33g/dL; P=.048). Unilateral PA is an independent risk factor for VF.

Background: Primary aldosteronism (PA) is a common cause of endocrine hypertension. Although adrenal venous sampling (AVS) is the gold standard for subtype classification, it is available in limited specialized centers. The aim of the study was to investigate the clinical significance of cosyntropin (ACTH) stimulation test for subtype classification in PA. Design and Methods: Sixty patients with PA who underwent ACTH stimulation test were studied. The subjects were diagnosed as having either unilateral (n = 41) or bilateral PA (n = 19) based upon AVS, adrenal scintigraphy, and/or adrenal surgery. We evaluated the diagnostic significance of ACTH stimulation test in differentiating unilateral PA from bilateral PA. Results: Peak PAC (P < 0.01) and peak PAC/cortisol (P < 0.05) after ACTH stimulation were significantly higher in patients with unilateral PA than those with bilateral PA. Peak PAC-basal PAC (ΔPAC) was higher in patients with unilateral PA than those with bilateral PA, although the difference was not statistically significant. Receiver operating characteristic curve analysis for the diagnosis of unilateral PA showed a peak PAC value of 403 pg/ml had a sensitivity of 70.7% and specificity of 79.0%, and a value of 596 pg/ml had a sensitivity of 46.3% and specificity of 100%. A peak PAC/cortisol value of 19.7 (cortisol, mcg/dl) had a sensitivity of 58.5% and specificity of 89.5%, and a value of 30.5 had a sensitivity of 26.8% and specificity of 100%. Conclusions: ACTH stimulation test could discriminate between unilateral and bilateral PA and is useful in selecting the patients who should undergo AVS before surgery.

Primary aldosteronism (PA) is the most common detectable cause of secondary hypertension. The majority of patients have either an adrenal aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH) demanding different therapeutic approaches. Screening tests and imaging cannot reliably distinguish between a unilateral or bilateral PA. This review article gives an overview concerning etiology, diagnostics, and therapeutic options of PA, and reviews the indication, the technique, and relevance of selective adrenal venous sampling (AVS) in the context of the current literature and the authors' experience. AVS can verify or exclude a unilaterally dominated secretion with a high success rate. Patients with PA and a unilateral APA can be treated curatively by adrenalectomy. AVS is an established diagnostic examination for differentiation of unilateral from bilateral adrenal disease in patients with PA. · Selective adrenal venous sampling (AVS) is a safe, reliable, and minimally invasive method to detect a unilateral or bilateral adrenal adrenal gland disease.. · Verification of lateralization by AVS has direct therapeutic relevance for patients with primary aldosteronism (PA).. · AVS can be performed with low radiation exposure, without contrast medium, and with a high success rate when performed by an experienced interventional radiologist.. · Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 - 666.

Background: Metabolic syndrome (MetS) is a common comorbidity associated with hypertension that occurs more often in primary aldosteronism (PA). Our work aims to investigate the prevalence of MetS and its determinants in unilateral PA and bilateral PA, as confirmed by adrenal venous sampling (AVS). Methods: This was a retrospective, cross-sectional study. We investigated metabolic indicators in 160 cases of PA, categorized by AVS—82 with unilateral PA and 78 with bilateral PA. A control group of 80 non-PA patients with essential hypertension, matched for age and sex, was also included. Results: Unilateral PA had a higher aldosterone–renin ratio and lower serum potassium levels than bilateral PA. Nevertheless, bilateral PA exhibited a higher prevalence of MetS (41% vs. 30.5%; p = 0.001), obesity, BMI, LDL hypercholesterolemia, and hypertriglyceridemia than unilateral PA. Conclusions: Bilateral PA presents a greater incidence of MetS than unilateral PA, in spite of the latter showing a higher aldosterone–renin ratio and lower serum potassium levels. The results suggest that the mechanisms underlying MetS may differ between unilateral and bilateral PA.

To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707-0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782-0.957]. The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.

Caution About the Overdiagnosis of Primary Aldosteronism