Role of radiologists in the diagnosis and management of adrenal disorders.

This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.

Predicting the resolution of hypertension following adrenalectomy in primary aldosteronism: Controversies and unresolved issues a narrative review.

BACKGROUND: Hypertension resolution following adrenalectomy in patients with primary aldosteronism (PA) remains a critical clinical challenge. Identifying preoperatively which patients will become normotensive is both a priority and a point of contention. In this narrative review, we explore the controversies and unresolved issues surrounding the prediction of hypertension resolution after adrenalectomy in PA. METHODS: A comprehensive literature review was conducted, focusing on studies published between 1954 and 2024 that evaluated all studies that discussed predictive models for hypertension resolution post-adrenalectomy in PA patients. Databases searched included MEDLINE®, Ovid Embase, and Web of Science databases. RESULTS: The review identified several predictors and predictive models of hypertension resolution, including female sex, duration of hypertension, antihypertensive medication, and BMI. However, inconsistencies in study designs and patient populations led to varied conclusions. CONCLUSIONS: Although certain predictors and predictive models of hypertension resolution post-adrenalectomy in PA patients are supported by evidence, significant controversies and unresolved issues remain. While the current predictive models provide valuable insights, there is a clear need for further research in this area. Future studies should focus on validating and refining these models.

Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma.

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.

Primary aldosteronism and hypokalemia-induced rhabdomyolysis in a patient with aldosterone-producing adenoma: A case report and literature review.

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

Multimodal integration of radiology and pathology signatures for distinguishing between aldosterone-producing adenomas and nonfunctional adrenal adenomas.

OBJECTIVE: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). METHODS: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. RESULTS: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000). CONCLUSION: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.

Intracellular Calcium Dynamics in Primary Human Adrenocortical Cells Deciphered with a Novel Pipeline.

INTRODUCTION: The fluctuations of the intracellular Ca2+ concentration ([Ca2+]i) are key physiological signals for cell function under normal conditions and can undergo profound alterations in disease states, as high blood pressure due to endocrine disorders like primary aldosteronism (PA). However, when assessing such fluctuations several parameters in the Ca2+ signal dynamics need to be considered, which renders their assessment challenging. AIM: Aim to develop an observer-independent custom-made pipeline to analyze Ca2+ dynamics in terms of frequency and peak parameters, as amplitude, full width at half maximum (FWHM) and area under the curve (AUC). METHODS: We applied a custom-made methodology to aldosterone-producing adenoma (APA) and APA adjacent cells (AAC) and found this pipeline to be suitable for monitoring and processing a wide-range of [Ca2+]i events in these cell types delivering reproducible results. CONCLUSION: The designed pipeline can provide a useful tool for [Ca2+]i signal analysis that allows comparisons of Ca2+ dynamics not only in PA, but in other cell phenotypes that are relevant for the regulation of blood pressure.

Distinguishing between aldosterone-producing adenomas and non-functional adrenocortical adenomas using the YOLOv5 network.

BACKGROUND: You Only Look Once version 5 (YOLOv5), a one-stage deep-learning (DL) algorithm for object detection and classification, offers high speed and accuracy for identifying targets. PURPOSE: To investigate the feasibility of using the YOLOv5 algorithm to non-invasively distinguish between aldosterone-producing adenomas (APAs) and non-functional adrenocortical adenomas (NF-ACAs) on computed tomography (CT) images. MATERIAL AND METHODS: A total of 235 patients who were diagnosed with ACAs between January 2011 and July 2022 were included in this study. Of the 215 patients, 81 (37.7%) had APAs and 134 (62.3%) had NF-ACAs' they were randomly divided into either the training set or the validation set at a ratio of 9:1. Another 20 patients, including 8 (40.0%) with APA and 12 (60.0%) with NF-ACA, were collected for the testing set. Five submodels (YOLOv5n, YOLOv5s, YOLOv5m, YOLOv5l, and YOLOv5x) of YOLOv5 were trained and evaluated on the datasets. RESULTS: In the testing set, the mAP_0.5 value for YOLOv5x (0.988) was higher than the values for YOLOv5n (0.969), YOLOv5s (0.965), YOLOv5m (0.974), and YOLOv5l (0.983). The mAP_0.5:0.95 value for YOLOv5x (0.711) was also higher than the values for YOLOv5n (0.587), YOLOv5s (0.674), YOLOv5m (0.671), and YOLOv5l (0.698) in the testing set. The inference speed of YOLOv5n was 2.4 ms in the testing set, which was the fastest among the five submodels. CONCLUSION: The YOLOv5 algorithm can accurately and efficiently distinguish between APAs and NF-ACAs on CT images, especially YOLOv5x has the best identification performance.

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.

Cardiovascular Outcomes of KCNJ5 Mutated Aldosterone-Producing Adenoma: A Systematic Review.

BACKGROUND: While clinical features of KCNJ5-mutated aldosterone-producing adenoma (APA) have been reported, evidence of its clinical outcomes is lacking. We aimed to synthesize available literature about the associations between KCNJ5 mutation with cardiovascular and metabolic outcomes among patients with APA. METHODS: In this systematic review of observational studies, MEDLINE and Embase were searched through August 2022. Two independent authors screened the search results and extracted data from eligible observational studies investigating cardiovascular or metabolic outcomes between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs. Risk of Bias In Non-randomized Studies of Interventions was used to assess the quality of the included studies. RESULTS: A total of 573 titles/abstracts were screened and after the expert opinion of the literature, full text was read in 20 titles/abstracts, of which 12 studies were included. Across 3 studies comparing the baseline or change in the cardiac function between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs, all studies reported the association between impaired cardiac functions and KCNJ5 mutation status. Among 6 studies evaluating the cure of hypertension after surgery, all studies showed that KCNJ5 mutation was significantly associated with the cure of hypertension. In quality assessment, 7 studies were at serious risk of bias, while the remaining studies were at moderate risk of bias. CONCLUSIONS: This systematic review provided evidence of the significant association between KCNJ5 mutation and unfavorable cardiovascular outcomes in patients with primary aldosteronism. Further research is needed to improve the quality of evidence on this topic and elucidate the underlying mechanisms of the potential burden of KCNJ5 mutation.

Clinical prediction model for primary aldosteronism subtyping and special focus on adrenal volumetric assessment.

PURPOSE: Our aim was to develop a prediction model based on a simple score with clinical, laboratory, and imaging findings for the subtype diagnosis of primary aldosteronism (PA). The contribution of adrenal volumetric assessment to PA subtyping was also investigated. METHODS: Thirty-five patients with adequate cannulation in adrenal venous sampling (AVS) were included. Laboratory data, the saline infusion test (SIT), and the AVS results of patients with PA were retrospectively evaluated. Volumetric assessment was performed using magnetic resonance imaging (MRI) and the ratio of adrenal volumes was calculated after adjusting for gender- and side-specific mean reference values of both adrenal glands. RESULTS: The AVS was consistent with unilateral PA in 49% and bilateral in 51% of the patients. Hypertension as a reason for work-up, the highest aldosterone/lowest potassium value higher than 12, the percentage of plasma aldosterone concentration (PAC) reduction after SIT by equal or less than 43.5%, the use of oral potassium replacement, unilateral disease at pre-AVS imaging, and a ratio of adjusted adrenal volumes equal to or below 1.7 were indicative of unilateral disease in univariate logistic regression analysis concerning the distinction of PA subtyping (p < 0.05). Multivariate logistic regression analysis also revealed that adrenal volumetric assessment has an impact on PA subtyping (p < 0.05). In the prediction model, when each of the six parameters that were significant in the univariate logistic regression analysis was assigned one point, < 4 predicted bilateral PA, whereas ≥ 4 predicted unilateral PA (AUC:0.92, p < 0.001). CONCLUSION: This prediction model before AVS may serve as a convenient and practical approach, while an adjusted adrenal volumetric assessment can make a positive contribution to PA subtyping.

Double somatic mutations in CTNNB1 and GNA11 in an aldosterone-producing adenoma.

Double somatic mutations in CTNNB1 and GNA11/Q have recently been identified in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis of APA due to these mutations, an association with pregnancy, menopause, or puberty has been proposed. However, because of its rarity, characteristics of APA with these mutations have not been well characterized. A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation and was diagnosed as having primary aldosteronism after endocrinologic examinations. Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling demonstrated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. The resected right adrenal tumor was histologically diagnosed as adrenocortical adenoma and subsequent immunohistochemistry (IHC) revealed diffuse immunoreactivity of aldosterone synthase (CYP11B2) and visinin like 1, a marker of the zona glomerulosa (ZG), whereas 11ß-hydroxylase, a steroidogenic enzyme for cortisol biosynthesis, was mostly negative. CYP11B2 IHC-guided targeted next-generation sequencing identified somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Immunofluorescence staining of the tumor also revealed the presence of activated ß-catenin, consistent with features of the normal ZG. The expression patterns of steroidogenic enzymes and related proteins indicated ZG features of the tumor cells. PA was clinically and biochemically cured after surgery. In conclusion, our study indicated that CTNNB1 and GNA11-mutated APA has characteristics of the ZG. The disease could occur in adults with no clear association with pregnancy or menopause.

Bilateral or Unilateral Aldosterone Hypersecretion and Responsiveness to Therapy Are Associated with Differences in Calcium/Phosphate Homeostasis in Patients with Primary Aldosteronism.

Introduction Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. Methods A total of 96 patients with primary aldosteronism were analyzed to identify differences in the regulation of serum calcium/phosphate balance between patients with unilateral and bilateral aldosterone hypersecretion and to determine whether or not adrenalectomy or mineralocorticoid receptor blockers affected such differences. Results Serum phosphate concentrations were significantly lower in patients with unilateral aldosterone hypersecretion than in patients with bilateral aldosterone hypersecretion (2.96±0.45 vs. 3.36±0.55 mg/dL, p<0.05), and recovered after adrenalectomy (2.96±0.45 vs. 3.49±0.32 mg/dL, p<0.01). In patients with bilateral aldosterone hypersecretion, the baseline serum phosphate levels were significantly lower in responders to mineralocorticoid receptor blocker treatment, defined as post-treatment plasma renin activity ≥1 ng/mL/h, than in non-responders. In responders, these levels tended to recover after treatment. A weak negative correlation between the plasma aldosterone concentration (PAC) and serum phosphate was observed, but there were no associations between the PAC and serum calcium concentration or between the aldosterone renin ratio and serum calcium and phosphate concentrations. Conclusion The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

Urine steroid metabolomics as a diagnostic tool in primary aldosteronism.

Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs.

The predictors of long-term outcomes after targeted therapy for primary Aldosteronism.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.

Postoperative ACTH-stimulated aldosterone predicts biochemical outcome in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is the most common surgically curable cause of hypertension. Unilateral aldosterone-producing adenoma can be treated with adrenalectomy. Clinical and biochemical outcomes are assessed 6-12 months after adrenalectomy according to primary aldosteronism surgical outcome (PASO) consensus criteria. Earlier prediction of biochemical remission would be desirable as it could reduce cumbersome follow-up visits. We hypothesized that postoperative adrenocorticotropic hormone (ACTH) stimulated plasma aldosterone concentrations (PAC) measured shortly after adrenalectomy can predict PASO outcomes. DESIGN: Retrospective cohort study. METHODS: We analyzed 100 patients of the German Conn's registry who underwent adrenalectomy and postoperative ACTH stimulation tests within the first week after adrenalectomy. Six to twelve months after adrenalectomy we assessed clinical and biochemical outcomes according to PASO criteria. Serum cortisol and PAC were measured by immunoassay at baseline and 30 min after the intravenous ACTH infusion. We used receiver operating characteristics (ROC) curve analysis and matched the parameters to PASO outcomes. RESULTS: Eighty-one percent of patients had complete, 13% partial, and 6% absent biochemical remission. Complete clinical remission was observed in 28%. For a cut-off of 58.5 pg/mL, stimulated PAC could predict partial/absent biochemical remission with a high sensitivity (95%) and reasonable specificity (74%). Stimulated PAC's area under the curve (AUC) (0.89; confidence interval (CI) 0.82-0.96) was significantly higher than other investigated parameters. CONCLUSIONS: Low postoperative ACTH stimulated PAC was predictive of biochemical remission. If confirmed, this approach could reduce follow-up visits to assess biochemical outcome.

Application of a Radiomics Machine Learning Model for Differentiating Aldosterone-Producing Adenoma from Non-Functioning Adrenal Adenoma.

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734-1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic-Radscore model had an AUC of 0.994 [95% CI, 0.978-1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma.

Recurrence of Primary Aldosteronism After Surgery in Aldosterone-producing Adenoma With KCNJ5 Gene Mutation.

Primary aldosteronism (PA) is a major cause of secondary hypertension. Aldosterone-producing adenoma (APA) is a subtype of PA, and adrenalectomy is the gold-standard treatment. Recently, a high prevalence of the KCNJ5 gene mutation has been reported in APA, particularly in Japan. Herein, we present 2 extremely rare cases of PA recurrence more than 10 years after adrenalectomy for APA. In the first case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. In the second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Somatic mutations in KCNJ5 were detected in the resected tissues in both cases. We recommend careful follow-ups after adrenalectomy in APA cases, especially in those with a KCNJ5 gene mutation.

Sjogren's Syndrome Complicated With Aldosterone-Producing Adenoma: A Case Report.

Hypokalemia may be present in some patients with Sjogren's syndrome. When a patient with Sjogren's syndrome presents with hypokalemia, we would first consider it to be a result of the renal involvement of Sjogren's syndrome. However, in this case report, we present a young woman with Sjogren's syndrome who presented with hypokalemia that was not caused by renal tubular acidosis but by the presence of a coexisting aldosterone-producing adenoma. Cases of Sjogren's syndrome coexisting with aldosterone-producing adenoma are extremely rare. This finding underscores the need for more careful differential diagnosis in patients with Sjogren's syndrome who also have hypokalemia.