Conn´s syndrome after kidney transplantation.

Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least a triple combination of antihypertensives, including a diuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria. In addition to arterial hypertension and hypokalaemia, the diagnosis of Conn's syndrome relies on examination of serum renin and aldosterone concentrations, plasma renin activity, exercise or furosemide stimulation tests, and imaging studies, preferably computed tomography. The method of treatment of Conn's syndrome is adrenalectomy. In patients with primary hyperaldosteronism with underlying bilateral adrenal cortical hyperplasia or patients contraindicated for surgery, mineralocorticoid receptor antagonists are administered in combination with antihypertensives targeted for optimal blood pressure control.In the group of patients after kidney transplantation, the exact incidence of primary hyperaldosteronism is unknown. Based on a cross-sectional study performed in 2020, it is estimated to be approximately 15% in the group of patients with unsatisfactorily compensated arterial hypertension; in the cohort of normotensive recipients, the incidence of primary hyperaldosteronism is not documented. Diagnosis of Conn's syndrome in patients in the early period after kidney transplantation is problematic, as the prevalence of arterial hypertension in transplanted patients is high (70-90%) according to the literature. Mineral abnormalities, including hypokalaemia, are also common in the early post-transplant period, mainly due to factors such as duration of cold ischaemia, onset of graft function, donor parameters, post-transplant tubulopathy, and diuretics, the effects of immunosuppressive drugs (especially calcineurin inhibitors and corticosteroids), and possibly potassium-restricted dietary habits that the patient brings from the pre-transplant period, which may mask the effect of hyperaldosteronism on potassium.We present the case of a patient who was diagnosed with Conn's syndrome 7 months after primary kidney transplantation from a deceased donor based on persistent hypokalaemia unresponsive to replacement therapy. At the time of the first manifestation of severe hypokalaemia, the patient was treated with a dual combination of antihypertensives (amlodipine at a daily dose of 5 mg and carvedilol at a daily dose of 50 mg), without the need for a diuretics.We consider the case interesting because the spectrum of mineral and acid-base abnormalities in advanced renal failure and in the early post-transplant period, as well as acid-base and mineral imbalances, including hypokalaemia, and the high prevalence of arterial hypertension in the post-transplant period, may mask the picture of Conn's syndrome (Fig. 3, Ref. 19). Text in PDF www.elis.sk Keywords: kidney transplantation, primary hyperaldosteronism, hypokalaemia, metabolic alkalosis, secondary arterial hypertension.

Imaging Concordance With Vein Sampling for Primary Aldosteronism: A Cohort Study and Literature Review.

INTRODUCTION: Adrenal venous sampling (AVS) is used to distinguish unilateral from bilateral aldosterone hypersecretion as a cause of primary aldosteronism (PA). Unilateral disease is treated with adrenalectomy and bilateral hypersecretion managed medically. METHODS: We performed a single institution retrospective cohort study of adult patients undergoing adrenalectomy for PA from July 2013 to June 2022. Concordance of imaging findings with AVS was evaluated. Statistical analysis was performed with Mann-Whitney U and chi-squared Fisher's exact. Literature review performed via triple method search strategy. RESULTS: Twenty-one patients underwent AVS and adrenalectomy for PA. Two patients did not have imaging findings and 19 were localized with an adenoma. For patients with image localization, AVS was concordant in nine, discordant in four, and nondiagnostic in six. For patients with discordant findings, age range was 35.8 to 72.4 y compared with concordant patient age range of 49.8 to 71.7 y. Overall discordance between imaging results and AVS was 40%. The aldosterone level was associated with concordance with a median of 52 ng/dL compared with 26 ng/dL if discordant (P = 0.002). There was a significant reduction in antihypertensive medications for the entire cohort from a median of three medications (interquartile range 2-4) to 1 medication (interquartile range 1-2), P < 0.001. CONCLUSIONS: In this cohort, 40% of patients with selective AVS had discordant imaging and AVS results. Aldosterone level was associated with concordance. Hypertension was significantly improved with a median decrease of two antihypertensives. Our results support performance of AVS on all candidates for adrenalectomy for PA.

A case of primary aldosteronism with excessive secretion of renin that was unmasked by kidney transplantation.

A 42-year-old man showed marked hypokalemia after kidney transplantation. He was diagnosed with hypertension and suffered from acute myocardial infarction at 33 and 38 years of age. At 40 years of age, hemodialysis was introduced. A left adrenal tumor was noted and suspected as a non-functional adrenal adenoma at that time. Therefore, he received a living-donor kidney transplant at 42 years of age. After kidney transplantation, the serum creatinine level dropped. His blood pressure remained high, and the serum potassium level decreased. The PRA and PAC were elevated, and ARR was not elevated. Based on the results of various confirmatory tests and vein sampling, he was diagnosed with excessive secretion of renin from the native kidneys that was complicated by primary aldosteronism (PA), and left nephrectomy and adrenalectomy were performed. The overproduction of aldosterone in the resected adrenal adenoma and over secretion of renin in the kidney with arteriolosclerosis were immunohistologically confirmed. After surgery, the PAC decreased, but the PRA did not decrease. The postoperative serum potassium level improved, and the blood pressure was well controlled with a small dose of medication. This is the first reported case of PA with hyperreninemia after kidney transplantation. It should be noted that PA in dialysis patients and kidney transplant recipients may not fulfill the usual diagnostic criteria of an elevated ARR. In such patients, PA should be suspected based on the absolute value of the PAC and responsiveness to ACTH stimulation, and adrenal and renal vein sampling is required for a definitive diagnosis.

The where, who and how of adrenal vein sampling in Australia and New Zealand.

INTRODUCTION: Primary aldosteronism (PA) causes 10-15% of cases of hypertension, and it is increasingly recognised as being under-diagnosed. An interventional radiology procedure, adrenal vein sampling (AVS), is a necessary and important diagnostic procedure for complete workup of PA. There is an anticipated increase in demand for AVS as detection of PA improves. This study aims to describe the current landscape of AVS in Australia and New Zealand (NZ). METHODS: Two surveys exploring AVS methodology and performance were conducted of (i) Endocrinology Unit Heads and (ii) interventional radiologists who perform AVS, at public hospitals with Endocrinology Units across Australia and NZ. RESULTS: Responses were received from 48/53 Endocrinology Unit Heads (91%) and 35 radiologists from 26 sites (87% of AVS sites). AVS was provided at 28/48 Endocrinology sites (58%) across Australia and NZ. In Australia, sites were concentrated in Victoria, New South Wales and Queensland with none in the Northern Territory; in NZ, sites were more evenly distributed across the North and South Islands. AVS was performed by 1-2 dedicated radiologists at 24 sites, 2-3 radiologists at two sites and a rotating roster of radiologists at two sites. Responses to both surveys revealed significant variation in AVS methodology and interpretation of AVS results. CONCLUSION: There is significant heterogeneity in the availability of AVS, the procedural details and the interpretation of results across Australia and NZ, which potentially impacts the quality of patient care and ability to scale up AVS capacity to meet increasing demand.

Diagnostic consistency between computed tomography and adrenal vein sampling of primary aldosteronism: leading to successful curative outcome after adrenalectomy; a retrospective study.

BACKGROUND: Adrenal computed tomography (CT) is a useful tool for locating adrenal lesion in primary aldosteronism (PA) patients. However, adrenal vein sampling (AVS) is considered as a gold standard for subtype diagnosis of PA. The aim of this study was to investigate the consistency of CT and AVS for the diagnosis of PA subtypes and evaluate the concordance of surgical outcomes. MATERIALS AND METHODS: This retrospective study included 264 PA patients having both CT and AVS. Diagnostic consistency between CT and AVS was accessed, and clinical and biochemical outcomes were evaluated at 6 months after adrenalectomy. RESULTS: Of all, 207 (78%) had a CT unilateral lesion, 31 (12%) CT bilateral lesion, and 26 (10%) CT bilateral normal findings. Among the CT unilateral lesion group, 138 (67%) had ipsilateral AVS lateralization. For CT bilateral lesion and bilateral normal, AVS unilateral lateralization was found in 17 (55%) and 2 (8%), respectively. The consistency between CT lesion and AVS lateralization including CT unilateral with AVS ipsilateral, and CT bilateral lesion with AVS bilateral patients was 63.8% (152/238). Of 77 patients with available data out of 138 patients who underwent adrenalectomy with consistency between CT and AVS, the clinical success rate was 96%, for 17 inconsistency patients out of 22 patients who underwent adrenalectomy, the clinical success rate was 94% after adrenalectomy following the lateralization result of AVS. CONCLUSION: CT is a useful tool to diagnose the adrenal lesion in PA patients. However, AVS is more sufficient to detect the unilateral PA subtype, which could provide curable treatment to surgical candidates of PA such that AVS can identify patients with contralateral PA in CT unilateral lesion and unilateral PA in CT bilateral lesion. The surgical outcome was successful when an adrenalectomy was performed according to the AVS lateralization result.

Transvenous Radiofrequency Catheter Ablation for an Aldosterone-Producing Tumor of the Left Adrenal Gland: A First in Human Case Report.

PURPOSE: To describe a novel technique of transvenous radiofrequency catheter ablation of an aldosterone-producing adenoma (APA) of the left adrenal gland using the GOS System (Japan Lifeline, Tokyo, Japan). Using the GOS system, a flexible radiofrequency tip catheter can be inserted into the adrenal central and tributary veins, the drainers for functional tumors. MATERIALS AND METHODS: An APA at the left adrenal gland, which was diagnosed by segmental adrenal venous sampling following administration of 0.25 mg cosyntropin, was ablated using the GOS catheter inserted into adrenal tributary veins via a right femoral vein 7-Fr sheath. The effect of radiofrequency ablation on APA was assessed using the international consensus on surgical outcomes for unilateral primary aldosteronism (PA). RESULTS: No device-related complications were observed. The patient was deeply sedated under blood pressure and heart rate control with continuous administration of ß-blockers. Then, the tumor and surrounding adrenal gland were cauterized at 7000 J two times each in sequence. The output time was 7-11 min for each ablation and 80 min in total. For blood pressure and pulse rate control, esmolol hydrochloride and phentolamine mesylate were used. The contrast enhancement of APA disappeared on dynamic CT immediately after the procedure. PA was biochemically cured until 12 months after the procedure. CONCLUSION: Using the radiofrequency device with the GOS catheter and system is a method for cauterizing adrenal tumors from blood vessels. This approach resulted in a marked reduction in aldosterone concentrations and a complete biochemical cure of PA over the observation period.

Liddle syndrome presenting with normal aldosterone levels: A case report.

INTRODUCTION: Liddle syndrome is an autosomal dominant disorder characterized by hypertension, hypokalemia, low aldosterone levels, and reduced renin activity. Atypical Liddle syndrome can be easily misdiagnosed due to its clinical phenotypes resembling hyperaldosteronism. PATIENT CONCERN: The patient was diagnosed with primary aldosteronism due to hypertension and hypokalemia, and underwent left adrenalectomy. After the operation, the patient still had hypertension and hypokalemia that were not easy to control and correct, and had acute cerebral infarction. DIAGNOSIS: The genetic test showed that the base duplication in the coding region of SCN1B gene caused a frameshift mutation:c.1789dupC (p.Arg597fs), Liddle syndrome was diagnosed. INTERVENTION AND OUTCOMES: The patient was treated with a low-sodium diet and oral triamterene. The serum potassium level returned to normal and the blood pressure was controlled. LESSONS: Some Liddle syndrome may present with normal aldosterone levels, genetic testing is necessary for the diagnosis. If the diagnostic test of primary aldosteronism is positive, but the treatment with spironolactone is ineffective, we should actively search for other causes.

Advances in the molecular imaging of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. It predisposes to adverse outcomes such as nephrotoxicity and cardiovascular damage, which are mediated by direct harm from hypertension to the target organs. Accurate subtype diagnosis and localization are crucial elements in choosing the type of treatment for PA in clinical practice since the dominant side of aldosterone secretion in PA affects subsequent treatment options. The gold standard for diagnosing PA subtypes, adrenal venous sampling (AVS), requires specialized expertise, the invasive nature of the procedure and high costs, all of which delay the effective treatment of PA. Nuclide molecular imaging is non-invasive and has wider applications in the diagnosis and treatment of PA. This review aims to provide a summary of the application of radionuclide imaging in the diagnosis, treatment management and prognostic assessment of PA.

Feasibility of single-port laparoscopic partial adrenalectomy with selective adrenal venous sampling and high-resolution ultrasound for unilateral aldosterone-producing adenomas.

BACKGROUND: The surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy for patients with aldosterone-producing adenomas are unknown. Precise diagnosis of intra-adrenal aldosterone activity and a precise surgical procedure may improve outcomes. In this study, we aimed to determine the surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy with preoperative segmental selective adrenal venous sampling and intraoperative high-resolution laparoscopic ultrasound in patients with unilateral aldosterone-producing adenomas. We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. METHODS: A single-center, retrospective cohort study. All patients with unilateral aldosterone-producing adenomas diagnosed by selective adrenal venous sampling and treated surgically between January 2012 and February 2015 were included. Follow-up with biochemical and clinical assessments was set at 1 year after surgery for short-term outcomes and was performed every 3 months after surgery. RESULTS: We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. Single-port surgery was associated with shorter operative and laparoscopic times (odds ratio, 0.14; 95% confidence interval, 0.039-0.49; P = .002 and odds ratio, 0.13; 95% confidence interval, 0.032-0.57; P = .006, respectively). All single-port and multi-port partial adrenalectomy cases showed complete short-term (median 1 year) biochemical success, and 92.9% (26 of 28 patients) who underwent single-port partial adrenalectomy and 100% (13 of 13 patients) who underwent multi-port partial adrenalectomy showed complete long-term (median 5.5 years) biochemical success. No complications were observed with single-port adrenalectomy. CONCLUSION: Single-port partial adrenalectomy is feasible after selective adrenal venous sampling for unilateral aldosterone-producing adenomas, with shorter operative and laparoscopic times and a high rate of complete biochemical success.

Tako-Tsubo Syndrome Following Pulmonary Vein Isolation for Atrial Fibrillation in a Patient with Primary Aldosteronism.

Tako-tsubo syndrome (TTS) can be triggered by emotional or physical stress and is characterized by transient left ventricular dysfunction with apical ballooning. Some neurologic disorders and pheochromocytoma serve as triggers for TTS, however, its association with primary aldosteronism (PA) is not well known. Pulmonary vein isolation (PVI) with catheter ablation for atrial fibrillation (AF) has been performed worldwide, and TTS following PVI has been reported as a rare complication. Sympathetic stimulation can play an important role in TTS development, however, its mechanism and risk factors are not yet understood.We describe a 72-year-old woman with PA who developed TTS after PVI with radiofrequency catheter ablation (RFCA) for symptomatic paroxysmal AF. Complete isolation of the pulmonary vein was carried out without any complications, however, she complained of epigastric discomfort 7 hours after the procedure. An electrocardiogram showed recurrent AF with a new negative-T wave and prolonged QT interval. Transthoracic echocardiography revealed apical ballooning and basal hypercontraction, characteristic of TTS, and coronary angiography showed no significant stenosis. She was diagnosed with TTS following RFCA for AF and managed well with conservative therapy.The present case suggests that TTS should be recognized as a complication associated with AF ablation. Moreover, PA may be involved in TTS development by increasing sympathetic activity. Further studies on the mechanism and characteristics of TTS are required.

The outcomes of transcatheter adrenal ablation in patients with primary aldosteronism: a systematic review and meta-analysis.

BACKGROUND: The use of transcatheter adrenal ablation as an alternative treatment for primary aldosteronism (PA) patients remains a subject of debate, with outcomes varying widely across existing studies. This meta-analysis aims to evaluate the results of adrenal ablation and estimate the effectiveness and safety of this therapeutic approach. METHODS: A comprehensive search was conducted across PubMed, Embase, and Cochrane Library databases for studies published up to October 2022. Outcomes analyzed included the combined clinical success rate, biochemical success rate, and complication rate, which were assessed using a random-effects model. RESULTS: Five studies, comprising 234 PA patients, were included in the analysis. The combined clinical success rate was 74% (95% CI: 69%-79%), and the biochemical success rate was 74% (95% CI: 53%-95%). Subgroup analysis revealed that the combined clinical success rate from Unilateral PA (72%, 95% CI: 46%-98%) was similar to the rate from Unilateral + Bilateral (73%, 95% CI: 52.0%-94.0%), while the clinical success rate of the PASO subgroup (78%, 95% CI: 66.0%-89.0%) was higher than the rate of other criteria (51%, 95% CI: 40.0%-63.0%). The combined complication rates were as follows: mild fever, 23% (95% CI: 12%-33%); back pain, 84% (95% CI: 77%-91%); and pleural effusion, 9% (95% CI: 0%-18%). All complications resolved within one week following the procedure. No late complications or ablation-related deaths were reported. CONCLUSIONS: Transcatheter adrenal ablation for PA patients is safe and demonstrates a relatively high clinical success rate. Presently, this approach is suitable for PA patients who are unwilling to undergo surgery or receive long-term mineralocorticoid receptor antagonist (MRA) treatment. SYSTEMATIC REVIEW REGISTRATION: INPLASY, identifier 2022110076.

Unilateral adrenalectomy in bilateral adrenal hyperplasia with primary aldosteronism.

PURPOSE: Mineralocorticoid receptor antagonists are the first-line treatment for bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA), while unilateral adrenalectomy is the standard treatment for aldosterone-producing adenoma (APA). In this study, we investigated the outcomes of patients with BAH after unilateral adrenalectomy and compared them with those of patients with APA. METHODS: From January 2010 to November 2018, 102 patients with a diagnosis of PA confirmed by adrenal vein sampling (AVS) and available NP-59 scans were enrolled. All patients underwent unilateral adrenalectomy based on the lateralization test results. We prospectively collected the clinical parameters over 12 months and compared the outcomes of BAH and APA. RESULTS: A total of 102 patients were enrolled in this study: 20 (19.6%) had BAH and 82 (80.4%) had APA. Significant improvements in serum aldosterone-renin ratio (ARR), potassium level, and reduction of antihypertensive drugs were observed in both groups at 12 months after surgery (all p < 0.05). Patients with APA showed a significant decrease in blood pressure after surgery (p < 0.001) than those with BAH. Additionally, multivariate logistic regression analysis indicated that APA was associated with biochemical success (odds ratio: 4.32, p = 0.024) compared to BAH. CONCLUSION: Patients with BAH had a higher failure rate in clinical outcomes, and APA was associated with biochemical success after unilateral adrenalectomy. However, significant improvements in ARR, hypokalemia, and a decreased use of antihypertensive drugs were noted in patients with BAH after surgery. Unilateral adrenalectomy is feasible and beneficial in selected patients, and could potentially serve as a treatment option.

Evaluation of standardized uptake value on 131I-6ß-iodomethyl-19-norcholesterol scintigraphy for diagnosis of primary aldosteronism and correspondence with adrenal venous sampling.

PURPOSE: Adrenal venous sampling (AVS) is a reliable method for lateralization of adrenal hormone secretion, which is important for discriminating between aldosterone-producing adenoma and bilateral adrenal hyperplasia, both of which cause primary aldosteronism (PA). The aim of this study was to evaluate the diagnostic accuracy of the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) of 131I-6ß-iodomethyl-19-norcholesterol (NP-59) single-photon emission computed tomography (SPECT) for PA and its correspondence with AVS. METHODS: Adrenal NP-59 scintigraphy was performed in 14 patients with suspected PA, and AVS was also performed in 7 of them. SUVmax and SUVmean of the adrenal lesions on the dominant side and their ratios to the values on the non-dominant side (SUVRmax and SUVRmean, respectively) were calculated on SPECT images using ordered-subset conjugate gradient minimization (OSCGM) and three-dimensional ordered-subset expectation maximization (3D-OSEM) reconstruction algorithms. RESULTS: SUVmax and SUVmean on NP-59 SPECT images were significantly higher for aldosterone-producing adenoma than for bilateral adrenal hyperplasia or non-functioning adenoma and slightly superior to SUVRmax and SUVRmean (P = 0.0475 and P = 0.0447 vs. P = 0.124 and P = 0.132, respectively, with OSCGM). The respective areas under the receiver-operating characteristic curve for SUV and SUVR were 0.933 and 0.725 with OSCGM and 0.844 and 0.750 with 3D-OSEM, while SUVmax and SUVRmax had exactly the same diagnostic accuracy as SUVmean and SUVRmean. SUV and SUVR were associated with the diagnostic features on AVS and consistent with lateralization by AVS in most patients. CONCLUSION: In this study, SUV on NP-59 SPECT helped in the diagnosis of PA and was consistent with the results of AVS in nearly all cases.

Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

Discordant imaging: adrenal vein sampling in almost half of patients with primary aldosteronism and a unilateral adrenal adenoma.

BACKGROUND: Primary hyperaldosteronism (PHA) is an underdiagnosed cause of secondary hypertension, with an increased risk of cardiovascular and renal complications compared with those with essential hypertension alone. Distinguishing between unilateral and bilateral aldosterone secretion is important as management differs. Adrenal vein sampling (AVS) is the gold standard for determining lateralisation. Current international guidelines suggest AVS may be omitted in those aged <35 years with PHA and a unilateral adrenal adenoma on imaging. AIM: To characterise all patients referred for AVS at Waitemata District Health Board (WDHB), review the success rate of AVS and compare concordance of AVS with imaging. METHODS: All patients who underwent AVS in WDHB from January 2015 to September 2020 were retrospectively assessed. Clinical records, laboratory data and radiological findings were reviewed. RESULTS: Ninety-six patients underwent AVS, with four excluded as private records were unable to be obtained. Of the 92 patients included, age ranged from 22 to 79 years. AVS was successful on first attempt in 89 (96.7%) patients. AVS and imaging findings were concordant in 62.2% of patients. One (14.3%) of seven aged <35 years had discordant results, and 16 (47%) of 34 patients with a unilateral adenoma on imaging had discordant results to AVS. CONCLUSIONS: AVS at WDHB is successful on first attempt in most patients. AVS is essential in the management of PHA for those deemed to be surgical candidates, regardless of age.

Lateralization in 11 C-Metomidate PET and outcome of adrenalectomy in primary aldosteronism.

INTRODUCTION: Subtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone 11 C-metomidate positron emission tomography (11 C-MTO-PET) for subtype classification. METHODS: Postoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative 11 C-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on 11 C-MTO-PET alone and those with concordant or discordant lateralization in 11 C-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure. RESULTS: Adrenalectomy side was based on 11 C-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after 11 C-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant 11 C-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with 11 C-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery. CONCLUSIONS: Outcomes of adrenalectomy based on clinically significant lateralization in 11 C-MTO-PET alone correspond to those based on 11 C-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with 11 C-MTO-PET in case of discordant lateralization studies.

Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma.

Hypertension due to primary aldosteronism poses a risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation in aldosteroene producing adenoma (APA) in 2011 and the development of specific CYP11B2 antibodies in 2012 have greatly advanced our understanding of the pathophysiology of primary aldosteronism. In particular, the presence of CYP11B2-positive aldosterone-producing micronodules (APMs) in the adrenal glands of normotensive individuals and the presence of renin-independent aldosterone excess in normotensive subjects demonstrated the continuum of the pathogenesis of PA. Furthermore, among the aldosterone driver mutations which incur excessive aldosterone secretion, KCNJ5 was a major somatic mutation in APA, while CACNA1D is a leading somatic mutation in APMs and idiopathic hyperaldosteronism (IHA), suggesting a distinctive pathogenesis between APA and IHA. Although the functional detail of APMs has not been still uncovered, its impact on the pathogenesis of PA is gradually being revealed. In this review, we summarize the integrated findings regarding APA, APM or diffuse hyperplasia defined by novel CYP11B2, and aldosterone driver mutations. Following this, we discuss the clinical implications of KCNJ5 mutations to support better cardiovascular outcomes of primary aldosteronism.

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS).

INTRODUCTION: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS. METHODS AND ANALYSIS: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT. ETHICS AND DISSEMINATION: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles. TRIAL REGISTRATION NUMBER: NL9625.

Machine learning approach to predict subtypes of primary aldosteronism is helpful to estimate indication of adrenal vein sampling.

INTRODUCTION: Primary aldosteronism (PA) is a common disease. Especially in unilateral PA (UPA), the risk of cardiovascular disease is high and proper localization is important. Adrenal vein sampling (AVS) is commonly used to localize PA, but its availability is limited. Therefore, it is important to predict the unilateral or bilateral PA and to choose the appropriate cases for AVS or watchful observation. AIM: The purpose of this study is to develop a model using machine learning to predict bilateral or unilateral PA to extract cases for AVS or watchful observation. METHODS: We retrospectively analyzed 154 patients diagnosed with PA and who underwent AVS at our hospital between January 2010 and June 2021. Based on machine learning, we determined predictors of PA subtypes diagnosis from the results of blood and loading tests. RESULTS: The accuracy of the machine learning was 88% and the top predictors of the UPA were plasma aldosterone concentration after the saline infusion test, aldosterone to renin ratio after the captopril challenge test, serum potassium and aldosterone-to-renin ratio. By using these factors, the accuracy, sensitivity, specificity and the area under the curve (AUC) were 91%, 70%, 99% and 0.91, respectively. Furthermore, we examined the surgical outcomes of UPA and found that the group diagnosed as unilateral by the predictors showed improvement in clinical findings, while the group diagnosed as bilateral by the predictors showed no improvement. CONCLUSION: Our predictive model based on machine learning can support to choose the performance of adrenal vein sampling or watchful observation.