Cases Of Primary Aldosteronism Research Articles

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.

FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism

Abstract Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None. Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (<39.2) with a plasma renin activity (PRA) of <0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA<0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to <1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling. Presentation: Friday, June 16, 2023

FRI154 Saline Suppression Testing And Acute Hypocalcemia: Impacts On Diagnostic Testing For Primary Aldosteronism

Abstract Disclosure: W.W. Parksook: None. J.M. Brown: Consulting Fee; Self; Bayer, Inc. J. Milks: None. A. Moore: None. Y. Niebuhr: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; HRA Pharmaceuticals, Mineralys. Background: Calcium ion signaling is a critical factor required for the physiologic production of aldosterone. Emerging evidence has revealed that the majority of cases of primary aldosteronism involve pathogenic somatic mutations that ultimately increase calcium signaling and autonomous aldosterone production. Therefore, testing for primary aldosteronism that modulates calcium homeostasis may influence the diagnostic interpretation of the results. Method: Overweight to obese participants with metabolic risk factors and pre-hypertension or stage 1 hypertension (n=56) underwent a standard seated saline suppression test (SSST). Measurement of blood pressure, plasma aldosterone, serum calcium, as well as other factors, was performed at times 0, 120, and 240 minutes during SSST. Linear regression models were used to analyze the association between changes in calcium and each parameter. Results: Following 2 liters of saline infusion during SSST, all 56 participants (100%) had a significant decrease in serum calcium levels from baseline, with 26 (47%) developing new-onset frank hypocalcemia (calcium <8.6 mg/dL). The mean baseline serum calcium was 9.2 ± 0.3 mg/dL, which declined to 8.9 ± 0.4 mg/dL at 120 mins (P<0.001), and to 8.6 ± 0.4 mg/dl (P<0.001) at 240 mins when the SSST concluded. Consistent with the known vasopressor effect of calcium, greater drops in serum calcium levels were associated with lower blood pressure at 240 minutes (β;= 13.5, P<0.01 for DBP; β;= 10.7, P= 0.06 for SBP). Among those with post-SSST aldosterone levels <10 ng/dl (a categorical threshold used to exclude primary aldosteronism), greater reductions in serum calcium levels were associated with larger drops in aldosterone levels (β;= 9.9, P<0.05). Conclusion: The standard SSST induced a substantial decline in serum calcium levels in 100% of participants, with nearly half of all participants developing frank hypocalcemia at the end of saline infusion. Since calcium is known to play a critical role in physiologic and pathophysiologic production of aldosterone, these findings raise the question whether hypocalcemia induced by the acute loading of 2 liters of saline may confound the interpretation of aldosterone changes. Further research should focus on better understanding the diagnostic implications of these results and potential limitations of the SSST to exclude primary aldosteronism. Presentation: Friday, June 16, 2023

The value of CT-based energy imaging to discriminate dominant side lesions in primary aldosteronism.

The current clinical discrimination of the dominant side of primary aldosteronism (PA) mainly relies on invasive adrenal venous sampling (AVS) examination. This study investigated the feasibility of dual-energy CT energy imaging parameters as a novel biomarker in identifying bilateral adrenal dominant lesions. Fifty PA patients with bilateral lesions who underwent CT and AVS of the adrenal glands at Shaanxi Provincial People's Hospital from October 2019 to June 2021 were retrospectively analyzed. Forty-eight patients had successful bilateral blood collection and two failed right-sided blood collection due to venous variation. Forty patients who were classified based on AVS underwent unilateral adrenalectomy and pathological findings confirmed adenoma in all cases. Quantitative dual-energy CT parameters were measured for all adrenal lesions, and the differences in dual-energy CT energy spectrum imaging parameters between the dominant and nondominant adrenal lesions were compared. Among forty-eight PA patients with bilateral lesions, forty patients with preoperative AVS-determined lesions on the dominant side underwent unilateral adrenalectomy, and eight patients without the dominant side were treated with medication. The iodine concentration difference (ICD) in the arteriovenous phase was more significant in the 40 cases of primary aldosteronism with dominant adrenal lesions than in the nondominant adrenal lesions (1.18 ± 0.45 vs 0.41 ± 0.42). The NICAP was higher in the dominant adrenal lesions than in the non-dominant lesions (0.39 ± 0.39 vs 0.14 ± 0.05). The sensitivity and specificity of the diagnosis of the dominant adrenal lesion were 88.2% and 82.4% using the ICD of 0.68 as the threshold value. Conventional CT has lower diagnostic value for dominant adrenal lesions, and CT-based energy imaging can be a new assessment method as a complement to AVS in identifying bilateral dominant adrenal lesions.

NP-59 Scintigraphy for Primary Aldosteronism Lateralization in a Patient With Polycystic Kidney Disease

A 65-year-old-male presented to the endocrine clinic for further evaluation and treatment of primary aldosteronism (PA). His past medical history was notable for polycystic-kidney-disease (PCKD) leading to a kidney-transplantation at age 48, as well as a diagnosis of PA at the age of 52. The patient had initially elected for medical management of PA; thus, PA sub-type-classification was not pursued. Despite treatment with spironolactone and potassium supplements, subsequent blood-pressure control was poor, with progressive renal failure and persistent hypokalemia. Currently, the patient was being prepared for a staged-bilateral-nephrectomy to relieve some of the mass-effect from the giant polycystic-kidneys. The upcoming surgery gave rise to the option of a concomitant adrenalectomy as a potential cure for PA. However, at this point, PA-sub-type classification was quite challenging. Anatomically, the large cysts grossly distorted the retroperitoneum, hiding the adrenal glands from view on CT imaging ( Figure A). Biochemically, adrenal-vein-sampling (AVS) seemed both technically difficult due to the distorted vascular anatomy as well as potentially risky due to the expected prolonged exposure to radio-contrast in a kidney transplant patient pre-existing advanced chronic kidney disease (CKD). Following a multidisciplinary consultation, NP-59 SPECT/CT was performed (Figure B-D). Very few case reports of PA in patients with PCKD have been reported thus far ((1)Hoorn E.J. Hesselink D.A. Kho M.M. Roodnat J.I. Weimar W. Van Saase J.L. Van Den Meiracker A.H. Zietse R. A case of primary aldosteronism revealed after renal transplantation.Nature Reviews Nephrology. 2011; 7: 55-60Crossref PubMed Scopus (8) Google Scholar). In the setting of PCKD, a diagnosis of PA may be delayed or missed entirely due to pre-existing alternative explanations for resistant hypertension and CKD. Furthermore, adrenal adenomas may be overlooked on planar imaging due to their small size and distorted abdominal anatomy associated with PCKD. In general, AVS is considered the gold-standard For PA sub-type classification, but in complex cases such as with PCKD, alternative diagnostic methods may be useful. NP-59 (I-131-iodo-cholesterol) is a marker of adrenocortical cholesterol uptake. Dexamethasone-suppression NP-59 scintigraphy has been suggested for the differentiation of PA sub-types, but its use is limited by low resolution allowing for false negatives as well as limited tracer availability ((2)Nomura K, Kusakabe K, Maki M, Ito Y, Aiba M, Demura H. Iodomethylnorcholesterol uptake in an aldosteronoma shown by dexamethasone-suppression scintigraphy: relationship to adenoma size and functional activity. J Clin Endocrinol Metab. 1990 Oct;71(4):825-830. doi: 10.1210/jcem-71-4-825. PMID: 2401712.Google Scholar). The addition of SPECT/CT over planar imaging NP-59 scintigraphy, has been shown to increase sensitivity to 82%, including the detection of aldosterone producing adenomas smaller than 1.5 cm ((3)Yen R.F. Wu V.C. Liu K.L. Cheng M.F. Wu Y.W. Chueh S.C. Lin W.C. Wu K.D. Tzen K.Y. Lu C.C. TAIPAI Study Group131I-6β-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results.Journal of Nuclear Medicine. 2009; 50: 1631-1637Crossref PubMed Scopus (94) Google Scholar). In our patient, NP-59 SPECT/CT clearly identified a functional left-adrenal cortical adenoma (Figures B-D). Subsequent left adrenalectomy and nephrectomy resulted in normalization of potassium levels and improved blood-pressure control allowing for a reduction in the number of his anti-hypertensive medications. Pathological evaluation identified a 3cm cortical adenoma. Thus, NP-59 SPECT/CT should remain a part of the diagnostic armamentarium, especially for challenging cases of PA sub-type classification.

How the algorithms can change during the COVID-19 pandemic: A case of primary hyperaldosteronism

Abstract Introduction Primary hyperaldosteronism (PA) is an important reason of secondary endocrine hypertension. The etiology is either an aldosterone producing adenoma or bilateral adrenal hyperplasia in 90% of cases. The diagnosis is based on specific algorithms starting with screening the population at risk and continues with confirmatory testing of positive resulted individuals. According to current recommendations, adrenal vein sampling (AVS) and imaging should both be used to classify the subtypes of PA; but during the COVID-19 pandemic, the algorithms may have to be changed. Here, we present a case diagnosed with PA and successfully treated during pandemic. Clinical Case A fifty-one-year-old male patient was referred to our department from internal medicine clinic with hypertension and hypokalemia. He was hypertensive since 30 years old, but he had no history or clinical symptoms of hypokalemia or hypertension associated organ injury. His blood pressures (BP) were under control with 10 mg of amlodipine. But for the last 2 years, his blood pressures couldn't be managed with just amlodipine. Despite losing weight, BP was still higher than 160/100 mmHg. When he evaluated by his internal medicine physician, K level was significantly low (2.57 mEq/L). After oral potassium replacement and discontinuation of thiazide, it increased to only the lower limit (3.4 mEq/L). Abdominal CT showed bilateral adrenal thickness with 13 HU on the right and 10 HU on the left. On physical examination, he had no characteristic findings of hypercortisolemia or acromegaly. His BP was 180/100 mmHg, even he adopted salt-free diet and antihypertensive therapy with candesartan, thiazide, amlodipine. His echocardiography and retinal examination were normal. His catecholamine excretion on 24h urine was normal. After discontinuing aldosterone receptor blocker and thiazide, aldosterone and plasma renin activity were 73 ng/dL and 0.59 ng/mL/h respectively. The ratio was 123.7 and suspected highly of PA. The patient didn't want to be admitted to hospital for saline infusion test. He was directed to AVS. After medically controlling his BP, AVS was performed successfully in May 2022. His results are shown in Table-1. After this result, right adrenal gland was considered as PA source and right adrenalectomy was performed. The patient is on follow-up with single dose of candesartan within normal BP limits and normal K levels. Conclusion COVID-19 pandemic has indisputably changed certain algorithms in every field. On this matter, patient specific approaches have become more important. Most specifically for this case, even when the hypertension started early-on-set, clinicians should seek the hypertensive end-organ injuries to understand the onset of the secondary reasons of hypertension. It should be remembered that not every early-on-set hypertension is secondary, and not every late-on-set hypertension is essential.

PS-R07-10: A MOTHER AND HER DAUGHTER CASES OF PRIMARY ALDOSTERONISM

The majority of cases of primary aldosteronism (PA) occur sporadically. Familial forms of PA are rare with four subtypes defined. We reported a case of familial cluster of primary aldosteronism in two members, daughter and her mother. Case presentation Case 1: Daughter A 20-year-old woman with a history of hypertension and proteinuria for three years without treatment, was admitted for the treatment of accelerated hypertension of 182/121 mmHg and end stage kidney disease. Blood examination revealed low plasma renin activity (PRA) of 0.7 ng/ml/h, and high plasma aldosterone concentration (PAC) of 349 pg/mL, high aldosterone/renin ratio (ARR) of 498.6, and serum potassium (sK) of 4.9 mEq/L. (Plasma ACTH 12.9 pg /mL, plasma cortisol 7.4 mcg/dL) These findings suggested PA. Abdominal CT scan showed no adrenal mass. After control of accelerated hypertension with nifedipine GITS and alpha adrenoceptor blocker, confirmatory tests for PA, saline infusion test (SIT) were carried out and was positive test (PAC 240 min after infusion 264pg/mL). Adrenal venous sampling revealed bilateral hyper-aldosterone secretion. She was given diagnosis of bilateral adrenal hyperaldosteronism. Her blood pressure was decreased to 118/77 along with administration of spironolactone 25 mg/day. Her parents have hypertension. We investigate the cause of hypertension in her parents. Blood test of her father revealed PRA 3.4 ng/m/h, PAC 18.3 pg/ml, and sK 4.7 mEq/L. Case 2: Mother A 45-year-old women with hypertension treated with amlodipine 5 mg was referred to our hospital to examine the renal function after renal donation to her daughter. Blood test revealed mild renal dysfunction (eGFR 72,2), normal sK(4.0 mEq/L), low PRA (0.9 ng/ml/h), high PAC (118 pg/mL) for high salt intake (11.6 g/day as high as salt loading test). Abdominal CT scan showed no adrenal mass. SIT was positive (PAC 240 min after infusion 60.0 pg/mL). She was given diagnosis of PA. Discussion: Potential factors leading to BHA include rare disease-predisposing germline variants, circulating angiotensin II type 1 receptor autoantibodies, and paracrine activation of aldosterone production by adrenal mast cells have been reported. Primary hyperaldosteronism in 2 family members, a mother and daughter, suggests familial hyperaldosteronism which caused by germline mutation. We now investigate germline variants for BHA.

Aldosterone-Producing Adenomas of Increased Size Are Associated With Higher Steroidogenic Activity.

There are inconsistent results and insufficient evidence as to whether an association exists between the size and aldosterone-producing ability of aldosterone-producing adenomas. We further investigated this possible association retrospectively. A total of 142 cases of primary aldosteronism diagnosed as unilateral by adrenal venous sampling at 2 referral centers between 2009 and 2019 were included. We classified these individuals into small and large tumor groups using a diameter of 14 mm as a cutoff. This size was the median diameter of the tumor on the affected side of the adrenal gland. We compared plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio, PAC from a saline infusion test (SIT), urinary aldosterone secretion (uAld), and serum potassium as indices of aldosterone-producing ability between the 2 groups. In some cases, we conducted histopathological evaluations and detection of the KCNJ5 mutation. PAC, PAC to PRA ratio, PAC from SIT, and uAld were higher and serum potassium was lower in the large tumor group. PAC, PAC from SIT, uAld, and serum potassium significantly correlated with tumor diameter. PRA was not associated with tumor diameter. Clear cell-dominant cases were more common in the large tumor group, while cases showing a strong expression of CYP11B2 were not significantly different between the groups. KCNJ5 mutations tended to be more common in the large tumor group. The higher aldosterone-producing ability in larger adenomas can be used to infer the responsible lesion and disease type.

A case of primary aldosteronism

Primary aldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension. It is a disorder of the adrenal glands that is caused by the hypersecretion of the hormone aldosterone from the adrenal glands.

In Silico Analysis of the Gene Expression Patterns between Aldosterone-Producing Adenoma and Nonfunctional Adrenocortical Adenoma.

Primary aldosteronism is the most common form of secondary hypertension, and aldosteronoma makes up a significant proportion of primary aldosteronism cases. Aldosteronoma is also called aldosterone-producing adenoma (APA). Although there have been many studies about APA, the pathogenesis of this disease is not yet fully understood. In this study, we aimed to find out the difference of gene expression patterns between APA and nonfunctional adrenocortical adenoma (NFAA) using a weighted gene coexpression network (WGCNA) and differentially expressed gene (DEG) analysis; only the genes that meet the corresponding standards of both methods were defined as real hub genes and then used for further analysis. Twenty-nine real hub genes were found out, most of which were enriched in the phospholipid metabolic process. WISP2, S100A10, SSTR5-AS1, SLC29A1, APOC1, and SLITRK4 are six real hub genes with the same gene expression pattern between the combined and validation datasets, three of which indirectly or directly participate in lipid metabolism including WISP2, S100A10, and APOC1. According to the gene expression pattern of DEGs, we speculated five candidate drugs with potential therapeutic value for APA, one of which is cycloheximide, an inhibitor for phospholipid biosynthesis. All the evidence suggests that phospholipid metabolism may be an important pathophysiological mechanism for APA. Our study provides a new perspective regarding the pathophysiological mechanism of APA and offers some small molecules that may possibly be effective drugs against APA.

A case of primary aldosteronism with a negative aldosterone-to-renin ratio

BackgroundPrimary aldosteronism (PA), as a cause of secondary hypertension, can cause more serious cardiovascular damage than essential hypertension. The aldosterone-to-renin ratio (ARR) is recommended as the most reliable screening method for PA, but ARR screening is often influenced by many factors. PA cannot be easily excluded when negative ARR.Case presentationWe report the case of a 45-year-old Chinese man with resistant hypertension. Three years ago, he underwent a comprehensive screening for secondary hypertension, including the ARR, and the result was negative. After that, the patient's blood pressure was still poorly controlled with four kinds of antihypertensive drugs, the target organ damage of hypertension progressed, and hypokalaemia was difficult to correct. When the patient was hospitalized again for comprehensive examination, we found that aldosterone levels had significantly increased, although the ARR was negative. An inhibitory test with saline was further carried out, and the results suggested that aldosterone was not inhibited; therefore, PA was diagnosed. We performed a unilateral adenoma resection for this patient, and spironolactone was continued to control blood pressure. After the operation, blood pressure is well controlled, and hypokalaemia is corrected.ConclusionWhen the ARR is negative, PA cannot be easily excluded. Comprehensive analysis and diagnosis should be based on the medication and clinical conditions of patients.

Screening for primary aldosteronism in the hypertensive obstructive sleep apnea population is cost-saving

BackgroundGuidelines recommend screening for primary aldosteronism in patients diagnosed with hypertension and obstructive sleep apnea. Recent studies have shown that adherence to these recommendations is extremely low. It has been suggested that cost is a barrier to implementation. No analysis has been done to rigorously evaluate the cost-effectiveness of widespread implementation of these guidelines. MethodsWe constructed a decision-analytic model to evaluate screening of the hypertensive obstructive sleep apnea population for primary aldosteronism as per guideline recommendations in comparison with current rates of screening. Probabilities, utility values, and costs were identified in the literature. Threshold and sensitivity analyses assessed robustness of the model. Costs were represented in 2020 US dollars and health outcomes in quality-adjusted life-years. The model assumed a societal perspective with a lifetime time horizon. ResultsScreening per guideline recommendations had an expected cost of $47,016 and 35.27 quality-adjusted life-years. Continuing at current rates of screening had an expected cost of $48,350 and 34.86 quality-adjusted life-years. Screening was dominant, as it was both less costly and more effective. These results were robust to sensitivity analysis of disease prevalence, test sensitivity, patient age, and expected outcome of medical or surgical treatment of primary aldosteronism. The screening strategy remained cost-effective even if screening were conservatively presumed to identify only 3% of new primary aldosteronism cases. ConclusionsFor patients with hypertension and obstructive sleep apnea, rigorous screening for primary aldosteronism is cost-saving due to cardiovascular risk averted. Cost should not be a barrier to improving primary aldosteronism screening adherence.

Learning curve of adrenal vein sampling.

Adrenal venous sampling (AVS) is one of the recognized effective methods for the identification of primary aldosteronism, and the success rate is related to the skill level of the operator. This study aims to analyze the learning curve of AVS and to determine the number of staged cases of AVS procedure success rate, and to provide a reference for the standardized use of AVS. The age, gender, blood pressure, surgery success rate, operation time, radiation dose, and operation-related complications of 120 patients with primary aldosteronism who underwent continuous AVS in the Second Xiangya Hospital from August 2015 to February 2021 were retrospectively collected. The cumulative sum analysis was used to analyze the learning curve of the operator. The minimum cases who were proficient in the operation was determined according to the learning curve, and the patients were divided into 4 groups a, b, c, and d according to the time sequence of receiving AVS based on the cut-off point. The AVS success rate, radiation dose, operation time, and complications of each group were analyzed. The cumulative sum analysis showed that the learning curves were divided into a learning stage and a mastery stage with 30 cases as the cut-off point, and the operation experience of the surgeon was from raw to mature. The success rates of the a, b, c, and d groups were 66.7%, 86.7%, 93.3%, and 96.7%, respectively. Compared with b, c, and d groups, the success rate in group a was significant decreased (all P<0.05), the operative time in group a was significantly lengthened (all P<0.05), and the radiation dose in group a was significantly increased (all P<0.05). After accumulating the AVS experience of 30 cases of primary aldosteronism, the operation time is obviously shortened, the radiation dose is significantly decreased, the operative complications are significantly reduced, and the learning curve enters a plateau. In the future, the success rate of AVS procedure may be improved through further standardized training.

Pathology of Aldosterone Biosynthesis and its Action.

Aldosterone plays pivotal roles in renin-angiotensin-aldosterone system in order to maintain the equilibrium of liquid volume and electrolyte metabolism. Aldosterone action is mediated by both mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Its excessive actions directly induced tissue injuries in its target organs such as myocardial and vascular fibrosis in addition to chronic kidney diseases. Excessive aldosterone actions were also reported to be involved in unbalanced electrolyte metabolism in inflammatory bowel disease and development of pulmonary diseases. Hyperaldosteronism is tentatively classified into primary and secondary types. Primary aldosteronism is more frequent and has been well known to result in secondary hypertension with subsequent cardiovascular damages. Primary aldosteronism is also further classified into distinctive subtypes and among those, aldosterone-producing adenoma is the most frequent one accounting for the great majority of unilateral primary aldosteronism cases. In bilateral hyperaldosteronism, aldosterone-producing diffuse hyperplasia and aldosterone-producing micronodules or nodules are the major subtypes. All these aldosterone-producing lesions were reported to harbor somatic mutations including KCNJ5, CACNA1D, ATP1A1 and ATP2B3, which were all related to excessive aldosterone production. Among those mutations above, somatic mutation of KCNJ5 is the most frequent in aldosterone-producing adenoma and mostly composed of clear cells harboring abundant aldosterone synthase expression. In contrast, CACNA1D-mutated aldosterone-producing micronodules or aldosterone-producing nodules were frequently detected not only in primary aldosteronism patients but also in the zona glomerulosa of normal adrenal glands, which could eventually lead to an autonomous aldosterone production resulting in normotensive or overt primary aldosteronism, but their details have remained unknown.

A case report of severe hypoaldosteronism following unilateral adrenalectomy for aldosteronoma

Primary aldosteronism is characterized by hypertension and accounts for about 10% of hypertensive patients. Hyperkalemia and renal disease post adrenalectomy has been described in the literature. We present а case of primary aldosteronism with long standing hypertension (more than 10 years) with severe hypokalemia (1.9 mmol/l). Post unilateral adrenalectomy he had reduction in the blood pressure and became eukalemic. However, after 8 weeks of adrenalectomy patient developed hyperkalemia and increased serum creatinine, which resolved with fludrocortisone and attempt to discontinue fludrocortisone resulted in hyperkalemia and rising creatinine.&#x0D; Screening of developing post-operative hyperkalemia should be actively considered in high-risk patients: older age, longer duration of hypertension, higher levels of aldosterone and severe hypokalemia before surgery, impaired estimated glomerular filtration rate and long-term treatment with spironolactone.

A rare case of primary hyperaldosteronism associated with chronic kidney disease-difficulties in diagnosis and treatment

A rare case of primary hyperaldosteronism associated with chronic kidney disease-difficulties in diagnosis and treatment

Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.

The application of advanced genetic techniques has recently begun to unravel the genetic basis for familial primary aldosteronism type 2 (FH-II). Whole-exome sequencing in a large family with FH-II revealed a shared rare damaging heterozygous variant in CLCN2 (chr.3: g.184075850C>T, p.Arg172Gln) in three severely affected members. The gene encodes a chloride channel, ClC-2. A cohort of 80 unrelated individuals diagnosed with early-onset primary aldosteronism was also examined for CLCN2 mutations finding three further occurrences of p.Arg172Gln mutations and four single cases of other potentially damaging heterozygous mutations for an overall prevalence of 9.9%. A concurrent report also found a different CLCN2 mutation (p.Gly24Asp) in a single severely affected patient from a cohort of 12 with early-onset PA for a prevalence of 8.3%. Cases of primary aldosteronism associated with CLCN2 mutations appear to be bilateral and respond well to medical treatment. In the adrenal, ClC-2 has been demonstrated to localize predominantly to the zona glomerulosa (ZG), and functional analysis suggests that mutations in ClC-2 predispose ZG cells to depolarization, thus leading to calcium influx via activation of voltage-gated calcium channels and increased aldosterone production. Germline CLCN2 mutations appear to account for a substantial proportion of early-onset primary aldosteronism cases, and genetic testing for mutations in this gene should be considered in appropriate cases.

Timeline of Advances in Genetics of Primary Aldosteronism.

The overwhelming majority of cases of primary aldosteronism (PA) occur sporadically due to a unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic adrenal hyperplasia. Familial forms of PA are rare with four subtypes defined to date (familial hyperaldosteronism types I-IV). The molecular basis of familial hyperaldosteronism type I (FH type I or glucocorticoid-remediable aldosteronism) was established in 1992; two decades later the genetic variant causing FH type III was identified and germline mutations causing FH type IV and FH type II were determined soon after. Effective diagnostic protocols and methods to detect the overactive gland in unilateral PA by adrenal venous sampling followed by laparoscopic adrenalectomy have made available APAs for scientific studies. In rapid succession, following the widespread use of next-generation sequencing, recurrent somatic driver mutations in APAs were identified in genes encoding ion channels and transporters. The development of highly specific monoclonal antibodies against key enzymes in adrenal steroidogenesis has unveiled the heterogeneous features of the diseased adrenal in PA and helped reveal the high proportion of APAs with driver mutations. We discuss what is known about the genetics of PA that has led to a clearer understanding of the disease pathophysiology.

A15382 Primary Hyperparathyroidism in a Patient with Primary Aldosteronism

Objectives: Primary aldosteronism is sometimes complicated with hyperparathyroidism, which can be classified into secondary hyperparathyroidism due to increased urinary calcium excretion. Low calcium intake has been reported to be a risk of primary hyperparathyroidism, however, it is unclear whether primary aldosteronism is causally related to the occurrence of primary hyperparathyroidism. Herein, we report an interesting case of primary aldosteronism complicated with primary hyperparathyroidism. Methods: This is a case report. Results: A 58-year-old woman, who had a history of parathyroidectomy for primary hyperparathyroidism due to parathyroid adenoma at the age of 43, was admitted for 20-years history of hypertension without remarkable family histories including hypertension. Her hypertension had been gradually worsening and was not improved by the parathyroidectomy. The laboratory findings were as follows: creatinine, 0.61 mg/dL; potassium, 4.0 mEq/L; corrected alcium, 8.9 mg/dL; plasma aldosterone concentration, 156 pg/mL; plasma renin activity, < 0.1 ng/mL/h; intact PTH, 73 pg/mL. Confirmatory tests and adrenal venous sampling revealed idiopathic hyperaldosteronism. Conclusion: We presented a case of primary aldosteronism, who experienced primary hyperparathyroidism. Her hyperaldosteronism might have contributed to the development of primary hyperparathyroidism through high urinary calcium excretion. We may need to carefully consider a possible complication of not only secondary but also primary hyperparathyroidism in patients with primary aldosteronism.

Application of strict criteria in adrenal venous sampling increases the proportion of missed patients with unilateral disease who benefit from surgery for primary aldosteronism.

Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed. Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated. Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization. Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.