Abstract 12591: Impact of Aldosterone Producing Adenoma on Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

Background: Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs) activity. Primary aldosteronism (PA) is a most common cause of secondary hypertension. Recent studies have shown that risk of cardiovascular events is higher in patients with PA than in patients with essential hypertension (EH). However, there is little information on the relationship between subtype of PA and the grade of atherosclerosis. The purpose of this study was to evaluate the vascular function and ROCK activity in patients with PA. Methods: Vascular function, including flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation, and ROCK activity in peripheral leukocytes were evaluated in 21 patients with aldosterone producing adenoma (APA) group (50.7±14.3 years, 9 males), 23 patients with idiopathic hyperaldosteronism (IHA) group (55.8±9.9 years, 12 males), and 33 age-, gender-, and blood pressure-matched EH group (54.9 ± 10.7 years, 18 males). Results: FMD was significantly lower in the APA group than in the IHA group and EH group (3.2±2.0% vs. 4.6±2.3% and 4.4±2.2%, P<0.05, respectively), whereas there was no significant difference in FMD between the IHA group and EH group. There was no significant difference in the response of nitroglycerine in three groups. ROCK activity was significantly higher in the APA group than in the IHA group and EH group (1.29±0.57 vs. 1.00±0.46 and 0.81±0.36, P<0.05 and P<0.001, respectively), whereas there was no significant difference in ROCK activity between the IHA group and EH group. FMD correlated with age (r=-0.31, P<0.01), brachial arterial diameter (r=-0.44, P<0.01), plasma aldosterone concentration (PAC) (r=-0.35, P<0.01) and plasma renin activity ratio (ARR) (r=-0.34, P<0.01). ROCK activity correlated with age (r=-0.24, P=0.04), PAC (r=0.33, P<0.01) and ARR (r=0.46, P<0.01). Conclusions: APA was associated with both endothelial dysfunction and increased ROCK activity compared with those in IHA and EH. These findings suggest that APA may have a higher risk of future cardiovascular events.

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Abstract 17413: Influence of Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

Circulation ◽

10.1161/circ.132.suppl_3.17413 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Takeshi Matsumoto ◽

Yukihito Higashi ◽

Akimichi Iwamoto ◽

Masato Kajikawa ◽

Nozomu Oda ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Primary Aldosteronism ◽

Vascular Function ◽

Cardiovascular Events ◽

Plasma Renin ◽

Secondary Hypertension ◽

Peripheral Arterial Tonometry ◽

Plasma Aldosterone Concentration ◽

Significant Difference ◽

Rock Activity

Background: Primary aldosteronism (PA) is a most common cause of secondary hypertension and patients are divided into two subtypes in clinically, aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Hypertension is associated with endothelial dysfunction. It is well known that endothelial dysfunction is an independent predictor of cardiovascular events. Rho-associated kinases (ROCKs), one of the first downstream targets of the small GTP-binding protein Rho A, mediate various cellular physiologic functions. It has been reported that an increase in ROCK activity is associated with cardiovascular diseases, including hypertension. However, there is little information on the relationship between subtype of PA and the grade of atherosclerosis. The purpose of this study was to evaluate the vascular function and ROCK activity in patients with PA. Methods: Vascular function, including peripheral arterial tonometry (PAT) and ROCK activity in peripheral leukocytes were evaluated in 18 patients with APA group (49.5±15.5 years, 7 males), 14 patients with IHA group (56.1±11.0 years, 8 males), and 23 age-, gender-, and blood pressure-matched EH group (55.6 ± 9.9 years, 13 males). Results: PAT ratio was significantly lower in the APA and IHA groups than in the EH group (0.62±0.23 vs. 0.62±0.24 and 0.79±0.28, P<0.05, respectively), whereas there was no significant difference in PAT ratio between the APA group and IHA group. ROCK activity was significantly higher in the APA group than in the IHA group and EH group (1.36±0.58 vs. 0.95±0.51 and 0.80±0.39, P<0.05 and P<0.001, respectively), whereas there was no significant difference in ROCK activity between the IHA group and EH group. PAT ratio correlated with plasma aldosterone concentration (PAC) (r=-0.36, P<0.01) and plasma renin activity ratio (ARR) (r=-0.26, P=0.05). ROCK activity correlated with serum potassium (r=-0.27, P=0.05), PAC (r=0.39, P<0.01) and ARR (r=0.49, P<0.01). Conclusions: APA and IHA were associated with endothelial dysfunction and APA increased ROCK activity compared with those in IHA and EH. These findings suggest that APA may have a higher risk of future cardiovascular events.

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SAT-563 The Unsuppressed Plasma Renin Activity May Not Enough for Management of Non-Surgically Treated Primary Aldosteronism

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1393 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Takamasa Ichijo ◽

Moe Hayasaka ◽

Takayuki Suzuki ◽

Ayako Suzuki ◽

Manabu Saito ◽

...

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Primary Aldosteronism ◽

Cardiovascular Events ◽

Plasma Renin ◽

Renin Activity ◽

Plasma Aldosterone Concentration ◽

Significant Difference ◽

The Mean

Abstract It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Those patients with bilateral hyperaldosteronism, called idiopathic hyperaldosteronism (IHA), or unwilling for surgical treatment are treated by mineralcorticoid receptor antagonists (MRAs). Although it had been unclear how titrate MRAs to prevent atherosclerotic cardiovascular events, a managemental target for those patients was recently reported as plasma renin activity (PRA) ≥ 1.0 ng/ml/hr to prevent cardiovascular events (Hundemer GL, et. al. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59). Thus, we investigated 77 cases of adrenal venous sampling performed patients with PA and followed up for 3 years in our hospital since 2007, including 24 males and 53 females, and their mean age was 56.3 ± 12.5 years old. All patients underwent AVS and showed bilateral hyperaldosteronism and treated with MRAs and followed up more than 3 years. We collected blood pressure, serum sodium and potassium concentration, estimated glomerular filtration ratio (eGFR), PRA, plasma aldosterone concentration (PAC), atherosclerotic parameter, such as mean intima media thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). We evaluated the relationship of those patients’ PRA and aldosterone to renin ratio (ARR) with eGFR, IMT, baPWV, and ABI. The change of mean IMT after 3 year-follow up were 0.03 ± 0.11 mm vs. 0.06 ± 0.09 mm for well controlled (PRA ≥ 1.0 ng/ml/hr) and poorly controlled (PRA < 1.0 ng/ml/hr), respectively, and no significant difference between them. In the other hand, the change of mean IMT after 3 year-follow up showed 0.03 ± 0.10 mm vs. 0.08 ± 0.10 mm for well controlled (PRA ≥ 1.0 ng/ml/hr and ARR <20) and poorly controlled (PRA < 1.0 ng/ml/hr or ARR ≥ 20), respectively, and the mean IMT increase was significantly lower in this group. The mean IMT increase showed significantly lower only with PRA ≥ 1.0 ng/ml/hr and ARR <20 rather than PRA ≥ 1.0 ng/ml/hr alone. In our results, both PRA ≥ 1.0 ng/ml/hr and ARR<20 are important to prevent or improve atherosclerosis, rather than only PRA ≥ 1.0 ng/ml/hr and should be titrated MRAs to achieve this target. In conclusion, our result revealed the titration of MRAs is important to prevent atherosclerotic cardiovascular event and not only PRA ≥ 1.0 ng/ml/hr, but both PRA and ARR <20 should be achieved.

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The relation among aldosterone, galectin-3, and myocardial fibrosis: a prospective clinical pilot follow-up study

Journal of Investigative Medicine ◽

10.1136/jim-2015-000014 ◽

2016 ◽

Vol 64 (6) ◽

pp. 1109-1113 ◽

Cited By ~ 12

Author(s):

Che-Wei Liao ◽

Yen-Tin Lin ◽

Xue-Ming Wu ◽

Yi-Yao Chang ◽

Chi-Sheng Hung ◽

...

Keyword(s):

Myocardial Fibrosis ◽

Primary Aldosteronism ◽

Plasma Renin ◽

Secondary Hypertension ◽

Left Ventricular ◽

Galectin 3 ◽

Registration Number ◽

Cyclic Variations ◽

Pressure Concentration ◽

Aldosterone Producing Adenoma

Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy.Trial registration number200611031R; Results.

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A Reappraisal of the Diagnostic Criteria for Primary Aldosteronism

Clinical Science ◽

10.1042/cs063097s ◽

1982 ◽

Vol 63 (s8) ◽

pp. 97s-100s ◽

Cited By ~ 5

Author(s):

E. L. Bravo ◽

R. C. Tarazi ◽

F. M. Fouad ◽

S. C. Textor

Keyword(s):

Primary Aldosteronism ◽

Excretion Rate ◽

False Negative ◽

False Negative Rate ◽

Plasma Renin ◽

Dietary Sodium ◽

Screening Tests ◽

Plasma Aldosterone Concentration ◽

Salt Loading ◽

Aldosterone Producing Adenoma

1. Results in 80 patients with primary aldosteronism (70 with tumour, 10 with hyperplasia) who underwent stimulation and suppression tests were analysed to assess the usefulness of several screening techniques. 2. On normal dietary sodium, normokalaemia was found in 27.5% of patients; 12.5% remained so despite 3 days of salt loading. Suppressed plasma renin activity (PRA: less than 1.43 pmol/l after stimulated conditions) gave a false-negative rate of 36%. Thus sole reliance on either hypokalaemia (serum potassium less than 3.5 mmol/l) or suppressed PRA as primary screening tests would have overlooked about a third of the patients in this series. 3. The single best diagnostic test for primary aldosteronism was the measurement of aldosterone excretion rate after 3 days of salt loading. 4. An anomalous postural fall in plasma aldosterone concentration when present, coupled with adrenal venous sampling, provided the best indicators of the presence of an aldosterone-producing adenoma.

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Minireview: Primary Aldosteronism—Changing Concepts in Diagnosis and Treatment

Endocrinology ◽

10.1210/en.2003-0279 ◽

2003 ◽

Vol 144 (6) ◽

pp. 2208-2213 ◽

Cited By ~ 256

Author(s):

William F. Young

Keyword(s):

Plasma Renin Activity ◽

Primary Aldosteronism ◽

Activity Ratio ◽

Cardiovascular Effects ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Receptor Blockade ◽

Plasma Aldosterone Concentration ◽

Aldosterone Producing Adenoma

Abstract Primary aldosteronism affects 5–13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of primary aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with primary aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperaldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.

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Abstract 13211: Atrial Fibrillation is an Independent Predictor for Cardiovascular Events in Hypertensive Patients Due to Primary Aldosteronism

Circulation ◽

10.1161/circ.142.suppl_3.13211 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Shintaro Sakaguchi ◽

Ryuji Okamoto ◽

Chisa Inoue ◽

Kohei Kamemura ◽

Isao Kurihara ◽

...

Keyword(s):

Atrial Fibrillation ◽

Primary Aldosteronism ◽

Cardiovascular Events ◽

Cox Regression ◽

Left Ventricular ◽

Male Gender ◽

Older Age ◽

Plasma Aldosterone Concentration ◽

Hypertensive Patients ◽

Significant Difference

Introduction: A higher risk of cardiovascular events has been reported in patients with hypertension due to primary aldosteronism (PA) than essential hypertension. Hypothesis: This study sought to determine the independent predictors for the risk of cardiovascular events in hypertensive patients with PA. Methods: The nation-wide PA registration study (JPAS/JRAS) included patients aged 20 years and older. Data were collected between January 2006 and January 2019, with a mean follow-up duration of approximately 4 years. Characteristics of patients with or without atrial fibrillation (AF) on the diagnosis of PA were compared. Patients were treated by surgery or MR antagonists and incident cardiovascular events were followed up. Results: A total of 3,647 patients with PA were included at the time of analysis. Prevalence of AF was 2.4% (87/ 3,647). PA patients with AF were older, more male and had longer duration of hypertension than those without AF. Each prevalence of cerebral infarction, chronic kidney disease, coronary artery disease, heart failure and left ventricular hypertrophy evaluated by echocardiography was higher in PA patients with AF than those without AF. Patients with AF had more kinds of antihypertensive drugs. There was no significant difference of basal plasma aldosterone concentration, plasma renin activity, unilateral subtype and rate of surgery between the 2 groups. PA patients with AF had higher rates of cardiovascular events compared to those without AF (14.9% vs 6.7%, P=0.002). Multivariate cox regression analyses demonstrated AF in addition to older age, male gender, duration of hypertension and surgery performance as an independent prognostic factor for cardiovascular events (HR, 1.950 [95%CI, 1.021-3.726], P<0.05; HR, 1.023 [95%CI, 1.008-1.039], P=0.003; HR, 1.385 [95%CI 1.025-1.870], P<0.05; HR, 1.023 [95%CI, 1.008-1.038], P=0.002; HR, 1.580 [95%CI, 1.168-2.138], P=0.003;respectively). Conclusions: Among patients with PA, male gender, older age, and longer duration of hypertension are the predisposing factors of AF in PA patients. In addition, AF was an independent risk factor for cardiovascular events in PA patients. It is warranted to prevent and to treat appropriately AF in patients with PA.

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Atrial fibrillation is an independent predictor of cardiovascular events in patients with primary aldosteronism

European Heart Journal ◽

10.1093/eurheartj/ehab724.2316 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Sakaguchi ◽

R Okamoto ◽

C Inoue ◽

K Kamemura ◽

I Kurihara ◽

...

Keyword(s):

Heart Failure ◽

Primary Aldosteronism ◽

Cardiovascular Events ◽

Independent Predictor ◽

Left Ventricular ◽

Older Age ◽

Plasma Aldosterone Concentration ◽

Cardiothoracic Ratio ◽

Significant Difference ◽

Confirmatory Tests

Abstract Background A higher risk of cardiovascular events has been reported in patients with hypertension due to primary aldosteronism (PA) than essential hypertension. This study sought to determine the independent predictors for the risk of cardiovascular events in hypertensive patients with PA. Methods The Japan Primary Aldosteronism Study (JPAS) has retrospectively recruited 3,654 patients with PA between January 2006 and January 2019 as a nationwide registry and we evaluated the differences between patients with and without AF from these data. The patients underwent general laboratory test, electrocardiography, echocardiography, diagnostic confirmatory tests including saline-loading, captopril-challenge, and upright furosemide-loading tests and adrenal venous sampling (AVS). We evaluated the cardiovascular events including myocardial infarction, stroke, heart failure and renal failure, with a mean follow-up duration of approximately 4 years. Results The prevalence of AF was 2.4% (88/ 3,654). PA patients with AF were older (60.3 vs 52.8 years old), more male (77.3% vs 46.6%) and had longer duration of hypertension (14.3 vs 8.3 years) than those without AF. Each prevalence of cerebral infarction (12.5% vs 3.5%), chronic kidney disease (12.5% vs 4.8%), coronary artery disease (CAD) (10.2% vs 1.7%), heart failure (5.7% vs 0.7%) and left ventricular hypertrophy evaluated by echocardiography (46.4% vs 31.9%) was higher in PA patients with AF. Patients with AF had more kinds of antihypertensive drugs (1.3 vs 1.1). There was no significant difference of basal plasma aldosterone concentration (PAC), plasma renin activity, each confirmatory tests, lateralized ratio in AVS after stimulation with adrenocorticotropic hormone (ACTH) and laterality between the 2 groups. Logistic regression analysis showed that age, cardiothoracic ratio (CTR), past history of CAD and heart failure were independent determinants for AF. PA patients with AF had higher rates of cardiovascular events compared to those without AF (Figure, P<0.005). Multivariate Cox regression analyses demonstrated AF in addition to adrenal PAC before ACTH stimulation, age, hypokalemia and duration of hypertension as independent prognostic factors for cardiovascular events (hazard ratio [HR] 1.993, 95% confidence interval [CI] 1.042–3.815, P<0.05; HR 1.ehab724.231608, 95% CI 1.ehab724.231604–1.ehab724.231612, P<0.0005; HR 1.03, 95% CI 1.012–1.048, P<0.005; HR 1.748, 95% CI 1.242–2.461, P<0.005; HR 1.029, 95% CI 1.013–1.044, P<0.0005, respectively). Conclusions This study provides evidence that comorbid AF is associated with older age, male sex, X-ray CTR and prevalence of CAD and heart failure. Furthermore, AF is an independent predictor of cardiovascular events in patients with PA, in addition to the adrenal venous concentration of aldosterone, hypokalemia, older age and duration of hypertension. Earlier recognition and intervention of AF can prevent cardiovascular events in PA. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

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Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320321999491 ◽

2021 ◽

Vol 22 (1) ◽

pp. 147032032199949

Author(s):

Miaomiao Sang ◽

Yu Fu ◽

Chenmin Wei ◽

Jing Yang ◽

Xueting Qiu ◽

...

Keyword(s):

Essential Hypertension ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Primary Aldosteronism ◽

Cardiovascular Events ◽

Statistical Significance ◽

Enzyme Linked Immunosorbent Assay ◽

Microvascular Endothelial ◽

Pai 1 ◽

Microvascular Endothelial Function

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

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Comparison of Clinical Features between Primary Aldosteronism and Essential Hypertension in Chinese Patients: A Case-Control Study

International Journal of Endocrinology ◽

10.1155/2021/6685469 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Xiaoyu Huang ◽

Shuang Yu ◽

Huangmeng Xiao ◽

Ling Pei ◽

Yan Chen ◽

...

Keyword(s):

Essential Hypertension ◽

Insulin Secretion ◽

Clinical Features ◽

Primary Aldosteronism ◽

Structural Damage ◽

Case Control ◽

Secondary Hypertension ◽

Left Ventricular ◽

Chinese Patients ◽

Significant Difference

Primary aldosteronism (PA) is one of the most common forms of secondary hypertension. Recent studies suggest that, compared with essential hypertension (EH), PA presents more severe disorders of glycolipid metabolism and organ damages. This case-control retrospective study aimed to ascertain clinical features and metabolic parameters between Chinese patients of PA and EH. 174 PA patients and 174 matched EH patients were recruited. Their clinical features, biochemistry parameters, the ventricular septal thickness, and left ventricular mass index (LVMI) were compared. HOMA-β% and HOMA-IR were calculated to evaluate glucose metabolism. The results showed that there was no significant difference regarding BMI, waist-to-hip ratio, and blood pressure between the two groups. The blood potassium level was significantly lower in PA patients than those in EH patients. The abnormal glucose tolerance and the incidence of diabetes in the PA group were not significantly different from those in EH group, but the insulin secretion levels at 0 min and 30 min were significantly weaker than those in the EH group, and the HOMA-β% was also lower in the PA group than those in the EH group. Left ventricular structural abnormalities in PA patients were more severe than those in EH patients. Subtype analysis indicated that patient with aldosterone-producing adenoma (APA) has more serious hypokalemia and lower levels of HOMA-β% and HOMA-IR comparing to those in the idiopathic adrenal hyperplasia (IHA) patient. These findings demonstrated that PA patients showed more impaired insulin secretion function and more severe left ventricular structural damage compared with EH patients.

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Primary aldosteronism in Klinefelter’s syndrome: two cases

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0126 ◽

2019 ◽

Vol 2019 ◽

Author(s):

Yasufumi Seki ◽

Satoshi Morimoto ◽

Naohiro Yoshida ◽

Kanako Bokuda ◽

Nobukazu Sasaki ◽

...

Keyword(s):

Luteinizing Hormone ◽

Primary Aldosteronism ◽

Luteinizing Hormone Receptor ◽

List Type ◽

Klinefelter’S Syndrome ◽

Klinefelter's Syndrome ◽

Plasma Aldosterone Concentration ◽

Lh Receptor ◽

Serum Lh ◽

Aldosterone Producing Adenoma

Summary Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered. Learning points: The pathogenesis of primary aldosteronism is still unclear. Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma. Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

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