scholarly journals KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism

2019 ◽  
Vol 104 (10) ◽  
pp. 4695-4702 ◽  
Author(s):  
Leticia A P Vilela ◽  
Marcela Rassi-Cruz ◽  
Augusto G Guimaraes ◽  
Caio C S Moises ◽  
Thais C Freitas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Somatic Mutation ◽  
Primary Aldosteronism ◽  
Antihypertensive Drugs ◽  
Independent Predictor ◽  
Blood Pressure Response ◽  
Antihypertensive Medications ◽  
Unilateral Adrenalectomy ◽  
Molecular Features ◽  
Endocrine Hypertension

AbstractContextPrimary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear.ObjectiveTo determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.MethodsWe retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.ResultsKCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004).ConclusionThe presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

scholarly journals OR04-6 Predictors of Clinical Outcome after Adrenalectomy for Unilateral Primary Aldosteronism

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Caio Moises ◽  
Natalia Alencar ◽  
Thaís Castanheira ◽  
Leticia Vilela ◽  
Marcela Rassi-Cruz ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Primary Aldosteronism ◽  
Independent Predictor ◽  
Clinical Success ◽  
Univariate Analysis ◽  
Multivariate Logistic Regression Analysis ◽  
Unilateral Adrenalectomy ◽  
Common Cause ◽  
Molecular Features ◽  
Endocrine Hypertension

Abstract Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT) with an estimated prevalence of 10% in referred populations and 15-20% in patients with resistant hypertension. The most common cause of unilateral PA is aldosterone-producing adenomas (APAs). HT and hypokalemia improve in nearly 100% of patients with unilateral PA after unilateral adrenalectomy. However, complete clinical success (defined as blood pressure ≤130x80 mmHg without anti-hypertensive drugs) has been reported in about 50% (range, 35-80%) of patients with unilateral PA after surgery. HT duration and severity have been associated with clinical outcome after adrenalectomy, but few reports with a limited number of cases evaluated the prognostic role of somatic KCNJ5 mutations. In this study, our aim was to determine clinical and molecular features associated with complete clinical success after unilateral adrenalectomy in unilateral PA patients. We retrospectively evaluated 103 PA patients (42 males; median age 49 yrs, 20-74) with a median follow-up of 25 months. Hypokalemia was present in 78% of the cases. Anatomopathological analysis revealed 94 APAs and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 mutations were identified in 27 out of 67 (40%) tumors: p.Gly151Arg (n= 13), p.Leu168Arg (n= 13) and p.Glu145Gln (n= 1). Complete clinical success was reported in 32 out of 103 (31%) patients. In univariate analysis, HT duration, body mass index (BMI kg/m2), female sex and somatic KCNJ5mutations were associated with HT resolution after adrenalectomy. Complete clinical success was reported in 50% of patients with HT duration ≤5 yrs (vs. 24% with HT duration &gt;5 yrs; p= 0.011), in 40% of patients with BMI &lt;25 (vs. 22% with BMI ≥25; p= 0.042), in 38% of women (vs. 21% of men; p= 0.079) and in 70% of the patients with tumors harboring KCNJ5 somatic mutations (vs. 30% with WT tumors; p= 0.003). According to a stepwise multivariate logistic regression analysis, only the presence of a somatic KCNJ5 mutation was an independent predictor of complete success after adrenalectomy (relative risk 4.8, 95% confidence interval 1.24 to 19.21; p= 0.023). In conclusion, the presence of a somatic KCNJ5 mutation was an independent predictor of complete clinical success after unilateral adrenalectomy in patients with unilateral PA.

scholarly journals SAT-558 A Dedicated Endocrine Hypertension Service Increases the Timely Diagnosis of Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jun Yang ◽  
Yin Y Lim ◽  
Renata Libianto ◽  
Jimmy Shen ◽  
Morag Jennifer Young ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Care ◽  
Primary Aldosteronism ◽  
Pressure Control ◽  
Organ Damage ◽  
Antihypertensive Medications ◽  
Endocrine Hypertension ◽  
Treatment Naïve ◽  
Hypertension Diagnosis ◽  
The Impact

Abstract Background: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk that could be averted with targeted treatment. An Endocrine Hypertension Service (EHS), encompassing an education program, streamlined diagnostic tests and dedicated PA clinic, was developed to address this issue. Aims: To analyse the impact of Victoria’s first dedicated EHS on the pattern of PA diagnoses. Methods: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (N=267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2), and Year 3 (Y3), based on their first visit. Results: The proportion of referrals from primary care increased (20% in Y1 to 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1 to 19% in Y3). Patients with a hypertension diagnosis of 5 years or less at the time of referral to EHS increased from 34% in Y1 to 45% in Y3 whilst the percentage of patients with a hypertension diagnosis of more than 10 years decreased from 50% in Y1 to 35% in Y3. Consistent with an earlier presentation, the proportion of patients with end-organ damage at the time of referral decreased from 44% in Y1 to 29% in Y3. Almost a third of the PA patients had unilateral disease; all of those who underwent adrenalectomy had biochemical cure. Patients with bilateral PA were treated with spironolactone. Their systolic/diastolic blood pressure decreased by 15/12 mmHg in Y1, 17/13 mmHg in Y2 and 23/11 mmHg in Y3; while the mean number of antihypertensive medications decreased from 2.9 to 1.8 in Y1, 2.7 to 2.0 in Y2 and 2.2 to 1.6 in Y3 Conclusion: The EHS has facilitated an increase in referrals for PA screening from primary care, resulting in the earlier diagnosis of PA, when less complications are present, and optimised patient outcomes. A broader uptake of such a clinical service, integrated with education outreach, will bridge the gap between the reported high prevalence of PA and the actual low diagnostic rates.

scholarly journals Primary hyperaldosteronism- a resistant endocrine hypertension- A case report

2009 ◽  
Vol 4 (2) ◽  
pp. 49-50
Author(s):  
Syed Ali Ahsan ◽  
Md Rubayat Rahman ◽  
Mohammad Salman ◽  
Md Ashraful Haque ◽  
Ahmed Saiful Bari ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Post Partum ◽  
Adrenal Adenoma ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Primary Hyperaldosteronism ◽  
Uncontrolled Hypertension ◽  
Unilateral Adrenalectomy ◽  
Endocrine Hypertension

 A thirty years old lady presented with uncontrolled hypertension and dizziness during working for last 5 years. She had history of termination of pregnancy due to treatment-resistant hypertension. Even in the post-partum period her blood pressure remains uncontrolled with more than three antihypertensive drugs. Her serum K+ level was low and USG of KUB & adrenal glands showed slightly increased right renal cortical echotexture; CT scan of abdomen revealed right Adrenal adenoma. She underwent unilateral adrenalectomy. Now, she has no complaints and her blood pressure is normal without any antihypertensive drugs. There is no target organ damage. Key words: Primary hyperaldosteronism, unilateral adrenal adenoma, resistant endocrine hypertension   doi:10.3329/uhj.v4i2.2077 University Heart Journal Vol. 4 No. 2 July 2008 p.49-50

scholarly journals Aldosterone Suppression on Contralateral Adrenal During Adrenal Vein Sampling Does Not Predict Blood Pressure Response After Adrenalectomy

2014 ◽  
Vol 99 (11) ◽  
pp. 4158-4166 ◽  
Author(s):  
Silvia Monticone ◽  
Fumitoshi Satoh ◽  
Andrea Viola ◽  
Evelyn Fischer ◽  
Oliver Vonend ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Response ◽  
Blood Pressure Reduction ◽  
Great Majority ◽  
Adrenal Vein ◽  
Curative Surgery ◽  
Adrenal Vein Sampling ◽  
Unilateral Adrenalectomy ◽  
Contralateral Suppression ◽  
Bilateral Adrenal Hyperplasia

Context: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. Objective: The objective of the study was to retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. Setting: The study was carried out in eight different referral centers in Italy, Germany, and Japan. Patients: From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. Results: Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared with basal procedures (90% vs 77%). The CL ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P = .02 and P = .01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters, and patients with CL suppression underwent a significantly larger reduction in the aldosterone levels after adrenalectomy. Conclusions: For patients with lateralizing indices of greater than 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.

Study on clinical and endocrine characteristics of dexamethasone-suppressible hyperaldosteronism compared with those in primary aldosteronism owing to aldosterone-producing adenoma

1989 ◽  
Vol 121 (3) ◽  
pp. 334-344 ◽  
Author(s):  
Noriyoshi Yamakita ◽  
Keigo Yasuda ◽  
Nobuyasu Noritake ◽  
Leilani B. Mercado-Asis ◽  
Hiroshi Murase ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Blood Pressure Response ◽  
Laboratory Data ◽  
Japanese Patients ◽  
Pressure Response ◽  
Plasma Aldosterone ◽  
Vascular Damage ◽  
Aldosterone Producing Adenoma

Abstract. The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasonesuppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.

scholarly journals Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism

2013 ◽  
Vol 168 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Verena Fourkiotis ◽  
Oliver Vonend ◽  
Sven Diederich ◽  
Evelyn Fischer ◽  
Katharina Lang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Primary Aldosteronism ◽  
Treatment Initiation ◽  
Newly Diagnosed ◽  
Antihypertensive Medications ◽  
Cross Sectional ◽  
Spot Urine ◽  
Treatment Regimens ◽  
Urine Albumin

ObjectivePrimary aldosteronism (PA) has deleterious effects on kidney function independent of blood pressure levels. Up to now, data on effectiveness of different PA therapies regarding renal function are scarce.Design and methodsThis prospective multi-center study included 29 patients with newly diagnosed PA evaluated before and 1 year after treatment initiation, and a second cohort including 119 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Glomerular filtration rate (GFR), spot urine albumin excretion/urinary creatinine (UAE/Ucrea) ratio, biochemical parameters, and 24-h blood pressure were measured. In a larger cross-sectional cohort, renal function was evaluated depending on the type of treatment (adrenalectomy (ADX; n=86); spironolactone (n=65); and eplerenone (n=18)).ResultsGFR and UAE/Ucrea ratio significantly decreased in newly diagnosed PA patients after treatment initiation. In the second cohort, GFR and UAE/Ucrea ratio did not change during study period, and blood pressure was well controlled. In the larger cross-sectional cohort, no differences were seen in GFR and UAE/Ucrea ratio between PA patients on different treatment regimens. However, eplerenone treatment showed lower potassium levels and higher number of required antihypertensive medications.ConclusionsRenal dysfunction with elevated albuminuria was seen in PA patients and was reversible after treatment initiation. Medical therapies with spironolactone or eplerenone seem to be as effective as ADX regarding renal function and blood pressure; however, sufficient daily doses need to be given.

scholarly journals Predictors of blood pressure response after renal denervation beyond pretreatment blood pressure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Schmieder ◽  
C Delles ◽  
L Lauder ◽  
C Ott ◽  
M Boehm ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Antihypertensive Drugs ◽  
Blood Pressure Response ◽  
Methodological Approach ◽  
Large Degree ◽  
Initial Value ◽  
Study Population ◽  
Pre Treatment

Abstract Background The principle of initial value (Wilder's law of initial value) proposes that the “direction of response of body function to any agent depends to a large degree on the initial value of that function”. Indeed, in several trials on renal denervation (RDN), pre-treatment blood pressure (BP) has been consistently and repeatedly found to predict the decrease in BP after RDN. Efforts to discover further statistically significant and clinically meaningful predictors of BP response to RDN failed. Objective By use of a new methodological approach, we aimed to determine predictors of BP response after RDN in patients with resistant hypertension. Methods The study population comprised 266 patients with resistant hypertension (mean age 62 years, 34% females, mean BMI 30.5 kg/m2, 27% had coronary heart disease, 42% had diabetes mellitus and 61% had hypercholesterolaemia) who underwent radiofrequency RDN with the Symplicity catheter at the Universities of Homburg and Erlangen. Clinical data including 24h ambulatory BP (ABP) were obtained prior to, and 3, 6 and 12 months after RDN. The primary parameter of response was defined as change in 24-hour systolic ABP after 6 months from pre-treatment values. As expected, change in 24h systolic ABP correlated with pre-treatment 24h systolic ABP (r2 linear = 0.225, p&lt;0.001), with change in 24h systolic ABP = 73.82 + 0.55 x pre-treatment 24h systolic ABP. To overcome the predominant role of the pre-treatment BP that may mask other factors, we calculated for each individual patient the “expected systolic ABP decrease” by applying this regression equation and the “excessive systolic ABP decrease” by subtracting the measured from expected change in 24h systolic ABP. We divided the study population into 2 groups (above [responders] and below [non-responders] of the median change in excessive 24h systolic ABP. Results Neither pre-treatment 24h systolic or diastolic ABP, nor office systolic or diastolic BP differed between the two groups (all p&gt;0.20). Following RDN, 24h systolic ABP decreased in the responders by −23.3±16 vs non-responders +1.4±11 mmHg at 6 month, and 24h systolic ABP values were also significantly lower in responders at 3 and 12 months (all p&lt;0.001), without difference in number of antihypertensive drugs between the groups. Of all clinical variables at baseline, office heart rate (65.6 vs 68.7±12 bpm, p=0.024) and HbA1c (6.07±0.88 vs. 6.37±1.23%, p=0.035) were lower in responders compared with non-responders. Finally, a multiple regression analysis confirmed that pre-treatment 24h systolic ABP (beta +0.565, p&lt;0001), HbA1c (beta −0.167, p=0.004) and office HR (beta +0.106, p=0.057) were independent predictors of decrease in 24h systolic ABP. Conclusion In patients with resistant hypertension, lower HbA1c and office HR were identified as predictors of BP response in addition to pre-treatment BP. This finding may help to identify hypertensive patients who benefit most from RDN. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Extramural grant provided vy Medtronic INc

scholarly journals Prospective Screening for Primary Aldosteronism in Patients With Suspected Obstructive Sleep Apnea

Hypertension ◽  
2021 ◽  
Author(s):  
Min Ru Chee ◽  
Jesse Hoo ◽  
Renata Libianto ◽  
Stella M. Gwini ◽  
Garun Hamilton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Primary Aldosteronism ◽  
Blood Pressure Monitoring ◽  
Apnea Hypopnea Index ◽  
Hypertension Status ◽  
Antihypertensive Medications ◽  
Sleep Study ◽  
Obstructive Sleep

Several studies have demonstrated a bidirectional relationship between obstructive sleep apnea and primary aldosteronism (PA); however, many of these studies are limited to patients with known obstructive sleep apnea, hypertension, or PA. We evaluated the role of screening for PA in all patients referred for a diagnostic sleep study without selecting for prior diagnoses with these conditions. Plasma aldosterone and renin concentration were measured after an overnight polysomnography. Blood pressure was measured at the sleep center for all patients, while a proportion underwent 24-hour blood pressure monitoring. Of the 85 participating patients, 2 (2.4%) were identified to have likely PA based on an elevated aldosterone:renin ratio and/or clinical characteristics. Another 10 (11.8%) were identified to have possible PA based on their low or normal plasma renin concentration despite taking antihypertensive medications that are known to elevate renin. In participants with both obstructive sleep apnea and hypertension (n=40), the prevalence of likely or possible PA was 30%. However, there was no correlation between aldosterone, rennin, or aldosterone:renin ratio and the apnea-hypopnea index using multiple regression analysis adjusted for interfering medications and hypertension status. The observed high prevalence of possible PA among those with both hypertension and obstructive sleep apnea suggests that they should be routinely screened for PA.

scholarly journals The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism

2021 ◽  
Vol 12 ◽  
Author(s):  
Piotr Jędrusik ◽  
Bartosz Symonides ◽  
Jacek Lewandowski ◽  
Zbigniew Gaciong
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drug ◽  
Primary Aldosteronism ◽  
Angiotensin Receptor Blockers ◽  
Suboptimal Control ◽  
Aldosterone Secretion ◽  
Antihypertensive Medications ◽  
Specific Patient ◽  
Drug Classes ◽  
Cardiovascular Morbidity And Mortality

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

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