“Relieving the Pressure” With Unilateral Adrenalectomy in a Case of Chronic Resistant Hypertension From Primary Aldosteronism

Abstract Introduction: Primary aldosteronism is an under-recognized cause of resistant hypertension that is associated with an increased risk of cardiovascular disease and mortality. While surgical intervention may not lead to complete resolution of hypertension, partial success (defined by reduction in blood pressure and/or medications) can be achieved and future cardiovascular risks can be minimized. We present a case of a patient with primary aldosteronism whose chronic resistant hypertension improved significantly after unilateral adrenalectomy. Clinical Case: A 54-year-old female with resistant hypertension for 17 years and hypokalemia was diagnosed with primary aldosteronism. The patient had uncontrolled hypertension despite atenolol 50 mg, nifedipine XL 60 mg, triamterene-hydrochlorothiazide 37.5-25 mg, lisinopril 40 mg daily. Laboratory evaluation was significant for plasma aldosterone concentration (PAC) 26.8 ng/dL (reference: 0.0–30.0 ng/dL), plasma renin activity (PRA) 0.168 ng/mL/hr (reference: 0.167–5.380 ng/mL/hr), PAC/PRA ratio 159.5, and potassium of 3.2 mmol/L (reference: 3.5–4.5mmol/L). Other workup showed plasma normetanephrines 128 pg/mL (reference: 0–145 pg/mL), metanephrines 25 pg/mL (reference: 0–62 pg/mL), and two normal midnight salivary cortisol tests. Saline infusion testing confirmed primary aldosteronism with a non-suppressed aldosterone level of 15.6 ng/dL (normal <5 ng/dL). Abdominal imaging revealed two low-density right adrenal nodules consistent with adenomas and thickening of the left adrenal gland. The patient underwent adrenal vein sampling (AVS) with cosyntropin stimulation, which showed lateralization to the right adrenal. Despite adding clonidine 0.1 mg three times daily, hydralazine 25 mg three times daily and spironolactone 100 mg daily (which substituted triamterene-hydrochlorothiazide) after AVS, her blood pressure remained uncontrolled with blood pressure ranging from 150–180/90–110 mmHg. A laparoscopic right adrenalectomy was performed. Pathology revealed two adrenal cortical adenomas. At the one-month post-operative visit, her potassium was normal, PAC was 4.3 ng/dL, and blood pressure improved on a reduced regimen of atenolol, lisinopril, and nifedipine. Conclusion: In patients with chronic uncontrolled hypertension due to primary aldosteronism, surgical intervention may not lead to complete resolution of hypertension but may lead to partial clinical success. Residual hypertension may be due to underlying vascular changes associated with long-term exposure to elevated aldosterone. The post-operative PAC in our case was less than 5 ng/dL suggesting biochemical cure and potentially reduced cardiovascular risk. This case emphasizes that adrenalectomy should be considered in resistant hypertension, even if complete clinical cure may not be attainable to reduce future cardiovascular events.

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Primary Hyperaldosteronism in Pregnancy: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.310 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A153-A154

Author(s):

Jefferson Li ◽

Alaa Kubbar ◽

Eunice Kim ◽

Dennis Nunez Pelaez ◽

Giovanna Rodriguez ◽

...

Keyword(s):

Blood Pressure ◽

Primary Aldosteronism ◽

Cardiovascular Health ◽

Normal Sinus Rhythm ◽

Insulin Dose ◽

Plasma Renin ◽

Primary Hyperaldosteronism ◽

Uncontrolled Hypertension ◽

Plasma Aldosterone Concentration ◽

In Pregnancy

Abstract Background: Primary aldosteronism (PA) is a renin-independent hypersecretion of aldosterone that remains an underdiagnosed etiology of hypertension. Less than 50 cases of primary hyperaldosteronism in pregnancy have been reported in literature that are associated with pregnancy complications including preeclampsia. Clinical Case: A 41-year-old female G9P4 at 32 weeks gestation was admitted for suspected preeclampsia due to elevated blood pressure during a routine prenatal visit. Her comorbidities include type 2 diabetes, uncontrolled hypertension, and preeclampsia in a previous pregnancy. Home medications included Lisinopril 10 mg once daily which was discontinued upon pregnancy and switched to Labetalol 400 mg twice daily and Nifedipine ER 30 mg daily. She was on a total of 220 units of insulin daily. On presentation, patient complained of anxiety but denied any headache, nausea, visual disturbances, chest pain, palpitations, muscle cramps, or fatigue. Her blood pressure was 180/100 mmHg with heat rate of 73. Laboratory values was notable for potassium: 2.8 mmol/L (n 3.5–5 mmol/L), bicarbonate: 28 mmol/L (n 24–31 mmol/L), and magnesium: 1.4 mEq/L (n 1.3–1.9 mEq/L). Liver function test and platelet count were normal. Spot protein-creatinine ratio was 0.3 (n 0–0.2). ECG was normal sinus rhythm with a heart rate of 82 without decreased T wave amplitude or U waves. She received three doses of oral 40 mEq potassium chloride over twelve hours and potassium level post repletion was 3.0 mmol/L. Initially, her hypokalemia was attributed to high insulin dose requirements. Despite down titration of insulin, patient continued to have hypokalemic episodes (nadir 2.7 mmol/L) refractory to oral and parenteral potassium supplementation. She remained hypertensive despite Labetalol 600 mg every 8 hours, Nifedipine ER 30 mg every 12 hours, with as needed hydralazine 10 mg IV pushes, and underwent urgent cesarean delivery. Uncontrolled hypertension persisted postpartum with recurrent episodes of hypokalemia. Further investigations revealed a plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels of 43.5 ng/dL (n <10 ng/dL) and 1.67 ng/mL/hr (n 0.17–5.38 ng/mL/hr) respectively, potassium at time of testing was 3.6 mmol/L. PAC to PRA ratio was greater than 20:1 with an absolute PAC greater than 15 ng/dL, which is highly suggestive of PA. Conclusion: We present a case of suspected PA with spontaneous hypokalemia potentially masked by the use of ACE inhibitors uncovered during pregnancy. Given the changes to the renin-angiotensin-aldosterone system (RAAS) during pregnancy, the diagnosis of PA is difficult to establish during gestation. Still, little is known on how to optimally treat these patients. Reference: Morton, A., 2015. Primary Aldosteronism and Pregnancy. Pregnancy and hypertension. An International Journal of Women’s Cardiovascular Health, Volume 5 Issue 4, 259–262.

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A Case of Primary Hyperaldosteronism Presenting as Hemorrhagic Stroke

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.625 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A306-A307

Author(s):

Azeen Anjum ◽

Gayane Tumyan ◽

Kevin Tayon

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Coronary Artery ◽

Primary Aldosteronism ◽

Hemorrhagic Stroke ◽

Secondary Hypertension ◽

Uncontrolled Hypertension ◽

Mineralocorticoid Receptor Antagonist ◽

Plasma Aldosterone Concentration ◽

Vessel Coronary Artery

Abstract Background: Primary aldosteronism (PA) is the most common form of secondary hypertension. Patients with PA are more likely to suffer from end-organ damage compared to matched controls with essential hypertension. We present a case of PA identified in a patient who presented with hypertensive emergency and hemorrhagic stroke. Clinical Case: A 52-year-old man with hypertension and chronic kidney disease presented with sudden onset left-sided weakness. He had a ten year history of hypertension and was taking carvedilol, losartan, and hydralazine prior to presentation. On arrival, his blood pressure was 263/142 mmHg. He had 3/5 grade weakness in the left upper and lower extremities. Laboratory analysis showed a potassium level of 2.8 mmol/L (n = 3.5–5 mmol/L) and a bicarbonate level of 33 mmol/L (n = 21–29 mmol/L). Screening labs for PA were drawn after potassium repletion. CT Head without contrast revealed an acute 2.5-centimeter intracerebral hemorrhage of the right basal ganglia. He was admitted to the intensive care unit and was started on a nicardipine drip with an improvement of blood pressure. His weakness improved and he was discharged home on carvedilol, hydralazine, nifedipine, and losartan. Screening for PA revealed a plasma aldosterone concentration (PAC) of 22.8 ng/dL (n < 16 ng/dL) and a plasma renin activity (PRA) of 0.1 ng/ml/hr (n = 0.2–1.6 ng/ml/hr). The PAC/PRA ratio was therefore extremely elevated at 228. The presence of spontaneous hypokalemia, very low renin, and PAC >20 ng/dL confirmed the diagnosis of primary aldosteronism. He underwent an adrenal MRI which revealed two left adrenal nodules, the largest measuring 10 mm, and a 7.3 mm right adrenal nodule, consistent with bilateral adrenal adenomas. The patient did not desire surgery, therefore adrenal vein sampling was deferred. His hypertension improved with the addition of a mineralocorticoid receptor antagonist. Eight weeks after his stroke the patient was readmitted due to chest pain. He was found to have severe multi-vessel coronary artery disease and underwent a four vessel coronary artery bypass. Conclusion: Patients with PA have higher rates of adverse cardiovascular events compared to age-, sex-, and blood pressure-matched controls with essential hypertension. Studies demonstrate that aldosterone excess has blood pressure independent proinflammatory and profibrotic effects on the vessel wall which leads to endothelial dysfunction and thus accelerated atherosclerosis. Appropriate treatment can eliminate the excess cardiovascular risk associated with PA. This case highlights the importance of including PA in the differential diagnosis of secondary hypertension, particularly among patients presenting with spontaneous hypokalemia, severe uncontrolled hypertension and early onset cardiovascular or cerebrovascular disease.

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Device therapy of resistant hypertension

Orvosi Hetilap ◽

10.1556/oh.2013.29543 ◽

2013 ◽

Vol 154 (6) ◽

pp. 203-208 ◽

Cited By ~ 1

Author(s):

Gábor Simonyi ◽

J. Róbert Bedros ◽

Mihály Medvegy

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Resistant Hypertension ◽

Carotid Sinus ◽

Maximum Tolerated Dose ◽

Reduce Blood Pressure ◽

Nerve Fibers ◽

Uncontrolled Hypertension ◽

Sympathetic Nerve Fibers ◽

Treatment Of Hypertension

It is well known that hypertension is an independent cardiovascular risk factor. Treatment of hypertension frequently includes administration of three or more drugs. Resistant hypertension is defined when blood pressure remains above target value despite full doses (the patient’s maximum tolerated dose) of antihypertensive medication consisting of at least three different classes of drugs including a diuretic. Pharmacological treatment of hypertension is often unsuccessful despite the increasing number of drug combinations. Uncontrolled hypertension, however, increases the cardiovascular risk. Device treatment of resistant hypertension is currently testing two major fields. One of them the stimulation of baroreceptors in the carotid sinus and the other is radiofrequency ablation of sympathetic nerve fibers around renal arteries to reduce blood pressure in drug resistant hypertension. Orv. Hetil., 2013, 154, 203–208.

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Should all Hypertensive Patients be Screened for Primary Aldosteronism?

Current Hypertension Reviews ◽

10.2174/1573402114666180507153549 ◽

2019 ◽

Vol 15 (1) ◽

pp. 54-56

Author(s):

Stelina Alkagiet ◽

Konstantinos Tziomalos

Keyword(s):

Resistant Hypertension ◽

Primary Aldosteronism ◽

Large Scale ◽

Controlled Trial ◽

The Other ◽

Limited Data ◽

Hypertensive Patients ◽

Randomized Controlled ◽

Increased Risk ◽

Prospective Randomized Controlled Trial

Primary aldosteronism (PA) is not only a leading cause of secondary and resistant hypertension, but is also quite frequent in unselected hypertensive patients. Moreover, PA is associated with increased cardiovascular risk, which is disproportionate to BP levels. In addition, timely diagnosis of PA and prompt initiation of treatment attenuate this increased risk. On the other hand, there are limited data regarding the usefulness of screening for PA in all asymptomatic or normokalemic hypertensive patients. More importantly, until now, no well-organized, large-scale, prospective, randomized controlled trial has proved the effectiveness of screening for PA for improving clinical outcome. Accordingly, until more relevant data are available, screening for PA should be considered in hypertensive patients with spontaneous or diuretic-induced hypokalemia as well as in those with resistant hypertension. However, screening for PA in all hypertensive patients cannot be currently recommended.

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The Road to Better Management in Resistant Hypertension–Diagnostic and Therapeutic Insights

Pharmaceutics ◽

10.3390/pharmaceutics13050714 ◽

2021 ◽

Vol 13 (5) ◽

pp. 714

Author(s):

Elisabeta Bădilă ◽

Cristina Japie ◽

Emma Weiss ◽

Ana-Maria Balahura ◽

Daniela Bartoș ◽

...

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renin Angiotensin System ◽

Drug Regimen ◽

Secondary Hypertension ◽

Adverse Outcomes ◽

Uncontrolled Hypertension ◽

White Coat Hypertension ◽

Mineralocorticoid Receptor Antagonist ◽

Mortality And Morbidity

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes—greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

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Developing a Research Database of Primary Aldosteronism: Rationale and Baseline Characteristics

10.21203/rs.3.rs-228327/v1 ◽

2021 ◽

Author(s):

Wen Wang ◽

Yuanmei Li ◽

Qianrui Li ◽

Tingting Zhang ◽

Wei Wang ◽

...

Keyword(s):

Blood Pressure ◽

Primary Aldosteronism ◽

Prospective Cohort ◽

Research Database ◽

High Quality ◽

Plasma Aldosterone Concentration ◽

Confirmatory Testing ◽

The Mean ◽

High Level

Abstract BackgroundManagement of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. MethodsThe establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables.ResultsTotally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 mmHg, mean diastolic blood pressure (DBP) was 97.2 mmHg. Among included patients, the mean serum potassium level was 2.85 mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 ng/dL. The characteristics patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. ConclusionThrough integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.

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Long-Term Use of Aldosterone-Receptor Antagonists in Uncontrolled Hypertension: A Retrospective Analysis

International Journal of Hypertension ◽

10.4061/2011/368140 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Pieter M. Jansen ◽

Koen Verdonk ◽

Ben P. Imholz ◽

A. H. Jan Danser ◽

Anton H. van den Meiracker

Keyword(s):

Blood Pressure ◽

Multivariate Analysis ◽

Essential Hypertension ◽

Primary Aldosteronism ◽

Treatment Duration ◽

Uncontrolled Hypertension ◽

Receptor Antagonists ◽

Aldosterone Receptor

Background. The long-term efficacy of aldosterone-receptor antagonists (ARAs) as add-on treatment in uncontrolled hypertension has not yet been reported.Methods. Data from 123 patients (21 with primary aldosteronism, 102 with essential hypertension) with difficult-to-treat hypertension who received an ARA between May 2005 and September 2009 were analyzed retrospectively for their blood pressure (BP) and biochemical response at first followup after start with ARA and the last follow-up available.Results. Systolic BP decreased by22±20and diastolic BP by9.4±12 mmHg after a median treatment duration of 25 months. In patients that received treatment >5 years, SBP was33±20and DBP was 16 ± 13 mmHg lower than at baseline. Multivariate analysis revealed that baseline BP and follow-up duration were positively correlated with BP response.Conclusion. Add-on ARA treatment in difficult-to-treat hypertension results in a profound and sustained BP reduction.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00531 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4695-4702 ◽

Cited By ~ 11

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.

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Guest Editorial: Challenges in Resistant Hypertension

European Cardiology Review ◽

10.15420/ecr.2016:20:1 ◽

2016 ◽

Vol 11 (1) ◽

pp. 18

Author(s):

Thomas Kahan ◽

Keyword(s):

Blood Pressure ◽

Blood Pressure Control ◽

Resistant Hypertension ◽

Blood Pressure Monitoring ◽

Premature Death ◽

Pressure Control ◽

Secondary Hypertension ◽

Uncontrolled Hypertension ◽

Caregiver Support ◽

The Individual

Hypertension is the major risk factor for disease and premature death. Although the efficacy of antihypertensive therapy is undisputed, few patients reach target blood pressure. Steps to improve treatment and control include assessment of global cardiovascular risk for the individual patient, improving caregiver support, education and organisation, increasing treatment persistence, using out of office blood pressure monitoring more often, detecting secondary hypertension forms, and referring patients with remaining uncontrolled hypertension to a specialist hypertension centre. In conclusion, there is room for improvement of blood pressure control in hypertensive patients. The clinical benefit of improved blood pressure control may be considerable. This may be particularly true for patients with resistant hypertension.

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May the brief physical activity assessment tool accurately measure physical activity in patients with resistant hypertension?

European Journal of Cardiovascular Nursing ◽

10.1093/eurjcn/zvab060.033 ◽

2021 ◽

Vol 20 (Supplement_1) ◽

Author(s):

S Lopes ◽

J Mesquita-Bastos ◽

C Garcia ◽

D Figueiredo ◽

P Carvalho ◽

...

Keyword(s):

Physical Activity ◽

Blood Pressure ◽

Resistant Hypertension ◽

Assessment Tool ◽

Physical Activity Assessment ◽

Major Health Problem ◽

Activity Assessment ◽

Specificity And Sensitivity ◽

Increased Risk ◽

Active Patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): FEDER Funds through the Operational Competitiveness Factors Program—COMPETE National Funds through the Portuguese Foundation for Science and Technology (FCT) “PTDC/DTP-DES/1725/2014”. SL is a PhD fellow supported by the FCT (Grant Ref: SFRH/BD/129454/2017). Introduction Resistant hypertension is a major health problem due to the increased risk of cardiovascular events and mortality. Physical activity and exercise reduces blood pressure in resistant hypertension and is associated with lower cardiovascular risk and mortality. It is presently recommended that physical activity assessment should be a priority in all visits to health settings Purpose This study aims to determine if the Brief Physical Activity Assessment Tool (BPAAT), a 2-question tool to assess physical activity, is a valid instrument to detect inactive patients with resistant hypertension. Methods Sixty patients with a diagnosis of resistant hypertension were recruited. Outcome measures included clinical data, blood pressure and daily physical activity. Physical activity was objectively measured over a 7-day period with an accelerometer and subjectively assessed (self-assessment) by the BPAAT. The association between the BPAAT and accelerometry, according to the BPAAT scoring categories, was assessed bythe percentage of agreement, Cohen’s Kappa and sensitivity and specificity. Results Patients (33 were male) had a mean age of 59.4 ± 9.1years, were on average overweight (BMI 29.5 ± 4.5 kg/m2) and on an average of 4.5 ± 0.7 antihypertensive medications. Forty-two patients (70%) were classified as insufficiently active by the BPAAT compared to the 38 (63.3%) insufficiently active patients identified by the accelerometry data. Regarding the questionnaire’s specificity and sensitivity, the BPAAT correctly identified 32 [84.2 (73.1 – 95.3) %] of the 38 ‘insufficiently active’ patients and 12 [54.5 (34.3 – 74.7) %] of the 22 ‘sufficiently active’ patients identified by accelerometry. The agreement between BPAAT and accelerometry to identify sufficiently/insufficiently active patients, according to the BPAAT’s cut-off values was fair to moderate (Kappa = 0.403 (0.162 – 0.674), with a percentage of agreement of 73.3%. Conclusion The BPAAT, a 2-question tool to assess physical activity, seems to be a valid and fast solution to identify insufficiently active adults with resistant hypertension during routine clinical visits.

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