Medical Management of Aldosterone-Producing Adenomas

Ghose, Ranjan P.; Hall, Phillip M.; Bravo, Emmanuel L.

doi:10.7326/0003-4819-132-7-200004040-00023

Cited by 19 publications

(20 citation statements)

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“…The present results are consistent with the notion that ENaC is the final common pathway of MR activation . In addition to its well‐known renal tubular location, ENaC has been found in vascular endothelial cells, brain, and in skin fibroblasts, in which there appears to be a stimulatory effect on collagen synthesis and fibrosis . It has also been suggested that ENaC modulates the activity of vasopressinergic neurons .…”

Section: Discussionsupporting

confidence: 92%

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Maintenance of long‐term blood pressure control and vascular health by low‐dose amiloride‐based therapy in hyperaldosteronism

Izzo

Hong

Hussain

et al. 2019

J of Clinical Hypertension

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Whether aldosterone itself contributes directly to macro‐ or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long‐term single‐practice experience in an unusual group of five patients with chronic hyperaldosteronism (HA, including three with glucocorticoid‐remediable aldosteronism, GRA) treated with low‐dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5‐10 (mean 7) mg daily for 14‐28 (mean 20) years. Except for one GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normalized within 1‐4 weeks after starting amiloride and office BP’s remained well controlled throughout the next two decades. 24‐hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, reflection magnitude), regional pulse wave velocities, pulse stiffening ratio, ankle‐brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio were measured after a mean of 18 years; all of these indicators were essentially normal. Over two additional years of observation (100 patient‐years total), no cardiovascular or renal event occurred. We conclude that long‐term ENaC blockade with amiloride can normalize BP and protect macro‐ and microvascular function in patients with HA. This suggests that either (a) putative vasculopathic effects of aldosterone are mediated via ENaC or (b) aldosterone may not play a direct role in age‐dependent vasculopathic changes in humans independent of blood pressure. These findings, coupled with our literature review in both animal and human results, underscore the need for additional studies.

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Section: Discussionsupporting

confidence: 92%

“…Nongenetic forms of HA are often treated surgically but chronic oral MR antagonism, generally with spironolactone, has also been used successfully to lower BP and maintain serum potassium . A potentially useful but often forgotten drug is amiloride, a specific ENaC inhibitor .…”

Section: Introductionmentioning

confidence: 99%

Maintenance of long‐term blood pressure control and vascular health by low‐dose amiloride‐based therapy in hyperaldosteronism

Izzo

Hong

Hussain

et al. 2019

J of Clinical Hypertension

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“…Successful spironolactone daily dose ranges for treatment of primary hyperaldosteronism have been reported at 12.5 mg to 100 mg, 3,4 25 mg to 50 mg, 5 25 mg to 200 mg, 6 100 mg to 300 mg, 7 50 mg to 400 mg, 8 and 100 mg to 400 mg 9 . Medical treatment of primary hyperaldosteronism due to adrenal adenoma has been reported using spironolactone 100 mg to 200 mg 10 . Usually, however, dosages >100 mg daily carry little additional impact on BP 3 …”

Section: Case Discussionmentioning

confidence: 99%

Overlapping Spironolactone Dosing in Primary Aldosteronism and Resistant Essential Hypertension

Handler

2012

J of Clinical Hypertension

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A 65-year-old man presented to our hypertension clinic with refractory hypertension and hypokalemia. At age 11 he was beaten up, suffering a left renal injury that required hospitalization. Subsequent diastolic blood pressures (BPs) rose to 105 mm Hg throughout high school and into college, gradually resolving off of medication. He had been treated with antihypertensive therapy for more than 25 years with poor control. Amlodipine and nifedipine were not tolerated due to edema. Hypokalemia was noted and prior to spironolactone initiation, the patient required 100 mEq of potassium replacement daily. On spironolactone 25 mg, potassium was reduced to 40 mEq daily. A daughter of the patient, age 20, was being treated for hypertension, but there was no family history of stroke or myocardial infarction. He was treated with a regimen of lisinopril 40 mg, hydrochlorothiazide (HCTZ) 25 mg, atenolol 75 mg, terazosin 10 mg, and potassium chloride (KCl) 40 mEq daily. BPs had recently improved, but were still within the range of 150 ⁄ 90 mm Hg.The patient was taken off spironolactone and potassium was advanced to 100 mEq daily in preparation for testing for primary aldosteronism. A month later, his BP was 181 ⁄ 91 mm Hg. The laboratory workup included sodium 143 mEq ⁄ L (normal 135-145 mEq ⁄ L), potassium 3.5 mEq ⁄ L (normal 3.5-5.0 mEq ⁄ L), carbon dioxide 32.4 mEq ⁄ L (normal 21-31 mEq ⁄ L), creatinine 1.2 mg ⁄ dL (0.7-1.3 mg ⁄ dL), fasting glucose 111 mg ⁄ dL (normal 70-99 mg ⁄ dL), aldosterone 12.0 ng ⁄ dL (normal28 ng ⁄ dL), peripheral renin activity (PRA) 0.07 ng ⁄ mL ⁄ hour (0.25-5.82 ng ⁄ mL ⁄ hour), aldosterone ⁄ PRA ratio 171.43 (normal 0.9-28.9), 24-hour urine aldosterone 12.1 lg ⁄ 24 hours (normal 2.3-21 lg ⁄ 24 hours), 24-hour urine-free cortisol 59 lg ⁄ 24 hours (normal<138 lg ⁄ 24 hours), 24-hour urine metanephrines normal, and 17 ketosteroid fractionation normal. Genetic testing for glucocorticoid-remediable aldosteronism was negative. A computed tomography (CT) scan of the adrenal glands was normal. An intravenous saline suppression test had to be discontinued due to systolic pressures <200 mm Hg.When the spironolactone dose was advanced to 50 mg daily, BPs became 130 to 132 ⁄ 70 to 74 mm Hg within 2 weeks and remained stable with a continuing need for 40 mEq daily potassium replacement (Figure 1). CASE DISCUSSION Spironolactone Dosing for Primary Hyperaldosteronism and Resistant Essential HypertensionSpironolactone is used to treat both primary hyperaldosteronism and resistant hypertension in the absence of secondary etiologies. The dose ranges for these two conditions overlap significantly. In a study of 76 patients with African American participation, spironolactone 12.5 mg to 50 mg was similarly effective in those with and without biochemical evidence of primary hyperaldosteronism.1 The mean dosage was 30 mg ⁄ d in this study, but patients with primary aldosteronism were more likely to require the 50-mg dose. The mean BP reduction at 6 months in patients taking a mean of 4.1 antihypertensive medications a...

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“…While some authorities recommend full investigation and laparoscopic adrenalectomy if excessive aldosterone secretion can be lateralised to one of the glands[8,9], surgery is not without risks and 60% of adrenalectomised subjects require antihypertensive therapy[10]. In addition, those who have a good response to surgery also show a good response to spironolactone[11] and long term drug treatment is safe and effective[12]. Furthermore, there remains some debate about the true distinction between genuine autonomous primary aldosteronism and relative aldosterone excess association with low renin hypertension.…”

Section: Introductionmentioning

confidence: 99%

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

Parthasarathy

Al-Hashmi

McMahon

et al. 2007

BMC Cardiovasc Disord

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BackgroundHigh blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.Methods/designThe study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazideDiscussionThe numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.

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Medical Management of Aldosterone-Producing Adenomas

Cited by 19 publications

References 4 publications

Maintenance of long‐term blood pressure control and vascular health by low‐dose amiloride‐based therapy in hyperaldosteronism

Maintenance of long‐term blood pressure control and vascular health by low‐dose amiloride‐based therapy in hyperaldosteronism

Overlapping Spironolactone Dosing in Primary Aldosteronism and Resistant Essential Hypertension

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

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