Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 26-23: Primary Aldosteronism + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Hypertension may be severe or drug-resistant Hypokalemia (in minority of patients) may cause polyuria, polydipsia, muscle weakness Low plasma renin; elevated plasma and urine aldosterone levels +++ General Considerations ++ Excessive aldosterone production Increases sodium retention and suppresses plasma renin Increases renal potassium excretion that can lead to hypokalemia Cardiovascular events are more prevalent in patients with aldosteronism (35%) than in those with essential hypertension (11%) May be caused by a unilateral aldosterone-producing adrenal cortical adenoma (Conn syndrome, 25%) More common in women with a 2:1 ratio Peaks between ages 30 and 50 years More commonly caused by adrenal cortical hyperplasia (75%) More common in men with a 4:1 ratio Peaks between ages 50 and 60 years Bilateral aldosteronism may be corticosteroid suppressible due to an autosomal-dominant genetic defect allowing ACTH stimulation of aldosterone production Malignant ovarian tumors are rare cause of hyperaldosteronism +++ Demographics ++ Accounts for about 8% of cases of stage 2 (mild) hypertension and about 13% of cases of stage 3 (moderate) hypertension Should also be suspected with early onset hypertension or stroke before age 50 years (or both) Patients of all ages may be affected, but the peak incidence is between 30–60 years + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Hypertension is typically moderate but may be severe Some patients have only diastolic hypertension, without other symptoms and signs Edema (rare) Muscle weakness (at times with paralysis simulating periodic paralysis), paresthesias with frank tetany, headache, polyuria, and polydipsia may be seen in patients with hypokalemia +++ Differential Diagnosis ++ Essential hypertension Hypokalemic thyrotoxic periodic paralysis Renal vascular hypertension (hypertension and hypokalemia, but plasma renin activity is high) Hypokalemia due to other cause, eg, diuretics Secondary hyperaldosteronism (dehydration, heart failure) Congenital adrenal hyperplasia: 11beta-hydroxylase deficiency, 17alpha-hydroxylase deficiency Cushing syndrome Excessive real licorice ingestion Syndrome of cortisol resistance + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Plasma potassium should be determined in hypertensive individuals; however, hypokalemia is present in only 37% of affected patients An elevated serum bicarbonate (HCO3) concentration indicates metabolic alkalosis and is commonly present Testing for primary aldosteronism should be considered for all hypertensive patients with any of the following: Sustained hypertension above 150/100 mm Hg on 3 different days Hypertension resistant to three conventional antihypertensive drugs, including a diuretic Controlled blood pressure requiring four or more antihypertensive drugs Hypokalemia, particularly when unrelated to diuretics Personal or family history of early onset hypertension or CVA at age ≤ 40 years First-degree relative with primary aldosteronism Presence of an adrenal mass Low plasma renin activity Testing protocol For at least 2 weeks prior to testing, patients should Have any hypokalemia corrected and then consume a diet high in NaCl (> 6 g/day) Hold certain medications: all diuretics, ACE inhibitors, ARBs (stimulate plasma renin activity [PRA]); beta-blockers, clonidine, NSAIDs (suppress PRA), oral estrogens, and oral contraceptives Medications that are allowed include extended-release verapamil, hydralazine, terazosin, and doxazosin The patient should be out of bed for at least 2 hours and seated for 15–60 minutes before blood is drawn, which should preferably be obtained between 8 AM and 10 AM Patients with primary aldosteronism have a suppressed PRA that is below or near 1.0 ng/mL/h or direct renin assay (DRA) < 0.36 ng/mL Suppressed PRA or DRA with a serum aldosterone concentration > 15 ng/dL (420 pmol/L) indicates probable primary hyperaldosteronism Serum aldosterone (ng/dL):PRA (ng/mL/h) ratios < 24 exclude primary aldosteronism Between 24 and 30 are indeterminate Between 30 and 64 are suspicious > 64 helps confirm the diagnosis of primary aldosteronism Diagnosis of primary aldosteronism is confirmed when Patients have a suppressed PRA or DRA plus a serum aldosterone ≥ 20 ng/day Suppressed PRA or DRA but lower serum aldosterone levels with a urine aldosterone over 12 mcg/24 h is present (33 nmol/24 h) +++ Imaging Studies ++ Thin-section CT scan Used to screen for a rare adrenal carcinoma In the absence of a large adrenal carcinoma, scanning cannot reliably distinguish unilateral from bilateral aldosterone excess +++ Diagnostic Procedures ++ Adrenal vein sampling Most accurate way to determine whether primary aldosteronism is due to unilateral aldosterone excess Indicated only to direct the surgeon to the correct adrenal and should be performed only if surgery is contemplated Useful for patients who are not hypokalemic, over age 40 years, or who have an adrenal adenoma < 1 cm diameter Genetic testing for familial glucocorticoid remediable aldosteronism is recommended for patients with Confirmed primary aldosteronism by age 20 years A family history of primary aldosteronism or stroke at young age (< age 40) + Treatment Download Section PDF Listen +++ +++ Medications ++ Spironolactone or eplerenone Long-term therapy is an option for Conn syndrome Used to treat bilateral adrenal hyperplasia Spironolactone Has anti-androgen activity and frequently causes breast tenderness, gynecomastia, or reduced libido Initial dose: 12.5–25 mg once daily orally Dose may be titrated to 200 mg daily Contraindicated in pregnant women Eplerenone Does not have anti-androgen effects Must be given twice daily in oral doses of 25–50 mg due to short half-life Blood pressure must be monitored daily when beginning these anti-mineralocorticoid medications Significant drops in blood pressure have occurred when these drugs are added to other antihypertensive agents Other antihypertensive drugs may be required, particularly amlodipine, ACE inhibitors, or ARBs Suppression with low-dose glucocorticoids for glucocorticoid-remediable aldosteronism (which is very rare) +++ Surgery ++ Laparoscopic adrenalectomy for Conn syndrome (unilateral aldosterone-secreting adrenal adenoma) + Outcome Download Section PDF Listen +++ +++ Complications ++ The incidence of cardiovascular complications from hypertension are higher in primary aldosteronism than in idiopathic hypertension Following unilateral adrenalectomy for Conn syndrome, suppression of the contralateral adrenal may result in temporary postoperative hypoaldosteronism, characterized by hyperkalemia and hypotension +++ Prognosis ++ Hypertension remits after surgery in about two-thirds of cases but persists or returns despite surgery in one-third Prognosis much improved by early diagnosis and treatment Only 2% of aldosterone-secreting adrenal tumors are malignant + References Download Section PDF Listen +++ + +Byrd JB et al. Primary aldosteronism. Circulation. 2018 Aug 21;138(8):823–35. [PubMed: 30359120] + +Miller BS et al. Refining the definitions of biochemical and clinical cure for primary aldosteronism using the primary aldosteronism surgical outcome (PASO) classification system. World J Surg. 2018 Feb;42(2):453–63. [PubMed: 29134312] + +Nanba AT et al. Adrenal vein sampling lateralization despite mineralocorticoid receptor antagonists exposure in primary aldosteronism. J Clin Endocrinol Metab. 2019 Feb 1;104(2):487–92. [PubMed: 30239792] + +Sam D et al. Discordance between imaging and adrenal vein sampling in primary aldosteronism irrespective of interpretation criteria. J Clin Endocrinol Metab. 2019 Jun 1;104(6):1900–6. [PubMed: 30590677] + +Velema M et al; SPARTACUS investigators. Quality of life in primary aldosteronism: a comparative effectiveness study of adrenalectomy and medical treatment. J Clin Endocrinol Metab. 2018 Jan 1;103(1):16–24. [PubMed: 29099925] + +Williams TA et al. Management of endocrine disease: diagnosis and management of primary aldosteronism: the Endocrine Society guideline 2016 revisited. Eur J Endocrinol. 2018 Jul;179(1):R19–29. [PubMed: 29674485]