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A 63-year-old woman had a history of hypertension for 30 years. She was taking 3 medications (amlodipine, irbesartan, and indapamide) but still had not achieved optimal blood pressure control. She experienced a stroke 15 years ago but had no residual disability. She was found to have hypokalemia (serum potassium, 2.1 mEq/L [to convert to mmol/L, multiply by 1]) and was referred to a cardiologist, who discontinued her diuretic because of suspected diuretic-induced hypokalemia. Her hypokalemia persisted, and evaluation for primary aldosteronism was performed. The plasma aldosterone and renin levels were 19.0 ng/dL (to convert to pmol/L, multiply by 27.74) and 0.6 μIU/mL (to convert to pmol/L, multiply by 0.0375), respectively, resulting in an elevated aldosterone-to-renin ratio (31.7; reference: <2.0). The plasma aldosterone concentration after saline suppression testing was high (19.0 ng/dL; reference, <8.0 ng/dL), confirming a diagnosis of primary aldosteronism.
The patient underwent computed tomography of the adrenal glands followed by adrenal vein sampling, which revealed a left adrenal adenoma as the source of aldosterone excess. She underwent laparoscopic left adrenalectomy. After surgery, her serum potassium, plasma aldosterone–to–renin ratio normalized, as did her blood pressure level (110-130/60-70 mm Hg) despite discontinuation of all antihypertensive medications.
Hypertension is common, and most patients have essential hypertension responsive to lifestyle modification and medications. However, about 15% of patients have secondary hypertension, including 30% of those younger than 40 years.1,2 Primary aldosteronism is a common cause of secondary hypertension, occurring in 5% to 10% of patients with hypertension.3 The classic presentation of primary aldosteronism includes hypertension and spontaneous hypokalemia. However, 9% to 37% of these patients have hypokalemia.3 Guidelines recommend evaluation for primary aldosteronism in patients with severe hypertension (blood pressure level above 150/100 mm Hg on 3 separate days or with blood pressure level >140/90 mm Hg despite the concurrent use of 3 conventional antihypertensive drugs, including a diuretic, or controlled blood pressure requiring ≥4 antihypertensive drugs); spontaneous or diuretic-induced hypokalemia; adrenal incidentaloma; sleep apnea; family history of early-onset hypertension or stroke, or at least 1 first-degree relative with primary aldosteronism. Testing begins with measurement of plasma aldosterone, plasma renin, and aldosterone-to-renin ratio (Figure). Measurements should be performed in the morning and generally do not require stopping antihypertensive medications unless there is a concern for false-negative results because antihypertensive medications rarely cause false-positives. The finding of an elevated aldosterone-to-renin ratio strongly suggests primary aldosteronism, and these patients should be referred to an endocrinologist for further evaluation. Patients with aldosterone levels higher than 20 ng/dL, suppressed renin, and spontaneous hypokalemia do not require additional testing because only primary aldosteronism causes these findings. All other patients require confirmatory testing (eg, saline infusion test) to confirm the diagnosis.
CT indicates computed tomography; MR, mineralocorticoid receptor; PA, primary aldosteronism.
This figure was used with permission.3
aOur recommended cutoff for positive ratio: 2.4 ng/dL per mIU/L if using chemiluminescence assay for direct renin concentration or 20 ng/dL per ng/mL/h if using radioimmunoassay for plasma renin activity; some investigators recommend checking both aldosterone-to-renin ratio and aldosterone.
bWith hypokalemia, undetectable renin, and plasma aldosterone level higher than 20 ng/dL (to convert to pmol/L, multiply by 27.74), confirmatory test could be skipped.
cIf surgery is not desired, mineralocorticoid receptor antagonist treatment is recommended.
dIf younger than 35 years, with marked PA and unilateral cortical adenoma on CT, adrenal vein sampling could be skipped.
Once primary aldosteronism is confirmed, most patients who are candidates for adrenalectomy should undergo computed tomography scanning of the adrenal glands and adrenal vein sampling to determine if elevated plasma aldosterone levels are owing to a unilateral adenoma or bilateral adrenal hyperplasia. Adrenal vein sampling can be skipped in patients younger than 35 years with spontaneous hypokalemia, markedly elevated serum aldosterone levels, and unilateral cortical adenoma on computed tomography. Because computed tomography results can be misleading in older patients, adrenal vein sampling is needed to localize the source of excess aldosterone secretion. Adrenalectomy is recommended for patients with a unilateral lesion, while treatment with mineralocorticoid receptor antagonists is warranted for those with bilateral adrenal hyperplasia, which accounts for most cases.
Screening for primary aldosteronism should have been considered when the patient in this case developed resistant hypertension.4 Earlier diagnosis may also have reduced her risk of stroke because primary aldosteronism is associated with increased cardiovascular risk independent of blood pressure. Unfortunately, appropriate evaluation for primary aldosteronism is uncommon, resulting in marked underdiagnosis.5 Clinicians, especially general internists, should be aware of the high prevalence of primary aldosteronism and should consider screening in appropriately selected patients.
Corresponding Author: Qifu Li, MD, PhD, Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Chongqing 400016, China (firstname.lastname@example.org).
Published Online: March 16, 2020. doi:10.1001/jamainternmed.2020.0361
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
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Yang S, Hu J, Li Q. Not All Hypertension Is a Lifelong Disease: A Teachable Moment. JAMA Intern Med. Published online March 16, 2020. doi:10.1001/jamainternmed.2020.0361
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