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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 September 16, 2025 e135

that occur because of drugs and other agents have been associated with the development of hyperten­ sion and with worsening BP control in a patient who already has hypertension. A careful history should be taken with close attention paid to prescription medi­ cations and over-the-counter substances, illicit drugs, and herbal products. A change in BP may also result from drug-drug or drug-food interactions.13 When fea­ sible, drugs associated with increased BP should be reduced or discontinued and alternative agents used. 2.	 Spontaneous hypokalemia is present only in 20%

to 50% of patients with primary aldosteronism,1,2 and therefore, the decision to perform primary aldosteronism screening should not rely on a history of hypokalemia alone. Screening for pri­ mary hyperaldosteronism may require sodium loading to induce aldosterone suppression if plasma screening by the aldosterone-to-renin ratio is inconclusive (Section 3.2.3.1, “Primary Aldosteronism”).3

3 Diagnosis of many secondary causes of hypertension

requires a complex set of tests and measurements combined with specialized technical expertise in data interpretation. Similarly, specific treatment often requires additional training and experience. Clinical expertise in secondary forms of hypertension, such as primary aldosteronism, pheochromocytoma, Cushing syndrome, and renovascular hypertension, is practical for prognosis and treatment plans.

3.2.3.1 Primary Aldosteronism

Recommendations for Primary Aldosteronism COR LOE Recommendations

1 C-EO 1 In adults with hypertension, screening for primary

aldosteronism is recommended in the presence of any of the following conditions to increase rates of detection, diagnosis, and specific targeted therapy: resistant hypertension (regardless of whether hypo­ kalemia is present), hypokalemia (spontaneous or diuretic induced), OSA, incidentally discovered adre­ nal mass, family history of early-onset hypertension, or stroke at a young age (<40 years).

2b C-EO 2 In adults with stage 2 hypertension, screening

for primary aldosteronism may be considered to increase rates of detection, diagnosis, and specific targeted therapy.

Prevalence Indications for Additional Testing Physical Examination Findings Screening Tests Confirmatory Tests

Aortic coarctation (undiagnosed or repaired)23 0.1% Young adult with hypertension (age <30 y) BP higher in upper ex­ tremities than in lower extremities; absent femoral pulses; con­ tinuous murmur over patient’s back, chest, or abdominal bruit; left thoracotomy scar (postoperative) Echocardiogram Thoracic and abdominal CT angiogram or magnetic resonance arteriography Cushing syndrome24 <0.1% Rapid weight gain, especially with central distribution; proximal muscle weakness; depression; hyperglycemia Central obesity, “moon” face, dorsal and supraclavicular fat pads, wide (1 cm) violaceous striae, hirsutism Overnight 1-mg dexa­ methasone suppression test 24-h urinary free cortisol ex­ cretion (preferably multiple); midnight salivary cortisol Primary hyperparathyroidism20 Rare Hypercalcemia Usually none Serum calcium Serum parathyroid hormone Congenital adrenal hyperplasia20 Rare Hypertension and hypokalemia; virilization (11-beta-hydroxylase deficiency [11-beta-OH]); incomplete masculinization in men and primary amenorrhea in women (17-alpha-hydroxylase deficiency [17-alpha-OH]) Signs of virilization (11-beta-OH) or in­ complete masculiniza­ tion (17-alpha-OH) Hypertension and hypoka­ lemia with low or normal aldosterone and renin 11-beta-OH: elevated DOC, 11-deoxycortisol, and androgens; 17-alpha-OH; decreased androgens and estrogen but elevated DOC and corticosterone Mineralocorticoid excess syndromes other than primary aldosteronism20 Rare Early-onset hypertension; resis­ tant hypertension; hypokalemia or hyperkalemia Arrhythmias (with hy­ pokalemia) Low aldosterone and renin Urinary cortisol metabolites; genetic testing Acromegaly25 Rare Acral features, enlarging shoe, glove, or hat size; headache, vi­ sual disturbances; diabetes Acral features; large hands and feet; frontal bossing Serum growth hormone ≥1 ng/mL during oral glu­ cose load Elevated age- and sexmatched IGF-1 level; MRI scan of the pituitary Modified with permission from Whelton et al.14 Copyright 2018 American College of Cardiology Foundation and American Heart Association, Inc. ACEi indicates angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; BP, blood pressure; AF, atrial fibrillation; CKD, chronic kidney disease; CT, computed tomography; DOC, 11-deoxycorticosterone; h, hour; IGF-1, insulin-like growth factor-1; IV, intravenous; MAO, monoamine oxidase; mg, milligrams; MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory drugs; OH, hydroxylase; OSA, obstructive sleep apnea; RCT, randomized clinical trial; VEGF, vas­ cular endothelial growth factor; wk, week; and y, years.

Table 10.  Continued

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