This prospective, single-center observational study aims to evaluate whether a steroid-based screening method can more accurately identify Primary Aldosteronism (PA) in hypertensive patients who remain on their usual antihypertensive medications, compared with the conventional aldosterone-to-renin ratio (ARR). PA is a common, potentially curable subtype of secondary hypertension that carries increased cardiovascular risk when undiagnosed or untreated. However, current screening protocols recommend "medication washout" or switching to minimally interfering drugs, which may pose safety concerns and add complexity.

In this study, approximately 406 participants (ages 18-75) with diagnosed hypertension and on at least one interfering antihypertensive drug (such as ACE inhibitors, ARBs, beta-blockers, diuretics, or calcium channel blockers) will be enrolled at the Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University. Each participant will undergo two rounds of blood sampling-first while continuing their usual antihypertensive regimen (the "on-medication" state) and second following a standardized washout/switch period (the "standard state"), if medically feasible. At both stages, levels of plasma aldosterone, renin, and a broad panel of adrenal steroid hormones will be measured by liquid chromatography-tandem mass spectrometry.

By comparing diagnostic performance (e.g., sensitivity, specificity, and area under the receiver operating characteristic curve) of the steroid-based screening versus the ARR, the study seeks to determine whether steroid profiling improves accuracy under real-world treatment conditions. Findings may help refine PA screening strategies, reduce the need for extensive medication adjustments, and contribute to better clinical management of hypertension.

Inclusion Criteria:

1. Aged 18-75 years, with no sex restriction.
2. Diagnosed with hypertension, defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg measured on at least two different days.
3. Currently receiving at least one antihypertensive medication that interferes with aldosterone or renin (ACEI/ARB, β-blockers, dihydropyridine CCBs, or diuretics including MRA) for ≥4 consecutive weeks.
4. Fully informed about the study procedures and risks, and willing to participate by signing a written informed consent form.

Exclusion Criteria:

1. Confirmed secondary hypertension of other etiologies (e.g., renovascular hypertension, renal artery stenosis, reninoma, pheochromocytoma, Cushing's syndrome, Liddle syndrome), excluding obstructive sleep apnea.
2. Severe cardiac, hepatic, or renal impairment or serious infections, including but not limited to New York Heart Association (NYHA) Class III-IV heart failure, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2.5 times the upper limit of normal, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², or severe infections (e.g., diabetic foot, sepsis, pneumonia, refractory infections).
3. History of major cardiovascular or cerebrovascular events within the past 3 months.
4. Pregnant or breastfeeding women.
5. Currently using medications (other than the listed antihypertensives) that may affect aldosterone or renin secretion, including but not limited to sex hormones (e.g., oral contraceptives, estrogen replacement therapy), glucocorticoids (e.g., prednisone, dexamethasone), nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin, ibuprofen), or antipsychotics (e.g., chlorpromazine, olanzapine).
6. Individuals lacking or having restricted capacity for independent decision-making or action.
7. History of psychiatric disorders.
8. Poor compliance likely to compromise study completion.

This study will enroll adult patients diagnosed with hypertension (aged 18-75) who are receiving at least one antihypertensive medication that interferes with aldosterone or renin. Participants are recruited from the Endocrinology Outpatient Clinic at The First Affiliated Hospital of Chongqing Medical University between April 2025 and December 2026. All candidates must meet the predefined inclusion criteria (e.g., on interfering antihypertensive drugs for ≥4 weeks) and provide written informed consent. Patients with other confirmed forms of secondary hypertension or severe comorbidities are excluded. The anticipated sample size is approximately 406 participants.

We do not intend to share individual participant data from this study due to concerns regarding participant privacy, regulatory constraints, and the limited scope of the current study. Aggregated or summary results will be made publicly available through publication or the results section on ClinicalTrials.gov.