68Ga-Pentixafor PET/CT Versus Adrenal Vein Sampling in Primary Aldosteronism: The GAPA Randomized Clinical Trial

This is a multicenter randomized noninferiority clinical trial involving patients with primary aldosteronism (PA) patients with adrenal nodule (≥1cm) who completed AVS or 68Ga-Pentixafor PET/CT.We will enroll 320 PA patients with adrenal nodule (≥1cm) .All paticipants will be randomized into 68Ga-Pentixafor PET/CT group(Intervention group) and AVS group(Control group) to compare the long-term outcomes of patients with PA.

1 Inclusion Criteria

Participants must meet all of the following criteria:

• .Ability to understand the trial procedures and provide written informed consent.
• .Age 18 to 70 years.
• .Hypertension with a confirmed diagnosis of primary aldosteronism.
• .Adrenal gland CT or MRI scan showing an adrenal nodule of 1 cm or larger.
• .Willingness to undergo adrenalectomy if lateralizing primary aldosteronism is identified.

A confirmed diagnosis of primary aldosteronism will be defined as a positive screening result and at least one positive aldosterone suppression test. A positive screening result will be defined as an aldosterone-to-renin ratio of ≥20(pg/mL)/(mIU/L) or≥30 (ng/dL)/(ng/mL/hr). A positive aldosterone suppression test will be defined as a plasma aldosterone concentration of≥110 pg/mL after the captopril challenge test or ≥80pg/mL after the seated saline infusion test.

2 Exclusion Criteria

Participants will be excluded if any of the following criteria are met:

• .Autonomous cortisol secretion,defined as a serum cortisol levels ≥ 50 nmol/L after a 1-mg overnight dexamethasone suppression test.
• .Fulfillment of prespecified criteria for bypassing AVS, defined as age younger than 35 years, typical features of aldosterone-producing adenoma, plasma aldosterone concentration >300 pg/mL, spontaneous hypokalemia, and a unilateral low-density adrenal nodule >1 cm on CT.
• .Compliacted with other secondary hypertension (such as Cushing's syndrome, renal artery stenosis, but not including obstructive sleep apnea syndrome).
• .Onset of hypertension before 20 years of age with hypokalemia and a family history suggestive of familial hyperaldosteronism, Liddle syndrome, or another hereditary form of hypertension.
• . Adrenal nodules with imaging characteristics suggestive of pheochromocytoma, adrenocortical carcinoma, adrenal cysts, adrenal hematomas, or adrenal myelolipomas.
• .Active malignant disease.
• .Previous adrenal surgery.
• .Adrenal insufficiency requiring glucocorticoid replacement therapy.
• .Long-term glucocorticoid therapy that cannot be discontinued.
• .Allergy or intolerance to contrast media or contraindication to AVS.
• .Pregnancy or lactation.
• .Alcohol or drug abuse, or psychiatric illness that would interfere with trial participation.
• .New York Heart Association class III or IV heart failure.
• .Hospitalization for worsening chronic heart failure within the previous 3 months.
• .Stroke or acute coronary syndrome within the previous 3 months.
• .Severe anemia, defined as hemoglobin <6 g/dl.
• .Severe liver disease, defined as alanine aminotransferase ≥3 times the upper limit of the normal range.
• .Severe kidney disease, defined as dialysis treatment or an estimated glomerular filtration rate <30 mL/min/1.73 m².
• .Systemic inflammatory response syndrome.
• .Uncontrolled diabetes, defined as fasting blood glucose ≥13.3 mmol/L.
• .Severe obesity, defined as a body-mass index ≥35 kg/m², or underweight status, defined as a body-mass index ≤18 kg/m².
• .Untreated aneurysm or any other condition that, in the investigator's judgment, would interfere with safe participation or continued treatment for primary aldosteronism.