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

1 Inclusion Criteria

Participants must meet all of the following criteria:

1. .Ability to understand the trial procedures and provide written informed consent.
2. .Age 18 to 70 years.
3. .Hypertension with a confirmed diagnosis of primary aldosteronism.
4. .Adrenal gland CT or MRI scan showing an adrenal nodule of 1 cm or larger.
5. .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:

1. .Autonomous cortisol secretion,defined as a serum cortisol levels ≥ 50 nmol/L after a 1-mg overnight dexamethasone suppression test.
2. .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.
3. .Compliacted with other secondary hypertension (such as Cushing's syndrome, renal artery stenosis, but not including obstructive sleep apnea syndrome).
4. .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.
5. . Adrenal nodules with imaging characteristics suggestive of pheochromocytoma, adrenocortical carcinoma, adrenal cysts, adrenal hematomas, or adrenal myelolipomas.
6. .Active malignant disease.
7. .Previous adrenal surgery.
8. .Adrenal insufficiency requiring glucocorticoid replacement therapy.
9. .Long-term glucocorticoid therapy that cannot be discontinued.
10. .Allergy or intolerance to contrast media or contraindication to AVS.
11. .Pregnancy or lactation.
12. .Alcohol or drug abuse, or psychiatric illness that would interfere with trial participation.
13. .New York Heart Association class III or IV heart failure.
14. .Hospitalization for worsening chronic heart failure within the previous 3 months.
15. .Stroke or acute coronary syndrome within the previous 3 months.
16. .Severe anemia, defined as hemoglobin <6 g/dl.
17. .Severe liver disease, defined as alanine aminotransferase ≥3 times the upper limit of the normal range.
18. .Severe kidney disease, defined as dialysis treatment or an estimated glomerular filtration rate <30 mL/min/1.73 m².
19. .Systemic inflammatory response syndrome.
20. .Uncontrolled diabetes, defined as fasting blood glucose ≥13.3 mmol/L.
21. .Severe obesity, defined as a body-mass index ≥35 kg/m², or underweight status, defined as a body-mass index ≤18 kg/m².
22. .Untreated aneurysm or any other condition that, in the investigator's judgment, would interfere with safe participation or continued treatment for primary aldosteronism.