Primary aldosteronism is the most common form of secondary hypertension, a condition in which tiny hormone-secreting tumors on the adrenal glands drive blood pressure to dangerous heights by flooding the body with aldosterone. For decades, the gold standard for deciding which adrenal gland is the culprit has been adrenal venous sampling, or AVS, a technically demanding catheter procedure that requires patients to stop their mineralocorticoid receptor antagonists for at least four weeks beforehand. A new prospective study published in BMC Endocrine Disorders suggests that a molecular imaging technique called 68Ga-Pentixafor PET/CT could match the diagnostic performance of AVS even in patients who cannot safely interrupt their medication, a finding that may reshape how clinicians work up this curable form of hypertension.
The study, conducted at the First Affiliated Hospital of Fujian Medical University in Fuzhou, China, and registered as clinical trial NCT05188872, prospectively enrolled 98 patients with biochemically confirmed primary aldosteronism. All participants underwent both successful bilateral adrenal venous sampling and 68Ga-Pentixafor PET/CT. The primary analysis focused on 41 patients who had a CT-detected unilateral adrenal adenoma meeting predefined radiological criteria. Of these, 21 were receiving continuous mineralocorticoid receptor antagonist therapy before lateralization testing, while 20 were not, allowing the researchers to directly test whether the drugs distort the imaging signal.
The technical logic behind the comparison is elegant. 68Ga-Pentixafor is a radiolabeled tracer that binds to the chemokine receptor CXCR4, which is overexpressed on the cells of aldosterone-producing adenomas. When injected into a patient, the tracer accumulates in the hormone-producing lesion, and a combined positron emission tomography and computed tomography scan reveals exactly which adrenal gland harbors the overactive tissue. In principle, this offers a non-invasive window into adrenal function that a standard CT scan, which can only show anatomy, cannot provide. The critical question was whether medications that block the mineralocorticoid receptor would blunt this signal and cause the imaging to disagree with AVS.
That question matters because the current guidelines create a genuine clinical dilemma. Mineralocorticoid receptor antagonists such as spironolactone are often the only drugs capable of controlling blood pressure and restoring potassium levels in these patients. Withdrawing them for four or more weeks, as AVS protocols demand, can expose patients to refractory hypertension, dangerous hypokalemia, and heightened cardiovascular risk. For many patients, particularly those with severe disease, the recommended washout period is simply unfeasible. A reliable imaging alternative that works regardless of medication status would therefore fill a real gap in clinical practice.
The researchers’ findings were strikingly reassuring. Baseline aldosterone and serum potassium levels were comparable between the medicated and unmedicated groups, with the only significant biochemical difference being a higher direct renin concentration in the MRA group, an expected pharmacological effect of receptor blockade. When the team determined the optimal imaging threshold, an SUVmax cutoff of 7.60 yielded a maximum Youden index of 0.907, indicating excellent discriminatory performance for identifying the hormone-secreting side. The concordance between 68Ga-Pentixafor PET/CT and AVS was 90.00 percent in the non-medicated group and 85.71 percent in the medicated group, a difference that was not statistically significant.
Importantly, this high agreement held up under further scrutiny. The researchers stratified their results by the laterality of the lesion and by the diameter of the CT-detected adenoma, and the concordance remained consistently high across all subgroups. This robustness matters because adrenal adenomas vary widely in size, and smaller nodules are precisely the ones where anatomical imaging alone is least informative. The fact that tracer uptake continued to lateralize correctly in patients on continuous receptor antagonist treatment suggests that CXCR4 expression on aldosterone-producing cells is not meaningfully suppressed by the drugs, at least within the studied population.
The study did not stop at diagnostic agreement; it also followed patients through treatment. Among those who underwent laparoscopic adrenalectomy, the postoperative clinical and biochemical success rates, whether complete or partial, were 88.89 percent and 94.44 percent in the non-medicated group, compared with 85.71 percent and 92.86 percent in the medicated group. No significant differences were observed between the two cohorts. In other words, patients identified for surgery by the imaging pathway did just as well as those identified through the conventional route, providing an outcome-based validation of the imaging approach rather than a purely radiological one.
The implications extend beyond the technical question of drug washout. Adrenal venous sampling, while accurate in experienced hands, is an invasive procedure with a notable failure rate, since catheterizing the small right adrenal vein is notoriously difficult and success depends heavily on operator expertise and center volume. It is also costly and uncomfortable for the patient. A non-invasive scan that can be performed as an outpatient, without catheters or medication withdrawal, could dramatically simplify the diagnostic pathway for the many patients worldwide whose hypertension is driven by a unilateral aldosterone-producing adenoma and who could be cured with a targeted operation.
The authors are careful to frame the result appropriately. In this selected cohort of primary aldosteronism patients with a CT-detected unilateral adrenal adenoma, 68Ga-Pentixafor PET/CT showed high concordance with AVS, including among patients receiving continuous mineralocorticoid receptor antagonist therapy. They position the technique as a complementary, non-invasive tool for selected patients in whom AVS is technically challenging or in whom medication withdrawal would be clinically unsafe, rather than as an outright replacement for the established gold standard. The cohort size of the primary analysis, 41 patients split into two groups, is modest, and broader validation in larger and more diverse populations will be needed before guidelines change.
Nevertheless, the study represents a meaningful step toward personalized, less invasive care for a disease that affects an estimated five to ten percent of people with hypertension and remains underdiagnosed in many health systems. If larger trials confirm these results, patients with refractory hypertension and a visible adrenal nodule could one day undergo a single PET/CT scan, keep the medications that keep them safe, and proceed directly to curative surgery without ever entering an interventional radiology suite. For a condition whose burden falls disproportionately on patients whose blood pressure resists multiple drugs, that would be a genuinely transformative shift in practice.
Subject of Research: Concordance of 68Ga-Pentixafor PET/CT with adrenal venous sampling for lateralizing primary aldosteronism during mineralocorticoid receptor antagonist treatment
Article Title: Impact of continuous mineralocorticoid receptor antagonist treatment on the concordance between 68Ga-Pentixafor PET/CT and adrenal venous sampling in primary aldosteronism patients with a CT-detected unilateral adrenal adenoma
Article References: Impact of continuous mineralocorticoid receptor antagonist treatment on the concordance between 68Ga-Pentixafor PET/CT and adrenal venous sampling in primary aldosteronism patients with a CT-detected unilateral adrenal adenoma. (n.d.). https://doi.org/10.1186/s12902-026-02645-9
Image Credits: AI Generated
DOI: 10.1186/s12902-026-02645-9
Keywords: primary aldosteronism, 68Ga-Pentixafor PET/CT, adrenal venous sampling, mineralocorticoid receptor antagonists, aldosterone-producing adenoma, lateralization, hypertension, molecular imaging, CXCR4, adrenalectomy, nuclear medicine, endocrine disorders
News Source: Ophelia Keating. (October 12, 2026). PET Imaging May Spare Patients Risky Drug Withdrawal Before Adrenal Vein Test. Scienmag.
