The patient arrived at Hebei General Hospital complaining of nausea, vomiting, and pervasive fatigue. His blood pressure had climbed as high as 200/110 mmHg despite ten years of treatment, and laboratory tests told a consistent story: his serum potassium had fallen to 2.5 mmol/L, well below the normal range, while his plasma aldosterone concentration reached 771.100 pg/mL during upright renin-angiotensin-aldosterone system testing. The aldosterone-to-renin ratio exceeded 37, far above the screening threshold of 30 that strongly suggests primary aldosteronism, and a captopril suppression test failed to rein in his aldosterone levels, confirming that the hormone was being produced autonomously rather than under normal regulatory control.

Primary aldosteronism is an endocrine disorder in which the zona glomerulosa, the outermost layer of the adrenal cortex, secretes aldosterone without regard to the physiological signals that normally govern it. The resulting sodium retention expands plasma volume and suppresses renin activity, producing hypertension that is often resistant to conventional drugs, sometimes accompanied by dangerously low potassium. Aldosterone-producing adenomas, or APAs, are among the most common subtypes, and they typically appear as a single tumor on one adrenal gland. Bilateral involvement, in which multiple adenomas arise on both glands simultaneously, is rare and diagnostically treacherous, because it upends the standard assumption that removing one gland will cure the disease.

Contrast-enhanced computed tomography revealed multiple bilateral adrenal adenomas in this patient, each showing mild-to-moderate heterogeneous enhancement with a rapid wash-in and wash-out pattern characteristic of benign adrenal masses. But CT has a fundamental limitation: it can depict structure without revealing function. Small adenomas under one centimeter in diameter are frequently missed altogether, and even when lesions are seen, the scan cannot determine which of them are actually secreting aldosterone. The team turned to adrenal vein sampling, the invasive catheter-based procedure considered the diagnostic gold standard for lateralizing aldosterone excess, but the attempt failed to identify a dominant side, a failure that in itself hinted at bilateral disease.

That is where gallium-68 pentixafor entered the picture. The tracer is a high-affinity ligand for CXCR4, a G-protein-coupled receptor that sits on the cell membrane of APA cells and correlates strongly with the expression of aldosterone synthase, the enzyme encoded by the CYP11B2 gene that catalyzes the final step of aldosterone synthesis. Because the receptor is abundantly displayed on functional aldosterone-producing cells, a positron emission tomography scan with pentixafor can visualize not just where adrenal nodules are, but which ones are metabolically equipped to produce the hormone. Thirty minutes after an intravenous injection of 3.5 mCi, or 129.5 MBq, of the tracer, the PET/CT images revealed five distinct nodular lesions across both adrenal glands, every one of them taking up the radioactive signal to a measurable degree.

The quantitative details were remarkable. The nodule in the medial branch of the left adrenal gland showed the highest metabolic activity, with a maximum standardized uptake value, or SUVmax, of 31.3, against a mean SUV of 2.26 for normal liver parenchyma and 3.41 for normal adrenal cortex. The lesion-to-liver ratios for the five lesions ranged from 2.38 to 13.85, and the lesion-to-normal-adrenal ratios ranged from 1.58 to 9.18. Established diagnostic thresholds for APA on pentixafor PET/CT are a lesion-to-liver ratio of at least 2.5 and a lesion-to-normal-adrenal ratio of at least 2.4, and every one of the five nodules exceeded both cutoffs. Integrating these functional findings with the laboratory data and the CT morphology, the clinical team classified all five adenomas as functional aldosterone-producing lesions.

The therapeutic implication was decisive. Because the disease was bilateral and multifocal, with no single dominant gland to remove, surgery was unsuitable; excising one adrenal would leave the contralateral tumors free to keep secreting. Instead, the patient opted for conservative medical management, and his regimen was switched to a mineralocorticoid receptor antagonist, a drug class that blocks the action of aldosterone at its receptor. Within thirty days, his serum potassium had normalized to 4.3 mmol/L and his blood pressure remained within normal limits, a rapid and gratifying response that validated the diagnostic reasoning behind the treatment choice.

The case also carries a broader scientific signal. Prior research has shown that functional APAs take up gallium-68 pentixafor significantly more avidly than nonfunctional adrenal nodules on the opposite side, with more than 90 percent of functional nodules demonstrating tracer uptake, and that CXCR4 expression correlates significantly with CYP11B2. In this patient, the SUVmax of the left medial nodule was markedly higher than those of the other four, suggesting a potential positive correlation between tracer uptake and the intensity of aldosterone secretion. If confirmed in larger cohorts, SUVmax measurements could serve as an indirect, noninvasive readout of the hormone-producing capacity of individual adrenal lesions, allowing clinicians to rank nodules by function rather than merely by size.

For decades, the diagnostic pathway for primary aldosteronism has rested on an awkward pairing: CT, which finds anatomy but not function, and adrenal vein sampling, which probes function but requires catheterizing the tiny adrenal veins, a technically demanding procedure with complication risks that has limited its widespread adoption. Bilateral disease imposes further constraints on AVS, because excess aldosterone pouring from both sides can obscure the identification of any dominant source. A single pentixafor PET/CT scan, by contrast, delivers simultaneous morphological and functional assessment in one noninvasive session, compensating for the weaknesses of both conventional tools and proving especially valuable in multifocal or bilateral adrenal pathologies of exactly the kind seen here.

The authors of the report are careful to note that a single case cannot establish clinical practice, and that the diagnostic thresholds and the SUVmax-aldosterone correlation they observed require validation in larger sample sizes. They also caution that CXCR4 is not exclusive to APAs; it is detectable in other adrenal lesions, including cortisol-producing adenomas, so interpretation must always be anchored in the full clinical and laboratory context. Even with those caveats, the case stands as a compelling proof of concept: one scan, five glowing lesions, and a treatment decision that restored a long-suffering patient’s potassium and blood pressure to normal within a month. As molecular imaging of endocrine hypertension matures, scans like this one may become the decisive instrument for untangling which adrenal nodules matter, and what to do about them.

Subject of Research: Molecular PET/CT imaging of bilateral aldosterone-producing adrenal adenomas using the CXCR4-targeted tracer 68Ga-pentixafor

Article Title: Case Report: Five positive lesions on bilateral adrenal glands detected by a single 68Ga-pentixafor PET/CT

Article References: Mao, Z., Zheng, L., Hua, R., Wu, D., Shi, Y., Zhang, X., Hu, Y., & Bian, Y. (2026). Case Report: Five positive lesions on bilateral adrenal glands detected by a single 68Ga-pentixafor PET/CT. Frontiers in Nuclear Medicine, 6, Article 1676221. https://doi.org/10.3389/fnume.2026.1676221

Image Credits: AI Generated

DOI: 10.3389/fnume.2026.1676221

Keywords: primary aldosteronism, aldosterone-producing adenoma, 68Ga-pentixafor, PET/CT, CXCR4, adrenal glands, hypertension, hypokalemia, adrenal vein sampling, molecular imaging, mineralocorticoid receptor antagonist, case report