The goal of this observational study is to evaluate the diagnostic accuracy of 68 68

Ga-Pentixafor-CXCR4 PET/CT in identifying the dominant side of hormone excess in adult patients (aged 18-80 years) with primary aldosteronism and concomitant mild autonomous cortisol secretion (PA+MACS) who are candidates for unilateral adrenalectomy or ablation. The main questions it aims to answer are:

What is the overall diagnostic performance of 68 68 Ga-Pentixafor-CXCR4 PET/CT for lateralizing the dominant source of aldosterone and cortisol co-secretion, as measured by the area under the receiver operating characteristic curve (AUC)?

How do the PET/CT-based lateralization results compare with adrenal venous sampling (AVS) and metanephrine-corrected AVS, and are there clinical or biochemical factors that predict discordance between these methods?

Researchers will compare the dominant side determined by PET/CT with the reference standard derived from postoperative PASO outcomes and cortisol-related hormonal outcomes (supplemented by histopathology) to assess sensitivity, specificity, accuracy, and agreement. They will further compare PET/CT results to conventional AVS and metanephrine-corrected AVS to determine concordance and identify potential predictors of discordant cases.

Participants will:

Provide written informed consent and undergo baseline clinical, biochemical, and imaging assessments as part of routine PA+MACS work-up.

Undergo a single 68 68 Ga-Pentixafor-CXCR4 PET/CT scan, along with AVS and metanephrine-corrected AVS, typically within a 4-week window.

Be discussed by a multidisciplinary team that integrates all diagnostic information to formulate an individualized surgical plan.

If surgery proceeds, be followed at 1, 3, 6, and 12 months postoperatively to assess blood pressure, antihypertensive medication use, serum potassium, aldosterone/renin/cortisol levels, and 1-mg overnight dexamethasone suppression test results.

Inclusion Criteria:

• Age 18-80 years.

Confirmed diagnosis of PA+MACS according to guideline-directed algorithms: elevated aldosterone-to-renin ratio (ARR) and at least one positive confirmatory test for primary aldosteronism, together with serum cortisol >1.8 µg/dL (>50 nmol/L) after a 1 mg overnight dexamethasone suppression test (1 mg-ONDST).

Scheduled to undergo [⁶⁸Ga]Pentixafor-CXCR4 PET/CT imaging.

Meeting surgical indications, scheduled for adrenalectomy or adrenal ablation, having provided written informed consent, and agreeing to a follow-up of at least 12 months.

Exclusion Criteria:

• Previous adrenal surgery or confirmed adrenal malignancy.

Pregnancy or lactation.

Severe renal impairment (eGFR <30 mL·min-¹·1.73 m-²) or contraindication to contrast agents/radiopharmaceuticals.

Inability to discontinue medications that interfere with diagnostic testing according to protocol, or presence of severe infection/unstable comorbidities that preclude relevant examinations.

Definite overt Cushing's syndrome (CS).

Critical missing data, inability to complete the required examinations, or anticipated inability to attend follow-up.

The study population consists of adult patients aged 18-80 years with a confirmed diagnosis of primary aldosteronism and concomitant mild autonomous cortisol secretion (PA+MACS), who are scheduled to undergo [⁶⁸Ga]Pentixafor-CXCR4 PET/CT imaging and meet clinical indications for unilateral adrenalectomy or adrenal ablation. Participants are recruited consecutively from outpatient and inpatient settings at Peking University First Hospital, including both prospectively enrolled patients and retrospectively identified patients with previously confirmed PA+MACS and available clinical data. All participants must provide written informed consent and be willing to complete at least 12 months of postoperative follow-up.