AIM: To present the diagnostic approach, surgical management, and early outcomes of patients with mediastinal ectopic parathyroid adenoma (MEPA) causing primary hyperparathyroidism.

CASE PRESENTATION: Between January 2015 and January 2025, patients with mediastinal ectopic parathyroid adenoma identified among 458 patients who underwent surgery for a solitary parathyroid adenoma were retrospectively reviewed, and five cases were identified (1%; n = 5). Diagnostic evaluation included cervical ultrasonography, technetium-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT), and CT. The surgical strategy was individualized according to lesion location and proximity to major vascular structures. Intraoperative confirmation was achieved using radioguided surgery, frozen section analysis, and intraoperative parathyroid hormone (ioPTH) monitoring. Patients were followed for one year with serial serum calcium and parathyroid hormone (PTH) measurements.

RESULTS: The median age was 62 years (range, 40–70 years), and three patients were female. Bone pain and fatigue were the most common presenting symptoms, whereas one patient was asymptomatic. Preoperative albumin-corrected serum calcium levels ranged from 11.24 to 13.43 mg/dL, and PTH levels ranged from 161 to 1493 pg/mL. Lesion size ranged from 8 × 8 mm to 35 × 22 mm, and four lesions were located in the anterior mediastinum. Four patients underwent J-shaped partial median sternotomy, and one underwent a transcervical approach. The 10-minute ioPTH decline ranged from 48.3% to 85.5%. No major surgical complications occurred. All patients remained normocalcemic and clinically stable at the 1-year follow-up.

CONCLUSIONS: In patients with MEPA, the combined use of functional and anatomical imaging, supported by multiple intraoperative confirmation modalities, may facilitate curative resection with low morbidity through an individualized surgical strategy.