Persistence and Recurrence of Primary Hyperparathyroidism

Persistent and recurrent primary hyperparathyroidism (PHPT) represent significant challenges in the management of PHPT. Persistent PHPT is defined as persistence of hypercalcemia following parathyroidectomy (PTX) or the recurrence of hypercalcemia within the first 6 months following surgery. Recurrent PHPT is defined as recurrence of hypercalcemia after 6 months following PTX and requires normalization of serum calcium prior to the recurrence. These conditions are often attributed to missed or ectopic glands, multiglandular disease, surgeon inexperience, or rare causes such as parathyromatosis and parathyroid carcinoma. Diagnosis requires a detailed biochemical evaluation, imaging studies, and exclusion of other causes of hypercalcemia as well as secondary causes of hyperparathyroidism. Preoperative imaging modalities, including neck ultrasound, SPECT-CT with 99m Tc-sestamibi scan, 4D-CT, 18F-Fluorocholine PET/CT, and PET/MRI are helpful in localizing abnormal parathyroid glands in cases requiring repeat surgery. Repeat surgery is associated with higher risk and requires an experienced surgeon. When surgery is not indicated or possible, medical management with cinacalcet and antiresorptive therapies may be considered. This review highlights the etiology, diagnostic approaches, and management strategies for persistent and recurrent PHPT, emphasizing the importance of multidisciplinary care in order to optimize outcomes.