Update on the current management of persistent and recurrent primary hyperparathyroidism after parathyroidectomy

Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10% of pHPT patients. Preoperative localization imaging is highly valuable. It includes ultrasound, computed tomography (CT), single-photon-emission CT, sestamibi scintigraphy and magnetic resonance imaging. The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months. Ongoing hypercalcemia during this period is defined as persistence, and recurrence is defined as hypercalcemia after six months of normocalcemia. Vitamin D is a crucial factor for a good outcome. Intraoperative parathyroid hormone (PTH) monitoring can safely predict the outcomes and should be suggested. PTH ≤ 40 pg/mL or the traditional decrease ≥ 50% from baseline minimizes the likelihood of persistence. Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology. Risk factors for recurrence are cardiac history, obesity, endoscopic approach and low-volume center (at least 31 cases/year). Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/ recurrence. A 6-mo calcium > 9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up. 18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation. With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement, the recurrence rate has dropped to 2.5%-5%. Six-month serum calcium ≥ 9.8 mg/dL and parathyroid hormone ≥ 80 pg/mL indicate a risk of recurrence. Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels are predictors of multiglandular disease, which brings an increased risk of persistence and recurrence. Bilateral neck exploration was considered the gold-standard diagnostic method. Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques. Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence. Long-term follow-up, even up to 10 years, is necessary.