Williams syndrome (WS) is a rare genetic disorder with multisystem involvement associated with hypercalcemia. The cause of this hypercalcemia is poorly understood and while primarily associated with WS children, it is also observed in adults. A 51-year-old woman with intellectual disability, renal insufficiency, recurrent pancreatitis, and intermittent hypercalcemia despite partial parathyroidectomy presented with hypercalcemia to 14 mg/dL (3.49 mmol/L; normal 8.6-10.5 mg/dL [2.12-2.62 mmol/L]) at routine follow-up. Laboratory testing was notable for acute-on-chronic renal failure with unremarkable vitamin D, urine calcium, and parathyroid hormone. She presented to the emergency department and was admitted. Treatment with bisphosphonates, calcitonin, and intravenous fluids decreased calcium to 9.4 mg/dL (2.35 mmol/L) and improved kidney function. She was discharged with recommendations for increased oral hydration, a low-calcium diet, and outpatient follow-up. Her phenotype was suspicious for WS, later confirmed with genetic testing. This case exemplifies both the increased risk of hypercalcemia in WS adults and the need to consider WS in hypercalcemic adults with intellectual disability. It also serves to illustrate the importance of recognizing WS features in potentially undiagnosed adults and reviews guidelines for hypercalcemia surveillance and management in WS adults.

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.