What is the next step in managing a patient with hypercalcemia, elevated parathyroid hormone (PTH) level of 48, normal 24-hour urine calcium, and a negative parathyroid scan?

From the Guidelines

The next step in managing a patient with hypercalcemia, elevated PTH level of 48, normal 24-hour urine calcium, and a negative parathyroid scan is to proceed with surgical exploration and parathyroidectomy. Despite the negative imaging, the biochemical profile strongly suggests primary hyperparathyroidism, and surgery remains the definitive treatment, as indicated by the most recent guidelines 1. The surgeon should plan for a bilateral neck exploration to identify and remove the abnormal parathyroid gland(s), as this approach is necessary in cases of discordant or nonlocalizing preoperative imaging or when there is high suspicion for multigland disease 1.

Prior to surgery, additional localization studies could be considered, such as 4D-CT scan, MRI, or ultrasound by an experienced operator, which may detect lesions missed on the initial scan. Intraoperative PTH monitoring should be utilized during surgery to confirm adequate removal of hyperfunctioning tissue, as it is a crucial step in ensuring the success of the surgical procedure 1. The patient should be optimized preoperatively with adequate hydration and possibly bisphosphonates if hypercalcemia is severe. Postoperatively, patients should be monitored for hypocalcemia and may require calcium supplementation (typically 1-2g elemental calcium daily) and calcitriol (0.25-0.5 mcg daily) temporarily. Surgery is recommended because primary hyperparathyroidism rarely resolves spontaneously, and continued hypercalcemia can lead to complications including osteoporosis, nephrolithiasis, and neurocognitive symptoms, highlighting the importance of prompt and effective treatment 1.

Key considerations in the management of this patient include:

• The role of imaging in primary hyperparathyroidism is to localize the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery, but it has no utility in confirming or excluding the diagnosis of primary hyperparathyroidism 1.
• The importance of intraoperative PTH monitoring in confirming the removal of hyperfunctioning parathyroid tissue.
• The need for careful postoperative monitoring and management to prevent complications such as hypocalcemia.
• The potential benefits of surgical treatment in preventing long-term complications of primary hyperparathyroidism, such as osteoporosis and nephrolithiasis, as supported by the latest clinical practice recommendations 1.

From the Research

Next Steps in Managing Hypercalcemia

• The patient's elevated parathyroid hormone (PTH) level of 48 and normal 24-hour urine calcium suggest primary hyperparathyroidism 2, 3.
• Despite the negative parathyroid scan, further diagnostic testing is necessary to localize the parathyroid adenoma, which may include neck ultrasound and 99mTc MIBI scintigraphy 4, 2, 3.
• The patient's vitamin D level should be measured and normalized before surgery, as vitamin D deficiency can affect bone mineral density and postsurgical outcomes 3, 5.
• Surgical resection of the adenoma is the only curative therapy for primary hyperparathyroidism, and the indication for surgery depends on the patient's age, existing complications, and preference 2, 3, 6.
• In the meantime, medical management with cinacalcet and bisphosphonates or denosumab may be considered to control hypercalcemia and improve bone mineral density, especially if surgery is delayed 6.

Diagnostic Evaluation

• Kidney ultrasound to detect nephrocalcinosis or kidney stones 3.
• Dual-energy X-ray absorptiometry (DXA) to determine bone mineral density (BMD) at the lumbar spine, femoral neck, total femur, and distal forearm 3.
• Measurement of parathyroid hormone, creatinine/glomerular filtration rate, phosphate, 25-OH vitamin D3, and 24-hour urine values for differential diagnosis 3.

Treatment Considerations

• Normalization of vitamin D levels before surgery to prevent postsurgical hypocalcemia and hungry-bone disease 3.
• Postsurgical calcium and vitamin D administration to optimize bone mineral density outcomes 3.
• Medical management with cinacalcet and bisphosphonates or denosumab as a temporary measure until parathyroidectomy can be performed safely 6.