From the Guidelines
High ionized calcium with low spot urine calcium suggests primary hyperparathyroidism or familial hypocalciuric hypercalcemia (FHH), and the first step is to measure parathyroid hormone (PTH) levels to guide further diagnosis and treatment. The diagnosis of primary hyperparathyroidism (PHPT) is typically made by biochemical testing, specifically serum calcium and serum PTH, as noted in the study by 1. If PTH is elevated or inappropriately normal with hypercalcemia, primary hyperparathyroidism is likely, typically requiring surgical removal of the affected parathyroid gland(s) as the treatment of PHPT is surgical excision of the abnormally functioning parathyroid tissue, as indicated by 1.
Some key points to consider in the diagnosis and management of PHPT include:
- The most common form of PHPT occurs when parathyroid glands autonomously overproduce PTH, typically resulting in hypercalcemia, as seen in the study by 1.
- PHPT can also occur from multiple adenomas, parathyroid hyperplasia, or, rarely, parathyroid carcinoma, with multigland disease affecting approximately 15% to 20% of patients with PHPT, as noted by 1.
- The role of imaging in PHPT is to localize the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery, as stated in the study by 1.
- To distinguish between primary hyperparathyroidism and FHH, calculate the calcium-to-creatinine clearance ratio using a 24-hour urine collection, with a ratio below 0.01 suggesting FHH, which requires no treatment as it's a benign genetic condition.
The treatment for PHPT typically involves surgical excision of the abnormally functioning parathyroid tissue, and there are two accepted curative operative strategies for PHPT: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP), as indicated by the study by 1. Additional workup should include serum phosphorus, 25-hydroxyvitamin D, and kidney function tests, and imaging studies like neck ultrasound or sestamibi scan may be needed if hyperparathyroidism is confirmed. The low urinary calcium excretion despite high serum calcium occurs because in FHH, the calcium-sensing receptors in the kidneys have reduced sensitivity to calcium, leading to increased renal calcium reabsorption, while in hyperparathyroidism, PTH directly increases renal calcium reabsorption, as suggested by the study by 1.
From the Research
Ionized Calcium High with Low Spot Urine Calcium
- Hypercalcemia, or elevated calcium levels in the blood, can be caused by various factors, including primary hyperparathyroidism, malignancy, and certain medications 2.
- In patients with hypercalcemia, an elevated or normal parathyroid hormone (PTH) concentration is consistent with primary hyperparathyroidism, while a suppressed PTH level indicates another cause 2.
- Hypercalcemia of malignancy is a common finding in patients with advanced stage cancers, and can be caused by several mechanisms, including parathyroid hormone-related peptide-mediated humoral hypercalcemia and 1,25 Vitamin D-mediated hypercalcemia 3, 4.
- The diagnosis of hypercalcemia of malignancy should include measurement of serum calcium, PTH, and other mediators of hypercalcemia, as well as imaging studies to evaluate for underlying malignancy 3.
- Treatment of hypercalcemia depends on the underlying cause and severity of symptoms, and may include hydration, bisphosphonates, denosumab, and glucocorticoids 2, 3, 5.
- In some cases, hypercalcemia may be refractory to conventional treatment, and alternative therapies such as prednisone or cinacalcet may be necessary 5, 6.
- The prognosis for patients with hypercalcemia of malignancy is generally poor, and treatment is often focused on palliation of symptoms and improvement of quality of life 3, 6.