From the Guidelines
The workup for hypercalcemia should begin with confirming the elevated calcium level with a repeat measurement, including ionized calcium if available, and initial laboratory tests should include parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, creatinine, albumin, complete blood count, and urinary calcium excretion, as recommended by recent clinical guidelines 1. The diagnostic approach to hypercalcemia involves a step-wise evaluation to determine the underlying cause. Key laboratory tests include:
- PTH to differentiate between primary hyperparathyroidism and other causes of hypercalcemia
- Phosphorus to assess for hyperphosphatemia, which may indicate severe hyperparathyroidism
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to evaluate for vitamin D-related hypercalcemia
- Creatinine and albumin to assess renal function and calcium binding
- Complete blood count to evaluate for underlying hematologic disorders
- Urinary calcium excretion to assess for hypercalciuria If PTH is elevated or inappropriately normal with hypercalcemia, primary hyperparathyroidism is likely, warranting parathyroid imaging with ultrasound and sestamibi scan, as suggested by studies on parathyroid disease 1. In cases of severe hyperparathyroidism associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy, parathyroidectomy may be recommended, with subtotal parathyroidectomy or total parathyroidectomy with parathyroid tissue autotransplantation being effective surgical options 1. For severe hypercalcemia (>14 mg/dL), immediate treatment with IV fluids, calcitonin, and bisphosphonates may be necessary while completing the diagnostic workup, with the goal of reducing calcium levels and preventing complications, as supported by clinical guidelines and studies on hypercalcemia management 1. The underlying cause of hypercalcemia determines long-term management, with parathyroidectomy for primary hyperparathyroidism and specific treatments for other etiologies, such as vitamin D-related hypercalcemia or malignancy-related hypercalcemia. In patients undergoing parathyroidectomy, postoperative management should include monitoring of ionized calcium levels and adjustment of calcium and vitamin D supplementation as needed to maintain normal calcium levels, as recommended by clinical guidelines 1.
From the Research
Initial Evaluation
The initial evaluation of hypercalcemia involves measuring serum intact parathyroid hormone (PTH) levels to distinguish between PTH-dependent and PTH-independent causes 2.
- PTH-dependent causes, such as primary hyperparathyroidism (PHPT), are characterized by elevated or normal PTH levels.
- PTH-independent causes, such as malignancy, are characterized by suppressed PTH levels (<20 pg/mL).
Further Investigation
Further investigation may involve imaging studies, such as:
- Ultrasound (US)
- Computed Tomography (CT)
- Magnetic Resonance Imaging (MRI)
- Nuclear medicine imaging techniques, including parathyroid scintigraphy and positron electron tomography (PET)/CT 3.
Treatment
Treatment of hypercalcemia depends on the underlying cause and severity of symptoms.
- Mild hypercalcemia may not require acute intervention, while severe hypercalcemia requires immediate treatment 2, 4.
- Initial therapy for symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 2, 4, 5.
- Glucocorticoids may be used as primary treatment for hypercalcemia due to excessive intestinal calcium absorption, such as vitamin D intoxication or granulomatous disorders 2, 4.
- Denosumab and dialysis may be indicated in patients with kidney failure 2.
Management of Underlying Causes
Management of the underlying cause of hypercalcemia is crucial.