How can I differentiate between primary and secondary hyperparathyroidism in a patient presenting with hypercalcemia?

To differentiate between primary and secondary hyperparathyroidism in a patient presenting with hypercalcemia, the key diagnostic step is to measure parathyroid hormone (PTH) levels concurrently with albumin-adjusted serum calcium. In primary hyperparathyroidism, PTH levels are typically elevated or inappropriately normal despite hypercalcemia, whereas in secondary hyperparathyroidism, PTH is elevated but calcium is usually low or normal, not high.

Specifically:

• Measure albumin-adjusted serum calcium to confirm hypercalcemia (≥2.6 mmol/L) ¹.
• Measure PTH concurrently with calcium. In primary hyperparathyroidism, PTH is elevated or above the midpoint of the reference range despite hypercalcemia ¹.
• If PTH is low or suppressed with hypercalcemia, consider causes other than primary hyperparathyroidism, such as malignancy (secondary hyperparathyroidism is usually associated with hypocalcemia or normocalcemia) ¹.
• Secondary hyperparathyroidism is often due to chronic hypocalcemia from causes like vitamin D deficiency or chronic kidney disease, so assess vitamin D levels and renal function to support diagnosis ¹,².
• Additional tests such as 24-hour urinary calcium excretion can help exclude familial hypocalciuric hypercalcemia, which can mimic primary hyperparathyroidism ¹.

Summary: Elevated calcium with elevated or inappropriately normal PTH suggests primary hyperparathyroidism. Elevated PTH with low or normal calcium suggests secondary hyperparathyroidism. Clinical context and additional investigations (vitamin D, renal function) assist differentiation ¹,².