How do I differentiate between primary hyperparathyroidism and malignancy as causes of hypercalcaemia in primary care?

To differentiate between primary hyperparathyroidism and malignancy as causes of hypercalcaemia in primary care, the key diagnostic step is to measure albumin-adjusted serum calcium and parathyroid hormone (PTH) levels concurrently.

1. Measure albumin-adjusted serum calcium in patients with symptoms or incidental hypercalcaemia. Repeat the measurement if elevated (≥2.6 mmol/L) to confirm hypercalcaemia.

2. Measure PTH levels if albumin-adjusted serum calcium is ≥2.6 mmol/L on at least two occasions or ≥2.5 mmol/L with features suggestive of primary hyperparathyroidism.

3. Interpretation of PTH results:

• If PTH is elevated or in the upper half of the reference range with hypercalcaemia, this supports a diagnosis of primary hyperparathyroidism.
• If PTH is suppressed (below the lower limit of normal) with hypercalcaemia, this suggests a non-PTH mediated cause such as malignancy.

4. Further evaluation: In suspected primary hyperparathyroidism, consider specialist referral for confirmation and management. In cases where PTH is low and malignancy is suspected, investigate for underlying cancer and liaise with oncology or palliative care as appropriate.

5. Additional clues: Primary hyperparathyroidism often presents with symptoms like thirst, frequent urination, constipation, osteoporosis, or renal stones, whereas malignancy-associated hypercalcaemia may present with more severe hypercalcaemia and systemic symptoms related to cancer.

6. Do not routinely measure ionised calcium for this differentiation in primary care.