A 52-year-old woman presents with bone pain, fatigue, and polyuria. Serum calcium is 11.2 mg/dL (normal 8.5–10.5), serum phosphate is 2.8 mg/dL (normal 2.5–4.5), and alkaline phosphatase is elevated. PTH level is 85 pg/mL (normal 15–65). Which investigation is most appropriate to confirm the diagnosis of primary hyperparathyroidism?

## Diagnostic Approach to Primary Hyperparathyroidism **Key Point:** The diagnosis of primary hyperparathyroidism is confirmed by demonstrating **elevated serum calcium WITH elevated or inappropriately normal PTH**. Once biochemical diagnosis is established, imaging is performed to localize the parathyroid lesion(s) before surgery. ### Why Parathyroid Imaging Is the Answer The patient has: - Hypercalcemia (11.2 mg/dL) - Elevated PTH (85 pg/mL) — inappropriate for the degree of hypercalcemia - Clinical features consistent with hyperparathyroidism (bone pain, fatigue, polyuria) The biochemical diagnosis of primary hyperparathyroidism is already established. **Parathyroid imaging (sestamibi scan or ultrasound) is the investigation of choice for LOCALIZATION** of the parathyroid adenoma or hyperplasia before surgical intervention. **High-Yield:** Sestamibi scan has ~90% sensitivity for adenomas >1.5 g; ultrasound is operator-dependent but useful as a first-line localizing study. Both are standard pre-operative investigations. ### Why Other Tests Are Not the Answer | Investigation | Role | Why Not Here | | --- | --- | --- | | Serum 1,25-dihydroxyvitamin D | Differentiates granulomatous disease, lymphomas | Already have PTH-mediated hypercalcemia; vitamin D level does not confirm PTH source | | 24-hour urinary calcium | Assesses nephrolithiasis risk, differentiates familial hypocalciuric hypercalcemia | Prognostic, not diagnostic; not needed to confirm primary hyperparathyroidism | | DEXA scan | Assesses bone density; guides treatment decisions | Evaluates consequences, not diagnosis; performed AFTER diagnosis is confirmed | **Clinical Pearl:** In familial hypocalciuric hypercalcemia (FHH), 24-hour urinary calcium is LOW (<200 mg/day), whereas in primary hyperparathyroidism it is normal or elevated—this distinction matters when PTH is borderline, but imaging is still required for surgical planning in confirmed primary hyperparathyroidism.