According to Professor Jiaqiang Zhou from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, the diagnosis of normocalcemic primary hyperparathyroidism (NPHPT) mainly includes the following aspects:
I. Core Testing Items
PTH assay:Second‑generation assays measure intact PTH (1–84) and inactive fragments, while third‑generation assays target only bioactive PTH (1–84). The two methods have similar performance, and third‑generation assays reduce interference from inactive fragments.
Calcium measurement:Albumin‑corrected total calcium and ionized calcium. Ionized calcium is preferred when available. Approximately 20% of patients with elevated ionized calcium have normal corrected total calcium. Samples must be processed immediately to avoid errors.
Other biochemical indicators:Concurrent measurement of 25‑hydroxyvitamin D (≥30 ng/ml after supplementation), eGFR (≥60 mL/min), serum phosphorus, and 24‑hour urinary calcium (>250 mg warrants evaluation for stone risk).II. Exclusion of Secondary Causes
Vitamin D deficiency:PTH normalization after vitamin D3 supplementation (initial 6000 IU/day for 8 weeks, then maintenance 1000–2000 IU/day) suggests secondary hyperparathyroidism.
Renal insufficiency:PTH is often elevated when eGFR <60 mL/min. Differentiation between primary and renal secondary hyperparathyroidism requires correlation with GFR and serum phosphorus levels.
Medications and other conditions:Bisphosphonates should be discontinued for at least 3 months before evaluation. Lithium, diuretics, and other drugs require assessment of medication history.Patients post‑Roux‑en‑Y gastric bypass are prone to calcium and vitamin D malabsorption.Familial hypocalciuric hypercalcemia (FHH) requires genetic testing for differentiation.III. Adjunctive Diagnostic Tools
Thiazide challenge test:Oral hydrochlorothiazide 50 mg/day for 2 weeks. PTH decreases in patients with secondary hyperparathyroidism, but shows no significant change in NPHPT patients.
Calcium‑phosphorus ratio (Ca/P):Ca/P >3.5 suggests PHPT/NPHPT, with 89% sensitivity and 91% specificity. Sensitivity decreases to 67% in NPHPT. Suitable for primary‑level screening.
Oral calcium challenge test:After oral administration of 1 g calcium, serum calcium and PTH are measured periodically over 0–120 minutes.The degree of PTH suppression is lower in NPHPT patients than in healthy individuals and those with secondary hyperparathyroidism.