Very low or undetectable intact parathyroid hormone levels in patients with surgically verified parathyroid adenomas

To report and explore potential reasons for undetectable or low-normal serum intact PTH levels in patients with surgically verified primary hyperparathyroidism with parathyroid adenomas, review the relevant literature, and offer suggestions for management of such patients occasionally encountered in clinical practice. For future research, to help understand mechanisms underlying 'undetectable' or inappropriately low serum intact PTH levels.

Serum intact PTH levels were measured pre- and postoperatively by immunochemiluminescent assay (ICMA) and the results were confirmed by at least two repeated measurements on different occasions in each patient.

We encountered two unusual patients with primary hyperparathyroidism who had suggestive biochemical and/or clinical features of primary hyperparathyroidism. However, serum intact PTH levels were either very low or undetectable in the context of hypercalcaemia, with no other obvious cause. A (99m)Tc sestamibi scan showed increased uptake in one of the parathyroid glands, suggesting a single adenoma in each case that was confirmed at surgery.

In the first patient, from India, mean +/- SD serum calcium was 2.6 +/- 0.32 mmol/l (reference range 2.12-2.74 mmol/l) with intact PTH of 0.11 pmol/l (reference range 1.1-7.59 pmol/l). In the second patient, from the USA, mean +/- SD serum calcium and intact PTH were 2.9 +/- 0.07 mmol/l (reference range 2.17-2.51 mmol/l) and 1.35 pmol/l (reference range 1.1-7.59 pmol/l), respectively. Following curative parathyroidectomy, serum calcium levels normalized in both patients. By contrast, serum intact PTH levels, which were either suppressed or very low before surgery, rose into the low-normal reference range in all patients.

When the clinical suspicion is high, the diagnosis of primary hyperparathyroidism should be pursued despite suppressed or low-normal serum intact PTH levels after carefully excluding other causes of hypercalcaemia. Further research on various intact PTH molecular species secreted by parathyroid adenomas or post-translational changes in the intact PTH molecule that might interfere with in vitro measurements should be undertaken to understand the precise reason(s) for such anomalous findings.