High third generation/second generation PTH ratio in a patient with parathyroid carcinoma: clinical utility of third generation/second generation PTH ratio in patients with primary hyperparathyroidism

Primary hyperparathyroidism (PHP) is caused by parathyroid adenomas or hyperplasia, and occasionally by parathyroid carcinoma. Recently a high third generation/second generation PTH ratio has been observed in some patients with parathyroid carcinoma. We report the case of a 60-year old woman who was presented a fourth episode of PTH-related hypercalcaemia due to a parathyroid carcinoma. Serum PTH levels were measured using a second generation assay and a third generation assay before, 4 and 7 months after the fourth surgery. Then, PTH levels were measured in 294 osteoporotic normocalcaemic patients as well as in 30 consecutive PHP patients. Before surgery of the patient with parathyroid carcinoma, second generation PTH was 229 pg/ml, third generation PTH was 675 pg/ml and third generation/second generation PTH ratio was 2.95. Four and 7 months after surgery the third generation/second generation PTH ratio was 0.70 and 0.66, respectively. All osteoporotic patients had a normal third generation/second generation PTH ratio (0.585 +/- 0.118) whereas only one patient (3.3%) with PHP had a third generation/second generation PTH ratio > 1 (1.54). A high third generation/second generation PTH ratio could be observed in patients with parathyroid carcinoma, is uncommon in benign PHP and is absent in osteoporotic patients without PHP. Therefore, PTH level can be measured using second and third generation assays in some PHP patients, and a specific surgical protocol for possible parathyroid carcinoma could be discussed in patients with a high third generation/second generation PTH ratio.