Context: In patients with primary hyperparathyroidism (PHP) one expects to find a serum PTH in the high or high-normal range. The presence of a low-normal PTH in PHP can be difficult to explain.

Objective: To investigate the cause of a low-normal serum PTH in a patient with primary hyperparathyroidism.

Patient: A 57 yr old asymptomatic white female from the private practice of FWL presented with an eight year history of a rising serum calcium from 10.5 to 11.5 mg/dL (2.63-2.88 mmol/L) and a low-normal serum Intact PTH of 29.2pg/ml. Following localization of a parathyroid adenoma by F-18 fluorodesoxyglucose PET scanning a 120 mg parathyroid adenoma was removed with the achievement of normocalcemia for the subsequent 2 yr. Our objective is to explain her low-normal serum PTH.

Methods: Routine pre- and postoperative serum Intact PTH assays were preformed at both the Quest Diagnostics regional laboratory in Pittsburgh, PA, and at the Quest Diagnostics Nichols Institute in California. In addition, Intact, Bio-intact, and C-terminal assays were measured in undiluted, 1:2 diluted, and 1:4 diluted sera at the Nichols Institute. PTH gene sequence analysis was performed from DNA extracted both from the parathyroid adenoma and the patient's peripheral blood leukocytes.

Results: Dilution, with correction for the dilution factor, of the preoperative serum produced a progressive rise in the Intact, Bio-intact, and the C-terminal assays whereas no dilutional effect was seen in postoperative serum. No intragenic mutations in the preproPTH coding region were found in either the parathyroid adenoma or matched blood DNA samples.

Conclusions: The discordant preoperative immunoassay curves with dilution could not be explained by the adenoma producing a mutated PTH. Furthermore, an auto-antibody against the PTH produced by the adenoma is ruled out by the prompt loss of the dilution effect in the three PTH assays within one week of the adenoma's excision. A posttranslational effect on the PTH molecule within the adenoma remains a possible explanation for the discordant immunoassay curves. Our report emphasizes that one cannot always rule out primary hyperparathyroidism because of a low-normal serum Intact or Bio-intact PTH. Repeated PTH measurements after serum dilution in suspected cases of primary hyperparathyroidism with low-normal PTH levels may be a useful method for detecting atypical forms of PTH.