title: Primary hyperparathyroidism with a low-normal, atypical serum parathyroid hormone as shown by discordant immunoassay curves.
abstract: BACKGROUND
  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
  Our objective was to investigate the cause of a low-normal serum PTH in a patient with PHP.
  
  
  METHODS
  A 57-yr-old asymptomatic white female from the private practice of F.W.L. presented with an 8-yr history of a rising serum calcium from 10.5-11.6 mg/dl (2.63-2.88 mmol/liter) and a low-normal serum intact PTH of 29.2 pg/ml. After localization of a parathyroid adenoma by [(18)F]fluorodesoxyglucose positron emission tomography scanning, a 120-mg parathyroid adenoma was removed with the achievement of normocalcemia for the subsequent 2 yr.
  
  
  METHODS
  Routine pre- and postoperative serum intact PTH assays were preformed at both the Quest Diagnostics regional laboratory in Pittsburgh, Pennsylvania, and at the Quest Diagnostics Nichols Institute in California. In addition, intact, biointact, 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, biointact, and the C-terminal assays, whereas no dilution effect was seen in postoperative serum. No intragenic mutations in the pre-pro-PTH 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 autoantibody against the PTH produced by the adenoma is ruled out by the prompt loss of the dilution effect in the three PTH assays within 1 wk 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 PHP because of a low-normal serum intact or biointact PTH. Repeated PTH measurements after serum dilution in suspected cases of PHP with low-normal PTH levels may be a useful method for detecting atypical forms of PTH.
authors.affiliation: University Suburban Health Center, 1611 South Green Road, Suite 147, Cleveland, OH 44121, USA. FWLafferty@aol.com
authors.forename: Fred W
authors.initials: FW
authors.lastname: Lafferty
authors.forename: Clive R
authors.initials: CR
authors.lastname: Hamlin
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Corrado
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Shuck
mesh_terms: D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood*; D007118:Immunoassay; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*
chemical_list: D010281:Parathyroid Hormone