Received October 21, 2005
Accepted on February 28, 2006

ORIGINAL ARTICLES

Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia

Toshio Arakawa ^*, Pierre D’Amour , Louise Rousseau , Jean-Hugues Brossard , Makoto Sakai , Hiroomi Kasumoto , Naoya Igaki , Takeo Goto , Tom Cantor ^||, and Masafumi Fukagawa ^*1

*Division of Nephrology & Dialysis Center, Kobe University School of Medicine, Kobe, Japan; Arakawa Renal Clinic, Takasago, Japan; Centre de recherche, Centre hospitalier de l’Université de Montréal, Hôpital Saint-Luc, and Département de médecine, Université de Montréal, Montréal, Québec, Canada; Department of Internal Medicine, Takasago Municipal Hospital, Takasago, Japan; and ||Scantibodies Laboratory Inc., Santee, California

¹ To whom correspondence should be addressed. E-mail: fukagawa{at}med.kobe-u.ac.jp.

	Abstract

Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.