Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism.
BACKGROUND
To separate non-(1-84)parathyroid hormone [non-(1-84)PTH] from PTH(1-84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1-84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure.


METHODS
Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15-20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84) structure requirement were used to measure basal and fractionated PTH values.


RESULTS
T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13 (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients [47 (35.1) vs 33.4 (26.1) pmol/L; P <0.01]. By contrast, CA-PTH concentrations were similar to or higher than T-PTH in three of five patients with primary hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA-PTH assay reacted with the hPTH(1-84) peak and with a minor peak different from the non-(1-84) peak recognized by the T-PTH assay. This minor peak was not recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25 (23)% in patients with primary hyperparathyroidism, and 22 (7)% in renal failure patients, assuming equimolar reactivity to hPTH(1-84) in the CA-PTH assay. It was not oxidized hPTH(1-84), which migrated differently on HPLC and reacted similarly in the CA and T-PTH assays.


CONCLUSIONS
This new molecular form of PTH has structural integrity of the (1-4) region but presumably is modified in the region (15-20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined.
D'Amour
Pierre
P
Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Hôpital Saint-Luc, Montréal, Québec H2X 1P1, Canada.
Brossard
Jean-Hugues
JH
Rousseau
Louise
L
Roy
Louise
L
Gao
Ping
P
Cantor
Tom
T
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism*; D007118:Immunoassay / Q000379:methods; D010281:Parathyroid Hormone / Q000096:biosynthesis* / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D051437:Renal Insufficiency / Q000378:metabolism
D010281:Parathyroid Hormone; D010446:Peptide Fragments