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Endocrinology and Metabolism |
1 Centre de Recherche, Centre Hospitalier de l’Université de Montréal (CHUM), Hôpital Saint-Luc, and Département de Médecine, Université de Montréal, Montréal, Québec H2X 1P1, Canada.
2 Scantibodies Laboratory, Inc., Santee, CA.
aAddress correspondence to this author at: Centre de Recherche CHUM, Hôpital Saint-Luc, 264 Blvd René-Lévesque est, Montréal, Québec H2X 1P1, Canada. Fax 514-412-7314; e-mail rechcalcium.chum{at}ssss.gouv.qc.ca.
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.
The following articles in journals at HighWire Press have cited this article:
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  H. Komaba, J. Shin, and M. Fukagawa Restoration of reversed whole PTH/intact PTH ratio and reduction in parathyroid gland vascularity during cinacalcet therapy for severe hyperparathyroidism in a uraemic patient Nephrol. Dial. Transplant., November 5, 2009; (2009) gfp578v1. [Abstract] [Full Text] [PDF]
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 R. Eastell, A. Arnold, M. L. Brandi, E. M. Brown, P. D'Amour, D. A. Hanley, D. S. Rao, M. R. Rubin, D. Goltzman, S. J. Silverberg, et al. Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 340 - 350. [Abstract] [Full Text] [PDF]
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 H. Komaba, Y. Takeda, J. Shin, R. Tanaka, T. Kakuta, Y. Tominaga, and M. Fukagawa Reversed whole PTH/intact PTH ratio as an indicator of marked parathyroid enlargement: five case studies and a literature review NDT Plus, August 1, 2008; 1(suppl_3): iii54 - iii58. [Abstract] [Full Text] [PDF]
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M. Tanaka, H. Komaba, K. Itoh, K. Matsushita, K. Matshushita, Y. Hamada, H. Fujii, and M. Fukagawa The whole-PTH/intact-PTH ratio is a useful predictor of severity of secondary hyperparathyroidism NDT Plus, August 1, 2008; 1(suppl_3): iii59 - iii62. [Abstract] [Full Text] [PDF]
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H. Komaba, Y. Takeda, T. Abe, K. Komaba, N. Otsuki, K.-i. Nibu, M. Umezu, and M. Fukagawa Spontaneous remission of severe hyperparathyroidism with normalization of the reversed whole PTH/intact PTH ratio in a haemodialysis patient Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1760 - 1762. [Full Text] [PDF]
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 A. J. Felsenfeld, M. Rodriguez, and E. Aguilera-Tejero Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1283 - 1305. [Abstract] [Full Text] [PDF]
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 M. R. Rubin, S. J. Silverberg, P. D'Amour, J.-H. Brossard, L. Rousseau, J. Sliney Jr, T. Cantor, and J. P. Bilezikian An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1 84) Is Overproduced in Parathyroid Carcinoma Clin. Chem., August 1, 2007; 53(8): 1470 - 1476. [Abstract] [Full Text] [PDF]
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L. M. Henrich, A. D. Rogol, P. D'Amour, M. A. Levine, J. B. Hanks, and D. E. Bruns Persistent Hypercalcemia After Parathyroidectomy in an Adolescent and Effect of Treatment With Cinacalcet HCl Clin. Chem., December 1, 2006; 52(12): 2286 - 2293. [Abstract] [Full Text] [PDF]
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F. W. Lafferty, C. R. Hamlin, K. R. Corrado, A. Arnold, and J. M. Shuck Primary Hyperparathyroidism with a Low-Normal, Atypical Serum Parathyroid Hormone as Shown by Discordant Immunoassay Curves J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3826 - 3829. [Abstract] [Full Text] [PDF]
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T. Arakawa, P. D'Amour, L. Rousseau, J.-H. Brossard, M. Sakai, H. Kasumoto, N. Igaki, T. Goto, T. Cantor, and M. Fukagawa Overproduction and Secretion of a Novel Amino-Terminal Form of Parathyroid Hormone from a Severe Type of Parathyroid Hyperplasia in Uremia Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 525 - 531. [Abstract] [Full Text] [PDF]
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P. Boudou, F. Ibrahim, C. Cormier, E. Sarfati, and J.-C. Souberbielle Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism Clin. Chem., April 1, 2006; 52(4): 757 - 760. [Abstract] [Full Text] [PDF]
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P. D'Amour, A. Rakel, J.-H. Brossard, L. Rousseau, C. Albert, and T. Cantor Acute Regulation of Circulating Parathyroid Hormone (PTH) Molecular Forms by Calcium: Utility of PTH Fragments/PTH(1-84) Ratios Derived from Three Generations of PTH Assays J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 283 - 289. [Abstract] [Full Text] [PDF]
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 P. Divieti, A. I. Geller, G. Suliman, H. Juppner, and F. R. Bringhurst Receptors Specific for the Carboxyl-Terminal Region of Parathyroid Hormone on Bone-Derived Cells: Determinants of Ligand Binding and Bioactivity Endocrinology, April 1, 2005; 146(4): 1863 - 1870. [Abstract] [Full Text] [PDF]
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P. D'Amour, J.-H. Brossard, A. Rakel, L. Rousseau, C. Albert, and T. Cantor Evidence That the Amino-Terminal Composition of Non-(1-84) Parathyroid Hormone Fragments Starts before Position 19 Clin. Chem., January 1, 2005; 51(1): 169 - 176. [Abstract] [Full Text] [PDF]
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T. K. Teal, J. L. Wood, P. E. Stevens, and E. J. Lamb Stability of Bio-Intact (1-84) Parathyroid Hormone ex Vivo in Serum and EDTA Plasma from Hemodialysis Patients Clin. Chem., September 1, 2004; 50(9): 1713 - 1714. [Full Text] [PDF]
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S. A. Santini, C. Carrozza, C. Vulpio, E. Capoluongo, G. Luciani, P. Lulli, B. Giardina, and C. Zuppi Assessment of Parathyroid Function in Clinical Practice: Which Parathyroid Hormone Assay Is Better? Clin. Chem., July 1, 2004; 50(7): 1247 - 1250. [Full Text] [PDF]
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F. R. Bringhurst Circulating Forms of Parathyroid Hormone: Peeling Back the Onion Clin. Chem., December 1, 2003; 49(12): 1973 - 1975. [Full Text] [PDF]
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