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Endocrinology and Metabolism |
1
Centre de recherche clinique du CHUM, Pavillon Saint-Luc, Montréal, Quebec, H2X 1P1 Canada.
2
Institut de Recherches Cliniques de Montréal and
Départements de
3
Médecine et de
4
Biochimie, Université de Montréal,
Montréal, Quebec, H3C 3J7 Canada.
a Address correspondence to this author at: Centre de recherche du CHUM, Pavillon Saint-Luc, 264 René Lévesque Blvd East, Montréal, Quebec, H2X 1P1 Canada. Fax 514-281-2492.
We have previously shown that the Nichols assay for intact parathyroid
hormone (I-PTH) reacts with a non-(1–84) molecular form of PTH. This
form behaves as a carboxy-terminal fragment and accumulates in renal
failure, accounting for 40–60% of the measured immunoreactivity. We
wanted to see whether this was a common event with other commercial
two-site I-PTH assays. We thus compared the ability of three commercial
kits [Nichols (NL), Incstar (IT), and Diagnostic System Laboratories
(DSL)] to measure I-PTH in 112 renal failure patients and to detect
hPTH(1–84) and non-(1–84)PTH on HPLC profiles of serum pools from
uremic patients with I-PTH concentrations of 10–100 pmol/L. The
behavior of synthetic hPTH(7–84), a fragment possibly related to
non-(1–84)PTH was also compared with hPTH(1–84) in the three assays.
The I-PTH concentrations measured with the three assays in the 112
uremic samples were highly related (r2 
0.89,
P <0.0001), and the values measured with NL were, on
average, 23% higher than IT. Values measured with DSL were 23% and
56% higher than IT for values less than and more than 40 pmol/L,
respectively. The three assays detected two HPLC peaks on four
different profiles corresponding to hPTH(1–84) and non-(1–84)PTH.
This last peak represented 36 ± 8.4% of the immunoreactivity
with NL, 24 ± 5.5% with IT, and 25 ± 2.8% with DSL (NL vs
IT or DSL: P <0.05). These differences were confirmed by a
50% lower immunoreactivity to hPTH(7–84) compared with hPTH(1–84)
for IT and DSL but not for NL. These results suggest that most of the
two-site I-PTH assays would cross-react with non-(1–84)PTH material,
thus explaining about one-half of the 2–2.5 x higher I-PTH
concentrations reported in uremic patients without bone involvement
than in subjects without uremia.
The following articles in journals at HighWire Press have cited this article:
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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.-C. Monier-Faugere, H. Mawad, and H. H. Malluche Opposite Effects of Calcitriol and Paricalcitol on the Parathyroid Hormone-(1-84)/Large Carboxy-Terminal-Parathyroid Hormone Fragments Ratio in Patients with Stage 5 Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1255 - 1260. [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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T. Cantor, Z. Yang, N. Caraiani, and E. Ilamathi Lack of Comparability of Intact Parathyroid Hormone Measurements among Commercial Assays for End-Stage Renal Disease Patients: Implication for Treatment Decisions Clin. Chem., September 1, 2006; 52(9): 1771 - 1776. [Abstract] [Full Text] [PDF]
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 J. Huan, K. Olgaard, L. B. Nielsen, and E. Lewin Parathyroid Hormone 7-84 Induces Hypocalcemia and Inhibits the Parathyroid Hormone 1-84 Secretory Response to Hypocalcemia in Rats with Intact Parathyroid Glands J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1923 - 1930. [Abstract] [Full Text] [PDF]
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C. Bieglmayer, K. Kaczirek, G. Prager, and B. Niederle Parathyroid Hormone Monitoring during Total Parathyroidectomy for Renal Hyperparathyroidism: Pilot Study of the Impact of Renal Function and Assay Specificity Clin. Chem., June 1, 2006; 52(6): 1112 - 1119. [Abstract] [Full Text] [PDF]
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 P. A. Friedman and W. G. Goodman PTH(1-84)/PTH(7-84): a balance of power Am J Physiol Renal Physiol, May 1, 2006; 290(5): F975 - F984. [Abstract] [Full Text] [PDF]
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K. Olgaard and E. Lewin Can Hyperparathyroid Bone Disease Be Arrested or Reversed? Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 367 - 373. [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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 K. Kaczirek, G. Prager, P. Riss, G. Wunderer, R. Asari, C. Scheuba, C. Bieglmayer, and B. Niederle Novel parathyroid hormone (1-84) assay as basis for parathyroid hormone monitoring in renal hyperparathyroidism. Arch Surg, February 1, 2006; 141(2): 129 - 134. [Abstract] [Full Text] [PDF]
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 J. T Potts Parathyroid hormone: past and present J. Endocrinol., December 1, 2005; 187(3): 311 - 325. [Abstract] [Full Text] [PDF]
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 P. Boudou, F. Ibrahim, C. Cormier, A. Chabas, E. Sarfati, and J.-C. Souberbielle Third- or Second-Generation Parathyroid Hormone Assays: A Remaining Debate in the Diagnosis of Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6370 - 6372. [Abstract] [Full Text] [PDF]
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Y. Maeno, M. Inaba, S. Okuno, T. Yamakawa, E. Ishimura, and Y. Nishizawa Serum Concentrations of Cross-Linked N-Telopeptides of Type I Collagen: New Marker for Bone Resorption in Hemodialysis Patients Clin. Chem., December 1, 2005; 51(12): 2312 - 2317. [Abstract] [Full Text] [PDF]
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T. Kawata, Y. Imanishi, K. Kobayashi, N. Onoda, Y. Takemoto, H. Tahara, S. Okuno, E. Ishimura, T. Miki, T. Ishikawa, et al. Direct in Vitro Evidence of Extracellular Ca2+-Induced Amino-Terminal Truncation of Human Parathyroid Hormone (1-84) by Human Parathyroid Cells J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5774 - 5778. [Abstract] [Full Text] [PDF]
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J.-C. Souberbielle, V. Fayol, C. Sault, E. Lawson-Body, A. Kahan, and C. Cormier Assay-Specific Decision Limits for Two New Automated Parathyroid Hormone and 25-Hydroxyvitamin D Assays Clin. Chem., February 1, 2005; 51(2): 395 - 400. [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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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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V. Carnevale, S. Dionisi, I. Nofroni, E. Romagnoli, F. Paglia, S. De Geronimo, J. Pepe, G. Clemente, G. Tonnarini, and S. Minisola Potential Clinical Utility of a New IRMA for Parathyroid Hormone in Postmenopausal Patients with Primary Hyperparathyroidism Clin. Chem., March 1, 2004; 50(3): 626 - 631. [Abstract] [Full Text] [PDF]
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M. Inaba, K. Nakatsuka, Y. Imanishi, M. Watanabe, Y. Mamiya, E. Ishimura, and Y. Nishizawa Technical and Clinical Characterization of the Bio-PTH (1-84) Immunochemiluminometric Assay and Comparison with a Second-Generation Assay for Parathyroid Hormone Clin. Chem., February 1, 2004; 50(2): 385 - 390. [Abstract] [Full Text] [PDF]
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P. D'Amour, J.-H. Brossard, L. Rousseau, L. Roy, P. Gao, and T. Cantor Amino-Terminal Form of Parathyroid Hormone (PTH) with Immunologic Similarities to hPTH(1-84) Is Overproduced in Primary and Secondary Hyperparathyroidism Clin. Chem., December 1, 2003; 49(12): 2037 - 2044. [Abstract] [Full Text] [PDF]
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S. J. Silverberg and J. P. Bilezikian "Incipient" Primary Hyperparathyroidism: A "Forme Fruste" of an Old Disease J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5348 - 5352. [Abstract] [Full Text] [PDF]
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S. J. Silverberg, P. Gao, I. Brown, P. LoGerfo, T. L. Cantor, and J. P. Bilezikian Clinical Utility of an Immunoradiometric Assay for Parathyroid Hormone (1-84) in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4725 - 4730. [Abstract] [Full Text] [PDF]
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 J. C. Estepa, I. Lopez, A. J. Felsenfeld, P. Gao, T. Cantor, M. Rodriguez, and E. Aguilera-Tejero Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1101 - 1107. [Abstract] [Full Text] [PDF]
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Y. Hatakeyama, K. Mizunashi, Y. Furukawa, S. Yabuki, Y. Sato, and T. Igarashi Plasma Levels of Parathyroid Hormone (1-84) Whole Molecule and Parathyroid Hormone (7-84)-Like Fragments in Pseudohypoparathyroidism Type I J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2250 - 2255. [Abstract] [Full Text] [PDF]
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H. Reichel, A. Esser, H.-J. Roth, and H. Schmidt-Gayk Influence of PTH assay methodology on differential diagnosis of renal bone disease Nephrol. Dial. Transplant., April 1, 2003; 18(4): 759 - 768. [Abstract] [Full Text] [PDF]
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A. H. Terry, J. Orrock, and A. W. Meikle Comparison of Two Third-Generation Parathyroid Hormone Assays Clin. Chem., February 1, 2003; 49(2): 336 - 337. [Full Text] [PDF]
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W. G. Goodman, I. B. Salusky, and H. Juppner New lessons from old assays: parathyroid hormone (PTH), its receptors, and the potential biological relevance of PTH fragments Nephrol. Dial. Transplant., October 1, 2002; 17(10): 1731 - 1736. [Full Text] [PDF]
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C. Bieglmayer, G. Prager, and B. Niederle Kinetic Analyses of Parathyroid Hormone Clearance as Measured by Three Rapid Immunoassays during Parathyroidectomy Clin. Chem., October 1, 2002; 48(10): 1731 - 1738. [Abstract] [Full Text] [PDF]
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 P. Divieti, M. R. John, H. Juppner, and F. R. Bringhurst Human PTH-(7-84) Inhibits Bone Resorption in Vitro Via Actions Independent of the Type 1 PTH/PTHrP Receptor Endocrinology, January 1, 2002; 143(1): 171 - 176. [Abstract] [Full Text] [PDF]
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 P. Lips Vitamin D Deficiency and Secondary Hyperparathyroidism in the Elderly: Consequences for Bone Loss and Fractures and Therapeutic Implications Endocr. Rev., August 1, 2001; 22(4): 477 - 501. [Abstract] [Full Text] [PDF]
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J.-C. Souberbielle, C. Cormier, C. Kindermans, P. Gao, T. Cantor, F. Forette, and E. E. Baulieu Vitamin D Status and Redefining Serum Parathyroid Hormone Reference Range in the Elderly J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3086 - 3090. [Abstract] [Full Text] [PDF]
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A. Fournier, M. E. C. Solal, R. Oprisiu, H. Mazouz, P. Morinire, G. Choukroun, and R. Bouillon Optimal Range of Plasma Concentration of True 1-84 Parathyroid Hormone in Patients on Maintenance Dialysis J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1840 - 1841. [Full Text]
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W. G. Goodman, M. R. John, H. Jüppner, and I. B. Salusky Parathyroid Hormone-Immunoradiometric Assays as Noninvasive Predictors of Renal Osteodystrophy: The Need for Bone Histomorphometric Validation J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1841 - 1842. [Full Text]
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 S. J. Marx Hyperparathyroid and Hypoparathyroid Disorders N. Engl. J. Med., December 21, 2000; 343(25): 1863 - 1875. [Full Text] [PDF]
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Y. Kumeda, M. Inaba, H. Tahara, Y. Kurioka, T. Ishikawa, H. Morii, and Y. Nishizawa Persistent Increase in Bone Turnover in Graves' Patients with Subclinical Hyperthyroidism J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4157 - 4161. [Abstract] [Full Text]
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J.-H. Brossard, R. Lepage, H. Cardinal, L. Roy, L. Rousseau, C. Dorais, and P. D'Amour Influence of Glomerular Filtration Rate on Non-(1-84) Parathyroid Hormone (PTH) Detected by Intact PTH Assays Clin. Chem., May 1, 2000; 46(5): 697 - 703. [Abstract] [Full Text] [PDF]
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A. Fournier, S. Ghitu, G. Bako, L. B. Amar, R. Oprisiu, C. Hottelart, M. E. C. Solal, G. Coen, P. Ballanti, and E. Bonucci Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients Nephrol. Dial. Transplant., November 1, 1999; 14(11): 2772 - 2774. [Full Text] [PDF]
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 J. Hilpert, A. Nykjaer, C. Jacobsen, G. Wallukat, R. Nielsen, S. K. Moestrup, H. Haller, F. C. Luft, E. I. Christensen, and T. E. Willnow Megalin Antagonizes Activation of the Parathyroid Hormone Receptor J. Biol. Chem., February 26, 1999; 274(9): 5620 - 5625. [Abstract] [Full Text] [PDF]
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H. Cardinal, J.-H. Brossard, L. Roy, R. Lepage, L. Rousseau, and P. D’Amour The Set Point of Parathyroid Hormone Stimulation by Calcium Is Normal in Progressive Renal Failure J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3839 - 3844. [Abstract] [Full Text]
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