An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1–84) Is Overproduced in Parathyroid Carcinoma

Rubin, Mishaela R.; Silverberg, Shonni J.; D'Amour, P; Brossard, Jean‐Hugues; Rousseau, Louise; Sliney, James; Cantor, Tom; Bilezikian, John P.

doi:10.1373/clinchem.2007.085506

Cited by 86 publications

(74 citation statements)

References 11 publications

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“…In the group 1 patients, PTH values decreased after surgery and were then lower when measured with the third-generation than with the secondgeneration PTH assays regardless of the assay used, as described previously (10 ). Our data and those reported previously (9,10 ) are consistent with the presence of a PTH molecule in some patients that is produced in excessive amounts by a parathyroid adenoma or carcinoma and regresses after parathyroidectomy, as shown in our study and by Räkel et al (10 ), or persists for the duration of a 12-month treatment with a calcimimetic agent (9 ). D'Amour et al (12 ) used HPLC to identify a new PTH form, amino PTH (N-PTH), which is distinct from PTH(1-84) and is overproduced in primary and secondary hyperparathyroidism.…”

confidence: 87%

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Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Boudou

Ibrahim²,

Cormier

et al. 2006

Clinical Chemistry

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Background: Third-generation parathyroid hormone (PTH) assays have been reported to measure only intact PTH(1–84), in contrast to second-generation assays, which also detect PTH(7–84) fragments. Higher PTH measurements were observed with third- than with second-generation PTH assays in a few patients with either severe primary hyperparathyroidism or parathyroid carcinoma. Methods: We analyzed biological data [second- and third-generation PTH assays, 25-hydroxyvitamin D (25-OHD), calcium, and phosphate concentrations] obtained before and after surgery for 2 groups of patients selected from a large series of consecutive patients with primary hyperparathyroidism (PHPT): 7 female patients with surgically and histologically confirmed PHPT (group 1) and a matched group (group 2). Results: For group 1 but not group 2, PTH concentrations measured by third-generation PTH assays before surgery were higher than those measured by the second-generation assays. Circulating 25-OHD, calcium, and phosphate concentrations were similar in both groups. In addition, PTH values measured with the third-generation PTH assays in group 1 decreased after surgery. Conclusions: Our results confirm that third-generation PTH assays do not measure only PTH(1–84). The frequency of this unexpected finding of markedly lower PTH concentrations than previously reported was ∼5% in patients with PHPT without malignancy. We do not know whether the presence of this unexpected profile is predictive of malignancy.

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confidence: 87%

“…We and others have demonstrated that subclinical atherosclerosis (4 ) and clinical coronary heart disease (CHD) (5)(6)(7)(8)(9) are associated with higher concentrations of circulating ox-LDL. Recently, we showed, in older adults in the Health, Aging, and Body Composition (Health ABC) cohort (10 ), that high CHD risk status (based on Framingham score) before…”

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confidence: 99%

Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Boudou

Ibrahim²,

Cormier

et al. 2006

Clinical Chemistry

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“…In contrast, for others, (9,10,13) this ratio stays for whole PTH/iPTH. In the exceptional cases in which the PTH-(1-84) level is paradoxically higher than that of iPTH, it is obvious that one cannot calculate PTH- as the difference between iPTH and PTH-(1-84), because this would yield a negative value.…”

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confidence: 79%

Whole or Fragmentary Information on Parathyroid Hormone?

Drüeke

Fukagawa

2007

Clinical Journal of the American Society of Nephrology

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M ore than a decade ago, Brossard et al. (1) drew attention to the fact that the so-called "intact," second-generation parathyroid hormone (PTH) assays measured not only the PTH-(1-84) molecule but also large PTH fragments in patients with chronic kidney disease (CKD). One of the major problems is that the proportion of PTH-(1-84) and its fragments in the circulation changes in response to the serum level of ionized calcium; therefore, in presence of hypercalcemia, the parathyroid gland releases less PTH-(1-84) but more PTH fragments. The reverse is true in the presence of hypocalcemia, where more active PTH-(1-84) is needed. The difference is particularly striking in patients with CKD. When considering the potential biologic relevance of this finding, it is even more disturbing that at least one of the fragments, namely PTH-(7-84), has been shown to act as a partial antagonist of PTH-(1-84), with opposite biologic activities (2-4). Progressive awareness of these methodologic problems and the underlying biologic complexity went along with the development of thirdgeneration PTH assays that recognize only PTH-(1-84), also called "whole," "bio-intact," or "biologically active" PTH (5).Theoretically, the assessment of second-and third-generation PTH assays combined should reflect parathyroid activity more adequately than second-generation assays alone, reflecting the sum of potentially opposing effects of PTH-(1-84) and its fragments. Several authors explored changes of serum PTH levels, as measured with various assays, with progression of CKD and in response to medical interventions. Reduction in GFR is accompanied by a higher increase in large PTH-related C-terminal fragments than in PTH-(1-84) in patients with CKD (6,7). The administration of cinacalcet to patients with stage 5 CKD and secondary hyperparathyroidism (8) or to patients with parathyroid cancer (9) did not change the ratio between intact PTH (iPTH) and PTH-(1-84). This is somewhat surprising because cinacalcet reduces serum calcium, and hypocalcemia is associated with changes in the PTH ratio. In contrast, surgical parathyroidectomy, which often leads to profound hypocalcemia, has been shown to normalize the ratio (10).In an original article in this issue, Monier-Faugere et al. (11) report the effects of the administration to long-term hemodialysis patients of calcitriol, the most active metabolite of vitamin D, and its active derivative paricalcitol on circulating levels of PTH-(1-84), iPTH, large C-terminal PTH fragments (C-PTH), and the PTH-(1-84)/C-PTH fragment ratio, also called PTH-(1-84)/C-PTH-(7-84) ratio. They present results that were obtained first in a longitudinal, crossover design study that compared paricalcitol with calcitriol and second in a cross-sectional study that compared paricalcitol with no vitamin D treatment. In the longitudinal study, they observe a lower PTH ratio in response to calcitriol but a higher PTH ratio in response to paricalcitol, as compared with respective baseline values. In the cross-sectional study, they fi...

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“…Third generation PTH assays are specific for the 1-84 PTH and do not cross-react with the C-terminal fragments, but they cross-react with a N-terminal molecular form of PTH (amino-PTH), a PTH phosphorylated on the serine in position 17, overproduced in parathyroid carcinoma [12,13] and in rare cases of severe primary hyperparathyroidism [14]. These assays are not as used as the "intact" PTH ones, since two manufacturers only (namely DiaSorin and Roche) present an automated version of these assays, even not available in every country.…”

Section: Pth Determinationmentioning

confidence: 99%

Considerations in parathyroid hormone testing

Cavalier

Plebani

Delanaye

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Parathyroid hormone (PTH) is a major player in phosphocalcic metabolism and its measurement is very important for the correct diagnosis and treatment of several diseases. PTH determination represents the paradigm of quality in laboratory medicine as many variables in the pre-, intra-, and post-analytical phases strongly affect the value of the clinical information. Analytical determination of PTH has been rendered difficult by the presence, in the circulation, of truncated fragments that can crossreact with the antibodies used for its determination. In addition, pre-analytical phase is complicated by the lack of stability of the peptide and the best sample to use for its determination remains controversial, as well as sample handling and storage. PTH secretion is also affected by circadian and seasonal rhythms and by physical exercise. Finally, from the post-analytical perspective, establishment of reliable reference ranges requires further efforts as the selection criteria for reference subjects should take into consideration new variables such as gender, race and vitamin D levels. Finally, clinical guidelines have recently revised and improved the criteria for a correct interpretation of PTH values.

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An N-Terminal Molecular Form of Parathyroid Hormone (PTH) Distinct from hPTH(1–84) Is Overproduced in Parathyroid Carcinoma

Cited by 86 publications

References 11 publications

Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Whole or Fragmentary Information on Parathyroid Hormone?

Considerations in parathyroid hormone testing

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