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Clinical Chemistry 53: 1470-1476, 2007. First published June 28, 2007; 10.1373/clinchem.2007.085506
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(Clinical Chemistry. 2007;53:1470-1476.)
© 2007 American Association for Clinical Chemistry, Inc.

Endocrinology and Metabolism

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

Mishaela R. Rubin1, Shonni J. Silverberg1, Pierre D’Amour2, Jean-Hugues Brossard2, Louise Rousseau2, James Sliney, Jr1, Tom Cantor3 and John P. Bilezikian1,a

1 College of Physicians and Surgeons, Columbia University, New York, NY.
2 Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Hôpital Saint-Luc, Montreal, Québec, Canada.
3 Scantibodies Laboratory Inc., Santee, CA.

aAddress correspondence to this author at: Department of Medicine, College of Physicians and Surgeons, 630 W. 168th St., New York, NY 10032. Fax 212-305-6486; e-mail jpb2{at}columbia.edu.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: A new parathyroid hormone (PTH) species, the N-terminal PTH form (N-PTH), is distinct from intact human PTH of 84 amino acid residues [hPTH(1–84)] and is recognized in a 3rd-generation assay of "whole" PTH (wPTH; the 1–2 epitope) but not in a 2nd-generation assay of "total" PTH (tPTH; the 12–18 epitope). N-PTH usually represents <15% of wPTH but can be overproduced in severe primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism. We investigated whether N-PTH is also overproduced in parathyroid cancer and whether N-PTH concentration is influenced by calcimimetic therapy.

Methods: We studied 8 patients with parathyroid carcinoma before and at week 16 of cinacalcet therapy, 6 patients with PHPT, and 6 control individuals. We fractionated sera with HPLC and analyzed fractions with the 2 assays to quantify hPTH(1–84), N-PTH, and non-(1–84) PTH fragments.

Results: Half of parathyroid carcinoma patients had an increased wPTH:tPTH ratio [mean (SD), 1.35 (0.29)]; the others had a typical ratio [0.72 (0.12)]. HPLC fractionation of sera from 2 high-ratio patients confirmed N-PTH overproduction [65% (12%) of wPTH]. The N-PTH fraction was <15% of wPTH in PHPT and healthy individuals. Calcimimetic therapy appreciably reduced calcium concentrations in parathyroid carcinoma patients but had little influence on PTH concentration, the wPTH:tPTH ratio, or the PTH HPLC profile.

Conclusion: N-PTH is overproduced in some parathyroid cancer patients, but calcimimetic therapy does not influence its production. The clinical implications of this finding in parathyroid carcinoma await additional studies with an emphasis on N-PTH’s biological activity and with larger numbers of patients.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Human parathyroid hormone (PTH)1 circulates both as the intact peptide of 84 amino acid residues [hPTH(1–84)] and as truncated molecules (1). Recently, our group described a new circulating PTH form, the N-terminal PTH form (N-PTH), that is distinct from previously recognized forms. We identified N-PTH with a 3rd-generation assay of "whole" PTH (wPTH) that contains a 1–2 epitope (2)(3). N-PTH was poorly reactive in 2nd-generation assays of "total" PTH (tPTH), in which the N-terminal epitope covers the 12–18 region of the PTH molecule (2)(3). We postulated that the inability of the 2nd-generation assay to detect this unusual PTH form could be due to a posttranslational modification of hPTH(1–84) in the 12–18 region, which is necessary for detection by the 2nd-generation assay. In healthy individuals, N-PTH usually represents <15% of the PTH immunoreactivity identified in the 3rd-generation wPTH assay (2)(3).

Rarely, N-PTH can be overproduced in patients with severe primary or secondary hyperparathyroidism, where it represents a much larger proportion of the circulating PTH immunoreactivity in the 3rd-generation assay (2)(4)(5). This overproduction is manifested as an increased ratio of the PTH immunoreactivity as measured with the 3rd-generation assay to the immunoreactivity measured with the 2nd-generation assay (2)(4)(5). Usually, this ratio is <0.8 because 2nd-generation PTH assays detect large non-(1–84) fragments (whereas 3rd-generation assays do not) that represent a much larger proportion of circulating PTH than N-PTH, which the 2nd-generation assay does not detect very well. Consequently, PTH values obtained with the 2nd-generation assay are generally higher than those obtained with the 3rd-generation PTH assay (1)(2)(3)(6).

Our objective was to determine whether N-PTH is overproduced in parathyroid cancer, the severest form of primary hyperparathyroidism (PHPT) and, if so, whether this overproduction is affected by therapy with the calcimimetic cinacalcet.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
study individuals
We selected and enrolled 8 patients with parathyroid cancer from a larger population of patients participating in a cinacalcet study and enrolled 6 healthy individuals and 6 PHPT patients as controls. The institutional review boards of Columbia University Medical Center and Saint-Luc Hospital approved the study procedures. All patients gave written informed consent.

protocol
Patients with parathyroid cancer initially received 30 mg cinacalcet twice daily; dosages were increased over 16 weeks to a maximum of 90 mg 4 times daily. Control individuals and PHPT patients were not treated with cinacalcet. Morning blood samples were obtained from these individuals after they had fasted overnight, and blood samples were obtained from the parathyroid cancer patients before cinacalcet doses at 0 and 16 weeks. Sera were frozen immediately and stored at –80 °C. Serum samples from 3 randomly selected patients with parathyroid cancer, 6 control individuals, and 6 PHPT patients were analyzed by HPLC. For 2 of the cancer patients, we conducted HPLC analyses on samples taken before and during cinacalcet therapy; for the 3rd patient, we analyzed only a sample taken during cinacalcet therapy.

biochemical measurements
Serum calcium, phosphate, and creatinine were measured with colorimetric methods adapted for multianalyzer analysis. We used ELISAs to measure cross-linked N-telopeptide of type I collagen (i.e., NTx; Inverness Medical Innovations/Ostex International; CV, 6.5%–9.5%) and bone-specific alkaline phosphatase (Esoterix Laboratory Services; CV, 9.9%–11.4%) in the serum of parathyroid cancer patients just before and at week 16 of cinacalcet therapy.

We measured PTH in serum samples and HPLC fractions with 2 PTH immunoradiometric assays (Scantibodies Laboratory). The same antibodies were used in both solid phase–capture assays and were purified by affinity chromatography against hPTH(39–84) (1)(6). The wPTH assay is a 3rd-generation assay with a 1–2 epitope region (1)(6) recognized by its revealing (labeled) antibody. This assay reacts with hPTH(1–84) but not with hPTH(7–84) or shorter C-terminal fragments (1)(6). After HPLC has separated serum PTH fractions, the assay recognizes the hPTH(1–84) peak and a separate peak for N-PTH, which is slightly less hydrophobic than hPTH(1–84) (2)(3)(4). The tPTH assay is a 2nd-generation PTH assay with a 12–18 epitope region recognized by its revealing antibody (3). The tPTH assay reacts equally well with hPTH(1–84) and hPTH(7–84). After HPLC has separated serum PTH fractions, this assay recognizes a peak corresponding to hPTH(1–84) and a peak corresponding to non-hPTH(1–84) fragments but reacts poorly with the N-PTH peak (3).

hplc analysis of serum
We extracted PTH molecular forms from the serum samples of all patients with Sep-Pak Plus C18 cartridges (Waters) as described by Bennett et al. (7). One C18 cartridge was used for up to 3 mL of serum. Samples were eluted from the cartridge with 6 mL of 800 mL/L acetonitrile in 1 g/L trifluoroacetic acid. The acetonitrile was evaporated from the eluate with nitrogen, and the residual volume was freeze-dried and reconstituted for HPLC analysis in 0.5 mL of 1 g/L trifluoroacetic acid. Each 0.5-mL sample was loaded on a Waters C18 µBondapak analytical column (300 mm x 3.9 mm i.d.) and eluted with a noncontinuous linear acetonitrile gradient in 1 g/L trifluoroacetic acid. The acetonitrile gradient ranged from 19% to 23% in 10 min, 23% to 30% in 5 min, and 30% to 33% in 30 min. The gradient was delivered at a rate of 1.0 mL/min with an Agilent Series 1100 solvent-delivery system. The 1.0-mL fractions were freeze-dried and reconstituted to 1 mL with 7 g/L BSA in water; adequate volumes of each fraction were then measured in the 2 PTH assays. We conducted control experiments by adding hPTH(1–84) calibrators and hPTH(1–84) to serum samples from patients with hypoparathyroidism to ensure that PTH degradation did not occur during the various extraction and reconstitution procedures. A single immunoreactivity peak coeluting with hPTH(1–84) or hPTH(7–84) was detected with the wPTH assay and the tPTH assay, respectively. The recovery of immunoreactive PTH through all of these procedures was >75% for all groups. Comparisons of original serum PTH values with values for the sum of PTH immunoreactivities of all the HPLC fractions indicated that our recoveries were 92.7% (8.2%) for the wPTH assay and 92.3% (11.4%) for the tPTH assay for the 5 parathyroid cancer HPLC runs (performed twice for 2 cancer patients and once for a 3rd cancer patient).

statistical analysis
Data are presented as the mean (SD). We used a one-way ANOVA followed by a Tukey test for 2 x 2 comparisons to analyze between-group differences in log-transformed data (Tables 1 and 2 ). We also used a paired Student t-test and log-transformed data to analyze within-group differences. We used log-transformed values and a 2-way repeated-measures ANOVA followed by a Tukey test for 2 x 2 comparisons to analyze changes in variables with time and differences between the parathyroid cancer groups with low and high wPTH:tPTH ratios (Table 3 ). HPLC profiles were evaluated planimetrically with Origin 4.1 software (Microcal Software) and corrected to 100% of the baseline PTH results.


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  		Table 1. Demographic, clinical, and biochemical characteristics of healthy individuals and hyperparathyroid and parathyroid cancer patients.1


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  		Table 2. Quantitative analysis of the wPTH and tPTH molecular forms in the various groups.1


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  		Table 3. Demographic, clinical, and biochemical characteristics of the cancer patients.1


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Table 1Up summarizes the demographic, clinical, and biochemical characteristics of the 3 patient and control groups. For the parathyroid cancer group, data are also given for the 0- and 16-week time points (before and during cinacalcet therapy). Healthy control individuals were younger than the patients in the 2 other groups. The numbers of male and female patients also varied among the groups. As expected, patients with parathyroid cancer had more severe disease than patients with PHPT; the highest mean calcium, wPTH, and tPTH concentrations; and the highest total alkaline phosphatase activities. The mean wPTH:tPTH ratio for the parathyroid cancer patients was significantly increased into the abnormal range (>1) compared with the PHPT patients (P <0.01) but not with respect to the healthy controls. PHPT patients were less hypercalcemic and had lower, but still increased, values for total alkaline phosphatase activity; wPTH and tPTH concentrations were well above the mean values for the healthy controls. In contrast to the parathyroid cancer patients, wPTH:tPTH ratios in PHPT patients were well below 1 and comparable to the values observed in the healthy controls.

Cinacalcet therapy of 16 weeks in parathyroid cancer patients was associated with an appreciable 1-mmol/L decrease in total calcium concentration. tPTH concentrations decreased, but the wPTH:tPTH ratio did not change. Bone alkaline phosphatase activity and serum N-telopeptide concentration increased appreciably over the same period of time.

Table 3Up presents the same parathyroid cancer patient characteristics as in Table 1Up , but the patients are divided into 2 groups of 4 patients according to the wPTH:tPTH ratio [>1 (high) or <1 (typical)] before initiation of calcimimetic therapy. Patients with a high ratio were more hypercalcemic initially, but the mean total calcium concentration for these patients decreased to a concentration at week 16 that was comparable to that of the group with a typical ratio. Patients with a high ratio tended to have higher creatinine and phosphate values. Total alkaline phosphatase, bone-specific alkaline phosphatase, and serum N-telopeptide concentrations were higher in patients with a high ratio at the beginning and at the end of the cinacalcet therapy period. wPTH concentrations, but not tPTH concentrations, were higher at both time points in the high-ratio group. The wPTH:tPTH ratio was not affected by therapy in either group.

Fig. 1 presents mean HPLC profiles obtained for healthy individuals (n = 6) and PHPT patients (n = 6), as well as individual HPLC profiles for 2 high-ratio cancer patients and 1 typical-ratio patient before and/or during cinacalcet therapy. Three regions of interest corresponding to non-(1–84) PTH fragments (region 22–32 min), N-PTH (region 34–39 min), and hPTH(1–84) (region 40–45 min) can be identified in all of the profiles. Table 2Up summarizes the planimetric evaluation of these profiles. In healthy individuals and PHPT patients, hPTH(1–84) constituted the dominant molecular form of circulating PTH, representing 90% of wPTH immunoreactivity and 79% of tPTH immunoreactivity. N-PTH accounted for the remaining 10% of wPTH immunoreactivity, and non-(1–84) PTH fragments constituted 21% of tPTH immunoreactivity. The situation was quite different in the 2 parathyroid cancer patients with a high ratio. In these patients, N-PTH was the dominant form at 65% of wPTH immunoreactivity, whereas hPTH(1–84) represented only 33% of the circulating immunoreactivity. In 1 cancer patient, hPTH(1–84) represented as little as 25% of the total circulating PTH. In the tPTH assay, N-PTH was 4–5 times less reactive but still represented 20% of the immunoreactivity. Even in the cancer patient with a low ratio, N-PTH represented 34% of wPTH immunoreactivity, a value higher than the values for the control individuals and PHPT patients. Cinacalcet therapy did not influence the HPLC profile in the 2 patients for whom a comparative study was available.


Figure 1
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  		Figure 1. HPLC profiles of tPTH (dashed line) and wPTH (solid line) in the various groups.

The HPLC profiles of healthy individuals and PHPT patients represent the mean of 6 HPLC profiles in each case. HPLC profiles for parathyroid cancer patients represent 1 low-ratio individual (cancer 1) and 1 high-ratio patient (cancer 2) before and during (on) cinacalcet treatment, and a 2nd high-ratio individual during cinacalcet therapy (cancer 3; serum sample before treatment not available). ACN, acetonitrile.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
We found that N-PTH is often overproduced in parathyroid cancer. These results extend earlier findings of N-PTH overproduction in patients with severe primary or secondary hyperparathyroidism (2)(4)(5). The high N-PTH concentrations detected in these profoundly hyperparathyroid groups contrasts markedly with the low concentrations typically detected in routine PHPT cases and in healthy control individuals.

We compared patients with parathyroid cancer with nonpathogenic control individuals and PHPT patients. We used both the wPTH assay, a 3rd-generation PTH assay that detects both hPTH(1–84) and N-PTH (2)(4)(5), and the tPTH assay, a 2nd-generation PTH assay that detects both hPTH(1–84) and non-(1–84) PTH fragments (2)(4)(5) but reacts poorly with N-PTH. Typically, values obtained with the tPTH assay are at least 20% higher than data obtained with the wPTH assay, because the non-(1–84) PTH fragments detectable with the tPTH assay represent a larger proportion of circulating PTH than N-PTH; however, we found an abnormally increased wPTH:tPTH ratio (>1) in 4 of the 8 cancer patients. The other 4 patients had ratios <1, similar to those seen in healthy individuals and patients with routine PHPT.

To understand why the wPTH:tPTH ratio was increased in half of the parathyroid cancer patients, we used HPLC to fractionate serum samples from 3 of the cancer patients and measured the immunoreactivities of specific PTH peaks. N-PTH was increased in 2 of the cancer patients. In contrast to healthy individuals and PHPT patients, in whom N-PTH represented 15% of the wPTH at most, N-PTH represented 65% of the tPTH immunoreactivity in these 2 cancer patients. Even in the cancer patient with a typical wPTH:tPTH ratio, HPLC analysis documented that N-PTH represented 34% of the wPTH immunoreactivity, more than twice as much as in the healthy and hyperparathyroid groups. In contrast to healthy individuals and PHPT patients, in whom hPTH(1–84) represented 90% of wPTH immunoreactivity, hPTH(1–84) represented no more than 66% of wPTH immunoreactivity in any of the 3 parathyroid cancer patients tested. Although the tPTH assay recognizes N-PTH poorly, the tPTH assay revealed that 15% of the PTH in the sera of parathyroid cancer patients (low and high PTH ratios) was N-PTH. The tPTH assay showed that the percentages of non-(1–84) PTH in the 3 groups were comparable.

Our observations help to confirm that N-PTH oversecretion may be indicative of clinically worse parathyroid disease. An increased wPTH:tPTH ratio has been found only rarely (<5%) in patients with benign PHPT (8). The source of the excess N-PTH has been associated with the pathologic parathyroid tissue itself (5). Internally labeled N-PTH obtained from parathyroid tissue of patients with primary and secondary hyperparathyroidism has been sequenced and, as expected, has an intact N-terminal structure (9). We have suggested that N-PTH can be phosphorylated on Ser17, because the different N-PTH immunoreactivities in the wPTH and tPTH assays have been associated with the 15–20 region of the PTH structure (2)(4)(5) and because phosphorylation of hPTH(1–84) in the 1–34 region has previously been demonstrated (10). More studies are required to elucidate this point.

Cinacalcet is effective in reducing calcium concentrations in parathyroid cancer patients and causes a small decrease in tPTH concentrations, although only in patients with a low wPTH:tPTH ratio. This decrease was not observed in the patients with a high ratio and had no impact on the ratio at week 16 of cinacalcet therapy in either group. The decline in serum calcium concentrations with cinacalcet therapy is difficult to explain, given the minimal or lack of changes in PTH concentrations and the wPTH:tPTH ratio. It is possible that the physiological relationship between PTH and calcium is altered in parathyroid carcinoma to produce an increase in the nonsuppressible fraction of PTH secretion. It is also possible that parathyroid cancer cells lack sufficient numbers of calcium-sensing receptors that are effectively coupled to the mechanisms that regulate PTH secretion. In addition, cinacalcet may act directly on the calcium-sensing receptor in the kidney; however, we did not measure urinary calcium excretion in response to this drug. Additional studies will be required to address these possibilities. As we expected from these results, the HPLC profiles of the 2 studied cancer patients did not change after cinacalcet therapy was initiated. We have described a similar lack of change in the PTH HPLC profile in a patient with severe PHPT who was treated with vitamin D and an intravenously administered bisphosphonate (4). In contrast, removal of the pathologic parathyroid gland appears to normalize the PTH HPLC profile, in both primary and secondary hyperparathyroidism (4)(11).

In conclusion, a new N-form of PTH appears to be oversecreted in patients with parathyroid cancer. Future studies with larger numbers of individuals are likely to provide more information about the structure, bioactivity, source, and regulation of this N-PTH variant and produce further useful insight into this rare disease, as well as into the more general regulation of PTH metabolism.


   Acknowledgments
 
Grant/funding support: S.J.S. is supported in part by K24 DK074457. This work was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases Grant 32333 and by Canadian Institutes of Health Research Grant MOP-7643.

Financial disclosures: Initial work that led to this study was supported by Amgen.


   Footnotes
 
1 Nonstandard abbreviations: PTH, parathyroid hormone; hPTH(1–84), intact human PTH of 84 amino acid residues; N-PTH, N-terminal PTH form; wPTH, whole PTH; tPTH, total PTH; PHPT, primary hyperparathyroidism.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Gao P, Scheibel S, D’Amour P, John MR, Rao SD, Schmidt-Gayk H, et al. Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 2001;16:605-614.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  2. D’Amour P, Brossard JH, Rousseau L, Roy L, Gao P, Cantor T. Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1–84) is overproduced in primary and secondary hyperparathyroidism. Clin Chem 2003;49:2037-2044.[Abstract/Free Full Text]
  3. D’Amour P, Brossard JH, Rakel A, Rousseau L, Albert C, Cantor T. Evidence that the amino-terminal composition of non-(1–84) parathyroid hormone fragments starts before position 19. Clin Chem 2005;51:169-176.[Abstract/Free Full Text]
  4. Rakel A, Brossard JH, Patenaude JV, Albert C, Nassif E, Cantor T, et al. Overproduction of an amino-terminal form of PTH distinct from human PTH(1–84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery. Clin Endocrinol 2005;62:721-727.[CrossRef][Medline] [Order article via Infotrieve]
  5. Arakawa T, D’Amour P, Rousseau L, Brossard J, Sakai M, Kasumoto H, et al. 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 2006;1:525-531.[CrossRef][Medline] [Order article via Infotrieve]
  6. John MR, Goodman WG, Gao P, Cantor TL, Salusky IB, Juppner H. A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure. J Clin Endocrinol Metab 1999;84:4287-4290.[Abstract/Free Full Text]
  7. Bennett HP, Solomon S, Goltzman D. Isolation and analysis of human parathyrin in parathyroid tissue and plasma: use of reversed-phase liquid chromatography. Biochem J 1981;197:391-400.[Web of Science][Medline] [Order article via Infotrieve]
  8. Boudou P, Ibrahim F, Cormier C, Sarfati E, Souberbielle JC. Unexpected serum parathyroid hormone profiles in some patients with primary hyperparathyroidism. Clin Chem 2006;52:757-760.[Abstract/Free Full Text]
  9. D’Amour P, Brossard JH, Rousseau L, Nguyen-Yamamoto L, Nassif E, Lazure C, et al. Structure of non-(1–84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism. Kidney Int 2005;68:998-1007.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  10. Rabbani SA, Kremer R, Bennett HP, Goltzman D. Phosphorylation of parathyroid hormone by human and bovine parathyroid glands. J Biol Chem 1984;259:2949-2955.[Abstract/Free Full Text]
  11. Tanaka M, Itoh K, Matsushita K, Matsushita K, Fujii H, Fukagawa M. Normalization of reversed bio-intact-PTH(1–84)/intact-PTH ratio after parathyroidectomy in a patient with severe secondary hyperparathyroidism. Clin Nephrol 2005;64:69-72.[Web of Science][Medline] [Order article via Infotrieve]



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