Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Abstract

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.

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

“…We also used a paired Student t-test Clinical Chemistry 53, No. 8,2007 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 ϫ 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).…”

“…An increased wPTH:tPTH ratio has been found only rarely (Ͻ5%) in patients with benign PHPT (8 ). The source of the excess N-PTH has been associated with the pathologic parathyroid tissue itself (5 ).…”

Primary and Secondary Hyperparathyroidism Testing and Assays

“…They also recognize a new form of hPTH(1-84) which is post-translationally modifi ed in region 15-20 and reacts poorly in I-PTH assays with a 13-20 epitope [ 24 ] . This new form of hPTH , called N-PTH, usually represents less than 10% of immunoreactive third-generation PTH in normal individuals and less than 15% in renal failure patients [ 25,26 ] but can be overproduced in some patients with pHPT, mainly patients with parathyroid cancer and patients with severe forms of the disease [ 27,28 ] , although this may not always be the case [ 29 ] . All these patients have been identifi ed because their third-generation PTH results were higher than their I-PTH results [27][28][29] .…”

“…This new form of hPTH , called N-PTH, usually represents less than 10% of immunoreactive third-generation PTH in normal individuals and less than 15% in renal failure patients [ 25,26 ] but can be overproduced in some patients with pHPT, mainly patients with parathyroid cancer and patients with severe forms of the disease [ 27,28 ] , although this may not always be the case [ 29 ] . All these patients have been identifi ed because their third-generation PTH results were higher than their I-PTH results [27][28][29] . Usually, third-generation PTH results are lower than second-generation PTH values in normal individuals and renal failure patients [24][25][26] .…”

“…Usually, third-generation PTH results are lower than second-generation PTH values in normal individuals and renal failure patients [24][25][26] . The normal range is from 5 to 40 pg/ml (0.53 to 4.2 pmol/L) in the fi rst assay developed [ 22,23 ] , but has varied between assays from different commercial sources [ 29 ] . One study found the fi rst third-generation PTH assay to be more sensitive in detecting patients with mild pHPT [ 30 ] , whereas another did not [ 31 ] discern any difference between third-and second-generation PTH results in this regard.…”