Immunologic differentiation of primary hyperparathyroidism from hyperparathyroidism due to nonparathyroid cancer

Riggs, B. Lawrence; Arnaud, Claude D.; Reynolds, James C.; Smith, Lynwood H.

doi:10.1172/jci106701

Cited by 158 publications

(34 citation statements)

References 11 publications

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“…The most striking difference was that the quantity of circulating COOH-terminal immunoreactive equivalents with mol wt of < 9,500 was seven times greater in primary HPT than in ectopic HPT. We believe that the decreased quantity of circulating biologically inactive COOHterminal fragments accounts for our previous observation (6) that, for a given serum calcium value, serum iPTH is relatively lower in ectopic HPT than in primary HPT.…”

Section: Recovery Of Ipth After Filtration and Concentrationmentioning

confidence: 63%

“…In both syndromes, plasma samples had an iPTH component that eluted well before PTH (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al 1971. J. Clin.…”

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confidence: 69%

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Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism

Benson¹,

Riggs²,

Pickard³

et al. 1974

J. Clin. Invest.

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123

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A B S T R A C T The immunoreactive forms of parathyroid hormone (iPTH) in the plasma of six patients wilth primary, adenomatous hyperparathyroidism and six patients with ectopic hyperparathyroidism due to nonparathyroid cancer were compared by using gel filtration on columns of Bio-Gel P-150 and radioimmunoassay of iPTH in eluted fractions after concentration. We found much less (p <0.001) small (mol wt < 9,500) COOHterminal fragments of iPTH in plasma samples from ectopic hyperparathyroid patients (0.52+0.13 ng eq/ml) than in samples from primary hyperparathyroid patients (3.70±1.15 ng eq/ml). The quantity of iPTH eluting with or before native bovine PTH was the same in both syndromes (ectopic hyperparathyroidism, 0.82± 0.22 ng eq/ml; primary hyperparathyroidism, 0.73±0.09 ng eq/ml), and these values correlated positively with plasma calcium concentration (ectopic hyperparathyroidism, r = 0.908; primary hyperparathyroidism, r = 0.919). In both syndromes, plasma samples had an iPTH component that eluted well before PTH (mol wt 9,500), but this component was present in much larger quantities in three patients with ectopic hyperparathyroidism. We conclude that (a) the decreased quantity of biologically inactive COOH-terminal fragments of iPTH circulating in ectopic hyperparathyroidism accounts for the previously reported relatively lower total serum iPTH values in this syndrome as compared with primary hyperparathyroidism (Riggs et al. 1971. J. Clin. Invest. 50: 2079; (b) there appears to be sufficient iPTH with presumed biologic activity to account for the hypercalcemia in both syndromes; (c) a large PTH component, not previously recognized in plasma, is present in both ectopic and primary hyperparathyroidism and may exist as the predominant immunoreactive form of the hormone in some patients with ectopic hyperparathyroidism.

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Section: Recovery Of Ipth After Filtration and Concentrationmentioning

confidence: 63%

mentioning

confidence: 69%

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism

Benson¹,

Riggs²,

Pickard³

et al. 1974

J. Clin. Invest.

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123

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“…MIarked differences were found among the tumors. Immunologic differences between circulating PTH in primary hyperparathyroidism and in ectopic hormone production by nonparathyroid neoplasms have been reported by Riggs, Arnaud, Reynolds, and Smith (20).…”

Section: Discussionmentioning

confidence: 73%

“…It was not until the last decade, with the development of immunologic techniques for the determination of polypeptide hormones, that a more systematic exploration of this field began (19,20).…”

Section: Discussionmentioning

confidence: 99%

Immunochemical Localization of Parathyroid Hormone in Cancer Tissue from Patients with Ectopic Hyperparathyroidism

1974

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A B S T R A C T Immunoreactive parathyroid hormone (PTH) in nonparathyroid malignant tumors associated with hypercalcemia and hypophosphatemia in the absence of demonstrable bone metastases was determined by radioimmunoassay and immunofluorescent techniques. Six of seven tumors contained material with immunological cross-reactivity to bovine PTH by radioimmunoassay and immunofluorescence. The intensity of the immunofluorescent stain varied considerably in the different tumors. From 15 to 90% of neoplastic cells were stained specifically with fluorescein-labeled anti-PTH. In contrast, normal parathyroid glands and parathyroid adenomas showed uniform distribution of immunofluorescence in all parenchymal cells. In one malignant tumor, PTH was localized also by immunoautoradiography. In every case PTH was detected only in the cytoplasm of parenchymal cells. One patient lacked detectable PTH in his tumor, yet showed regression of the hypercalcemia to normal values after removal of large masses of neoplastic tissue and recurrence of hypercalcemia when new growth occurred.Dilutional radioimmunoassay curves of nonparathyroid malignant tumors were in most cases different

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“…These observation may indicate the immunological heterogeneity of PTH produced from the ectopic source, which might explain the fact that plasma PTH levels in patients with pseudohyperparathyroidism were usually lower than those obtained from patients with primary hyperparathyroidism (Riggs et al, 1971).…”

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confidence: 96%

Radioimmunoassay of Parathyroid Hormone in Human Plasma and Tissue Using Commercially Available Antiserum and Modified Iodination

et al. 1974

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SynopsisThe human PTH radioimmunoassay has been developed by use of bovine PTH and anti-bovine PTH antiserum, both of which were commercially available. The iodination process was modified as to use acid solution resulting in the more stable 125I-PTH. However, the PTH radioimmunoassay employed this antiserum with 125I-bovine PTH revealed that the N-terminal portion of PTH molecule was reactive only slightly in this system, indicating that most of PTH determined by this radioimmunoassay might be an biologically inactive PTH.Plasma from normal subjects and patients with primary hyperparathyroidism or uremia showed dilutional curves parallel to the curve of the standard bovine PTH, indicating the immunological identity between human and bovine PTH in this radioimmunoassay system. The extract from the parathyroid adenoma showed an identical dilutional curve, but the extract from the ectopic PTH producing tumor showed a different dilutional curve from that of the standard PTH, which might indicate the immunochemical heterogeneity of PTH produced from the ectopic source. Plasma PTH levels obtained from normal subjects and patients with primary hyperparathyroidism, uremia or pseudohypoparathyroidism were compatible with those reported previously. These data indicate that the human PTH radioimmunoassay can be done by use of commercially available anti-bovine PTH antiserum and bovine PTH in conjunction with the modified iodination process and double antibody method. However, this assay was directed mainly to the C-terminal portion of PTH molecule and the PTH radioimmunoassay specific for the N-terminal portion will be required to evaluate the PTH regulation more precisely in man.

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Immunologic differentiation of primary hyperparathyroidism from hyperparathyroidism due to nonparathyroid cancer

Cited by 158 publications

References 11 publications

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism

Immunochemical Localization of Parathyroid Hormone in Cancer Tissue from Patients with Ectopic Hyperparathyroidism

Radioimmunoassay of Parathyroid Hormone in Human Plasma and Tissue Using Commercially Available Antiserum and Modified Iodination

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