Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia

Published on Jan 18, 1992in The Lancet79.323
· DOI :10.1016/0140-6736(92)90220-W
A. C. J. Hutchesson5
Estimated H-index: 5
(Selly Oak Hospital),
N. J. Bundred6
Estimated H-index: 6
(Selly Oak Hospital),
J. G. Ratcliffe4
Estimated H-index: 4
(Selly Oak Hospital)
Sources
Abstract
Abstract Parathyroid-hormone-related protein (PTHrP) has been implicated as a humoral mediator of hypercalcaemia in malignant disease. We have investigated the contributions of PTHrP and parathyroid hormone (PTH) to the hypercalcaemia seen in routine clinical practice by means of highly sensitive immunoradiometric assays. PTHrP concentrations in plasma and PTH concentrations in serum were measured in 121 consecutive patients with hypercalcaemia (corrected serum calcium above 2·65 mmol/l) identified from routine biochemical profiles in a district general hospital. Hypercalcaemia was due to primary hyperparathyroidism in 63 (52%) patients and to malignant disease in 40 (49%). Plasma PTHrP was detectable in 35 (88%) of 40 patients with solid tumours and 3 of 9 patients with haematological malignant disease; it was undetectable in 92% of patients with primary hyperparathyroidism. 7 patients with malignant disease had PTH concentrations above 4·0 pmol/l, consistent with coexisting primary hyperparathyroidism. Measurement of both PTH and PTHrP in all patients led to a change in the diagnosis in 7% of patients. This study provides direct evidence for a humoral role of tumour-derived PTHrP in hypercalcaemia, and shows how PTHrP assays can be used appropriately, in conjunction with PTH assays, to investigate hypercalcaemia in routine clinical practice.
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References24
Newest
#1H. M. Docherty (University of Birmingham)H-Index: 2
#2W. A. RatcliffeH-Index: 1
Last. K. DochertyH-Index: 1
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The expression of parathyroid hormone-related protein (PTHrP) in abnormal human parathyroids was investigated. Northern blot analysis of RNA extracted from human benign parathyroid adenomata (n=4) revealed multiple PTHrP mRNA species ranging in size from 1.8 to 4 kb. The relative abundance of PTHrP mRNA expressed in two of the adenomata was similar to that of a tumour (DAF) associated with humoral hypercalcaemia of malignancy, whereas PTHrP mRNA was of low abundance in a third and was undetectab...
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#1W.A. RatcliffeH-Index: 15
#2S NorburyH-Index: 3
Last. J G RatcliffeH-Index: 5
view all 4 authors...
This two-site immunoradiometric assay for human parathyrin-related protein 1-86 (PTHRP1-86) in plasma uses a mouse monoclonal antibody to PTHRP1-34 coupled to cellulose particles for immunoextraction of N-terminal immunoreactivity, and a rabbit antiserum to PTHRP37-67 that is indirectly labeled with 125I-labeled PTHRP37-67 for quantifying the bound analyte. The detection limit of the assay is 0.23 pmol/L, corresponding to 0.4 pg (0.04 fmol) per tube, for a sample volume of 200 microL. Recovery o...
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#1C. C. Shek (CUHK: The Chinese University of Hong Kong)H-Index: 2
#2A. NatkunamH-Index: 1
Last. R. SwaminathanH-Index: 1
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To determine the incidence and causes of hypercalcaemia in a hospital population in Hong Kong, all 29 107 samples received in the laboratory in one year were analysed for plasma calcium and albumin, and samples with a plasma calcium concentration adjusted for albumin greater than 2.55 mmol/l were investigated. Plasma calcium > 2.55 mmol/l was found in 462 patients. Repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183. The main causes of hypercalcaemia were malig...
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#1D WynickH-Index: 1
#2W A RatcliffeH-Index: 1
Last. S.R. BloomH-Index: 127
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Abstract Tumors from patients with humoral hypercalcemia of cancer produce a parathyroid Hormone-Related protein (PTHRP). We have developed two region-specific immunoassays capable of measuring PTHRP in plasma: an immunoradiometric assay directed toward PTHRP amino acid sequence 1 to 74 and a radioimmunoassay directed toward PTHRP amino acid sequence 109 to 138. Sixty normal subjects had low or undetectable plasma PTHRP(1 to 74) concentrations (mean, 1.9 pmol per liter) and undetectable PTHRP(10...
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#1Janet E. Henderson (McGill University)H-Index: 44
#2Chaim Shustik (McGill University)H-Index: 27
Last. David Goltzman (McGill University)H-Index: 98
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We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino-terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concent...
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A PTH-related peptide (PTHRP) has been identified and its cDNA cloned from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The human PTHRP gene has been recently isolated and found to be a complex transcriptional unit using multiple promoters and containing alternatively spliced 3′ exons which result in three mRNA classes, each class encoding a PTHRP with a unique carboxy-terminus. The PTHRP gene appears to be expressed in a number of normal tissues, and PTHRP t...
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#1A. A. Budayr (VA: United States Department of Veterans Affairs)H-Index: 3
#2Robert A. NissensonH-Index: 53
Last. Gordon J StrewlerH-Index: 32
view all 8 authors...
Study Objective: To measure the serum levels of a newly described parathyroid hormone-like protein (PLP), which was isolated from malignant tumors associated with hypercalcemia, and determine whether PLP is a humoral factor in malignancy-associated hypercalcemia
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Cited By111
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#1Michael T. Sheehan (Marshfield Clinic)H-Index: 10
#2Ya-Huei Li (Marshfield Clinic)H-Index: 1
Last. Adedayo A. Onitilo (Marshfield Clinic)H-Index: 23
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Context Hypercalcemia of malignancy (HCM) has not been studied in a fashion to determine all possible mechanisms of hypercalcemia in any given patient. Objective The 2 objectives were to assess the completeness of evaluation and to determine the distribution of etiologies of HCM in a contemporary cohort of patients. Methods A retrospective analysis was performed of patients with cancer who developed hypercalcemia over 20 years at a single health system. Laboratory data were electronically captur...
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Objective: Severe hypercalcemia is a medical emergency. Hyperparathyroidism, malignancy, vitamin D toxicity, infections such as tuberculosis, or systemic illness such as sarcoidosis are all possibl...
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#1Jeffrey M. Kroopnick (UMB: University of Maryland, Baltimore)
#2Ubaldo E. Martinez-Outschoorn (Thomas Jefferson University)H-Index: 65
Last. Caroline S. Kim (UPenn: University of Pennsylvania)H-Index: 4
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ABSTRACT Introduction Hypercalcemia of malignancy (HCM) portends a very poor prognosis and no established guidelines exist regarding its management. Most instances of HCM are due to local osteolysis or secretion of parathyroid hormone related-peptide (PTHrP) while less than 1% of all cases of are due to ectopic secretion of parathyroid hormone (PTH). Case Report We present an unusual case of HCM due to proposed co-secretion of both parathyroid hormone and parathyroid hormone-related protein in a...
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Calcium (Ca+2) is a divalent cation that plays a critical role in numerous body functions such as skeletal mineralization, signal transduction, nerve conduction, muscle contraction, and blood coagulation. Ca+2 metabolism is linked to magnesium (Mg+2) and phosphate metabolism. Ca+2 homeostasis is dependent on intestinal absorption, bone turnover, and renal reabsorption. The hormonal regulators of these processes are the parathyroid hormone (PTH), calcitriol {1,25-dihydroxyvitamin D [1,25(OH)2D]},...
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Hyperkalzamie findet sich im klinischen Alltag regelmasig. Zu den haufigsten Ursachen zahlen primarer Hyperparathyreoidismus und Malignome wie solide Tumoren und hamatologische Neoplasien. Bei Erstgenannten ist die Hyperkalzamie mit fortgeschrittenem Stadium und schlechter Prognose verbunden. Wegen unspezifischer Symptome und Vorliegen von Komorbiditaten wird die Hyperkalzamie bei Patienten mit Tumorerkrankung haufig erst spat erkannt. Neben Ursachensuche mittels eines differenziellen Algorithmu...
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#1Wei Xiong (SJTU: Shanghai Jiao Tong University)H-Index: 2
#2Yunfeng ZhaoH-Index: 3
Last. Xuejun Guo (SJTU: Shanghai Jiao Tong University)H-Index: 2
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BACKGROUND: Coagulation factor IV, also known as serum ionised calcium (SIC), participates in coagulative process and tends to elevate in patients with primary lung cancer. It may be an indicator of symptomatic pulmonary embolism (PE) due to primary lung cancer (LC). METHODS: A total of 388 patients who underwent CTPA and/or radionuclide ventilation perfusion scanning due to PE-suspected symptoms were stratified into LCPE (lung cancer and PE) group (n = 95), PE group (n = 99), LC group (n = 98) ...
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: Hypercalcemia due to malignant tumors including malignant lymphomas is relatively common. Among cancer patients with hypercalcemia, humoral hypercalcemia of malignancy is the most common and accounts for about 80% of all cases with hypercalcemia. 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-mediated hypercalcemia is relatively rare. Although malignant lymphoma has been also reported to cause 1,25(OH)2D3-mediated hypercalcemia, it is not known whether there is any association between 1,25(OH)2D3-media...
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#1Robert S. Schoaps (Penn State Milton S. Hershey Medical Center)H-Index: 2
#2Sprague W. Hazard (Penn State Milton S. Hershey Medical Center)H-Index: 6
Although the differential for hypercalcemia in the surgical patient is broad, a stepwise approach to the diagnosis and management will ensure adequate management of this common electrolyte abnormality. Hyperparathyroidism and malignancy account for 90% of hypercalcemic patients. Treatment is largely etiology specific and may be altered based on the presence or absence of associated symptoms.
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ABSTRACT Objective: To differentiate familial hypocalciuric hypercalcemia (FHH), a rare condition, from primary hyperparathyroidism (PHPT), one of the most common causes of hypercalcemia, leading to avoidance of unnecessary surgical treatment; and also to review FHH. Methods: We present the history, physical, laboratory investigations, and clinical course of a 42-year-old woman who presented to our endocrinology office with hypercalcemia. An updated review on FHH is also provided. Results: FHH i...
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#1Joon Jin (Chonnam National University)H-Index: 3
#2Jin Ook Chung (Chonnam National University)H-Index: 10
Last. Dong Jin Chung (Chonnam National University)H-Index: 13
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Background: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. Methods: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 20...
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