title: Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity.
abstract: Parathyroid hormone-related protein is responsible for the hypercalcaemia caused by many tumours. Measurement of parathyroid hormone-related protein is becoming more accessible with the introduction of commercial assays. We report a case of hypercalcaemia of malignancy secondary to parathyroid hormone-related protein in a woman with renal carcinoma. The parathyroid hormone-related protein was assayed using a new immunoradiometric assay. We demonstrated an initial fall in parathyroid hormone-related protein and calcium levels after surgery and a rise in both before clinical relapse. However, the clinical relapse was itself associated with a fall in serum parathyroid hormone-related protein, nephrogenous cAMP and calcium, suggesting that the tumour had stopped producing parathyroid hormone-related protein or perhaps that post-translational processing had occurred as the tumour advanced. The tumour was investigated for parathyroid hormone-related protein mRNA content using reverse transcriptase polymerase chain reaction, both at diagnosis in surgically removed material, and using post-mortem specimens. The level of parathyroid hormone-related protein mRNA, while present, was much reduced in the recurrent tumour suggesting that active parathyroid hormone-related protein production fell substantially as the tumour advanced. This case suggests that, although demonstration of parathyroid hormone-related protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this product may alter.
authors.affiliation: Department of Medicine, University of Liverpool, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Savage
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: C W
authors.initials: CW
authors.lastname: Bodmer
authors.forename: A F
authors.initials: AF
authors.lastname: Ginty
authors.forename: J A
authors.initials: JA
authors.lastname: Gallagher
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000150:complications* / Q000235:genetics; D001483:Base Sequence; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology*; D015592:Immunoradiometric Assay; D007680:Kidney Neoplasms / Q000097:blood / Q000150:complications* / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis*; D044162:Parathyroid Hormone-Related Protein; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011933:Reagent Kits, Diagnostic
chemical_list: D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D011933:Reagent Kits, Diagnostic