title: Direct and indirect assessment of the parathyroid hormone response to pamidronate therapy in Paget's disease of bone and hypercalcaemia of malignancy.
abstract: In patients with either Paget's disease or hypercalcaemia associated with malignancy (HCM) we have assessed the parathyroid response to pamidronate therapy, both by immunoassay of serum intact parathyroid hormone PTH (1-84) and by measurement of indirect parameters of PTH bioactivity, tubular maximum reabsorption of phosphate (TmPO4/GFR) and nephrogenous cyclic AMP (NcAMP). In 12 patients with Paget's disease, therapy with pamidronate produced a small but significant decrease in adjusted serum calcium within the reference interval which was accompanied by a progressive increase in PTH (1-84) secretion and a corresponding fall in TmPO4/GFR and increase in NcAMP. In 12 patients with HCM pretreatment, PTH (1-84) concentrations were suppressed, whilst mean TmPO4/GFR was reduced and NcAMP was increased, compatible in most patients, with parathyroid hormone-related peptide (PTHrP) driven hypercalcaemia. Therapy with pamidronate produced the expected fall in serum calcium but caused an increase in PTH (1-84) secretion in the presence of absolute hypercalcaemia. The initial subnormal TmPO4/GFR decreased further to a nadir on day 5, and there was a corresponding further increase in NcAMP. By day 7, however, when PTH (1-84) concentrations were maximal, there was a significant paradoxical rise in TmPO4/GFR and a corresponding decrease in NcAMP. These data are consistent with a variable trigger point for PTH (1-84) secretion, one consequence of which is a reduction in the risk of hypocalcaemia following pamidronate. The results have major clinical implications for the interpretation of PTH (1-84) measurements in patients who are being treated or about to be treated for bone disease or for hypercalcaemia of malignancy (HCM).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Biochemistry, Royal Infirmary, Glasgow, Scotland.
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: F C
authors.initials: FC
authors.lastname: Logue
authors.forename: S J
authors.initials: SJ
authors.lastname: Gallacher
authors.forename: D S
authors.initials: DS
authors.lastname: O'Reilly
authors.forename: G H
authors.initials: GH
authors.lastname: Beastall
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: I T
authors.initials: IT
authors.lastname: Boyle
mesh_terms: D000368:Aged; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010001:Osteitis Deformans / Q000188:drug therapy / Q000378:metabolism*; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates / Q000378:metabolism; D011506:Proteins / Q000378:metabolism
chemical_list: D004164:Diphosphonates; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates; D011506:Proteins; D000242:Cyclic AMP; D000077268:Pamidronate; D002118:Calcium