title: Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.
abstract: OBJECTIVE
  The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate).
  
  
  METHODS
  In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group.
  
  
  RESULTS
  In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy.
  
  
  CONCLUSIONS
  The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC, University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands, e.i.vanvliet@erasmusmc.nl.
authors.forename: Esther I
authors.initials: EI
authors.lastname: van Vliet
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Boen L R
authors.initials: BL
authors.lastname: Kam
authors.forename: Jaap J M
authors.initials: JJ
authors.lastname: Teunissen
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000097:blood* / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D009942:Organometallic Compounds; C447941:lutetium Lu 177 dotatate; D015282:Octreotide; D002118:Calcium