title: Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during 131I-metaiodobenzylguanidine treatment in children with neuroblastoma.
abstract: OBJECTIVE
  Treatment with (131)I-MIBG is associated with significant thyroid damage. This study was undertaken to investigate the long-term efficacy of current thyroid prophylaxis, to explore the relationship between thyroid dysfunction and thyroid volume after exposure to (131)I-MIBG and to evaluate the possible negative effects of (131)I(-) on the parathyroid glands.
  
  
  METHODS
  Of 81 long-term surviving patients with neuroblastoma treated with (131)I-MIBG during the period 1999-2012, 24 were finally evaluated. Patients received thyroxine (T4), methimazole and potassium iodide as thyroid protection. In all patients (para)thyroid function was evaluated and ultrasound investigation of the (para)thyroid gland(s) was performed. Thyroid dysfunction was defined as a plasma thyrotropin concentration >5.0 mU/L (thyrotropin elevation, TE) or as the use of T4 at the time of follow-up. Hyperparathyroidism was defined as a serum calcium concentration above the age-related reference range in combination with an inappropriately high parathyroid hormone level.
  
  
  RESULTS
  At a median follow-up of 9.0 years after (131)I-MIBG treatment, thyroid disorders were seen in 12 patients (50 %; 9 with TE, 5 with a thyroid nodule and 1 patient was subsequently diagnosed with differentiated thyroid carcinoma). No significant risk factors for the occurrence of thyroid damage could be identified. In 14 of 21 patients (67 %) in whom thyroid volume could be determined, the volume was considered small (<-2SD) for age and gender. Patients treated with T4 at the time of follow-up had significantly smaller thyroid volumes for age than patients without T4 treatment (p = 0.014). None of the patients was diagnosed with hyperparathyroidism.
  
  
  CONCLUSIONS
  Thyroid protection during treatment with (131)I-MIBG needs attention and must be further improved, as thyroid disorders are still frequently seen despite current thyroid prophylaxis. Reduced thyroid volume in neuroblastoma survivors may be related to previous (131)I-MIBG therapy or current T4 treatment. No deleterious effects of (131)I-MIBG on the parathyroid glands could be found.
authors.affiliation: Department of Pediatric Endocrinology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, PO box 22660, 1100 DD, Amsterdam, The Netherlands, s.c.clement@amc.uva.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Clement
authors.forename: R R
authors.initials: RR
authors.lastname: van Rijn
authors.forename: B L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.forename: A S P
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: H N
authors.initials: HN
authors.lastname: Caron
authors.forename: G A M
authors.initials: GA
authors.lastname: Tytgat
authors.forename: H M
authors.initials: HM
authors.lastname: van Santen
mesh_terms: D019797:3-Iodobenzylguanidine / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000517:prevention & control*; D007223:Infant; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control*; D009447:Neuroblastoma / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000517:prevention & control*
chemical_list: D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine