title: Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma--a systematic review.
abstract: BACKGROUND
  Treatment of differentiated thyroid carcinoma (DTC) often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. As DTC has favorable outcome and the incidence is increasing, concerns have been raised about the possible adverse effects of I-131 therapy. We systematically reviewed the literature to examine the risk of intermediate and long-term adverse effects of I-131 therapy in DTC patients.
  
  
  METHODS
  Multiple electronic databases were searched up to November 2014 for English-language, controlled studies that reported on the risk of salivary gland dysfunction, lacrimal gland dysfunction, gonadal dysfunction, female reproductive outcomes or second primary malignancies (SPM) after I-131 exposure. The certainty of the evidence found was assessed using GRADE.
  
  
  RESULTS
  In total, 37 articles met all inclusion criteria, no studies reporting on adverse effects after I-131 treatment focused solely on children. After exposure to I-131 for DTC, patients experienced significantly more frequently salivary gland dysfunction (prevalence range: 16-54%, moderate-level evidence), lacrimal gland dysfunction (prevalence: 11%, low-level evidence), transient male gonadal dysfunction (prevalence: 35-100%, high-level evidence), transient female gonadal dysfunction (prevalence: 28%, low-level evidence) and SPM (prevalence: 2.7-8.7%, moderate-level evidence) compared to unexposed patients. I-131 therapy seems to have no deleterious effects on female reproductive outcomes (very-low level evidence). The prevalence and severity of adverse effects were correlated to increasing cumulative I-131 activity.
  
  
  CONCLUSIONS
  Treatment with I-131 for DTC may have significant adverse effects, which seem to be dose dependent. These adverse effects of treatment must be balanced when choosing for I-131 therapy in patients with DTC.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. Electronic address: s.c.clement@amc.uva.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Clement
authors.affiliation: Department of Internal Medicine/Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands; Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Ronckers
authors.affiliation: Department of Endocrinology, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Department of Pediatric Surgery, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Nieveen van Dijkum
authors.affiliation: Department of Radiology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R R
authors.initials: RR
authors.lastname: van Rijn
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: H J H
authors.initials: HJ
authors.lastname: van der Pal
authors.affiliation: Department of Internal Medicine/Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Neggers
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L C M
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: B L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: Department of Pediatric Endocrinology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Santen
mesh_terms: D002277:Carcinoma / Q000532:radiotherapy*; D005128:Eye Diseases / Q000209:etiology*; D005260:Female; D006058:Gonadal Disorders / Q000209:etiology; D006801:Humans; D007247:Infertility, Female / Q000209:etiology*; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D007765:Lacrimal Apparatus; D008297:Male; D009381:Neoplasms, Radiation-Induced; D016609:Neoplasms, Second Primary; D009845:Oligospermia / Q000209:etiology*; D012466:Salivary Gland Diseases / Q000209:etiology*; D013964:Thyroid Neoplasms / Q000532:radiotherapy*
chemical_list: D007457:Iodine Radioisotopes
keywords: Adverse effects; Complications; Differentiated thyroid carcinoma; I-131; Radioactive iodine; Second primary malignancies