title: Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  Nodular goiter is common worldwide, but there is still debate over the medical treatment.
  
  
  OBJECTIVE
  The objective of the study was the measurement of the effect of a treatment with (nonsuppressive) T(4), iodine, or a combination of both compared with placebo on volume of thyroid nodules and thyroid.
  
  
  METHODS
  This was a multicenter, randomized, double-blind trial in patients with nodular goiter in Germany [LISA (Levothyroxin und Iodid in der Strumatherapie Als Mono-oder Kombinationstherapie) trial].
  
  
  METHODS
  The study was conducted in outpatient clinics in university hospitals and regional hospitals and private practices.
  
  
  METHODS
  One thousand twenty-four consecutively screened and centrally randomized euthyroid patients aged 18-65 yr with one or more thyroid nodules (minimal diameter 10 mm) participated in the study.
  
  
  METHODS
  Intervention included placebo, iodine (I), T(4), or T(4)+I for 1 yr. T(4) doses were adapted for a TSH target range of 0.2-0.8 mU/liter.
  
  
  METHODS
  The primary end point was percent volume reduction of all nodules measured by ultrasound, and the main secondary end point was a change in goiter volume.
  
  
  RESULTS
  Nodule volume reductions were -17.3% [95% confidence interval (CI) -24.8/-9.0%, P < 0.001] in the T(4)+I group, -7.3% (95% CI -15.0/+1.2%, P = 0.201) in the T(4) group, and -4.0% (95% CI -11.4/+4.2%, P = 0.328) in the I group as compared with placebo. In direct comparison, the T(4)+I therapy was significantly superior to T(4) (P = 0.018) or I (P = 0.003). Thyroid volume reductions were -7.9% (95% CI -11.8/-3.9%, P < 0.001), -5.2% (95% CI -8.7/-1.6%, P = 0.024) and -2.5% (95% CI -6.2/+1.4%, P = 0.207), respectively. The T(4)+I therapy was significantly superior to I (P = 0.034) but not to T(4) (P = 0.190).
  
  
  CONCLUSIONS
  In a region with a sufficient iodine supply, a 1-yr therapy with a combination of I and T(4) with incomplete suppression of thyrotropin reduced thyroid nodule volume further than either component alone or placebo.
authors.affiliation: Endokrinologie und Diabetologie im Zentrum, Sophienstrasse 40, D-70178 Stuttgart, Germany. martin@grussendorf.de.
authors.forename: M
authors.initials: M
authors.lastname: Grussendorf
authors.forename: C
authors.initials: C
authors.lastname: Reiners
authors.forename: R
authors.initials: R
authors.lastname: Paschke
authors.forename: K
authors.initials: K
authors.lastname: Wegscheider
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006801:Humans; D007455:Iodine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016606:Thyroid Nodule / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D007455:Iodine; D013974:Thyroxine