Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease

J Clin Endocrinol Metab. 2002 Oct;87(10):4490-5. doi: 10.1210/jc.2002-020580.


Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithyroid Agents / administration & dosage*
  • Graves Disease / blood
  • Graves Disease / drug therapy*
  • Graves Disease / radiotherapy
  • Humans
  • Iodine Radioisotopes / administration & dosage
  • Iodine Radioisotopes / therapeutic use*
  • Lithium / adverse effects
  • Lithium / blood
  • Lithium / therapeutic use*
  • Methimazole / administration & dosage*
  • Prospective Studies
  • Thyroid Hormones / blood*
  • Thyroxine / blood
  • Treatment Outcome
  • Triiodothyronine / blood


  • Antithyroid Agents
  • Iodine Radioisotopes
  • Thyroid Hormones
  • Triiodothyronine
  • Methimazole
  • Lithium
  • Thyroxine