Correspondence
Radioiodine Therapy for Hyperthyroidism
N Engl J Med 2011; 364:1978-1979May 19, 2011
- Article
To the Editor:
In his article on radioiodine (131I) therapy for hyperthyroidism (Feb. 10 issue),1 Ross describes the use of levothyroxine alone after radioiodine therapy once diminished thyroid function has stabilized. An article in a 1999 issue of the Journal by Bunevičius et al. suggested that treatment with thyroxine plus triiodothyronine in patients with hypothyroidism improved the quality of life for many as compared with treatment with thyroxine alone.2 Although other investigators have disputed this benefit, there is no question that a subgroup of patients perceives an improvement in their quality of life with the use of combination therapy. A 2009 study in the European Journal of Endocrinology also supports the use of combined therapy.3 As a physician of nuclear medicine who was treated with 131I for Graves' disease, I have had the anecdotal experience of a dramatic response when triiodothyronine was added to my thyroxine regimen.
Maryellen Amato-Stratmann, M.D.
Drury University, Springfield, MO
amatomd@aol.com No potential conflict of interest relevant to this letter was reported.
3 References1
Ross DS . Radioiodine therapy for hyperthyroidism. N Engl J Med 2011;364:542-550
Full Text | Web of Science | Medline2
Bunevicius R ,Kazanavicius G ,Zalinkevicius R ,Prange AJ Jr . Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999;340:424-429
Full Text | Web of Science | Medline3
Nygaard B ,Jensen EW ,Kvetny J ,Jarlov A ,Faber J . Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyroxine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Eur J Endocrinol 2009;161:895-902
CrossRef | Web of Science | Medline
To the Editor:
In the clinical vignette, Ross comments on a 37-year-old woman with Graves' disease who relapsed after she had taken methimazole for 1 year. Radioiodine treatment was recommended because she wishes to become pregnant.
An important point to consider is the possibility of fetal or neonatal Graves' thyrotoxicosis. Fetal and neonatal Graves' hyperthyroidism results from the transplacental passage of the maternal thyrotropin receptor antibody (TRAb). In the majority of patients, serum levels of TRAb increase after radioiodine treatment and begin to decrease long after treatment,1,2 reaching normal values more than 5 years after radioiodine therapy.2 As reported by some authors,3-5 there is a strong relationship between levels of TRAb and the risk of fetal or neonatal Graves' thyrotoxicosis. Women who want to get pregnant in the near future and are undergoing radioiodine treatment should be informed of the risks of fetal or neonatal hyperthyroidism developing during pregnancy.
Danilo Villagelin, M.D.
Roberto B. Santos, M.D., Ph.D.
João H. Romaldini, M.D., Ph.D.
Pontifícia Universidade Católica de Campinas, Campinas, Brazil
danilo28@terra.com. br No potential conflict of interest relevant to this letter was reported.
5 References1
McGregor AM ,McLachlan SM ,Smith BR ,Hall R . Effect of irradiation on thyroid-autoantibody production. Lancet 1979;2:442-444
CrossRef | Web of Science | Medline2
Laurberg P ,Wallin G ,Tallstedt L ,Abraham-Nordling M ,Lundell G ,Torring O . TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008;158:69-75
CrossRef | Web of Science | Medline3
McKenzie JM ,Zakarija M . Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH receptor antibodies. Thyroid 1992;2:155-159
CrossRef | Web of Science | Medline4
Clavel S ,Madec AM ,Bornet H ,Deviller P ,Stefanutti A ,Orgiazzi J . Anti TSH-receptor antibodies in pregnant patients with autoimmune thyroid disorder. Br J Obstet Gynaecol 1990;97:1003-1008
CrossRef | Medline5
Hamada N ,Momotani N ,Ishikawa N , et al. Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism. Endocr J 2011;58:55-58
CrossRef | Web of Science | Medline
Author/Editor Response
Approximately a dozen randomized, controlled trials and a meta-analysis1 have failed to show a benefit of combined treatment with thyroxine and triiodothyronine as compared with thyroxine alone in unselected patients with hypothyroidism. Type II iodothyronine deiodinase (DIO2) converts thyroxine into triiodothyronine in the central nervous system. The investigators from one large trial that had previously failed to show a benefit of combined treatment now report a benefit for a subgroup of patients with a polymorphism in DIO2 (16% of the study population). As compared with patients who had the predominant genotype, the subgroup had a poorer sense of psychological well-being at baseline when taking thyroxine alone and showed a greater response when triiodothyronine was added to their regimen, with no change in serum hormone levels.2 This finding suggests that there may be a physiological basis for Amato-Stratmann's preference for the combined treatment. When the combined treatment consists of a triiodothyronine dose that is excessive relative to the thyroxine dose, serum levels of triiodothyronine may be supraphysiologic and free thyroxine levels may be low. Elevated levels of triiodothyronine might precipitate an arrhythmia in a susceptible patient, and low levels of free thyroxine have been associated with poor outcomes in pregnancy. Triiodothyronine should be added to a regimen of thyroxine alone only for select cases in which patients feel poorly when taking thyroxine alone.
Fetal and neonatal Graves' hyperthyroidism occurs in approximately 2% of the offspring of mothers with Graves' disease.3 The risk is positively associated with a higher TRAb titer and the efficacy of transplacental transfer.3 After radioiodine therapy, the transient increase in TRAb titers reported in nonpregnant patients returns to baseline at 1 year but remains higher than in patients who continue taking antithyroid drugs or who have surgery.4 Patients are instructed to avoid pregnancy for 6 months after treatment with radioiodine; once a treated patient becomes pregnant, 20 more weeks elapse before the fetal thyroid is functional, and titers of TRAb commonly fall during pregnancy (resulting in spontaneous remission in Graves' hyperthyroidism in many pregnant women taking antithyroid drugs). Women with the highest TRAb titers frequently have moderately severe ophthalmopathy or large goiters, so radioiodine would be relatively contraindicated in these cases. I agree with Villagelin and colleagues that all women receiving treatment for Graves' hyperthyroidism and contemplating a pregnancy thereafter should be informed of the risk of fetal and neonatal hyperthyroidism. TRAb levels should be measured in these women during the second trimester.5
Douglas S. Ross, M.D.
Massachusetts General Hospital, Boston, MASince publication of his article, the author reports no further potential conflict of interest.
5 References1
Grozinsky-Glasberg S ,Fraser A ,Nahshoni E ,Weizman A ,Leibovici L . Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2006;91:2592-2599
CrossRef | Web of Science | Medline2
Panicker V ,Saravanan P ,Vaidya B , et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab 2009;94:1623-1629
CrossRef | Web of Science | Medline3
Lafranchi SH, Hanna CE. Graves' disease in the neonatal period and childhood. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's The thyroid: a fundamental and clinical text. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2004:1049-59.
4
Laurberg P ,Wallin G ,Tallstedt L ,Abraham-Nordling M ,Lundell G ,Torring O . TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008;158:69-75
CrossRef | Web of Science | Medline5
Abalovich M ,Amino N ,Barbour LA , et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2007;92:Suppl:S1-S47
CrossRef | Medline
