Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial

Abstract

Objective: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T 4 ) in patients with endemic goitre. Methods: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T 4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months. Results: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 mg/24 h at baseline, 415 mg/24 h at 6 months) compared with those receiving T 4 (47 mg/ 24 h at baseline, 165 mg/24 h at 6 months; P < 0.0001 compared with iodine group). T 4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (33 ml to 21 ml, P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo-and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine, thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them. Conclusion: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

Enhanced Iodination of Thyroglobulin Facilitates Processing and Presentation of a Cryptic Pathogenic Peptide

“…High doses of I can cause necrosis of hyperplastic thyroid glands of normal animals (13,44) or human thyroid follicles in vitro (45). This initial thyroid cell injury may be an important prerequisite for the subsequent development of autoimmune thyroiditis in goitrous nonobese diabetic mice (46), obese strain chickens (44), or humans with preexisting goiters (3,5,47,48). In addition, I can exhibit pleiotropic effects by influencing processes that interfere with immune function.…”

Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy

“…This may indicate an additive effect of an increase in iodine intake and a surge in thyroid autoimmunity on thyroid failure in patients with SCH. Supplementary iodine given to individuals with euthyroid Hashimoto's thyroiditis has previously been associated with increased risk of a decline in thyroid function without change in thyroid autoimmunity (44), whereas serum TSH and TPO-Ab increased in some patients with euthyroid endemic goitre treated with potassium iodide (45).…”

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

“…As discussed above, iodine has high affinity for thyroid hormones, so 80% of total body iodine is maintained in the thyroid by a specific iodide pump. The element is essential for normal thyroid function and although most individuals tolerate a wide range of dietary levels, some are dearly prone to the development of thyroid dysfunction (13). The toxicity of iodide has been related to its requirement for oxidation to the iodinum ion (21--2e' -4 [I2] -2e -+ 2I+) prior to its binding to tyrosine residues of thyroglobulin (8).…”