Effect of Iodine Restriction on Thyroid Function in Patients With Primary Hypothyroidism

Kanji Kasagi, Masahiro Iwata, Takashi Misaki, Junji Konishi


Thyroid. 2003;13(6) 

In This Article


Iodine excess is a well-known exogenous factor that causes hypothyroidism. Iodine induces suppression of TSH-stimulated cyclic AMP production and protein iodination in vitro.[12] Administration of excessive amounts of iodine induces thyroiditis in genetically susceptible animal strains.[13,14] Sundick et al.[15] reported that highly iodinated thyroglobulin synthesized by animals fed a high iodine diet was more immunogenic than thyroglobulin containing fewer iodine atoms.

According to Braverman et al.,[6] four of seven euthyroid patients with Hashimoto's thyroiditis who were given a solution of potassium iodide (180 mg of iodine) daily developed hypothyroidism after 4-8 weeks. Reinhardt et al.[7] reported that seven of 40 patients with underlying Hashimoto's thyroiditis living in an area of mild iodine deficiency given small amounts of iodine (250 µg daily) developed hypothyroidism.

The frequency of Hashimoto's thyroiditis in the reversible hypothyroidism group 1 (11 of 21, 52.3%) determined on the basis of TgAb or TPOAb detection is much higher than in healthy controls. Thus, patients with Hashimoto's thyroiditis appear susceptible to the development of iodine-induced hypothyroidism.[6]

As to the effect of administration of excess iodine to euthyroid subjects, supplementary doses of 1,500 µg daily for 2 weeks caused a subtle but significant increase in TSH concentrations.[16,17] In Japan, an area with high dietary iodine, serum TSH concentrations increased significantly in response to the administration of 27 mg of iodide for 28 days.[18]

In 1965, endemic goiter due to excessive intake of iodine was reported to occur in coastal regions of Hokkaido, Japan.[19] Recently, iodine-induced reversible hypothyroidism has been well documented mostly by Japanese investigators.[1,2,3,4,5,8]

Reversible hypothyroidism occurs occasionally at the recovery phase of postpartum hypothyroidism, subacute thyroiditis, and painless thyroiditis. Such cases were excluded by the patients' history. Furthermore, in order to prove that the iodine restriction was responsible for the recovery of the thyroid function, we confirmed that all patients had persistent hypothyroidism by evaluating thyroid functions at least twice before iodine restriction.

It is well known that the thyroid function in hypothyroid patients with detectable TSH receptor antibodies, especially those with the blocking type, is changeable.[11,20] There was one patient who was positive for TBII. She had detectable TSAb and undetectable TSBAb, indicating that TSH receptor antibodies do not appear to be involved in the manifestation of hypothyroidism.

In the present study, 21 of 33 patients (63.6%) with primary hypothyroidism showed recovery of thyroid function. The frequency was similar to that reported by other investigators: 12 of 22 (54.5%);[1] 49 of 116 (42.2%);[2] and 143 of 245 (58.4%).[3] It is very important for patients themselves to know whether they have irreversible hypothyroidism, requiring life-long thyroid hormone replacement therapy, or not. If they have permanent hypothyroidism, iodine restriction, which may not be beneficial for their health, is not necessary.

Thus, we have focused on the possible parameters that were predictive of the development of iodine-induced hypothyroidism. There was a good correlation between 99mTc uptake values and aTSH/bTSH ratios. 99mTc uptake values were significantly higher in group 1 (reversible) than in group 2 (irreversible). In accordance with the previous studies in which radioactive iodine uptake was measured,[1,2] determination of 99mTc uptake also predicted the patients' prognosis. The radioactive iodine uptake test is usually carried out after 1 week of restriction of iodine intake, when the thyroid function of the patients with iodine-induced hypothyroidism may be partially recovered. In contrast, the 99mTc uptake test can be carried out even at the patients' first visit. The significant correlation of 99mTc uptake with initial TSH values and with aTSH/bTSH values indicates that the responsiveness of the thyroid gland to endogenous TSH is preserved in spite of the impaired intrathyroidal synthesis of thyroid hormone in reversibly hypothyroid patients with increased 99mTc uptake. In contrast, it is conceivable that autoimmune destruction of the thyroid is severe enough to cause an impaired response to TSH in irreversibly hypothyroid patients with decreased 99mTc uptake.[1] In the present study, seven of 12 (58.3%) patients in group 2 (irreversible hypothyroidism) had Hashimoto's thyroiditis as judged from TgAb and TPOAb titers. Although it is inexplicable why the remaining five patients, especially patients 29 and 31, had irreversible hypothyroidism, undetectable TgAb and TPOAb in serum do not appear to be predictive of favorable response to iodine restriction, in agreement and disagreement with the previous studies [Tajiri et al.[1] and Okamura et al.,[2] respectively].

Hypoechogenicity of the thyroid is known to be a marker of autoimmune destruction,[21] supporting the diagnosis of Hashimoto's thyroiditis in most patients with irreversible hypothyroidism. However, there was no significant difference between the reversible and irreversible hypothyroid groups, in disagreement with the previous study,[5] since there were a considerable number of patients with hypoechogenicity in the reversible hypothyroid group, presumably due to hyperplastic epithelial changes.[8] Thus, the echogenicity does not appear to predict the spontaneous recovery of thyroid functions.

The free iodine measurement may be helpful for prediction of prognosis of reversible hypothyroidism to some extent, since the free iodine levels roughly correlated with aTSH/bTSH values, and they were significantly higher in group 1 (reversible) than in group 2 (irreversible). However, the iodine measurement can be replaced by inquiring of the patients whether they habitually ingest seaweed products or not. What is important is that the thyroid function recovered spontaneously irrespectively of the initial free iodine levels, since the seaweed had been ingested occasionally or every day and was restricted strictly in patients with reversible hypothyroidism.

We assume that escape of the Wolff-Chaikoff effect (inhibition of organic binding of iodide in the thyroid by excess iodide intake) may not occur or the serum iodine levels to cause escape may be elevated, at 5-100 µg/dL in our cases, for unknown reasons. This phenomenon does not necessarily relate to Hashimoto's thyroiditis, since 10 of 21 (47.6%) patients in group 1 had no findings to support the clinical diagnosis of Hashimoto's thyroiditis. In this regard, Mizokami et al.[8] proposed a new type of hypothyroidism, which is pathophysiologically similar to adenomatous goiter.

In conclusion, hypothyroidism observed in patients with high 99mTc uptake and non-hormonal iodine levels and undetectable or low titers of TgAb and TPOAb can be reversed, and we recommend starting thyroid hormone replacement therapy in those who are considered to have advanced Hashimoto's thyroiditis and history of infrequent ingestion of iodine-containing foods.


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