Volume 21, Issue 3, September 2005

Table of Contents 21-3

Congenital Hypothyroidism due to Excessive Iodine Intake

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It is well known that both iodine deficiency and iodine excess affect neonatal thyroid function. In Japan there is ingestion of large quantities of iodine-rich seaweed such as kombu (tangle weed, Laminaria japonica), which contains a high level of iodine (1.3 mg per gram of kombu). Rolled sushi is also an iodine-rich Japanese traditional food.

Nishiyama and colleagues studied the effects of maternal iodine ingestion during the perinatal and postnatal period on infant thyroid function. They measured the ingestion of iodine in the mother’s daily diet and the effect on breast milk, the infant’s concentration of iodine in serum and urine, as well as thyrotropin (TSH) and free thyroxine (FT₄) levels in 34 infants who were positive at congenital hypothyroidism screening. Excretion of over 20 μg/dL of urinary iodine in infants (normal controls; +2SD; normal age-matched controls 12.2 ± 3.5μg/dL [normal±SD]) was considered as the evidence of excess iodine intake by mothers during pregnancy. The hyperthyrotropinemia detected in 15 of the 34 infants was caused by excess iodine ingestion during the pregnancy. The urinary iodine level of these infants was 33.1 ± 16.5 μg/dL (mean ± SD). Infants were born at 37 to 40 weeks of gestation, after uncomplicated pregnancies, and to parents who did not have any thyroid disease. These 15 infants were subdivided into group A (serum iodine >17μg/dL [normal controls + 2SD], n=5) and group B (serum iodine <17 μg/dL, n=10). The serum and urine iodine concentrations and thyroid function levels of both groups, as well as those with congenital hypothyroidism and control normal infants, are shown (Table). No mutation was found in the thyroperoxidase (TPO) gene and TSH receptor gene analysis of 5 patients in group A.

*Congenital hypothyroidism

It was calculated that the mothers of group A infants ingested approximately 2300-3200 μg of iodine per day, and the mothers of group B consumed approximately 820-1400 μg of iodine per day. The mothers ate kombu, other seaweeds, and instant kombu soup containing a high level of iodine throughout their pregnancies. Mothers of age-matched normal control infants without thyroid disease consumed less than 500μg of iodine per day during pregnancy.

These 15 infants had normal physical and psychomotor development throughout the 2 years of follow-up. Twelve of these infants required levothyroxine treatment because of hypothyroxinemia or persistent hyperthyrotropinemia. The authors proposed that hyperthyrotropinemia related to excessive iodine ingestion by mothers during pregnancy is transient in most cases. However, consumption of iodine from breast milk of such mothers, baby foods flavored with kombu, and kombu products ingested in the postnatal period contributed to persistent hyperthyrotropinemia.

Nishiyama S, Mikeda T, Okada T, Nakamura K, Kotani T, Hishinuma A. Transient hypothyroidism or persistent hyperthyrotropinemia in neonates born to mothers with excessive iodine intake. Thyorid. 2004;14:1077-1083.

Editor’s Comment: In Japan blood TSH is used in the congenital hypothyroidism screening program. This paper showed that large quantities of iodine-rich seaweed such as kombu consumed by mothers during pregnancy altered the TSH levels of their infants. Large quantities of iodine from food consumed after birth also produced persistent hyperthyrotropinemia. It is well known that direct iodine overload in the perinatal period, by either antiseptic agents or contrast medium used for diagnostic studies, are causes of altered TSH and T₄ levels. The increased urinary iodine concentrations, as well as elevated serum iodine values found in these infants, confirmed the hypothesis that alterations in infant thyroid function resulted from iodine excess during pregnancy. High concentrations of thyroglobulin (Tg) levels detected in infants of mothers who consumed high iodine foods suggests that there was a mild blockade of thyroid hormone synthesis. The mean serum Tg value was 574 μg/dL in group A, 297 μg/dL in group B and 72 μg/dL in controls. The antithyroid effects of iodine excess are due to the Wolff-Chaikoff block of the uptake of iodine by the thyroid gland, which leads to reduced T₄ and increased TSH levels.

The ordinary intake of iodine by Japanese women is 500-1500 μg per day. This iodine intake is excessive as compared with the recommenced daily allowance of 150 μg of iodine for adults given by the United States National Research Council. However, the consumption of iodine in the US has also increased with the widespread use of iodized salt, reaching 240 - 740 μg of iodine per day in some areas. Thus, the assessment of iodine intake and urinary excretion should be made in infants with hyperthyrotropinemia.

Yoshikazu Nishi, MD

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