Competitive inhibitors of NIS, such as perchlorate, thiocyanate, and nitrate, can decrease the entry of iodine into the thyroid and lactating breast, thereby potentially exacerbating the effects of dietary iodine insufficiency. Low-level perchlorate exposure seems to be ubiquitous in the US, European, and South American population. Environmental perchlorate comes from a variety of sources, is extremely stable as an inorganic salt, and persists in low levels in soil and groundwater over long periods.73
In the United States, perchlorate has been found in many substances, including tobacco, alfalfa, tomato, cow’s milk,55
cucumber, lettuce, soybeans, eggs, and multivitamins (including prenatal multivitamins).74
Following the development of sensitive detection methods, perchlorate has been measured in the drinking water of communities around the United States.
When given in pharmacologic doses, perchlorate decreases the active transport of iodine into the thyroid and possibly breast milk by competitively inhibiting the NIS with 30 times its affinity for iodide.75
Furthermore, recent studies in lactating mice have suggested that perchlorate is actively transported into breast milk,76
thus potentially decreasing infants’ thyroidal iodine uptake. In the NHANES 2001 to 2002 survey, perchlorate was detected in all 2820 spot urine samples (median urine perchlorate concentration, 3.6 μg/L) and was a significant negative predictor of total T4
values and a positive predictor of TSH values in women, primarily those with urine iodine concentrations less than 100 μg/L.77,78
However, these relationships were not seen in men,78
a follow-up subset analysis of this dataset (which analyzed only women of childbearing age) using creatinine-adjusted urinary iodine values,79
or a large European study assessing serum thyroid function tests of iodine-deficient pregnant women.80
Recently, the US FDA reported in a Total Diet Study that infants and children have the highest estimated intakes of perchlorate by body weight.81
There are limited data regarding breast milk iodine82
and perchlorate concentrations in women in the United States. We reported that the median breast milk iodine concentration in 57 women in Boston area was 155 μg/L,54
similar to that of a 1984 study of 37 women (178 μg/L).52
However, the median breast milk iodine levels in our study were far higher than those (33.5, 43.0, and 55.2 μg/L) observed recently by Kirk and colleagues55,56
in 3 studies.57
Kirk and colleagues55
also measured perchlorate levels in the breast milk of 36 women from 18 states and found detectable levels in all the samples (range, 0.6–2.2 μg/L). Breast milk iodide and perchlorate levels were inversely correlated in the 6 samples with perchlorate concentrations of at least 10 μg/L, although there were no correlations between breast milk iodide and perchlorate in the full data set.55
We reported no correlation between breast milk and colostrum iodine and perchlorate concentrations, even in those breast milk samples with perchlorate concentrations of 10 μg/L or more.54,83
Similarly, exposures to thiocyanate, a metabolite of cyanide that is produced as a byproduct of cigarette smoke, and nitrate, which is produced naturally and is present in many prepared foods, are able to decrease NIS activity, thereby decreasing iodine availability. Naturally goitrogenic foods include those that contain cyanogenic glucosides (which become metabolized to thiocyanate), such as cassava, millet, maize, sweet potatoes, lima beans, and cruciferous vegetables (which contain thiocyanates and isothiocyanates), such as cabbage, Brussels sprouts, cauliflower, broccoli, and horseradish.18
However, the thiocyanate content of these foods is low, and their ingestion does not usually produce clinically significant sequelae unless severe iodine deficiency is present.
One recent study in Denmark concluded that cigarette smoking decreases breast milk iodine concentrations,84
and we demonstrated the same effect in a small cohort of lactating women in Boston area.54
Comparatively, perchlorate is a potent inhibitor of NIS; its effects are 15-fold greater than thiocyanate, 30-fold compared with iodide, and 240-fold compared with nitrate.75
Nonetheless, because exposure to thiocyanate and nitrate is ubiquitous, the additive effects on iodide uptake may be important when assessing iodine availability.
The urinary levels of selenium and iodine in pregnant women are closely correlated.85
Selenium is an important component of glutathione peroxidase and selonoproteins, which include the 3 thyroid hormone deiodinases. Thus, insufficient selenium may result in the accumulation of damaging peroxides in the thyroid and impair the peripheral deiodination process required to generate the active thyroid hormone, T3
, from T4
. Although selenium nutrition is generally adequate in humans, rare conditions resulting in selenium deficiency may be important in the pathogenesis of hypothyroidism.86
A recent study by Negro and colleagues87
reported that selenium supplementation of 200 μg/d during pregnancy and in the postpartum period reduced the prevalence of permanent maternal hypothyroidism (11.7%) compared with women who did not receive supplementation (20.3%) (P
<.01). The findings of this study are very preliminary, and currently there are no recommendations for selenium supplementation during pregnancy and lactation.