Iodine, Seaweed, and the Thyroid.

BACKGOUND: Even a minor iodine deficiency can result in adverse thyroidal health consequences while excess iodine intake can also result in thyroid function disorders. One source of iodine is seaweed which as a foodstuff is enjoying an increasing profile in Western countries. Apart from its potential involvement in thyroidal health, gaseous iodine released from seaweeds plays a significant role in influencing coastal climate through cloud formation. SUMMARY: Sources of dietary iodine, its assessment, recommended dietary intake, and consequences of iodine excess are outlined. The benefits and possible dangers of dietary intake of iodine-rich seaweed are described. Studies linking seaweed intake to breast cancer prevalence are discussed as is the role of gaseous iodine released from seaweeds influencing weather patterns and contributing to iodine intake in coastal populations. KEY MESSAGES: Universal salt iodization remains the optimum method of achieving optimum iodine status. Promoting increased dietary iodine intake is recommended in young women, in early pregnancy, and in vegan and vegetarian diets. Even where iodine intake is enhanced, regular assessment of iodine status is necessary. Caution against consumption of brown seaweeds (kelps) is required as even small amounts can have antithyroid actions while product labelling may be insufficient. Gaseous iodine produced from seaweeds can have a significant effect on cloud formation and associated global warming/cooling. Increased overall iodine deposition through rainfall and apparent uptake in populations dwelling in seaweed-rich coastal regions may provide a partial natural remedy to global iodine deficits.

50 years of the ETA: "the selenium connection".

The recent celebration of the 50 years of the ETA closely coincided with that of the 200 years since the discovery and description of selenium, an essential trace element for normal thyroid gland function and thus an adjuvant in the treatment of thyroid diseases. The aim of this commentary is to briefly outline the half centennial of the ETA while also signaling important moments in the history of selenium, developments in its availability round the world, details of its connection with thyroid function and, finally, its current and projected modes of application.

Can neonatal TSH screening reflect trends in population iodine intake?

BACKGROUND: The distribution of neonatal blood thyroid-stimulating hormone (TSH) concentrations has been used as an index reflecting population dietary iodine intake, with higher concentrations being indicative of lower iodine intake. We examined this distribution in neonates born in Ireland, where the pregnant population has shown a recent decline in urinary iodine (UI) excretion. Our objectives were to determine if any alteration was observed in the percentage of values > 5.0 mIU/L and whether a trend in neonatal blood TSH was apparent. METHODS: Samples drawn from the National Neonatal Screening Programme were assessed during the years 1995-2006 from winter (January n = 35,079) and summer (August n = 37,940) months, respectively, in view of the known seasonal variation in Irish dietary iodine intake. RESULTS: Apart from the first years studied (1995-1996), the proportion of individual blood TSH values >5.0 mIU/L did not exceed 3%, a value believed to be indicative of iodine deficiency. A significant declining trend in the proportion of blood TSH >5.0 mIU/L was observed in subsequent years (p < 0.01). While excluding severe iodine deficiency, these analyses failed to detect the slight but highly significant (p < 0.001) tendency toward increasing blood TSH within the 0-5.0 mIU/L interval in the study population between 1999 and 2006, which was greater in summer than in winter months (p < 0.001). CONCLUSIONS: These data support a link between fetal thyroid function and a fall in maternal iodine intake. While the findings of the proportion of blood TSH values >5.0 mIU/L exclude severe maternal or fetal iodine deficiency, a trend toward increasing TSH may provide an early indication of impending iodine deficiency. The findings assume greater importance in the context of declining UI reported from many developed countries even where the proportion of blood TSH values >5.0 mIU/L is <3%, thus excluding severe maternal and fetal iodine deficiency.

The thyroid and breast cancer.

PURPOSE OF REVIEW: The female predominance of diseases of the thyroid and breast makes difficult the separation of an expected association with a causal linkage. This review will examine recent reports on associations between thyroid disease and breast cancer, comparing them with previous studies, with a view to elucidating what pointers are available to suggest either a common pathogenesis or novel thyroid-related therapeutic approach, which might arise from this association. RECENT FINDINGS: Reports on thyroid-breast cancer associations are reviewed under the following headings: breast cancer prevalence in different thyroid disorders and their effect on risk and outcome; the possible role of thyroid autoimmunity, thyroid enlargement, effect of radioactive iodine treatment, role of stable iodine, possible joint antigens sodium iodide transporter and thyroid peroxidase and thyroid-breast cancer coincidence. SUMMARY: Current studies on thyroid and breast cancer associations confirm earlier findings of the lack of definitive evidence of a causal relationship. The predominant relationship continues to be hypothyroidism or autoimmune thyroid disease perhaps contributing to increased breast cancer risk or outcomes. However, despite many studies and the findings of meta-analyses, elucidating the mechanisms underlying the association remains elusive. At present, there is little justification for utilizing thyroid insights as a possible therapeutic intervention in breast cancer.

The thyroid, iodine and breast cancer.

A renewal of the search for a link between breast cancer and thyroid disease has once again demonstrated an increased prevalence of autoimmune thyroid disease in patients with breast cancer. This is the most recent of many studies showing an association between a variety of thyroid disorders and breast cancer. Such an association is not surprising as both diseases are female predominant with a similar postmenopausal peak incidence. The significance of the presence of thyroid autoantibodies, particularly thyroid peroxidase antibodies, in serum from patients with breast cancer is unknown, but it has been suggested that antibody positivity is associated with better prognosis. One area in which thyroid and breast functions overlap is in the uptake and utilization of dietary iodide. Experimental findings showing the ability of iodine or iodine-rich seaweed to inhibit breast tumour development is supported by the relatively low rate of breast cancer in Japanese women who consume a diet containing iodine-rich seaweed. However, there is as yet no direct evidence that iodine, iodinated compounds, or a combination of iodine and selenium is the antimammary carcinogenic element in the Japanese diet. It remains to be resolved whether the perceived breast cancer-thyroid disease relationship is thyroid or iodine related or, in the case of thyroid autoantibodies, is the consequence of an immune response to the carcinoma. Is this response breast specific and does it relate to iodine status? These and many other questions await resolution before a definitive role in the natural history of breast carcinoma can be assigned to the thyroid.

Role of iodine in antioxidant defence in thyroid and breast disease.

The role played in thyroid hormonogenesis by iodide oxidation to iodine (organification) is well established. Iodine deficiency may produce conditions of oxidative stress with high TSH producing a level of H_2O_2, which because of lack of iodide is not being used to form thyroid hormones. The cytotoxic actions of excess iodide in thyroid cells may depend on the formation of free radicals and can be attributed to both necrotic and apoptotic mechanisms with necrosis predominating in goiter development and apoptosis during iodide induced involution. These cytotoxic effects appear to depend on the status of antioxidative enzymes and may only be evident in conditions of selenium deficiency where the activity of selenium containing antioxidative enzymes is impaired. Less compelling evidence exists of a role for iodide as an antioxidant in the breast. However the Japanese experience may indicate a protective effect against breast cancer for an iodine rich seaweed containing diet. Similarly thyroid autoimmunity may also be associated with improved prognosis. Whether this phenomenon is breast specific and its possible relationship to iodine or selenium status awaits resolution.

The placenta as a compensatory iodine storage organ.

BACKGROUND: The production of iodine-containing thyroid hormones necessary for brain development in the fetus depends not only on maternal dietary intake but also on placental iodine transport. The optimum level of iodine nutrition during pregnancy and the proportion of the pregnant population reaching this level have previously been evaluated. Little information exists on the ability of the placenta to either accumulate or store iodine. This study aims to investigate iodine uptake and tissue iodine content within placental tissue obtained from women delivering at term. METHODS: Samples (∼1 cm(3)) obtained from placental cotyledons (n = 19), thyroid (n = 4), and uterine myometrial (n = 4) tissue were incubated for 6 hours with (125)I in the presence and absence of potassium perchlorate. To account for variation in tissue composition, results were expressed in cpm (125)I/µg DNA. RESULTS: Placental uptake of (125)I (375 cpm/µg DNA) was significantly higher than that of control myometrial tissue (226 cpm/µg DNA) (p < 0.05) and was ∼25% that of thyroid tissue (1702 cpm/µg DNA). Uptake of (125)I could be partially blocked in the thyroid and placenta, respectively, by potassium perchlorate (100 µM), which had no effect on uptake by myometrial tissue. Iodine content of tissue samples measured using an alkaline ashing technique with Sandell-Kolthoff colorimetry gave a mean value for total iodine of 30.4 ng/g placental tissue (range 21-50 ng/g), 1.74 ng/g myometrial tissue, and 1037 ng/g thyroid tissue. CONCLUSIONS: Placental iodine content was only ∼3% that of the thyroid, but on the basis that neonatal iodine stores are very low and highly sensitive to fluctuations in maternal iodine supply, we postulate that placental iodine bioavailability makes a significant contribution to protection against neonatal hypothyroidism. These findings suggest that the placenta has a role not only in uptake but also in storing iodine as a possible means of protecting the fetus from inadequacies in maternal dietary iodine intake.

Perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant women.

CONTEXT: Thyroid hormone, requiring adequate maternal iodine intake, is critical for fetal neurodevelopment. Perchlorate decreases thyroidal iodine uptake by competitively inhibiting the sodium/iodide symporter. It is unclear whether environmental perchlorate exposure adversely affects thyroid function in pregnant women. Thiocyanate, derived from foods and cigarette smoke, is a less potent competitive sodium/iodide symporter inhibitor than perchlorate. OBJECTIVE: Our objective was to determine whether environmental perchlorate and/or thiocyanate exposure is associated with alterations in thyroid function in pregnancy. DESIGN AND SETTING: We conducted a cross-sectional study at health centers in Cardiff, Wales, and Turin, Italy. PATIENTS: During 2002-2006, 22,000 women at less than 16 wk gestation were enrolled in the Controlled Antenatal Thyroid Screening Study. Subsets of 261 hypothyroid/hypothyroxinemic and 526 euthyroid women from Turin and 374 hypothyroid/hypothyroxinemic and 480 euthyroid women from Cardiff were selected based on availability of stored urine samples and thyroid function data. MAIN OUTCOME MEASURES: Urinary iodine, thiocyanate, and perchlorate and serum TSH, free T(4) (FT(4)), and thyroperoxidase antibody were measured. RESULTS: Urinary iodine was low: median 98 microg/liter in Cardiff and 52 microg/liter in Turin. Urine perchlorate was detectable in all women. The median (range) urinary perchlorate concentration was 5 microg/liter (0.04-168 microg/liter) in Turin and 2 microg/liter (0.02-368 microg/liter) in Cardiff. There were no associations between urine perchlorate concentrations and serum TSH or FT(4) in the individual euthyroid or hypothyroid/hypothyroxinemic cohorts. In multivariable linear analyses, log perchlorate was not a predictor of serum FT(4) or TSH. CONCLUSIONS: Low-level perchlorate exposure is ubiquitous but did not affect thyroid function in this cohort of iodine-deficient pregnant women.