Iodine status in schoolchildren and thyroid function

For schoolchildren, one study was identified on mild or moderate iodine deficiency and thyroid function.

In a cross-sectional study of schoolchildren from New Zealand (Skeaff et al., 2012), serum Tg, serum TSH, plasma fT4 and fT3 were measured. Tg was lower at UIC ≥100 µg/L (adequate UIC in children > 6 years) and higher at UIC <50 µg/L (moderate iodine

deficiency in children > 6 years). Compared with children who had UIC ≥50 µg/L, those with UIC <50 µg/L had statistically significantly higher Tg and fT3, while TSH and fT4 did not

85 differ according to this cut-off. Correspondingly, compared with children who had UIC

≥100 µg/L, those with UIC <100 µg/L had statistically significantly higher Tg and fT3, while TSH and fT4 did not differ between the groups.

Overview of studies included for mild to moderate iodine deficiency and thyroid dysfunction in sections 5.4.2.1-5.4.2.5 are presented in Tables 5.4.2-1 to 5.4.2-3.

Table 5.4.2-1 Overview of RCTs included for assessment of mild to moderate iodine deficiency and a range of thyroid function parameters (sorted by publication year and author).

Reference,

Intervention N, gender, age placebo daily for 3 months. decreased by 24% and 13% of baseline in the iodine and selenium plus iodine groups in effects were found for TSH, fT3, fT4, or ratio of for UIC spot urine in pregnant women at initial visit was 51 (32-58) µg/L in from weeks 17-18 of pregnancy to 12 higher in the control than in the intervention group.

There were no differences between the groups in the developments of T4, T3, ratio T4/T3 or fT4 during pregnancy or postpartum.

Maternal Tg was significantly higher in controls at all time points, except before initiation of iodine supplementation.

In the control group, TSH increased during pregnancy (p <0.01), but not in the intervention group. During the postpartum period, there was no difference in TSH between the groups.

86 Table 5.4.2-2 Overview of prospective cohort studies and included for assessment of mild to

moderate iodine deficiency and a range of thyroid function parameters (sorted by publication year and author).

Intervention N, gender, age Thyroid function

During follow-up (mean 11y) period, there was no change in median Tg in Copenhagen while Tg decreased significantly in Aalborg.

Regional differences in Tg before IF disappeared after IF. After IF, median Tg in non-users of iodine supplements was still higher than median Tg in iodine supplement users, indicating that the moderate IF might be insufficient to secure adequate iodine intake in the entire study population.

Rasmussen

All measures of iodine intake except one (an iodine intake index) were inversely associated with the thyroid volume outcomes. Likewise, all measures of iodine intake were inversely associated with Tg concentration. The association between iodine intake and the occurrence of thyroid nodules was less clear. Iodine measures most consistently and inversely related to thyroid nodules were iodine intake from diet/kg bw, milk intake, and total iodine intake (diet and supplements).

A low total iodine intake and a low milk intake were both risk factors for thyroid enlargement.

87 Table 5.4.2-3 Overview of prospective cross-sectional studies and included for assessment of mild to moderate iodine deficiency and a range of thyroid function parameters (sorted by publication year and author).

N, gender, age Thyroid function measures

Median UIC from spot urine was 205 µg/L.

UIC was inversely associated with the prevalence of isolated TgAb positivity but not seen with the prevalence of isolated TPOAb positivity or TSH. Both males and females with UIC<100 µg/L were more prone to have positive TgAbs.

Gestational reference ranges for thyroid function tests did not differ substantially by iodine status. We show that a lower UI/Creat was associated with significantly lower TSH, higher TT4, and a higher risk of TPOAb positivity. A lower UI/Creat was also associated with a higher fT4, fT3, and TT3, but these associations did not reach statistical significance. The fT4/fT3 and TT4/TT3 ratios were stable across the full range of UI/creatinine.

Sun et al., 2019 China ST30

Median UIC was 153.6 µg/L.

UIC was categorised into 5 groups: <100 µg/L (deficient

Iodine deficiency (UIC < 100 μg/L) was associated with higher risks of TPOAb positivity and TgAb positivity. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity increased risk of overt hypothyroidism, and increased risk of subclinical hypothyroidism. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb were higher than in TPOAb-negative women. The risk of overt hypothyroidism in women with a high TgAb titer was higher than in TgAb-negative women.

88

N, gender, age Thyroid function measures

Median UIC was 164.5 µg/L.

UIC was categorised into 4 groups: <100 µg/L (deficient

2808 adult men and women

3 outcomes:

TPOAb positivity, TgAb positivity, and TAI (defined as the presence of either TPOAb or TgAb or both)

The median UIC was 165 µg/L.

UIC was divided into four groups:

UIC<100 µg/L (deficient), UIC 100-199.9 µg/L (adequate), UIC 200-299.9 µg/L (more than adequate), and UIC ≥ 300 µg/L (excess). UIC was not associated with TPOAb or TgAb positivity alone, but there was a U-shaped association between iodine status and thyroid autoimmunity (TAI).

The findings showed that the U-shaped relationships between iodine intake and TAI risk, and that both iodine deficiency and excessive iodine status were risk factors of TAI among adults.

Abel et al., 2018 Norway) ST2

Median UIC in spot urine was 59 µg/L in non-supplement users and 98 µg/L in

Iodine intake measured by FFQ was not associated with thyroid function while UIC was inversely associated with fT3 (p=0.002) and fT4 (p<0.001). Current iodine supplement use was not

associated with the outcomes, but a recent initiation of iodine supplementation after GW 12 was significantly associated with lower mean fT4 (beta=-0.21) but not fT3 or TSH.

Fan et al., 2018 China ST9

Median UIC was 134 µg/L (IQR: 79-208 µg/L). There were 35.6% of the subjects whose UIC was lower than 100 µg, and

In the range of urine iodine levels investigated, the relationship between UIC and the occurrence of TNs showed a U-shaped curve.

Prevalence of TNs was 30.7%

among subjects with UIC between 50 and 99 µg/L, and 25.3%

among subjects with UIC in the range of 100-300 µg/L. The results showed that the prevalence of TNs was significantly decreased when the UIC was over 150 µg/L.

There were no findings for the other measures.

89

N, gender, age Thyroid function measures trimester was 117 g/L before and 103 µg/L after correction for Cr.

Median UIC in 3^rd

UIC/Cr was inversely associated with Tg, but not with fT4, fT3,

Median UIC spot urine was 68 (IQR: 50-95) µg/L.

1153 children 5-14y 611 boys

542 girls enrolled in 2002.

UIC was inversely associated with Tg and fT3, but not with TSH and fT4. This was seen when groups were compared using a cut-off for UIC at 50 µg/L or a cut-off for UIC

Median UIC in spot urine was 137 µg/L in and 21% belonged to the different categories, respectively. FFQ:

64% had iodine intake

≥160 µg/d.

Consumption of ≥200 µg/d supplemental iodine was associated with higher TSH levels (β=0.090 (95% CI: 0.003, 0.177) and increased risk of

hyperthyrotropinemia (TSH>3 µU/mL) compared to those consuming less than 100 µg/d (adjusted odds ratio=2.5 (95% CI;

1.2-5.4). The results showed no association between urinary iodine and TSH levels. Pregnant women from the area with the highest median iodine (168 µg/L) and highest supplement coverage (93%) had the lowest values of serum fT4 (geometric mean

=10.09 pmol/L (95% CI: 9.98, 10.19).

90

N, gender, age Thyroid function measures

Tg concentrations and Tvols were higher in the low and marginal groups than in the adequate iodine status group, while serum TSH and T4 did not differ between groups.