Iodine sufficiency and measurements of thyroid function in maternal hypothyroidism

To test the hypothesis that thyroglobulin (Tg) and free T4 (FT4) concentrations more than 2SD from the control mean are not increased in pregnancy in an iodine replete area in the absence of elevated TSH concentrations. The second hypothesis to be tested was that if such abnormalities in FT4 and Tg in the absence of elevated TSH concentrations were to exist they would not be associated with lowered IQs in the progeny.

Cross-sectional study in New England comparing TSH, Tg, antibodies to Tg and FT4 in volunteer nonpregnant women 20-40 years old with those in hypothyroid mothers and matched euthyroid control mothers. The results are contrasted with those from similar studies reported from iodine deficient areas.

Sera obtained at 17 weeks gestation and stored at -20 degrees C for 8 years were retrieved and analysed from 62 mothers with subclinical hypothyroidism and 124 matched euthyroid mothers. The diagnosis of hypothyroidism was made by finding a TSH concentration > 97.7 percentiile for 25 000 consecutive pregnant women. Sera were also analysed from 53 healthy nonpregnant volunteer women aged 20-40 years.

TSH, Tg and Tg antibodies were measured in the sera of the nonpregnant volunteers, and Tg and Tg antibodies in the sera of the pregnant women who had previously been analysed for TSH and FT4. The incidence of FT4 concentrations below the 2.3 percentile of nonpregnant laboratory controls was compared for the euthyroid and hypothyroid mothers and the laboratory normal controls.

Thirty-one per cent of the 62 hypothyroid mothers had FT4 concentrations below the 2.3 percentile compared with only one (0.8%) of the euthyroid mothers. Mean Tg concentrations did not differ between the nonpregnant controls and the euthyroid pregnant women, 14 +/- 10 vs. 16 +/- 10 micro g/l. Tg concentration in the hypothyroid mothers was 44 +/- 61, significantly greater than for either of the euthyroid control groups, P < 0.005. Positive antibodies to Tg were found in 9% and 10% of the control groups and 57% of the hypothyroid mothers, P < 0.0005. When TSH is included as an independent variable in multiple linear and logistic regressions, FT4 and Tg no longer correlate significantly with IQs.

The incidences of FT4 concentrations more than 2SD below the control mean and of Tg > 2SD above the control mean are significantly increased in hypothyroid mothers in iodlne-sufficient New England. However, in the absence of elevated TSH concentrations, the incidences of such abnormalities in FT4 and TG are negligible. Indeed, concentrations for FT4, Tg and Tg antibodies for nonpregnant and pregnant controls in our iodine-replete area do not differ significantly from each other or from previously reported normative concentrations with the methods used. Thus, pregnancy in New England neither increases Tg nor lowers FT4 concentrations.