Background: To examine the relationship between maternal TSH and free thyroxine (FT 4 ) concentrations in early pregnancy and the risk of miscarriage, fetal or neonatal death. Method: Cohort study of 2497 Dutch women. TSH, FT 4 , and thyroid peroxidase antibodies concentrations were determined at first booking. Child loss was operationalized as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. Results: Twenty-seven cases of child loss were observed. The mean TSH and FT 4 level in the women with child loss was 1.48 mU/l and 9.82 pmol/l compared with 1.11 mU/l and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (ORZ1.60 (95% confidence interval (CI): 1.04-2.47)) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratioZ1.80 (95% CI: 1.07-3.03)). This was not true for FT 4 concentrations (ORZ1.41 (95% CI: 0.21-9.40); PZ0.724). Conclusion: In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal FT 4 concentrations and child loss were not associated.

Objective: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT 4 ) combination in each individual. Subjects and methods: Twenty-one healthy volunteers (nine males and 12 females; mean age 60 years, range 51-74) were randomized to receive at 2300 h with 2-week intervals a single dose of placebo, 125 mg T 4 and 250 mg T 4 (arm 1, nZ10), or placebo, 25 mg triiodothyronine (T 3 ) and 50 mg T 3 (arm 2, nZ11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT 4 and T 3 . Results: Intra-and inter-individual variation and the individuality index of the four baseline serum samples were respectively 21.6%, 41.9% and 0.52 for TSH; 9.9%, 16.5% and 0.60 for FT 4 ; and 9.3%, 16.0% and 0.58 for T 3 . Substantial differences existed in the location of individual working points within the reference range. T 4 administration increased FT 4 (but not T 3 ) and decreased TSH, resulting in a log-linear relationship (log TSHZ1.50-0.059!FT 4 , P!0.05) for the whole group. T 3 administration increased T 3 and decreased TSH (but not FT 4 ), resulting in a log-linear relationship (log TSHZ0.790-0.245!T 3 , P!0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. Conclusion: Individuality indices of TSH, FT 4 and T 3 are all %0.6, thereby limiting the usefulness of the population-based reference values. Accurate assessment of individual setpoints of the HPT axis was not possible with the applied single doses of T 4 or T 3 , and will require either prolonged administration or higher single doses of thyroid hormone.

The increase in TSH and decrease in free T4 values during pregnancy correspond to previous reported studies. Pregnant Dutch women had consistently higher TSH values than the ethnic group, but corresponding free T4 levels and TPO-Ab did not differ between these ethnic groups.