Adjustment of levothyroxine substitutive therapy in pregnant women with subclinical, overt or postablative hypothyroidism

Objective Maternal hyperthyrotropinaemia is associated with an increased risk of adverse maternal and neonatal outcomes. Physiological changes during pregnancy require an increased production of thyroid hormones (or an increase in daily substitutive doses of L-T4in hypothyroid patients) to meet the maternal and foetal needs. The aim of the study was to evaluate variations of substitutive L-T4 doses that are able to maintain serum TSH between 0·5 and 2·5 mU/l in pregnant women with subclinical- (SH), overt- (OH) and post-ablative (PH) hypothyroidism. Design This was a retrospective study on hypothyroid pregnant women referred to the out-patient department between January 2004 and December 2006. Patients and measurements A total of 185 pregnant women were studied during gestation; 155 patients (76 SH, 52 OH, 27 PH) were already on L-T4before conception and 30 (SH) started L-T4therapy during gestation. Thyroid function and body weight were evaluated every 4-6 weeks. Results In the group of patients already treated before conception, 134 (86·5%) increased L-T4doses during gestation one or more times, eight (6%) reached a definitive therapeutic dosage within the 12th week of pregnancy, 64 (47·8%) within the 20th week and 62 (46·2%) within the 31st week. This initial L-T4 increase at the first evaluation during pregnancy was 22·9 ± 9·8 μg/day. The final L-T4 doses were significantly different depending on the aetiology, being 101·0 ± 24·6 μg/day in SH, 136·8 ± 30·4 μg/day in OH and 159·0 ± 24·6 μg/day in PH. The per cent increase of L-T4,expressed as Δ% of absolute dose, was +70% in SH, +45% in OH and +49% in PH as compared to baseline dose. In SH patients diagnosed during gestation, the starting L-T4dose was higher than L-T4dose before pregnancy of SH patients already treated (75·4 ± 14·5 and 63·2 ± 20·1 μg/day, respectively), whereas the final doses were similar. L-T4dose was increased one or more times in 24 patients (80%), 8 reached the definitive dosage within the second trimester (33·3%) and 16 within the third trimester (66·7%). Conclusions Serum TSH and FT4 measurements are mandatory in pregnant patients and the optimal timing for increasing L-T4 is the first trimester of pregnancy, though many patients require adjustments also during the second and third trimester. The aetiology of hypothyroidism influences the adjustment of L-T4 therapy and SH patients needed a larger increase than OH and PH. Close monitoring during pregnancy appears to be mandatory in hypothyroid women.