Study for optimal dose determination of levothyroxine in subclinical hypothyroidism in pregnancy

Abstract

Context: Subclinical thyroid dysfunction has been associated with pregnancy complications and affects both maternal and fetal outcomes such as impaired neuropsychological development in offspring and adverse obstetric outcomes-including miscarriage, premature birth, gestational hypertension, placental abruption, and fetal death. Endocrine Society guidelines recommend that all pregnant women with subclinical hypothyroidism be treated with Levothyroxine. The American Thyroid Association guidelines recommend that pregnant women with subclinical hypothyroidism and detectable thyroid-peroxidase antibodies receive Levothyroxine. But till date no authority has given any guideline about the initial dose of Levothyroxine. Aims: To formulate a dosage regime of levothyroxine which is optimal for urgent correction of hypothyroid state in pregnancy. Settings and Design: Prospective (longitudinal) study. Subjects and Methods: A total of 42 apparently normal pregnant women, with known last-menstrual period, with no known metabolic or hypertensive disorder who presented to the clinic had thyroid screening using a standardized method. Women with thyroid stimulating hormone (TSH) value in the range to be diagnosed as subclinical hypothyroidism were included in the study. All patients were followed-up till the time of delivery for the obstetric outcome. Levothyroxine was the mainstay of treatment. Levothyroxine dose were adjusted every trimester on the basis of thyroid function tests (TFTs) including free thyroxine (FT4) and TSH values. Anthropometric measurements included height and body weight at baseline. Statistical Analysis Used: Significance is assessed at 5% level of significance. Pearson and Spearmen correlation test used to find out correlation among normally and non-normally distributed data respectively. Analysis of variance (ANOVA) and Kruskal-wallis with distribution free multiple comparison test used to find the significance of study parameters between three or more groups of patients for normally distributed data and non-normally distributed data. Results: 81.25% of subjects achieved euthyroidism in third trimester. The mean levothyroxine dose used in the first trimester was 40.18 ± 13.78 μg. The mean levothyroxine dose used in the third trimester was 58.25 ± 18.57 μg. Significant increase in the mean dose of levothyroxine required in the third trimester (58.25 ± 18.57 μg) as compared to the first trimester (40.18 ± 13.78 μg, P = 0.0012). Conclusions: Significant improvement in the thyroid function as indicated by higher proportion of patients achieving normal TSH values with significant increase in the mean levothyroxine dose used during the course of treatment gives us guideline about the initial starting doses of levothyroxine.