Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th-14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1-1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1-12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Moreover, the universal screening has been shown to be more cost-effective. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless of the screening approach. This review summarizes the current knowledge on physiology of thyroid hormones in pregnancy, causes of maternal thyroid dysfunction and its effects on pregnancy course and fetal development. We discuss the question of case-finding versus universal screening strategies and we display an overview of the analytical methods and their reference intervals in the assessment of thyroid function and thyroid autoimmunity in pregnancy. Finally, we present our results supporting the implementation of universal screening.

Background: Insufficient function of the thyroid gland can cause low concentrations of thyroid gland hormones which are necessary for the proper development of the foetus brain, especially during the beginning of pregnancy. We determined the reference interval for TSH in the first trimester of pregnancy and the decision point for anti-TPO antibodies' positivity.Methods: We tested 5520 women from the central part of the Czech Republic during the first trimester of pregnancy for serum TSH, anti-TPO and FT4 by chemiluminometric immunoanalysis on an ADVIA Centaur system (Siemens). The reference interval for TSH during the first trimester of pregnancy was determined using the log transformation, and then summarized as the geometrical mean (95% CI); following which, a suitable decision point for anti-TPO positivity was set.Results: The reference interval for TSH was determined to be 0.06–3.67 mU/l. The suppression of TSH was found in 2.93% of the women; a raised concentration of TSH had been found in 4.48% of the women. For anti-TPO, the cut-off was established at 143 kU/l; 11.2% of the pregnant women were found to be anti-TPO positive.Conclusion: Determination of the reference interval for TSH during early pregnancy is one of the basic requirements when implementing a general examination of the thyroid gland at the beginning of pregnancy. The decision level for positivity of anti-TPO is more than double the manufacturer's reference interval.

Context: The guidelines of American Thyroid Association from 2011 include age over 30 as one of the risk factors for hypothyroidism in pregnancy. Objective: Our objective was to verify whether age increases the risk of autoimmune thyroid disease in pregnancy. Design: We performed a cross-sectional study in 2006–2008 with laboratory assessment in a single center using primary care gynecological ambulances in cooperation with a referral center. Patients: The study included 5223 consecutive pregnant women in gestational wk 9–12. Main Outcome Measure: We assessed the occurrence of pathological serum concentrations of TSH and/or antibodies against thyroperoxidase (TPOAb) with regard to age. Reference interval for TSH was 0.06–3.67 mU/liter; the upper cutoff value for TPOAb was 143 kU/liter. Results: Overall, 857 women (16.4%) were positively screened. Of these, 294 (5.63%) had TSH elevation, 146 (2.79%) had TSH suppression, 561 (10.74%) were TPOAb positive, and 417 (7.98%) were euthyroid and TPOAb positive. The average age of women was 31.1 yr. The prevalence of hypothyroidism was 5.5 and 5.8% in women aged 30 or older and those under 30 yr, respectively (P value nonsignificant). Using a logistic regression model, we didn't find any significant association between age and serum TSH suppression, TSH elevation, or TPOAb positivity (P = 0.553, P = 0.680, and P = 0.056, respectively) or between age and TSH elevation with TPOAb positivity (P = 0.967). In a subgroup analysis of risk factors for hypothyroidism in 132 hypothyroid women, addition of age 30 or older increased the proportion of women identified in a case-finding screening strategy from 55.3 to 85.6%. Conclusions: Prevalence of autoimmune thyroid disease does not increase with age in pregnant women; however, addition of age 30 or over to the case-finding screening strategy may substantially improve its efficiency due to a larger number of women screened.

The aim of the study was to verify differences between reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4), as well as the cut-off for anti-thyroid peroxidase antibodies (TPO Ab) in pregnant women. Additionally, to compare these reference intervals with those recommended by the manufacturers for a healthy population. Levels of TSH, FT4, and TPO Ab were determined in a group of pregnant women (n = 216) with no history of thyroid dysfunction. Simultaneously, reference intervals for thyroid function tests were established with 7 different analytical systems representing those immunoassays most often used globally. The reference intervals for FT4 were slightly different, according to the system used by each manufacturer. Those for Architect, Centaur, Modular E170, and RIA Immunotech were slightly higher than those for Immulite 2500 and AIA 2000; the lowest being for UniCel DxI (8.13–13.2 pmol/L). For TSH, a higher interval (0.25–3.86 mU/L) is recommended for Modular E170 and IRMA Immunotech; and a lower one (0.17–2.81 mU/L) for Immulite 2500 and AIA 2000. The established cut-off limits for TPO-Ab differ according to the system used and are similar to those recommended by their manufacturers.

Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.