Pregnancy is a physiological phenomenon in which there is the maternal adjustment of multiple organ systems, including metabolic and hormonal adjustments to supply adequate nutrition to the fetus. During this process, the thyroid gland adapts through regulating thyroid hormones via the hypothalamic-pituitary-thyroid axis [1]. Thyroid hormones are necessary to ensure the healthy development of the fetus, especially during the first trimester, during which the fetus is entirely dependent on maternal thyroid supply delivered through the placenta. Moreover, during pregnancy, there is increased maternal renal iodide loss, increased levels of serum total thyroxine-binding globulin (TBGs), and increased degradation of thyroid hormone by placental enzymes. Human Chorionic Gonadotropin (hCG) has a striking structural resemblance with Thyroid-stimulating hormone (TSH), leading to an increase in thyroid hormone production during pregnancy followed by a plateau phase around 16 weeks of gestation [2].
Thyroid gland dysfunction is encountered commonly during pregnancy and has an association with obstetric complications. Most frequently, the thyroid disorder encountered in pregnancy is maternal hypothyroidism [3]. This condition is associated with fetal loss, increased maternal blood pressure, preterm labor, and the child's abnormal mental development subsequently [4]. The prevalence of hyperthyroidism in pregnant women is 0.1–0.4%. On the other hand, around 3% of pregnant women are hypothyroid, of whom 0.5% have overt hypothyroidism and 2.5% present with subclinical hypothyroidism [5]. Almost 10 % of the women their reproductive age is positive for thyroid antibodies. Even without any detectable thyroid dysfunction, the presence of anti-thyroid peroxidase antibodies in pregnant women increases the risk of miscarriage, pregnancy-related complications, and preterm labor [6–8]. Gestational thyrotoxicosis is frequently reported in the Asian population compared to western women and pregnant females belonging to other ethnicities [9]. There is a wide geographical variation in the prevalence of thyroid disorders during pregnancy. Therefore, International Endocrine associations advised that each geographical area should establish its trimester-specific reference ranges for thyroid profile. These population-specific reference ranges will aid in the early detection of thyroid abnormalities in pregnant females and will ultimately prevent complications [2, 9, 10].
The most common cause of maternal hypothyroidism in iodine-rich areas is Hashimoto's thyroiditis, whereas, in iodine-deficient areas like Pakistan, it is iodine deficiency [11]. A study conducted by Elahi et al. in Lahore, Pakistan, revealed that around 79% of the pregnant females were iodine deficient, and 31% had goiter [12, 13].
Assessment of thyroid status during pregnancy is of utmost importance for the initiation of treatment of newly diagnosed patients as well as for dose adjustment of patients already on hormone therapy. A decrease in the upper and lower limit of TSH has been noticed in pregnant females compared to the healthy non-pregnant population [13]. In clinical practice, measurement of free T4 and TSH, exceptionally the cut-off values for lower Free T4 and upper TSH reference limit provides the data for evaluating thyroid functioning in population. Various studies have been carried out in different countries to establish reference ranges for thyroid hormones (Table 1). However, discrepancies in reported results are noticed because of using different assays; also, irregularities in pregnancy are associated with demographic, environmental, and genetic factors.
Table 1
Characteristics of various studies on reference ranges of thyroid functions TSH, FT3, FT4
Comparison of different studies |
Country/Year | Measure | TF Tests | Number of Patients (n=) | 1st Trimester | 2nd Trimester | 3rd Trimester | INSTRUMENT |
Tabriz, Iran, 2005[23] | Mean ± SD | TSH IU/mL | 229 | 1.71 + 1.38 | 1.89 ± 1.24 | 2.12 + 0.77 | Radio immunoassay/ Gammamatic II Gamma counter (Contron, Switzerland). |
New Delhi, India 2008[24] | 2008 5th − 95th percentile | TSH µ IU/mL | 541 | 0.6–5 | 0.435–5.78 | 0.74–5.7 | ECL/Elecsys 1010 Analyzer |
| FreeT4 pmol/L | | 12–19.45 | 9.48–19.58 | 11.3–17.71 |
Shanghai, China, 2013[22] | 2.5th − 95th percentile | TSH mIU/L | 2743 | 0.06–3.13 | 0.07–4.13 | 0.15–5.02 | Beckman Coulter UniCel™ DxI 600. |
FreeT4 pmol/L | | 8.72–15.22 | 7.10–13.55 | 6.16–12.03 |
Mean ± SD | FreeT3 pmol/L | | 14.90 ± 4.67 | 13.07 ± 3.06 | 6.91 ± 3.20 |
Current study | Mean ± SD | FreeT4 pg/ml | 436 | 13.15 ± 2.39 | 11.70 ± 2.40 | 10.365 ± 2.326 | MAGLUMI 800 (SNIBE) |
TSH µlU/L | | 1.376 ± 0.982 | 1.62 ± 1.04 | 1.64 ± 0.99 |
2.5th − 95th percentile | TSH | | 0.16-.29 | 0.258–4.58 | 0.34–4.62 |
To date, there is only limited data available on reference values of thyroid markers among pregnant females in the Pakistani population. This study is aimed to determine trimester-specific reference ranges for thyroid-stimulating hormones (TSH), Free T3 (FT3), and free T4 (FT4) in apparently healthy pregnant women attending tertiary care hospitals in Lahore.