|Year : 2016 | Volume
| Issue : 3 | Page : 106-109
Trimester specific ranges for thyroid hormones in normal pregnancy
Jidnyasa Mankar1, Anagha Sahasrabuddhe1, Shailesh Pitale2
1 Department of Physiology, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India
2 Pitale Diabetes and Hormone Center, Nagpur, Maharashtra, India
|Date of Web Publication||27-Oct-2016|
5 Charushree Apartments, Khare Town, Dharampeth, Nagpur - 440 010, Maharashtra
Source of Support: None, Conflict of Interest: None
Maternal and fetal thyroid profiles differ throughout gestation. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester specific reference intervals. American Thyroid Association strongly recommends to refer to population defined trimester-specific reference ranges with optimal iodine intake Though some studies have reported this reference range in South and a few in North, there has been no data from Central India yet. Aims and Objectives: To establish normative range of TSH in each trimester of pregnancy, To establish normative range of f T3 and f T4 in each trimester of pregnancy and to know the prevalence of subclinical hypothyroidism in normal pregnancies. Materials and Methods: in all 177 normal singleton pregnant women were screened and out of them 150 enrolled in the study(50 in each trimester). Their TSH, fT3, fT4 and urinary iodine was estimated. Observations and Results: The reference range of thyroid hormones for 1st trimester found in the present study are as follows: TSH: 0.24-4.17 (uIU/ml), fT3: 0.29-3 .1 (ng/100 ml), fT4: 01-2.2 (ng/100 ml). For 2 nd trimester: the reference range for TSH , fT3 and fT4 are 0.78-5.67 (uIU/ml) , 0.27-3.34(ng/100 ml) ,and 0.45-2.24 (ng/100 ml) respectively. For 3 rd trimester, the reference range for TSH , fT3 and fT4 are 0.47-5.78 (uIU/ml), 0.24-3.61(ng/100 ml) and 0.47-5.1 (ng/100 ml). Prevalence of subclinical hypothyroidism was found to be 4% in first and second trimesters and 8% in third trimester. No case was seen with clinical hypothyroidism. Conclusion: This study states the range of thyroid hormones in all 3 trimesters of pregnancy. The prevalence of subclinical hypothyroidism was found out to be 4% in first and second trimesters each and 8% in third trimester.
Keywords: Free T3, free T4, subclinical hypothyroidism, thyroid stimulating hormone
|How to cite this article:|
Mankar J, Sahasrabuddhe A, Pitale S. Trimester specific ranges for thyroid hormones in normal pregnancy. Thyroid Res Pract 2016;13:106-9
|How to cite this URL:|
Mankar J, Sahasrabuddhe A, Pitale S. Trimester specific ranges for thyroid hormones in normal pregnancy. Thyroid Res Pract [serial online] 2016 [cited 2021 Apr 12];13:106-9. Available from: https://www.thetrp.net/text.asp?2016/13/3/106/180192
| Introduction|| |
Pregnancy is a time of complex hormonal changes. To meet the challenge of increase in metabolic needs during pregnancy, the thyroid adapts through changes in thyroid hormone economy and in the regulation of hypothalamic pituitary thyroid axis. , Maternal and fetal thyroid profiles differ throughout gestation. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals. Under the influence of placental human chorionic gonadotropin (hCG), the levels of thyrotropin (thyroid stimulating hormone [TSH]) is decreased throughout pregnancy. , In essence, pregnancy is a stress test for thyroid, resulting in hypothyroidism in women with limited thyroid reserve or iodine deficiency.  Thyroid dysfunction and in particular hypothyroidism can have deleterious impact on pregnancy. 
The vast physiological changes in maternal hormones and their binding proteins complicate the assessment of normal levels of most hormones and the interpretation of the test's result during gestation, especially when there are no established gestation specific reference intervals. 
Only recently, Indian Thyroid Society (ITS) has endorsed the recommendations of American Thyroid Association regarding diagnosis and management of thyroid diseases during pregnancy. There are significant ethnic differences in serum TSH concentrations. Hence, American Thyroid Association strongly recommends referring to the population defined trimester-specific reference ranges with optimal iodine intake.  There is a need of designing multicentric study to define this range in India, considering the large population and existence of pleural society. Though some studies have reported this reference range in South and a few in North, there has been no data from Central India yet. This study has its significance here.
| Aims and objectives|| |
- To establish normative range of TSH in each trimester of pregnancy
- To establish normative range of fT3 and fT4 in each trimester of pregnancy
- To know the prevalence of subclinical hypothyroidism (SCH) in pregnancies.
| Materials and methods|| |
The study was carried out in NKP Salve Institute of Medical Sciences (NKPSIMS) and Research Centre, Nagpur. Institutional Ethics Committee approved the project. The work was started after receiving the approval from the committee. It is a cross-sectional study. In all 177 cases, attending ANC Clinic at NKPSIMS from August to November 2014, were screened for the study. Of these, 27 case were excluded after reviewing inclusion-exclusion criteria. Finally, 150 were enrolled in the study, 50 in each trimester.
The inclusion-exclusion criteria were as follows:
- Pregnant women ready to give written consent for drawing sample in the age group of 18-35 years
- All singleton normal pregnancies were included
- Patients with adequate diet intake (based on diet history) and urinary iodine excretion.
The patients were asked to report on given dates for the investigations. During first visit detailed history and clinical examination was done. Inclusion-exclusion criteria were reviewed. Last menstrual period was noted and weeks of gestation calculated. Wherever possible, Ultra Sonography (USG) was reviewed for the same. Trimester-specific visits were planned as follows:
- Patients who have conceived after the treatment for infertility or by assisted reproductive technology
- Patients with known thyroid disorders
- Patients with complicated pregnancies like pregnancy-induced hypertension, hyperemesis, diabetes mellitus, heart diseases, and other endocrine disorders
- History of polycystic ovarian disease
- Multiple pregnancies and history of recurrent abortions
- Patients with history of psychiatric illness or treatment for the same
- History of hepatitis and liver dysfunction
- History of drug intake affecting thyroid function and those suffering from any chronic illnesses
- Inadequate iodine intake as assessed by urinary iodine excretion.
For diagnosis of SCH and clinical hypothyroidism, current guidelines of ITS have been used.
- First trimester of pregnancy: 8-10 weeks
- Second trimester of pregnancy: 18-20 weeks
- Third trimester of pregnancy: 30-32 weeks.
Blood sample around 5 mL was drawn with all aseptic precautions. TSH, fT3, and fT4 estimation were done in central laboratory by chemiluminescence immunoassay method. KITS: TSH test − VIDAS TSH and urinary iodine content were assessed to ensure adequate iodine intake.
| Observations and results|| |
The mean age of the mothers was 25.38 ± 5.36 in completed years. Mean height recorded: 151.22 ± 4.35cm. Mean systolic and diastolic blood pressures in mmHg were 118 ± 11.37 and 72.14 ± 7.64, respectively.
[Table 1] shows values of trimester-specific thyroid hormones. The 5 th and 95 th centiles were used to determine reference ranges. The reference range of thyroid hormones for first trimester found in the present study is as follows:
|Table 1: Gestation specific values for fT3, fT4, TSH, and urinary iodine in different trimesters |
Click here to view
TSH: 0.24-4.17 (uIU/mL), fT3: 0.29-3.1 (ng/100 mL), fT4: 01-2.2 (ng/100 mL). For second trimester: The reference range for TSH, fT3, and fT4 are 0.78-5.67 (uIU/mL), 0.27-3.34 (ng/100 mL), and 0.45-2.24 (ng/100 mL), respectively. For third trimester, the reference range for TSH, fT3, and fT4 are 0.47-5.78 (uIU/mL), 0.24-3.61 (ng/100 mL), and 0.47-5.1 (ng/100 mL), respectively.
In first trimester, 2 cases had TSH levels beyond the recommended range of 0.1-2.5 mIU/L.
In second trimester, 2 cases had values of TSH above recommended range of 3.0 mIU/L; in third trimester, this number increased to 4. So the prevalence of SCH was found to be 4% in first and second trimesters and 8% in third trimester. No case was seen with clinical hypothyroidism.
It was also observed that the range of TSH is low in the first trimester, and then it increases in second and third trimester.
| Discussion|| |
The present study provides further documentation that average TSH levels are lower during pregnancy and more so in the first trimester. It provides the trimester-specific ranges of thyroid hormones in normal pregnancy. Also, the placenta of humans secrete huge amount of a hormone Called Hcg. TSH and Hcg are similar enough that hCG can bind and transduce signaling from the TSH receptor on the thyroid epithelial cells. Towards the end of first trimester of pregnancy in humans, when hCG levels are highest, a significant fraction of the thyroid stimulating activity is from hCG. The thyroid stimulating activity of hCG actually results in reduction in the levels of TSH. Hence, the regular upper limit of 5 for diagnosis of SCH has no relevance in first trimester when the levels of hCG are at peak.
Thyroid hormones have great impact on fetal development and growth. The fetus has two potential sources of thyroid hormones - its own thyroid and the thyroid of its mother. Human fetuses acquire the ability to synthesize thyroid hormones at roughly 12 weeks of gestation. In hypothyroid woman, when pregnancy does occur, there is increased risk of intrauterine fetal death and gestational hypertension. , SCH is increasingly being recognized as a cause of developmental disease.  Therefore, it is necessary to establish a reference range of thyroid hormones for all the 3 trimesters of pregnancy separately.
A study was carried out by Marwaha et al.  in 2008 to establish reference range for thyroid hormones in normal pregnant Indian women. The composition of reference population comprised of 107 women in first trimester, 137 in second trimester, and 87 in third trimester. The trimester wise values in the first, second, and third trimester were fT3 (0.149-0.455, 0.248-0.445, 0.256-0.436 ng/dL), fT4 (0.932-1.51, 0.736-1.521, 0.86-1.45 ng/dL), and TSH (0.6-5, 0.44-5.78, 0.74-5.7 mIU/L). The reference of thyroid hormones in present survey matches with this study. Our study has reported the following reference range for first trimester TSH: 0.24-4.17 (uIU/mL), fT3: 0.29-3.1 (ng/100 mL), and fT4: 01-2.2 (ng/100 mL). For second trimester: The reference range for TSH, fT3, and fT4 are 0.78-5.67 (uIU/mL), 0.27-3.34 (ng/100 mL), and 0.45-2.24 (ng/100 mL), respectively. For third trimester, the reference range for TSH, fT3, and fT4 are 0.47-5.78 (uIU/mL), 0.24-3.61 (ng/100 mL), and 0.47-5.1 (ng/100 mL), respectively. Our study also matches the findings of two other surveys; one done in Iranian pregnant women  and the other one in India by Kumar et al.  The trimester-specific reference range in Iranian study was found to be: In first, second, and third trimester TSH (0.2-3.9, 0.5-4.1, and 0.6-4.1). The major difference between these and our study is that they have estimated total T3 and total T4 while we have done free T3 and free T4. Thyroid binding globulin (TBG) is one of several proteins that transport thyroid hormones in blood and has the highest affinity for T4 of the group. Increased level of TBG leads to lowered free T4 concentrations, which results in elevated TSH secretions by the pituitary and consequently, enhanced production and secretion of thyroid hormones.  The net effect of elevated TBG synthesis is to force a new equilibrium between bound and free thyroid hormones and thus a significant increase in total T4 and T3 levels.
TSH is the most reliable test for diagnosing hypothyroidism, but pregnancy presents a challenge for establishing reliable reference ranges and cut-offs. 
We report SCH to be 4% in first and second trimesters and 8% in third trimester. This is relatively less as compared with other studies that have reported the same to be 21.5%  and 14.3%;  both reports are from India. A few studies by Bandela et al.  and Gayathri et al.  have findings that match ours who have reported SCH to be 10% and 2.8%. Thus, the prevalence of SCH reported in India is variable, and one of the reasons could be different upper limit cut-offs used for TSH. The higher prevalence in the above study could be a result of inclusion of high-risk individuals; for example, those with recurrent abortions, undiagnosed goiters were included in the above-mentioned study.  TSH levels more than 2.5 mU/L in first trimester of pregnancy predispose women to pregnancy loss even without thyroid autoimmunity. 
The strength of the present study is highly specific inclusion-exclusion criteria and estimation of urinary iodine that ensures adequacy of iodine intake. The major limitation is sample size.
Though there is no consensus worldwide about universal screening of all pregnant women for thyroid dysfunction, ITS recommends screening of all pregnant females at first antenatal visit by measuring TSH levels.
| Conclusions|| |
This study states the range of thyroid hormones in all 3 trimesters of pregnancy. The reference interval of thyrotropin and other thyroid hormones found in the current study differs from those reported by other countries and necessitate the importance of applying trimester-specific reference ranges to each population. The prevalence of SCH was found to be 4% in first and second trimesters each and 8% in third trimester.
| Acknowledgments|| |
The study was completed as a part of ICMR STS scheme.
| References|| |
van Raaij JM, Vermaat-Miedema SH, Schonk CM, Peek ME, Hautvast JG. Energy requirements of pregnancy in The Netherlands. Lancet 1987;2:953-5.
Glinoer D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
Krejewski DA, Burman KD. Thyroid disorders in pregnancy in endocrine disorders of pregnancy. Endocrinology and metabolism Clinics 2011;40:739-63.
Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol 2008;20:784-94.
Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med 1994;331:1072-8.
Ausó E, Lavado-Autric R, Cuevas E, Del Rey FE, Morreale De Escobar G, Berbel P. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology 2004;145:4037-47.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al
. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081-125.
Marwaha RK, Chopra S, Gopalakrishnan S, Sharma B, Kanwar RS, Sastry A, et al.
Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG 2008;115:602-6.
Mehran L, Amouzegar A, Delshad H, Askari S, Hedayati M, Amirshekari G, et al.
Trimester-specific reference ranges for thyroid hormones in Iranian pregnant women. J Thyroid Res 2013;2013:651517.
Kumar A, Gupta N, Nath T, Sharma JB, Sharma S. Thyroid function tests in pregnancy. Indian J Med Sci 2003;57:252-8.
Lambert-Messerlian G, McClain M, Haddow JE, Palomaki GE, Canick JA, Cleary-Goldman J, et al.
First- and second-trimester thyroid hormone reference data in pregnant women: A FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study. Am J Obstet Gynecol 2008;199:62.e1-6.
Rajput R, Goel V, Nanda S, Rajput M, Seth S. Prevalence of thyroid dysfunction among women during the first trimester of pregnancy at a tertiary care hospital in Haryana. Indian J Endocrinol Metab 2015;19:416-9.
Dhanwal DK, Prasad S, Agarwal AK, Dixit V, Banerjee AK. High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India. Indian J Endocrinol Metab 2013;17:281-4.
Bandela V, Havilah P, Hindumathi M, Prasad DK. Antenatal thyroid dysfunction Rayalaseema region: A preliminary cross-sectional study based on circulating serum thyrotropin levels. Int J Appl Biol Pharm Technol 2013;4:74-8.
Gayathri R, Lavanya S, Raghavan K. Subclinical hypothyroidism and autoimmune thyroiditis in pregnancy - a study in south Indian subjects. J Assoc Physicians India 2009;57:691-3.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010;95:E44-8.
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