EVALUATION OF THYROID FUNCTION IN PRE-ECLAMPSIA

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1 EVALUATION OF THYROID FUNCTION IN PRE-ECLAMPSIA K. Sunanda 1, P. Sravanthi 2, H. Anupama 3 1Assistant Professor, Department of Obstetrics & Gynaecology, Gandhi Medical College/Hospital. 2Post Graduate, Department of Obstetrics & Gynaecology, Gandhi Medical College/Hospital. 3Professor, Department of Obstetrics & Gynaecology, Gandhi Medical College/Hospital. ABSTRACT Hypertensive disorders of pregnancy complicate about 5-10 of all pregnancies. According to world health organisation (WHO) nearly one tenth of all maternal deaths are associated with hypertensive disorders of pregnancy in Asia. The majority of deaths due to preeclampsia and eclampsia are avoidable through the provision of timely and effective care to the women presenting with these complications. Optimizing health care to prevent and treat women with hypertensive disorders is a necessary step towards achieving the Millennium Development Goals. AIMS AND OBJECTIVES The present study is aimed to evaluate thyroid function in pre-eclampsia and to compare maternal and foetal outcome in of pre-eclampsia with and without hypothyroidism. METHODS The study was conducted at Gandhi Hospital, Secunderabad from September 2010 to September A observational study was conducted. Hundred pregnant women meeting the criteria of preeclampsia and eclampsia presenting to antenatal ward, delivery room and high risk unit in the third trimester were selected and compared to hundred normotensive pregnant women in the third trimester. RESULTS In the present study, thyroid stimulating hormone levels were raised in 38 of pre-eclampsia compared to 14 of normotensive (P value < ). TSH levels were significantly higher in pre-eclamptic group (3.4 miu/l) compared to normotensive group (2.4 miu/l). Difference of mean of TSH value between pre-eclampsia and normotensive is significant. There is no significant difference in FT3 and FT4 levels between pre-eclamptic women and normotensive women. Pre-eclampsia is associated with hypothyroidism. Pre-eclamptic patients with TSH > 3 miu/l had more complications compared to pre-eclamptic patients with TSH < 3 miu/l. CONCLUSION Pre-eclampsia is associated with hypothyroidism. Pre-eclamptic patients with raised thyroid stimulating hormone levels had poor maternal and foetal outcome compared to those with normal levels. Thyroid Function tests must be done in all pre-eclampsia. Therefore, identification of thyroid abnormalities and appropriate measures might affect the occurrence and severity of the morbidity and mortality associated with pre-eclampsia. KEYWORDS Pre-Eclampsia, Eclampsia, Hypothyroidism. HOW TO CITE THIS ARTICLE: Sunanda K, Sravanthi P, Anupama H. Evaluation of thyroid function in pre-eclampsia. J. Evolution Med. Dent. Sci. 2016;5(19): , DOI: /jemds/2016/219 INTRODUCTION Hypertensive disorders of pregnancy complicate about 5-10 of all pregnancies. According to world health organisation (WHO) nearly one tenth of all maternal deaths are associated with hypertensive disorders of pregnancy in Asia. The majority of deaths due to preeclampsia and eclampsia are avoidable through the provision of timely and effective care to the women presenting with these complications. Optimizing health care to prevent and treat women with hypertensive disorders is a necessary step towards achieving the Millennium Development Goals. Financial or Other, Competing Interest: None. Submission , Peer Review , Acceptance , Published Corresponding Author: Dr. K. Sunanda, Department of Obstetrics & Gynaecology, Gandhi Medical College/Hospital, Musheerabad, Hyderabad drsunanda62@gmail.com DOI: /jemds/2016/219 According to the study conducted by Richard J Levine (Department of Health and Human Services, Bethesda, USA 2009), increased serum concentration of soluble fms-like tyrosine kinase-1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years. 1 AIMS AND OBJECTIVES The aim of this study is to evaluate thyroid function in preeclampsia and to compare maternal and foetal outcome in of pre-eclampsia with and without hypothyroidism. MATERIALS & METHODS The study was conducted at Gandhi Hospital, Secunderabad from September 2010 to September A observational study was conducted. Hundred pregnant women meeting the criteria of preeclampsia and eclampsia presenting to antenatal ward, delivery room and high risk unit in the third trimester were selected and compared to hundred normotensive pregnant women in the third trimester attending the antenatal clinic during the study period. J. Evolution Med. Dent. Sci./ eissn , pissn / Vol. 5/ Issue 19/ Mar. 07, 2016 Page 942

2 Pre-eclamptic patients with blood pressure of >140/90 mmhg on at least two occasions, six hours apart, Eclamptic patients, Primi and multi gravida with Gestational age >28 weeks and with Singleton pregnancy are included in the study. Patients with history of chronic hypertension, underlying renal disease, thyroid disease during previous pregnancy or postpartum period, diabetes mellitus, collagen disease, heart disease and with history of treatment with anti-thyroid drugs, thyroxine, radioiodine, or thyroid surgery are excluded from the study. Informed consent of all the women meeting the selection criteria were taken. In addition to routine tests advised in pregnancy, special laboratory investigations like complete urine examination and 24 hrs urinary protein, complete blood count including platelet count, random blood sugar, blood urea, serum creatinine, serum uric acid, coagulation profile, liver function tests were done in pre-eclamptic patients. TSH (Thyroid-Stimulating Hormone) was measured using Ultra-Sensitive Sandwich Chemiluminescent Immunoassay. The normal range of Thyroid Stimulating Hormone in third trimester is miu/l as per the Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum. Those who had TSH >3 miu/l were screened for FT4 (Free serum thyroxine) and FT3 (Free serum triiodothyronine). The normal range of free triiodothyronine is pg/ml. The normal range of free thyroxine is ng/dl. FT4 and FT3 were measured using Competitive Chemiluminescent Immuno Assay. They were treated as per the treatment advised by endocrinologist. All patients were followed for 1 week after delivery. The complications during antenatal, intranatal and postnatal were studied. Perinatal outcome of the babies was studied. Mode of delivery of all the were noted. Data obtained is analysed statistically. RESULTS In the present study, 85 of pre-eclampsia and 96 of normotensive were in the age group years. In the present study, 75 of the pre-eclampsia and 52 of the normotensive were unbooked. In the present study, 82 of pre-eclampsia and 76 of normotensive belonged to lower socioeconomic status, as our hospital is a government hospital. In the present study, 62 of the pre-eclampsia were primigravidae. Primigravida is a risk factor for preeclampsia. In the present study, there is recurrence of preeclampsia in 39 of. TSH <3 miu/l TSH >3 miu/l Total 100 Preeclampsia of of of Total Table 1: Thyroid Stimulating Hormone Status Chi square value (X2) = P value < P value is highly significant. Pre-eclampsia is associated with hypothyroidism. Thyroid stimulating hormone levels were raised in 38 of pre-eclampsia and 14 of normotensive. TSH levels were significantly higher in preeclamptic group (3.4 miu/l) compared to normotensive group (2.4 miu/l). Preeclampsia Normal Standard Standard Range Deviation Deviation TSH(mIU/l) Table 2: Value of TSH Z Test The mean TSH value is 2.4 miu/l. The standard deviation is Pre-Eclampsia The mean TSH value is 3.4 miu/l. The standard deviation is Standard error = (Standard deviation1 2 /n1 +standard deviation2 2 /n2 ) = (0.78x0.78)/100 +(2.75x2.75)/100 =0.285 Z TEST = OBSERVED MEAN DIFFERENCE/STANDARD ERROR = 1/0.28 = 3.57 P value is < 0.05 P value is significant. Difference of mean of TSH value between pre-eclampsia and normotensive is significant. Normal range Preeclampsia FT3 (pg/ml) FT4 (ng/dl) Table 3: Values of FT3 & FT4 There is no significant difference in the mean value of FT3 and FT4 levels between pre-eclamptic women and normotensive women. J. Evolution Med. Dent. Sci./ eissn , pissn / Vol. 5/ Issue 19/ Mar. 07, 2016 Page 943

3 TSH<3 miu/l TSH>3 miu/l of of percentage percentage Mild preeclampsia Severe preeclampsia Total Table 4: Comparison of TSH Status in Relation to Severity of Preeclampsia 63 of the with TSH > 3 miu/l had severe preeclampsia. TSH < 3 miu/l (62) TSH > 3 miu/l(38) Total of of of Eclampsia Abruption HELLP Syndrome Acute Renal Failure Pulmonary Oedema DIC Table 5: Maternal Complications of Pre-Eclampsia In Relation to TSH Levels Pre-eclamptic patients with TSH > 3 miu/l had eclampsia in 31.57, abruption in 18.42, HELLP syndrome in 15.78, Acute renal failure in 18.42, Pulmonary oedema in 7.89, Disseminated intravascular coagulation in TSH< 3 miu/l TSH> 3 miu/l Cause of death 0 1 Antepartum eclampsia, pulmonary oedema Table 6: Maternal Death In Relation to TSH Levels Pre-eclamptic patients with TSH > 3 miu/l had death in one case due to antepartum eclampsia and pulmonary oedema. TSH < 3 miu/l(62) TSH > 3 miu/l (38) TOTAL (100) of of of Fresh still born Intrauterine death Prematurity Prematurity & IUGR IUGR NICU admissions Normal APGAR NICU deaths Table 7: Neonatal Outcome in Pre-Eclampsia in Relation to TSH Levels J. Evolution Med. Dent. Sci./ eissn , pissn / Vol. 5/ Issue 19/ Mar. 07, 2016 Page 944

4 Pre-eclamptic patients with TSH > 3 miu/l had fresh stillborn in 13.15, intrauterine death in 42.10, prematurity in 26.31, prematurity & intrauterine growth restriction in 18.42, intrauterine growth restriction in 34.21, NICU admissions in 21.05, normal APGAR in 23.68, NICU deaths in DISCUSSION In the present study conducted at Gandhi Hospital, Secunderabad from September 2010 to September 2012, hundred pregnant women meeting the criteria of preeclampsia and eclampsia in the third trimester were selected and compared to hundred normotensive pregnant women in the third trimester. In the present study, 85 of pre-eclampsia and 96 of normotensive were in the age group years. In the present study, 75 of the pre-eclampsia and 52 of the normotensive were unbooked. The high incidence of unbooked is due to the referrals from peripheral and suburban hospitals, as our hospital is a tertiary care center. In the present study, 82 of pre-eclampsia and 76 of normotensive belonged to lower socioeconomic status, as our hospital is a government hospital. In the present study, 62 of the pre-eclampsia were primigravidae. Primigravida is a risk factor for preeclampsia. In the present study, there is recurrence of preeclampsia in 39 of. In the present study, 28 of the pre-eclampsia delivered before 32 weeks, whereas 90 of the normotensive delivered at term. Early delivery of the pre-eclampsia is due to termination in view of complications of preeclampsia. According to the study conducted by Richard J Levine (Department of Health and Human Services, Bethesda, USA 2009), increased serum concentration of soluble fms-like tyrosine kinase-1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later year. 1 In the present study, thyroid stimulating hormone levels were raised in 38 of pre-eclampsia compared to 14 of normotensive (P value < ). TSH levels were significantly higher in pre-eclamptic group (3.4 miu/l) compared to normotensive group (2.4 miu/l). Difference of mean of TSH value between pre-eclampsia and normotensive is significant. There is no significant difference in FT3 and FT4 levels between pre-eclamptic women and normotensive women. Pre-eclampsia is associated with hypothyroidism. Comparison of My Study with Previous Studies SI. NO. STUDY YEAR P VALUE SIGNIFICANCE 1 Richard J Levine et al P =0.002 Significant 2 Khaliq F et al P <.001 Significant 3 Ashok Kumar et al P <0.001 Significant 4 Nahid Mostaghel et 2008 P >0.05 Not significant al. 4 5 Divya Sardana et al P <0.001 Significant 6 Nayereh Khadem et al P=0.386 Not significant 7 My study 2012 P < Highly significant Pre-eclampsia is associated with hypothyroidism. A study was conducted by Khaliq F et al., in 1999 reported that serum total tri-iodothyronine (TT3) and total thyroxine (TT4) were decreased significantly (P<0.001) and TSH was increased significantly (P <.001) in pre-eclampsia as compared to normal pregnancy. 2 Kumar et al., in 2005 reported that mean TSH levels were significantly higher in pre-eclamptic group as compared to controls (p<0.001). However, mean values of thyroid hormones were in the normal range 3. Nahid Mostaghel et al., in 2008 reported that of thyroid stimulating hormone (TSH) levels was not significantly higher in pre-eclamptic group as compared to controls (p>0.05) 4. Divya Sardana et al., in 2009 reported that TSH levels were higher in both pre-eclamptic & normotensive pregnant women compared to non-pregnant women J. Evolution Med. Dent. Sci./ eissn , pissn / Vol. 5/ Issue 19/ Mar. 07, 2016 Page 945

5 [p<0.001] and levels were lower in normotensive pregnant women compared to non-pregnant women [p<0.001]. 5 Nayereh Khadem et al., in 2012 reported that normal pregnant women were not significantly different from pre-eclampsia in the view of FT3 level (1.38 pg/ml vs pg/ml, p=0.803), FT4 level (0.95 pg/ml vs pg/ml, p=0.834) and TSH level (3.51 μiu/ml vs μiu/ml,p=0.386). The findings of this study do not support the hypothesis that changes in FT3, FT4 and TSH levels could be possible aetiology of preeclampsia. 6 In the present study, 32 of the mild pre-eclampsia had TSH > 3 miu/l. 43 of the severe pre-eclampsia had TSH > 3 miu/l. 63 of the with TSH > 3 miu/l had severe pre-eclampsia. Modest decrease in thyroid hormones along with increased TSH level in maternal serum is correlated with severity of pre-eclampsia and high levels of endothelin. 7 3 miu/l had eclampsia in 31.57, abruption in 18.42, HELLP syndrome in 15.78, Acute renal failure in 18.42, Pulmonary oedema in 7.89, Disseminated intravascular coagulation in Pre-eclamptic patients with TSH < 3 miu/l had eclampsia in 11.29, abruption in 6.45, HELLP syndrome in 3.22, Acute renal failure in 4.83, Pulmonary oedema in There were no of disseminate intravascular coagulation. Pre-eclamptic patients with TSH > 3 miu/l had more complications compared to pre-eclamptic patients with TSH < 3 miu/l. 3 miu/l had death in one case due to antepartum eclampsia, pulmonary oedema. 3 miu/l had fresh stillborn in 13.15, intrauterine death in 42.10, prematurity in 26.31, prematurity & intrauterine growth restriction in 18.42, intrauterine growth restriction in 34.21, NICU admissions in 21.05, normal APGAR in 23.68, NICU deaths in Pre-eclamptic patients with TSH < 3 miu/l had fresh stillborn in 3.22, intrauterine death in 19.35, prematurity in 29.03, prematurity & intrauterine growth restriction in 8.06, intrauterine growth restriction in 19.35, NICU admissions in 22.58, normal APGAR in 54.83, NICU deaths in Pre-eclamptic patients with TSH > 3 miu/l had increased perinatal mortality and morbidity compared to preeclamptic patients with TSH< 3 miu/l. 3 miu/l had babies with birthweight between kg in 42, birthweight >2.5 kg in Pre-eclamptic patients with TSH< 3 miu/l had babies with birthweight between kg in 43.54, birthweight >2.5 kg in Preeclamptic patients with TSH > 3 miu/l had more low birth weight babies compared to pre-eclamptic patients with TSH < 3 miu/l. CONCLUSION Pre-eclampsia is associated with hypothyroidism. Pre-eclamptic patients with raised thyroid stimulating hormone levels had poor maternal and foetal outcome compared to those with normal levels. Thyroid Function tests must be done in all pre-eclampsia. Therefore, identification of thyroid abnormalities and appropriate measures might affect the occurrence and severity of the morbidity and mortality associated with pre-eclampsia. However, further studies are required because of the small number of subjects in this study. A multi-centric study may answer the association and mechanism of thyroid abnormality in pre-eclamptic women in terms of the geographical variation. REFERENCES 1. Levine RJ, Vatten LJ, Horowitz GL, et al. Pre-eclampsia soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study. BMJ 2009;339:b Khaliq, Farah, Usha Singhal, et al. Thyroid functions in pre-eclampsia and its correlation with maternal age, parity, severity of blood pressure and serum albumin. Indian journal of physiology and pharmacology 1999;43(2): Kumar A, Ghosh BK, Murthy NS. Maternal thyroid hormonal status in pre-eclampsia. Indian J Med Sci 2005;59(2): Mostaghel N, Tavanyanfar E, Samani N. Association of maternal hypothyroidism with pre-eclampsia. Iranian Journal of Pathology 2008;(2): Sardana, Divya, Smiti Nanda, Simmi Kharb. Thyroid hormones in pregnancy and pre-eclampsia. J Turkish- German Gynecol Assoc 2009;10(3): Nayereh Khadem, Hossein Ayatollahi, Fatemeh Vahid Roodsari, et al. Comparison of serum levels of Triiodothyronine (T3), Thyroxine (T4), and Thyroid Stimulating Hormone (TSH) in pre-eclampsia and normal pregnancy. Iranian Journal of Reproductive Medicine 2012;10(1): Basbug M, Aygen E, Tayyar M, et al. Correlation between maternal thyroid function tests and endothelin in preeclampsia eclampsia. Obstet Gynecol 1999;94(4): J. Evolution Med. Dent. Sci./ eissn , pissn / Vol. 5/ Issue 19/ Mar. 07, 2016 Page 946