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Year : 2014 | Volume : 2 | Issue : 2 | Page : 84 - 88  


Original Articles
Correlation of Thyroid and Lipid Profile in Preeclampsia Patients

Sai Madhuri Kaveti1, V. Sampath Kumar2, A. R. Vijaya Lakshmi3, Alekhya Audi4, T. K. Rajasree5

1 II M.B.B.S. Student, Malla Reddy Institute of Medical Sciences, Hyderabad.

2 Professor and HOD, Department of Biochemistry, Malla Reddy Institute of Medical Sciences, Hyderabad.

3 Professor and HOD, Department of Obstetrics and Gynecology, Malla Reddy Institute of Medical Sciences, Hyderabad.

4 IV year Undergraduate, M.Sc, Integrated Chemistry, Indian Institute of Technology (IIT), Bombay.

5 Professor and HOD, Department of Anatomy, Malla Reddy Institute of Medical Sciences, Hyderabad.

Abstract:

Background: Preeclampsia is a common medical complication during pregnancy, which affects approximately 8-10% in India and 6-8% of all pregnancies worldwide, most commonly after the 32nd week. It is associated with complications like premature birth, low birth weight and postpartum hemorrhage.

Objectives: To estimate Lipid and Thyroid profile in Preeclampsia, Healthy pregnancy and Non pregnant women to assess the risk of lipid abnormalities and thyroid dysfunction in preeclampsia. To determine correlation of lipid and thyroid profile in preeclampsia patients and healthy pregnant women.

Methods: This study comprised of three age matched groups consisting of 30 healthy non-pregnant women, 30 healthy pregnant women and 30 preeclampsia patients attending antenatal OPD and all pregnant women were at ≥28 weeks of gestation. Blood samples were collected 8-10 hours after fasting and the thyroid and lipid profiles were analyzed for comparison and correlation among them.

Results: It was observed that T3, T4, TSH, total cholesterol, triglyceride and VLDL increased significantly in preeclampsia patients when compared to both healthy pregnant and non pregnant women. Whereas T3, T4, total cholesterol, triglyceride and VLDL were increased significantly in healthy pregnant women when compared to healthy non pregnant women. Significant positive correlation was seen between TSH and Triglycerides (p < 0.05) also seen between T3 and total cholesterol (p < 0.05), T3 and LDL (p < 0.05) in preeclampsia patients.

Conclusion: Correlation of Lipid and Thyroid profile, Screening for dyslipidemia and thyroid dysfunction in Preeclampsia is essential to prevent medical complications during Pregnancy.

Keywords: Preeclampsia, Thyroid profile, Lipid profile.

Corresponding Author: Dr. V. Sampath Kumar, Professor & Head, Dept of Biochemistry, Malla Reddy Institute of Medical Sciences. Email: Sampath.surya76@gmail.com

Introduction:

Pre-eclampsia is a common medical complication during pregnancy, which affects approximately 8-10% in India and 6-8% of all pregnancies worldwide, with onset of symptoms in the late second or third trimester, most commonly after the 32nd week. [1] It is characterized by high blood pressure and significant amounts of protein in the urine of a pregnant woman. If left untreated, it can develop into eclampsia, the life-threatening occurrence of seizures during pregnancy. [2] Pregnancy is a period of significant hormonal changes and metabolic demands which results in complex effects on thyroid function [3] Normal changes in thyroid function during pregnancy include a transient suppression of thyroid-stimulating hormone and stimulation of tri-iodothyronine. [4] Serum Total T4 and Total T3 steadily increase during pregnancy to approximately 1.5 times the non-pregnant level by mid second trimester. [5] Women with preeclampsia had higher Total T3, Total T4 levels as compared to non pregnant women , but preeclampsia Total T3,Total T4 levels were lower compared to normotensive pregnant women. TSH levels were higher in both preeclampsia & normotensive pregnant women compared to non-pregnant women. [6]

Lipid values in normal pregnancies change with gestational age. In a normotensive pregnancy, serum triglyceride, Total and HDL-cholesterol increase during pregnancy, but lipoprotein A levels decrease. These changes are reported to be secondary to hormonal changes during pregnancy. [7] An abnormal lipid profile is known to be strongly associated with atherosclerotic cardiovascular disease. Pre-eclampsia and related disorders are known to affect function of various organs involved in lipoprotein metabolism. Several studies have shown that endothelial dysfunction is related to hyperlipidemia. [8] Significantly elevated plasma concentration of triglycerides, phospholipids and total lipids and decreased high density lipoprotein – cholesterol (HDL-C) concentrations were found in women with preeclampsia in comparison to normal pregnancy. [9] Thyroid profile changes during pregnancy and preeclampsia is well documented and many studies reported that altered lipid levels due to abnormal lipoprotein metabolism, but present study conducted to correlate thyroid and lipid profile in preeclampsia and during pregnancy when compared to age matched healthy non pregnant women.

 

Materials and methods:

The prospective study was carried out in the Department of Biochemistry in association with Department of Obstetrics and Gynecology, Mallareddy institute of medical sciences and General Hospital, Hyderabad during the period of May 2013 to September 2013. After obtaining approval from Institutional Ethical Committee, informed consent was taken from all individual subjects included in the study. The study comprised of 30 healthy non-pregnant women, 30 healthy pregnant women and 30 preeclampsia patients attending antenatal OPD in the third trimester of pregnancy.

Inclusion criteria

Cases: The diagnosis of pre-eclampsia was based on the definition of American College of

Obstetrics and Gynecologists i.e. 1) Systolic blood pressure greater than 140 mm Hg or a rise

of at least 30 mmHg or 2) Diastolic blood pressure greater than 90 mm Hg or a rise of at least

15 mmHg (manifested on two occasions at least 6 hours apart) and 3) Proteinuria of 300 mg or greater in 24 hours urine collection or protein concentration of 1 gm/L (on two occasions of at least 6 hours apart).

Controls: Pregnant women with normal BP, no proteinuria and without any other systemic or endocrine disorder. They were age matched with the cases. All subjects included were in their third trimester with a gestational age of ≥28 weeks.

Exclusion criteria: Pregnancy associated with diabetes mellitus with or without treatment, obesity, Family history of Hyper lipidemia, severe anemia (Hb < 6gm %), Renal disease, Age

> 30 years and multiple gestations or subjects suffering from any other systemic or endocrine

disorder or any drugs alters thyroid or lipid metabolism were excluded from the study.

Sample collection: The blood samples were collected in a plain redtop by venipuncture tube without anti-coagulants for preparation of serum. The blood was allowed to clot and the specimens were centrifuged to separate the serum from the cells.

Methods of estimation: Serum samples were analysed for the following parameters by different methods. TSH, T3 and T4: Chemiluminescence immunoassay, Triglycerides: Glycerol 3- Phosphate Oxidase method, Total cholesterol: Cholesterol oxidase – peroxidase method, HDL - Cholesterol: Phosphotungstic acid method. LDL-Cholesterol: Calculated by Friedewald formula.

Results:

A total number of 90 subjects were divided into three groups i.e. healthy non-pregnant, healthy pregnant, and preeclampsia patients. Each group consisting of 30 members participated in this study. The diagnosis of preeclampsia was based on the definition of the association, American college of obstetrics and gynecologists. All the pregnant subjects selected were in their third trimester with a gestational age of ≥28 weeks. Blood samples were collected 8-10 hours after fasting and the thyroid and lipid profiles were analyzed. The mean and standard deviation values of all the data including demographic changes are tabulated.

The demographic data of healthy non-pregnant women, healthy pregnant women and preeclampsia patients are shown in table no.1.

The thyroid profile was compared in between the preeclampsia, pregnant women and non pregnant women subjects. It was observed that TSH, T3 and T4 increased significantly in preeclampsia patients when compared to both healthy pregnant and non pregnant women, whereas, Only T3 and T4 are increased in healthy pregnant women when compared to healthy non pregnant women.

The mean and standard deviation of thyroid values of healthy non-pregnant women, healthy pregnant women and preeclampsia patients are shown in table no.2.

The total cholesterol, triglyceride, and VLDL values are elevated in Preeclampsia when compared to healthy pregnant and non pregnant women. Total cholesterol, triglyceride, and

VLDL values of healthy pregnant women were also elevated when compared to healthy non pregnant women.

The mean and standard deviation of lipid values of healthy non-pregnant women, healthy pregnant women and preeclampsia patients are shown in table no.3.

The correlation had been done for all the parameters of thyroid and lipid profile in preeclampsia patients. It has been observed that positive correlation is seen between TSH and Triglycerides which is statistically significant. The significant positive correlation was also seen betweenT3 and total cholesterol, T3 and also with LDL in preeclampsia patients.

The Pearson correlation between thyroid and lipid profile in preeclampsia patients is shown in table no.4.

Discussion:

Pre-eclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity Worldwide. Pre-eclampsia is a multi-system disorder of pregnancy, between 5% and 15% of pregnant women experience thyroid abnormalities, a fact which justifies screening by means of clinical laboratory testing. There is a high incidence of thyroid dysfunction during pregnancy resulting in adverse maternal (miscarriages, anemia in pregnancy, pre-eclampsia, abruptio placenta and post-partum hemorrhage) and fetal effects (premature birth, low birth weight, increased neonatal respiratory distress) which may justify screening for thyroid function during pregnancy. Mothers, who had early-onset pre-eclampsia, were of significantly lower birth weight. Maternal thyroid dysfunction during pregnancy has been shown to be associated with a number of adverse outcomes. For example, elevated maternal thyroid-stimulating hormone (TSH) has been associated with an increased risk of pre-term birth, placental abruption, fetal death, and impaired neurological development in the child. There are limited numbers of studies on the levels of thyroid hormones in pre-eclampsia and has been suggested that there may be an existence of mutual influences between preeclampsia and thyroid function. Therefore, this study was undertaken to evaluate the influence of pre-eclampsia on thyroid profile. Also, this study intended to correlate thyroid profile parameters with lipid profile. [10] In our study it has been observed that mean BMI in both group of pregnant women (preeclampsia and pregnant women) is significantly increased may be due to elevated total lipid profile levels, where as both systolic and diastolic BP significantly elevated in only in preeclampsia patients could be associated with elevated oxidative LDL levels.

In pregnancy, the renal clearance of iodide increases significantly because of an increased glomerular filtration rate. Renal hyper filtration and increased clearance, observed for iodide and several other molecules (both smaller and larger) begins in the early weeks of gestation and persists until term, thereby constituting an obligatory renal iodine leakage.

The iodide loss tends to lower the circulating levels of inorganic iodide and induces, in turn, a compensatory increase in thyroidal iodide clearance, which reaches 60 ml / min and is accompanied by an absolute elevation of iodide entry into the gland. These mechanisms indicate that the thyroidal activity is increased during pregnancy, as has been suggested by early studies using radio labeled iodine administered to pregnant women, as well as histological studies of thyroid follicular cells obtained during pregnancy and showing marked functional activity. [11]

More specifically, both the Belgian [12] and Danish [13] studies, which showed a systematic increase in serum TSH near term, were carried out in well defined areas with a marginal iodine deficiency. As will be discussed later, the same investigators also showed that iodine supplementation during pregnancy significantly prevented these alterations in serum TSH. Conversely, a Dutch study, [14] which failed to show a difference in serum TSH between the third trimester and non-pregnant controls, was performed in an iodine-replete area.

The thyroid hormones levels were within the normal range and did not show any statistical difference between normal and women with pre-eclampsia. But TSH levels were higher in preeclampsia subjects which was significant.[10] Qublan et al in their study observed no significant differences in the levels of FT4, FT3 and TSH between normal and pre-eclampsia groups at various gestational ages. [15] They conclude that the thyroid function is not altered in severe pre-eclampsia; therefore it does not reflect the severity of pre-eclampsia. In the present study the result shows that T4 and T3 and TSH are significantly increased in preeclamptic patients and healthy pregnant women compared to the value of healthy non pregnant group similar to Rahman et.al. It is well established that there is a big increase in concentration of thyroid binding globulin (TBG) during pregnancy due to influence of high levels of circulating estrogens. [16]

Endothelial dysfunction is the most important event in the pathogenesis of preeclampsia and lipids have a role on this event. Triglycerides and total cholesterol levels gradually increased from the first to third trimester. Other lipid fractions–HDL, apolipoprotein A and B increased parallel to the gestational age but there was no statistically significant difference between trimesters. Human placental lactogen (HPL) is an important protein for fetus growth which is secreted from the placenta. HPL increases plasma free fatty acids via increasing lipolysis, and increases glucose uptake and inhibits gluconeogenesis. [17] Rosing et al reported that especially after the second trimester, levels of ApoA, ApoB, HDL, total cholesterol, and triglycerides were significantly increased. [18] Free fatty acid flow, triglycerides, LDL, HDL, total lipid, cholesterol and VLDL values are increased during preeclampsia. Beta oxidation is disturbed in the liver and VLDL, LDL and triglycerides are stored in liver. Lipid peroxidase and cytokines increase secondary to an increase at the levels of plasma lipids. Endothelial cells are disturbed directly or indirectly and vasoconstriction occurs all throughout the body. [19] In our study it has been observed that total cholesterol, Triglycerides, VLDL are significantly increased in preeclampsia patients when compare with healthy pregnant women. Similar findings observed even in healthy pregnant women when compare with healthy non pregnant women. This result is similar to all above mentioned studies on lipid profile except for LDL and HDL, which are not significant statistically because high values in healthy non pregnant women. This may be due to high LDL and HDL values in local population; further studies with larger data may be required to establish normal lipid profile values.

In the present study correlation was observed between all parameters of thyroid and lipid profile in preeclampsia patients. It has been observed that positive correlation is seen only between TSH and Triglycerides in preeclampsia patients. The principle modulator of this hyper triglyceridemia is hyperoestrogenemia in pregnancy that induces hepatic biosynthesis of Triglycerides. [20] Estrogens stimulate expression of TBG in liver, and the normal rise in estrogen during pregnancy induces roughly a doubling in serum TBG concentrations.

Increased levels of TBG lead to lowered free T3 and T4 concentrations, which results in elevated TSH secretion by the pituitary and, consequently, enhanced production and secretion of thyroid hormones. [21]

Conclusions:

In the present study it is observed that, Thyroid profile includes T3, T4 and TSH are elevated in both preeclampsia and healthy pregnant women due to the effect of estrogen, HCG, TBG and altered renal function. It has been observed that preeclampsia patients were associated with significantly elevated BP where as in both preeclampsia and healthy pregnant women BMI is elevated due to hyperlipidemic status during pregnancy. Among all the parameters of lipid profile Total Cholesterol, Triglycerides, and VLDL are increased significantly in preeclampsia patients when compare with healthy pregnant and non pregnant women due to endothelial dysfunction. There was significant positive correlation observed only between TSH and Triglycerides when compared to thyroid and Lipid profiles in preeclampsia patients due to increased estrogen and TBG. It is very much essential to diagnose preeclampsia as early as possible in early trimesters of pregnancy to prevent fetal, neonatal and maternal complications like premature birth, low birth weight, increased neonatal respiratory distress and postpartum hemorrhage. Further studies are required to identify markers for early diagnosis of preeclampsia associated abnormalities for appropriate treatment.

 

References:

  1. Kamath SA. Hypertension in pregnancy. J Assoc Physicians India. 2006 Apr;54: 269-70.
  2. Datta DC. Hypertensive disorders in pregnancy.  In:  Konar H, editor. Text book of obstetrics, 7th ed. New central book agency pvt limited: Hyderabad, 2013. P. 219 
  3. Fantz CR, Dagogo-Jack S, Ladenson JH, Gronowski AM. Thyroid function during pregnancy. Clin Chem. 1999;45(12):2250–8.
  4. Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A et al. Regulation of maternal thyroid function during pregnancy. J Clin Endocrinol Metab. 1990 Aug;71(2):276-87.
  5. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18:404-33.
  6. Guillaume J, Schussler GC, Goldman J. Components of the total serum thyroid hormone concentrations during pregnancy: high free thyroxine and blunted thyrotropin (TSH) response to TSH-releasing hormone in the first trimester. J Clin Endocrinol Metab 1985;60(4):678–84.
  7. Herrera E, Gomez DC, Lasuncion MA. Lipid metabolism in pregnancy. Biol Neonate. 1987;51(2):70-7.
  8. Dutta DC, Konar HL. Hypertensive disorders in pregnancy, In: Textbook of Obstetrics. 5th ed: New Central Book Agency; 2001:219.
  9. Banaczek Z1, Wójcicka-JagodziƄska J. Concentration of lipids and lipoproteins in serum of women with pregnancy induced hypertension. Ginekol Pol. 1995 Feb;66(2):72-5.
  10. Dhananjaya BS, Sendil kumaran D, Venkatesh G, Murthy N, Shashiraj HK. Thyroid Stimulating Hormone (TSH) Level as a Possible Indicator of Pre-eclampsia. J Clin Diagn Res. 2011;5(8):1542-3
  11. Aboul-Khair SA, Crooks J, Turnbull AC, Hytten FE. The physiological changes in thyroid function during pregnancy. Clin Sci. 1964;27:195–207
  12. Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab. 1990 Aug;71(2):276-87.
  13. Pedersen KM, Laurberg P, Iversen E, Knudsen PR, Gregersen HE, Rasmussen OS et al. Amelioration of some pregnancy-associated variations in thyroid function induced by iodine supplementation. J Clin Endocrinol Metab. 1993 Oct;77(4):1078-83.
  14. Berghout A1, Endert E, Ross A, Hogerzeil HV, Smits NJ, Wiersinga WM. Thyroid function and thyroid size in normal pregnant women living in an iodine replete area. Clin Endocrinol (Oxf). 1994 Sep;41(3):375-9.
  15. Qublan HS, Al-Kaisi IJ, Hindawi IM, Hiasat MS, Awamleh I, Hamaideh AH et al. Severe pre- eclampsia and maternal thyroid function. J Obstet Gynaecol. 2003 May;23(3):244-6.
  16. Rahman MH, Chowdhury MA, Alam MT. Serum thyroxine and triiodothyronine levels in normal pregnancy and pre-eclampsia. TAJ. 2007;20(1):06-10.
  17. Sattar N, Clark P, Greer IA, Shepherd J, Packard CJ. Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with preeclampsia. Atherosclerosis. 2000 Feb;148(2):407-11.
  18. Rosing U, Samsioe G, Olund A, Johansson B, Kallner A. Serum levels of apolipoprotein AI, AII and HDLcholesterol in second half of normal pregnancy and in pregnancy complicated by preeclampsia. Horm Metab Res. 1989 Jul;21(7):376-82.
  19. van den Elzen HJ, Wladimiroff JW, Cohen-Overbeek TE, de Bruijn AJ, Grobbee DE. Serum lipids in early pregnancy and risk of preeclampsia. Br J Obstet 1996 Feb;103(2):117-22.
  20. Glueck CJ, Fallat RW, Scheel D. Effects of estrogenic compounds on triglyceride kinetics. 1975 Apr;24(4):537-45.
  21. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997 Jun;18(3):404-33.

 

           

 

 

 

Tables:

Table 1: Demographic data of healthy non-pregnant women, healthy pregnant women and preeclampsia patients.

Parameters

Healthy

non-pregnant

women

Healthy pregnant

women

Preeclampsia patients

Age

22.4±1.53

22.76±2.66

22.6±2.69

BMI

22.03±2.25

25.86±1.22

27.4±1.47

Systolic pressure

112.33±5.68

114±4.98

144.33±10.4

Diastolic pressure

70.33±7.18

76.33±6.14

99.66±11.29

Weeks of

gestation

_

32.86±2.62

33.53±2.23

 

Table 2: Mean and standard deviation of thyroid values of healthy non-pregnant women, healthy pregnant women and preeclampsia patients

Parameter

(Normal range)

Healthy

non-pregnant

women

Healthy pregnant

women

Preeclampsia patients

T3 ( 0.50-20 ng/ml)

1.06± 0.32

2.15±080*

2.66±1.01*

T4 (4.8-11.6microgm/dl)

8.81±2.06

14.45±3.46*

16.53±3.87*

TSH (0.39-6.16 micro IU/ dl)

0.94±0.89

1.17± 0.75

3.15 ±1.57*

*Statistically Significant p<0.05

 

Table 3: Mean and standard deviation of lipid values of healthy non-pregnant women, healthy pregnant women and preeclampsia patients

Parameter

(Normal range)

Healthy

non-pregnant

women

Healthy pregnant

women

Preeclampsia patients

Total cholesterol

183.16±25.2

210.45±27.28*

244.7±55.92*

Triglycerides

114.4±36.93

148.45±56.2*

208.8±94.9*

HDL

23.93±8.68

34.87±4.1

36.53±3.09

LDL

131.76±40.18

145.8±23.76

146.59±77.19

VLDL

23.93±8.68

29.61±11.17*

51.02±30.60*

*Statistically significant (p < 0.05)

 

 Table 4: Pearson correlation between thyroid and lipid profile in preeclampsia patients

Relationship between

r-value

p-value

Significance

TSH

VS

TOTAL CHOLESTEROL

-0.059

0.759

NS

TRIGLYCERIDES

0.389

0.034*

S

LDL

0.071

0.71

NS

HDL

0.079

0.677

NS

T3

VS

TOTAL CHOLESTEROL

0.499

0.005*

S

TRIGLYCERIDES

-0.229

0.225

NS

LDL

0.488

0.006*

S

HDL

0.06

0.754

NS

T4

VS

TOTAL CHOLESTEROL

0.228

0.226

NS

TRIGLYCERIDES

-0.034

0.859

NS

LDL

0.167

0.377

NS

HDL

0.129

0.498

NS

*S-Significant

NS-Not Significant

Acknowledgement: ICMR STS, Indian Council of Medical Research, New Delhi. Sri Ch. Mallareddy Chairman, MRIMS, Hyderabad, Dr. Ch. Bhadra Reddy, Dr. Ch. Preeti Reddy, MRIMS, Hyderabad, Dean: Dr. Chandrakant Shirole, MRIMS, Hyderabad, Medical Superintendent: Dr. D. Ranganath, MRIMS, Hyderabad.            

Source of Support: Mallareddy Hospital, Hyderabad. Conflict of Interest: None.

 

 

Cite this article as: Sai Madhuri Kaveti, Sampath Kumar V, Vijaya Lakshmi AR, Alekhya A., T.K Rajasree. Correlation of Thyroid and Lipid Profile in Preeclampsia Patients. MRIMS J Health Sciences 2014;2(2):84-88.

 

 

 

 

 

 

 

 

 

 





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