Jibril M. El-Bashir, Randawa A. J, Abbiyesuku F. M, Aliyu I

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TRIMESTER SPECIFIC REFERENCE INTERVALS OF THYROID FUNCTION TESTS AMONG NIGERIAN PREGNANT WOMEN Jibril M. El-Bashir, Randawa A.J, Abbiyesuku F.M, Aliyu I.S, Akuyam S.A, Manu M, Adamu R, Suleiman H.M, Yusuf R, Mohammed A.

INTRODUCTION Thyroid disorders in pregnancy are harmful to maternal and foetal health. Pregnancy has a profound impact on thyroid gland and thyroid function. Normal pregnancy results in a number of hormonal changes that affect thyroid function. hCG (a weak thyroid stimulator)surge in 1st trimester and supresses TSH. Rise in oestrogen stimulates TBG synthesis with increase in T3 and T4 . Measurement of free thyroid hormones not total is necessary in pregnancy.

SIMILARITIES IN CLINICAL PRESENTATION WITH NORMAL PREGNANCY HYPERTHYROIDISM HYPOTHYROIDISM Anxiety palpitations dyspnoea sweating heat intolerance weakness irritability cardiac systolic murmurs Lethargy weight gain constipation

NEED FOR PREGNANCY REFERENCE INTERVALS American Thyroid Association (ATA) recommends Establishment of Trimester Specific Reference Intervals by each laboratory for proper interpretation If that is not possible, clinicians should use 0.1 – 2.5, 0.2 – 3.0 and 0.3 – 3.0 µIU/ml for TSH during 1st, 2nd and 3rd trimesters respectively.

AIM To establish trimester-specific thyroid function reference intervals in pregnancy among Nigerian pregnant population.

METHODOLOGY Three-hundred apparently healthy pregnant women were recruited into the study. Ages ranged between 14 – 40 years. Thyroid function tests (TSH, free T4, free T3 and TBG) were assayed using ELISA kits. Trimester-specific reference intervals (2.5th and 97.5th centiles) were calculated for 1st , 2nd and 3rd trimesters’ respectively after log transformation using Microsoft Excel software 2007.

RESULTS Trimester Specific Reference Intervals for TSH and Free T4 in subjects (2.5 and 97.5 percentiles)   Subjects n TSH (µIU/L) Free T4 (ng/mL) 1st trimester 75 (0.03 – 2.41) (0. 84 – 2.06) 2nd trimester 125 (0.14 – 3.55) (0.76 – 2.08) 3rd trimester 100 (0.21 – 3.12) (0.70 – 1.70)

RESULTS Trimester Specific Reference intervals for Free T3 and TBG in subjects (2.5 and 97.5 percentiles)   Subjects n Free T3 (pg/mL) TBG µg/mL 1st trimester 75 (1.92 – 3.51) (11.32 – 43.17) 2nd trimester 125 (1.65 – 3.96) (14.51 – 72.86) 3rd trimester 100 (1.74 - 3.65) (20.33 – 72.55)

DISCUSSION Establishment of local reference values in pregnancy is imperative for accurate diagnosis. In this study, TSH mirrored the change in free T4 The values obtained here agree with ATA suggested values and also with those obtained by Panesar et al 2001, Haddow et al 2004, Stricker et al 2007 and Bocos – Terraz et al 2009.

cont Samples from 120 reference individuals was recommended by IFCC as minimum for establishment of reference values. However, it was demonstrated by Horn et al 1998, Haddow et al 2004, Horrowitz et al 2008, and that less than 120 samples can be used. This is an important limitation of the study.

CONCLUSION Thyroid disease in pregnancy is common, clinically important and time sensitive. Hence, this study established Trimester specific thyroid function reference intervals for Nigerian pregnant population.

REFERENCES 1. Glinoer D. Thyroid regulation and dysfunction in the pregnant patient 2008. www.thyroidmanager.org 2. Stagnaro – green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R et.al. Guideline of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21(10): 1 – 46. 3. Haddow JE, Knight GJ, Palomaki GE, McClain MR, Pulkkinen AJ. The reference range and within person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy. J Med Screen 2004; 11: 170 – 174. Stricker R, Echenard M, Eberhart R, Chevailler MC, Perez V, Quinn FA, Sricker R. Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age – specific reference intervals. Eur J Endocrinol 2007; 157: 509 – 514.

5. Panesar NS, Li CY, Rogers MS 5. Panesar NS, Li CY, Rogers MS. Reference interval for thyroid hormones in pregnant Chinese women. Ann Clin Biochem 2001; 38: 329 – 332 6. Bocoz – Terraz JP, Izquierdo – Alvarez S, Bancalero – Florez JL, Alvarez – Lahuerta R, Aznar – Saucar A, Real – Lopez E, Ibanez – Marco R et al. Thyroid hormones according to gestational age in pregnant Spanish women. BMC Res Notes 2:237 7. Horn PS, Pesce JA, Copeland BE. A robust approach to reference interval estimation and evaluation. Clin Chem 1998; 44(3): 622 – 31. 8. Horowitz GL, Boyd JC, Altaie S. Defining, establishing and verifying reference interval in clinical laboratory ; Approved guideline. Third edition.