Jacky M. Burrin, PhD; Christopher R. Parmar, PhD; John C. Stevenson, MRCP; ... W. Booker, MRCOG; Malcolm I. Whitehead, MRCOG; and Colin H. Self, PhD.
Clinical Chemistry
The Use of an Enzyme-Amplified Immunoassay for TSH in the Assessment of Thyroid Function in Pregnant and Postpartum Women Downloaded from http://labmed.oxfordjournals.org/ by guest on March 19, 2016
Jacky M. Burrin, PhD; Christopher R. Parmar, PhD; John C. Stevenson, MRCP; Michael W. Booker, MRCOG; Malcolm I. Whitehead, MRCOG; and Colin H. Self, PhD The apparent clinically euthyroid status of a group of 56 pregnant women has been found to correlate better with the values obtained from a highly sensitive enzyme-amplified immunometric assay for thyroid-stimulating hormone (TSH) than with values obtained for TT4, TT3, or FT4. The parameters were measured on four occasions during normal pregnancy and in early postpartum. The mean serum TSH values obtained at any stage of pregnancy studied were not significantly different than values obtained in nonpregnant controls. In contrast, serum TT3 and TT4 increased with pregnancy, while the values obtained for FT4 decreased markedly during gestation. In the early postpartum while serum TT3 and TT„ remained elevated, the TSH level decreased significantly despite an apparent fall in FT4. These data support the use of sensitive TSH measurements in preference to FT4 estimation as a test of thyroid function in pregnant and postpartum women.
T
he large changes of many serum constituents in pregnancy make the accurate biochemical asessment of thyroid function difficult at just the time when the clinical picture may also be misleading. Assessment of triiodothyronine (T3) and thyroxine (T4) is complicated by large changes in thyroxine-binding globulin (TBG). Total T 3 (TT 3 ) and total T 4 (TT 4 ) measurements, therefore, are of limited use. It had been hoped that the determination of the "free" form would overcome this difficulty; however, conflicting studies usFrom the Departments of Chemical Pathology and Medicine, Royal Postgraduate Medical School, Hammersmith Hospital (Drs Burrin, Parmar. Stevenson, and Self), and the Academic Department of Obstetrics and Gynaecology, King's College School of Medicine and Dentistry (Drs Booker and Whitehead), London. Dr Stevenson is now with Cavendish Clinic in London.
ing free T, (FT4) measurements 1 4 have indicated that determination of the free form is not as useful in pregnancy as had been hoped. It appeared possible that these problems might be overcome by the new breed of highly sensitive TSH assays, able to determine both hyperthyroidism as well as hypothyroidism. Early studies, however, have indicated interference caused by human chorionic gonadotropin (HCG) with one of these assays.5 Because of the real value of a highly sensitive TSH assay, we have looked at the usefulness of another highly sensitive TSH method in pregnancy based on the application of the method of enzyme amplification 6 to TSH measurement. 78 T h e original studies employing highly sensitive T S H assays also
lacked accurate gestational staging and details of the obstetric outcome. We have, therefore, taken our studies with the amplified assay further to determine TSH levels on four occasions during gestation and once in the early postpartum period of a group of women who experienced entirely normal pregnancies, and in whom gestational age was accurately dated by early ultrasound examination. The samples were also analyzed for TT 3 , TT 4 , and FT 4 values by radioimmunoassays, and all the results were compared with nonpregnant controls. Patients and Methods Fasting blood samples were obtained from 47 healthy pregnant women (age range, 20 to 36 years) at ten to 12 weeks (n = 12), 20 to 22 weeks (n = 9), 30 to 32 weeks (n = 11), and 36 to 40 weeks (n = 15) of pregnancy. All were singleton pregnancies with gestational age accurately dated by early ultrasound examination. Antenatal course was normal in each case and resulted in full-term delivery. Results of thyroid function tests performed on these subjects were compared during the various stages of pregnancy. Results were also compared with samples (obtained five to seven days after delivery) from nine lactating postpartum women (age range, 22 to 33 years) and
LABORATORY MEDICINE • VOL. 19, NO. 12, DECEMBER 1988
811
20-
• •
10.015-
#
#
• •
Mean
cv%
1.0-
10-
*——• I 1.0
0.01-
i
i
i
i
20-22
30-32
36-40
Weeks of gestation
Fig 2. Serum TSH levels during and after normal pregnancy (dotted line indicates reference limit for nonpregnant controls). shown in Fig 1. The interassay CV was 9% at 0.3 mU/L and 6% at 2.5 mU/L. The lower limit of detection of this assay (calculated at three times the standard deviation of 20 zero standard measurements) was 0.028 mU/L. HCG cross-reactivity in the assay (defined as measured TSH mU/L expressed as a percentage of the added cross-reactant) was 1X10-5%. Student's t test was used for all statistical analyses following logarithmic transformation to normalize the data distribution where necessary.
Results The mean values of TT 4 , TT 3 , FT 4; and TSH for samples obtained during pregnancy, postpartum, and from nonpregnant controls are given in the Table. Serum TT 3 levels increased steadi-
Serum TT„, TT3, and FT, Levels During and After Pregnancy and in Nonpregnant Women' Pregnant Subjects (Weeks of Gestation)
(nmole/L)
111±23
113±21
TT3 (nmole/L)
1.5 ±0.4
2.1 ±0.4*
FT, (pmole/L) TSH (mU/L)
20-22
30-32
36-40
5-7 Days After Delivery
116 + 26
115±34
132±21f
176±28*
2.6 ±0.6*
2.6 ±0.5*
3.0 ±0.5*
18.6±3.2
18.3±3.4
14.4±3.2f
13.7±4.5f
14.3±2.4*
1.7±0.7
2.2+1.8
1.3±0.9
1.7 + 1.1
1.4 + 0.7
' Mean values ± SD are shown for each subject. tStatistically significant from nonpregnant value, P
