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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0568
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 9 3341-3347
Copyright © 2008 by The Endocrine Society

Variability in Thyroid-Stimulating Hormone Suppression by Human Chronic Gonadotropin during Early Pregnancy

James E. Haddow, Monica R. McClain, Geralyn Lambert-Messerlian, Glenn E. Palomaki, Jacob A. Canick, Jane Cleary-Goldman, Fergal D. Malone, T. Flint Porter, David A. Nyberg, Peter Bernstein, Mary E. D'Alton for the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy Research Consortium

The Warren Alpert Medical School of Brown University (J.E.H., M.R.M., G.L.-M., G.E.P., J.A.C.), Providence, Rhode Island 02903; Columbia University College of Physicians and Surgeons (J.C.-G., F.D.M., M.E.D.), New York, New York 10027; Royal College of Surgeons in Ireland (F.D.M.), Dublin 2, Ireland; University of Utah and Intermountain HealthCare (T.F.P.), Salt Lake City, Utah 84111; Swedish Medical Center (D.A.N.), Seattle, Washington 98122; and Montefiore Medical Center/Albert Einstein College of Medicine (P.B.), Bronx, New York 10461

Address all correspondence and requests for reprints to: James E. Haddow, M.D., Director, Division of Medical Screening, Women & Infants Hospital, 70 Elm Street, 2nd Floor, Providence, Rhode Island 02903. E-mail: jhaddow{at}ipmms.org.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objective: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation.

Study Design: The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study.

Results: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11–13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15–18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations.

Conclusions: In early pregnancy, a woman’s centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
The association between first-trimester levels of human chorionic gonadotropin (hCG) and TSH has been recognized for a number of years (1). Median levels of these two hormones go in opposite directions as early gestation proceeds, with TSH reaching a nadir at the same time that hCG peaks, apparently due to a weak TSH-like effect of the hCG molecule (1). When plotted on the same graph, the respective patterns of mean values display a mirror image that might lead a reader to expect a strong relationship between the two analytes within individual women. Considerable between-person variability exists in this hCG/TSH relationship, however, as indicated by an r2 value of 0.06 (1), even though the overall relationship from gestational week to gestational week has been repeatedly confirmed and found to be statistically significant. In individual cases in which high hCG levels and undetectable TSH levels occur together, free T4 levels are often elevated, as might be seen with hyperthyroidism (1, 2, 3, 4). Although some women with this constellation of measurements experience hyperemesis gravidarum (5), these symptoms are not clinical features of hyperthyroidism. Furthermore, other characteristic features of hyperthyroidism are usually absent, leading to the conclusion that careful clinical evaluation needs to take precedence over biochemical measurement in this situation (6).

The present study further explored the biochemical relationships between hCG, TSH, and free T4 within a general population of pregnant women at 11–18 wk, taking into account selected epidemiological parameters. This analysis was made possible by the availability of a large data set developed as part of a multicenter trial in which sequential serum samples were obtained from women in the late first and early second trimester (7).


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Women were participants in the multicenter First and Second Trimester Risk of aneuploidy trial, as previously described (7). Only women with singleton pregnancies were enrolled. At five of the 15 recruitment centers, participants were asked to give supplementary consent to allow their residual sample to be used for additional research studies. Samples from those centers (Montefiore Medical Center, Bronx, NY; Swedish Medical Center, Seattle WA; LDS Hospital, Salt Lake City, UT; Utah Valley Regional Medical Center, Provo, UT; and McKay Dee Hospital, Ogden, UT) were eligible for inclusion in the present study. Women who did not consent and those whose pregnancies were affected by Down syndrome were excluded.

Inclusion criteria required documentation that thyroid-related measurements were available from each woman in both the first and second trimesters and that gestational ages were established by ultrasound. From the 10,329 women who met those inclusion criteria, 111 with initial gestational dates less than 11 wk were excluded because the numbers were judged insufficient to provide meaningful results. Also excluded were 389 women with known hypothyroidism and an additional 267 women because the question about whether the woman had hypothyroidism was not answered; 9562 women remained for analysis. Samples were collected between 1999 and 2002, stored at –80 C, and tested between July 2004 and May 2005 (storage was for 3–6 yr). Levels of TSH, free T4, and antithyroperoxidase (TPO) and antithyroglobulin (TG) antibodies were measured using the Immulite 2000 methodology (Siemens Medical Solutions Diagnostics, Tarrytown, NY). Normative data involving these analytes have been published separately for this cohort (8). The lower limit for interpreting TSH measurements was 0.01 mIU/liter, but levels as low as 0.004 mIU/liter could be detected. Women’s antibody measurements were considered positive if anti-TPO antibodies were greater than 35 IU/ml or anti-TG antibodies were greater than 40 IU/ml (according to package inserts). Samples were thawed overnight before assay, and first- and second-trimester samples from each woman were assayed within 24 h of each other. Long-term coefficients of variation were 5.3, 6.9, and 3.8% at TSH concentrations of 0.53, 4.5, and 21.9 mIU/liter; 8.1, 6.5, and 7.9% at free T4 concentrations of 0.9, 1.8, and 3.2 ng/dl; 2.5, 6.6, and 4.7% at anti-TG concentrations of 20, 35, and 556 IU/ml; and 4.9, 7.5, and 5% at anti-TPO concentrations of 30, 39, and 546 IU/ml.

First- and second-trimester total hCG levels were measured using the Immulite 2000 and 1000, respectively (Diagnostic Products Corp., Los Angeles, CA). Second-trimester hCG levels were measured in fresh sera at the time of sample receipt, whereas first-trimester hCG levels were measured at the time of sample thaw for thyroid hormone testing. The lower reportable limit of the total hCG assay was 2 mIU/ml. First-trimester free β-hCG levels were measured at the time of sample receipt, in duplicate, using an immunoradiometric assay (Diagnostics Systems Laboratories, Webster, TX) with a lower reportable limit of 1 mIU/ml. Assay coefficients of variation were less than 15%, across the range of reported measurements.

Statistical analyses were performed after logarithmic transformation for all analytes. All analyses were performed using SAS version 9.1 (Cary, NC). Differences in group means were compared using the t test, and differences in variances using the F test. Tests for trend were performed using procedure general linear model (PROCGLM) for continuous variables and the Cochran-Armitage trend test for categorical variables. Multivariate regression analyses were performed using PROCGLM. Significance was two tailed at the 0.05 level. Graphics were created using GraphPad Prism version 4.03 (San Diego, CA).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The influence of selected maternal covariates on hCG, TSH, and free T4 levels

Table 1Go examines the relationship between selected maternal covariates and levels of hCG, TSH, and free T4 in the late first trimester. As hCG deciles increase (expressed as mass units), the median body mass index (BMI) of women decreases, along with the proportion of women who smoke. These associations are known to be independent and have been documented by others (9, 10). The percent of primigravid women also increases significantly as hCG deciles increase. This association has also been noted by several authors in both the first and second trimesters (11, 12, 13, 14). There is a negative association for Caucasian women, compared with those of other race/ethnicity.


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  		TABLE 1. Maternal covariates, as related to hCG, TSH, and free T4 deciles (first trimester)

 
Relationships between TSH and the proportions of women who smoke and who are primigravid are similar to hCG. Relationships for free T4 are also similar to hCG, except for maternal age. Relationships between the covariates and the three analytes are similar in the second trimester and are not shown.

Relationship between hCG and TSH at 11–18 wk gestation

Figure 1Go shows scatter plots of TSH values (horizontal axis) and hCG values (vertical axis) for the 9562 women at 11–13 wk (Fig. 1AGo), and at 15–18 weeks’ gestation (Fig. 1BGo). Correlations between the two analytes are weak in both trimesters (r2 = 0.03 and r2 = 0.02, respectively). Among the 1304 women (14%) with a BMI greater than 30 kg/m2, hCG values are shifted downward (as expected from the BMI association in Table 1Go), but the TSH values are appropriate for hCG levels when viewed in relation to the population as a whole (data not shown). There are 67 undetectably low TSH values in the first trimester (0.7%) and 27 the second (0.3%). As might be expected from Table 1Go, women with BMI greater than 30 kg/m2 are underrepresented in the group of 67 undetectable TSH values; only four (6%) are present.


Figure 1
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  		FIG. 1. Scatterplots of TSH vs. hCG at 11–13 and 15–18 wk gestation. A, At 11–13 wk, TSH values for the 9592 women are plotted on the horizontal logarithmic axis and hCG values on the vertical logarithmic axis. The 67 undetectable TSH values are shown in a column above the 0.001 mU/liter TSH interval. These are associated with hCG values between 36 and 235 IU/ml. The r2 value is 0.03. B, At 15–18 wk, TSH and hCG values for the same 9592 women are graphed in a similar format. The hCG values are lower in comparison with the first trimester, and 27 of the TSH values are undetectable. The r2 value is 0.02.

 
Figure 2AGo shows how TSH values are distributed, stratified by the hCG deciles at 11–13 wk gestation. The 95th, 75th, and 50th centiles of TSH values at the 10th hCG decile are somewhat lower than those at the first decile, but the 25th, 10th, fifth, and second TSH centiles are sharply lower at higher hCG deciles. For example, median first-trimester TSH values are 1.15 and 0.80 mIU/liter at the first and 10th hCG deciles, respectively, whereas the fifth centile TSH values fall from 0.27 to 0.012 mIU/liter. The dotted lines in Fig. 2AGo represent selected ratios of hCG to TSH. The 95th, 75th, and 50th centiles of TSH values at the 10th hCG decile are somewhat lower than those at the first decile, but the 25th, 10th, fifth, and second TSH centiles are sharply lower at higher hCG deciles. A similar analysis was performed for free β-hCG, with comparable results (data not shown). Figure 2BGo shows hCG and TSH values in the same format as Fig. 2AGo at 15–18 wk gestation. The hCG values are systematically lower, but the same drop in TSH occurs when the hCG to TSH ratio is in the range of 200,000 or higher. The percent of women with thyroid antibodies is evenly distributed throughout the deciles of hCG, but within each decile, the percent of thyroid antibodies is higher at higher TSH concentrations (data not shown).


Figure 2
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  		FIG. 2. Impact of hCG on TSH concentration at 11–13 and 15–18 wk gestation, stratified by hCG deciles. A, At 11–13 wk, TSH values for the 9562 women are plotted on the vertical logarithmic axis and hCG values are plotted on the horizontal logarithmic axis. The center of each hCG decile is designated by filled dots along the 50th centile TSH line. The selected TSH centiles at each hCG decile are connected by a solid line. Dotted lines show constant ratios of hCG to TSH (hCG values are converted into milliinternational units per milliliter to have equivalent units). The major impact of hCG on TSH values occurs at ratios above about 200,000 (200K), and the lower TSH centiles are most affected. B, At 15–18 wk, TSH and hCG values for the 9592 women are shown in a similar format, but the horizontal scale begins at 5 IU/ml, rather than at 30 IU/ml (the scale used in A). The same ratio-related effect is seen, but to a lesser extent, because the hCG deciles are lower than those in the first trimester.

 
We performed separate multivariate regression analyses for each trimester, using log-TSH as the dependent variable. Log-hCG and BMI were included as continuous variables and gravidity, race, and smoking as dichotomous variables. After setting BMI, gravidity, race, and smoking to the average, or most common, value, we found that the TSH values predicted by hCG (range 30–130 IU/ml) were virtually superimposable on the unadjusted medians shown in Fig. 2Go (details of regression analyses are available from authors).

Relationship between hCG and free T4 at 11 through 18 weeks’ gestation

Figure 3Go, A and B, are scatter plots of free T4 and hCG values for the 9562 women at 11–13 weeks’ and at 15–18 wk gestation, respectively. Free T4 values are plotted on the horizontal axis and hCG values on the vertical axis. Correlations between the two analytes are weak (r2 = 0.06 and r2 = 0.003, respectively). Figure 4Go shows how free T4 values are distributed within each of the hCG deciles, in both the first and second trimesters. At 11–13 wk gestation (Fig. 4Go, dashed lines), free T4 values become consistently higher as hCG deciles increase at all of the free T4 centiles selected for analysis (test for trend, P < 0.0001). This trend is not present at 15–18 wk (Fig. 4Go, solid lines), however, and free T4 concentrations are lower at comparable hCG centiles than in the first trimester.


Figure 3
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  		FIG. 3. Scatterplots of free T4 vs. hCG at 11–13 and 15–18 wk gestation. A, At 11–13 wk, free T4 values for the 9592 women are plotted on the horizontal axis; hCG values are on the vertical axis. Both are on a logarithmic scale. The r2 value is 0.06. B, At 15–18 wk, free T4 and hCG values for the same 9592 women are graphed in a similar format. The hCG and free T4 values are both shifted downward in comparison with the first trimester. The r2 value is 0.003.

 

Figure 4
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  		FIG. 4. Impact of hCG on free T4 concentration at 11–13 and 15–18 wk gestation, stratified by hCG deciles. Free T4 values for the 9562 women are plotted on the vertical logarithmic axis, and hCG values are plotted on the horizontal logarithmic axis. Dotted lines show free T4 centiles in the first trimester; and solid lines show free T4 centiles in the second trimester. The positions of hCG deciles in the first trimester are shown by filled circles along the 50th centile dotted line of free T4. In the second trimester, the hCG deciles are shown as closed circles along the 50th centile solid line for free T4. At 11–13 wk, free T4 values rise steadily with increasing hCG decile at all free T4 centiles. At 15–18 wk, the free T4 values do not rise appreciably as hCG deciles increase.

 
To further explore these relationships, we performed separate multivariate regression analyses for each trimester, using log-free T4 as the dependent variable. Log-hCG and BMI were again included as continuous variables and gravidity, race, and smoking as dichotomous variables. After setting BMI, gravidity, race, and smoking to the average, or most common, value, we found that free T4 values predicted by hCG (range 10–70 IU/ml) were virtually superimposable on the unadjusted medians shown in Fig. 4Go.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study further examines the relationships between hCG and thyroid-related measurements, using sequentially obtained samples from a large cohort of 9592 pregnant women. The gestational time span, however, is limited to 11–18 wk. The most important finding is that a woman’s centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland.

In 1990 Glinoer et al. (1) reported a comprehensive study of hCG and thyroid-related hormone measurements, encompassing the first trimester through term. Much of our current understanding about the relationships between hCG, TSH, and free T4 can be traced to that study, in which blood samples were collected from 606 women (most of them sampled at two stages of pregnancy) along with another blood sample after delivery. In the study by Glinoer et al., 13% of the first-trimester TSH values were undetectable vs. 0.6% in ours (a more sensitive assay is now available). Glinoer et al. also used a two step assay for free T4, whereas our current assay contains no dialysis step. In our population, the correlation between hCG and TSH levels at 11–13 wk is considerably weaker than that reported in the study by Glinoer et al. at 8–14 wk (r2 = 0.12; P < 0.001; n = 228). Weinans et al. (15) report a Spearman correlation coefficient of r2 = 0.04 for TSH and hCG in 115 control pregnancies at 9–11 wk, closer to our result. Ballabio et al. followed up 32 normal pregnancies (16) and reported that TSH and hCG levels correlated at 8–10 wk. One possible reason for these different degrees of correlation might be that the relationship is gestational age dependent; hCG peaks at about 10 wk gestation and the impact may be strongest at this time.

Despite the weak overall association, upper deciles of hCG values in our study are associated with sharply lower TSH values in a subset of women with TSH levels at, or below, the 25th centile. This is visible in both trimesters but is more obvious in the first trimester, when hCG values are higher. At that time, the fifth centile of TSH begins a downward slope at about 70 IU/liter. TSH appears to be substantially suppressed when the ratio of hCG to TSH is 200,000 or greater, suggesting a generalized, rather than selective, influence of hCG. Women with higher baseline TSH levels are less likely to experience a steep decline at any given hCG level, although the model in Fig. 2Go suggests that extremely high hCG levels, as might occur with twin or molar pregnancies, might suppress even the higher baseline TSH levels. In the second trimester, the steep descent of TSH is once again seen at about 70 IU/liter, but this is now restricted to the 10th hCG decile. At comparable hCG concentrations, therefore, the effect on TSH in this subset of women appears consistent, regardless of trimester. TSH levels among women with thyroid antibodies are higher, on average, than among those without antibodies, meaning that the former group ought to be less susceptible to the influence of hCG. This is, in fact, the case (data not shown).

The inverse relationship of hCG and TSH levels during early pregnancy has been extensively documented, but the nature of that relationship has not been clear (6). Although the molecular structure of hCG has features in common with TSH, its thyrotropic potential is weak due to the β-carboxyterminal portion of the molecule (17), which dampens its ability to stimulate the receptor (18, 19). Some women carry a variant form of hCG that lacks the β-carboxyterminal, and this may account for some of the observed variability in the relationship between hCG and TSH (20). Other hCG metabolites also have varying degrees of thyroid stimulating potential, but assays that are currently available clinically (other than free β-hCG) do not identify them separately, and their contributions to thyroid stimulation cannot be readily evaluated. In the present study, the fall in TSH levels appears to progressively affect higher TSH centiles as hCG levels rise, suggesting that the women with lower centile TSH levels are more sensitive to hCG. The hCG variants may also play a role because greater amounts of these might be expected with higher concentrations of total hCG. Altered TSH receptor status that confers enhanced susceptibility is not likely to be a factor; the one case documenting that phenomenon suggests that this is a rare event (21).

At 11–13 wk, median free T4 values in the present study increase consistently as hCG deciles increase but remain relatively unchanged in relation to hCG at 15–18 wk. The first-trimester data are consistent with the report by Glinoer et al. (1), who found that hCG concentration correlated directly with free T4 measurements at 6–20 wk gestation (r2 = 0.12; P < 0.001). Tanaka et al. (22) identified gestational transient hyperthyroxinemia (free T4) in 66 of 23,163 women screened between 6 and 14 wk gestation. Free T4 correlated with hCG in those women (r2 = 0.07, P < 0.05). Although this is consistent with the present findings, the analysis of Tanaka et al. is limited to the extreme upper end of the free T4 distribution.

The hCG/TSH relationship is of ongoing interest to the obstetric community because of its clinical association with hyperemesis gravidarum. In one large, population-based study, involving a cohort of 157,922 pregnancies, 1,301 women (0.8%) required hospitalization for hyperemesis (23). Whereas the general view is that hyperemesis is not caused by the very low TSH and elevated free T4 values that accompany high hCG levels in individual women, it is hypothesized that these measurements serve as markers for other hCG-induced hormonal change (such as its influence on estradiol) that might provoke the symptoms (24). Goodwin et al. (5) found biochemical hyperthyroidism in 44 of 67 women with hyperemesis (66%), as defined by increased free thyroxine index or suppressed TSH. The term biochemical hyperthyroidism indicates that symptoms of hyperthyroidism were not present. Bouillon et al. (25) found increased free T4 index in 24 of 33 women with severe hyperemesis (73%). Kauppila et al. (26) showed hCG values greater than 97.5th centile in 15 of 42 women with hyperemesis. Glinoer et al. (27) identified 62 pregnant women with TSH 0.20 mU/liter or less (representing 18% of all pregnancies). Both hCG and free-β hCG were markedly elevated; 10% of the women showed biochemical thyrotoxicosis, frequently associated with vomiting.

Nulliparity has previously been identified as a risk factor for hyperemesis (11, 12, 13, 14, 24, 28). When hCG is taken as a surrogate measure, findings in the present analysis are consistent with that observation, in that the proportion of primigravidas becomes steadily higher as hCG increases. Similarly, low maternal weight has been identified as a risk factor for hyperemesis, and the present data support that observation by showing a steady decrease in median maternal weight as hCG deciles increase (29, 30, 31). Cigarette smoking has been repeatedly documented to lower the risk for hyperemesis (10), and the present study shows that the proportion of smokers decreases steadily as hCG levels increase, once again supporting that observation.

Average free T4 levels are steadily higher at higher hCG deciles during the first trimester, but this relationship is not retained in the second trimester. The reason for this altered response cannot be explained by the lower overall hCG levels because the uppermost hCG deciles still represent high enough absolute hCG concentrations that an effect on free T4 would continue to be anticipated. Some adaptive process might have taken over by that time. The most important insight found in the present analysis is that the relationship between higher hCG levels and TSH is weak in most pregnant women, even during the first trimester. A stronger relationship exists, however, for a subgroup of these women with TSH values at lower centiles. This relationship is hCG dose dependent and appears to be determined by an individual woman’s centile TSH level.


   Acknowledgments
 
The authors acknowledge the work of the members of the First and Second Trimester Risk of aneuploidy Research Consortium: K. Welch, M.S., R. Denchy, M.S. (Columbia University, New York, NY); R. Ball, M.D., M. Belfort, M.D., B. Oshiro, M.D., L. Cannon, B.S., K. Nelson, B.S.N., C. Loucks, R.N.C., A. Yoshimura (University of Utah, and IHC Perinatal Centers, Salt Lake City, Provo, and Ogden, UT); D. Luthy, M.D., S. Coe, M.S. (Swedish Medical Center, Seattle, WA); C. Comstock, M.D., J. Esler, B.S. (William Beaumont Medical Center, Royal Oak, MI); R. Bukowski, M.D., G. Hankins, M.D., G. Saade, M.D., J. Lee, M.S., (University of Utah Medical Branch, Galveston, TX); R. Berkowitz, M.D., K. Eddleman, M.D., Y. Kharbutli, M.S. (Mount Sinai Medical Center, New York, NY); I. Merkatz, M.D., S. Carter, M.S. (Montefiore Medical Center, Bronx, NY); L. Dugoff, M.D., J. Hobbins, M.D., L. Schultz, R.N. (University of Colorado Health Science Center, Denver, CO); I. Timor-Tritsch, M.D., M. Paidas, M.D., J. Borsuk, M.S. (New York University Medical Center, New York, NY); S. Craigo, M.D., D. Bianchi, M.D., B. Isquith, M.S., B. Berlin, M.S. (Tufts University, Boston, MA); S. Carr, M.D., C. Duquette, R.D.M.S. (Brown University, Providence, RI); H. Wolfe, M.D., R. Baughman, M.S. (University of North Carolina, Chapel Hill, NC); J. Hanson, M.D., F. de la Cruz, M.D. (National Institute of Child Health and Human Development, Bethesda, MD); and K. Dukes, Ph.D., T. Tripp, M.A., D. Emig, M.P.H., L. Sullivan, Ph.D. (DM-STAT, Inc., Medford, MA).


   Footnotes
 
This work was supported by Grant RO1 HD 38652 from the National Institutes of Health and the National Institute of Child Health and Human Development.

First Published Online June 10, 2008

For editorial see page 3305

Abbreviations: BMI, Body mass index; hCG, human chorionic gonadotropin; PROCGLM, procedure general linear model; TG, thyroglobulin; TPO, thyroperoxidase.

Received March 11, 2008.

Accepted May 29, 2008.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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