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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 66
| Issue : 5 | Page : 359-364 |
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Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum
Haiyan Zheng1, Qian Wang1, Feng Chen2
1 Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
2 Department of Traditional Chinese Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| Date of Submission | 22-Mar-2023 |
| Date of Decision | 10-May-2023 |
| Date of Acceptance | 25-May-2023 |
| Date of Web Publication | 15-Sep-2023 |
Correspondence Address:
Dr. Feng Chen
Department of Traditional Chinese Medicine, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Maojian District, Shiyan 442000, Hubei
China
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/cjop.CJOP-D-23-00045
As previously demonstrated, serum beta-human chorionic gonadotropin (β-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum β-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. Versus those in the control group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum β-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that β-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum β-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, β-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.
Keywords: Beta-human chorionic gonadotropin, free thyroxine, free triiodothyronine, hyperemesis gravidarum, thyroglobulin antibody, thyroid hormone receptor antibody, thyroid peroxidase antibody, thyroid-stimulating hormone
How to cite this article:
Zheng H, Wang Q, Chen F. Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum. Chin J Physiol 2023;66:359-64 |
How to cite this URL:
Zheng H, Wang Q, Chen F. Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum. Chin J Physiol [serial online] 2023 [cited 2023 Dec 4];66:359-64. Available from: https://www.cjphysiology.org/text.asp?2023/66/5/359/385876 |
Haiyan Zheng and Qian Wang contributed equally to this paper.
| Introduction | |  |
Hyperemesis gravidarum (HG) is a severe kind of nausea and vomiting in pregnancy, marked by weight loss, dehydration, and electrolyte imbalances.[1] It is a disorder at the end of the pregnancy sickness spectrum, affecting 1%–2% of pregnant women.[2] HG requires hospitalization in approximately 1%–5% of patients[3] and raises the risk of negative results for mothers and babies. HG complexity impacts every aspect of a female's life in and after pregnancy.[4] There is a need for better therapeutic methods to decrease the burden of HG not only for the individual but also for society.[5]
Human chorionic gonadotropin (hCG) refers to one 237 amino acid glycoprotein hormone that is consisted of two dissimilar alpha (α) and beta (β) subunits noncovalently associated by charge interactions, and the two are both required for hormone biological activity.[6] The β subunit of hCG (β-hCG) is encoded by six genes classified as Type I and Type II.[7] β-hCG has been commonly utilized in early pregnancy (EP) assessment.[8] As previously demonstrated, serum β-hCG is linked to identifying early gestational abnormalities.[9] It is reported that hCG possesses thyroid-stimulating activity that affects thyroid function early in pregnancy when the levels of hCG are high. In addition, excessive hCG secretion might lead to hyperthyroidism in HG patients.[10] β-hCG is a specific marker of gestational trophoblastic disease, and it has a similar structure to the thyroid-stimulating hormone (TSH) molecule, interfering with levels of thyroid hormones.[11] Moreover, hCG is able to bind to the TSH receptor and stimulate thyroxine production because they have identical alpha subunits and similar beta subunits.[12] A previous study has demonstrated that β-hCG and free thyroxine (FT4) had a correlation with HG, and could be regarded as predictive markers.[13] As previously reported, in women who are clinically euthyroid, biochemically altered thyroid function has the ability to attribute to vomiting and prolonged second trimester.[14] It is reported that a higher FT4-to-free triiodothyronine (FT3) ratio late into pregnancy is involved in gestational diabetes mellitus (GDM) and negative pregnancy results.[15] Evidence has shown that serum thyroid markers (FT3, FT4, TSH, and thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)) are associated with GDM.[16] Consequently, this research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with HG, thus providing a distinct study direction and furnishing effective treatments for HG.
| Materials and Methods | | |
Ethics statement
The research was ratified by the Ethics Committee of Renmin Hospital, Hubei University of Medicine (approval number: 20200504), and patients of both groups provided written informed consent.
Study subjects
A total of 91 pregnant women with HG admitted to Renmin Hospital, Hubei University of Medicine from January 2020 to December 2021 were selected as the study group, who had frequent nausea and vomiting in the early stage of pregnancy, vomiting ≥ 3 times a day, accompanied by more than 5% weight loss, significant deprivation of body fluids, severe enough to require hospitalization, and at least 2 (+) ketonuria on a urinalysis test. Eighty-four normal pregnant women were selected as the control group.
Inclusion criteria: (i) pregnant women's age < 35 years; (ii) natural conception pregnant women; (iii) those without gestational diabetes or hypertension; (iv) those with good cognitive function; and (v) patients who were aware of the study and had given the written consent form. Exclusion criteria: (i) those with multiple gestations; (ii) those with severe hepatic and renal dysfunction; (iii) those combined with thyroid disease; (iv) those vomiting due to Staphylococcus and other reasons; (v) those combined with digestive system disease; (vi) patients with malignant tumors; and (vii) patients with hematological system disease.
Serum indicator detection
In the morning of the 2nd day of enrollment, 3 mL of venous blood was collected from all study subjects and then centrifuged at 3000 rpm for 10 min utilizing a medical centrifuge. Next, the serum was isolated and kept at −20°C for future use. Serum β-hCG levels were tested by chemiluminescence immunoassay and the kits were procured from Roche Diagnostics (Shanghai) Limited (Shanghai, China). Serum FT4, FT3, TSH, TPOAb, thyroid-stimulating hormone receptor antibody (TRAb), and TgAb levels were measured by chemiluminescence microparticle immunoassay, and the kits were available from Bio-Rad (CA, USA).
Assessment of hyperemesis gravidarum degree
Visual analog scale (VAS)[17] was implemented for assessment. A ruler with a scale between 0 and 10 on the front was utilized. The side marked “1–10” was turned back to the patients and the patients were asked to mark the corresponding position on the ruler that represented their degree of HG. The practitioner gave her a score based on the position marked, ranging from 0 to 10, with 0 being no nausea and vomiting and 10 being the most severe nausea and vomiting that cannot be tolerated.
Pregnancy staging
Pregnant women with HG were staged based on gestational weeks. Those with gestational weeks ≤ 12 weeks were included in the EP group; those with gestational weeks between 13 and 27 weeks were included in the mid-pregnancy (MP) group; those with gestational weeks ≥ 28 weeks were included in the late pregnancy (LP) group.
Statistics
SPSS 22.0 software (IBM Corp., Armonk, NY, USA) was applied for statistical processing. Measurement data were presented as mean ± standard deviation, and t-test and ANOVA combined with Tukey's post hoc test were, respectively, utilized for two-group and multi-group comparisons. Enumeration data were presented as the number of cases and tested by Chi-squared test or Fisher's exact test. Pearson test was implemented to analyze the correlation between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. P < 0.05 was an indicator of statistical significance.
| Results | | |
General data of the two groups of pregnant women
At first, general data of the two groups of pregnant women were compared. No notable differences were presented in age, weight, gestational week, gestation, delivery, and pregnancy status between the two groups of pregnant women, which were comparable. The VAS scores of pregnant women in the study group were higher compared with those in the control group (P < 0.001) [Table 1].
β-hCG and thyroid function between the two groups of pregnant women
As reported, HG is linked to elevated levels of free β-hCG, and these changes are independent of serum indicators of thyroid function.[18] Therefore, we compared β-hCG and thyroid function between the two groups of pregnant women. It was observed that compared to those in the control group, serum β-hCG, FT3, FT4, TPOAb, TRAb, and TgAb levels of pregnant women in the study group were higher while TSH levels were lower (all P < 0.001) [Table 2]. | Table 2: Comparison of ß-hCG and thyroid function between the two groups of pregnant women
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β-hCG and thyroid function among pregnant women with hyperemesis gravidarum at different gestation periods
β-hCG and FT4 titers have been revealed to be higher in patients with HG, but none of the patients display hyperthyroidism signs.[19] In the meantime, TPOAb can positively alleviate gestational thyroid responses to hCG in pregnancy, and during the first half of pregnancy, TgAb can interfere with thyroidal responses to hCG.[20] We compared β-hCG and thyroid function among pregnant women with HG at different gestation periods. Compared to those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, and TgAb levels were lower and TSH levels were higher in the MP and LP groups, with the increase and reduction in the LP group being more significant than those in the MP group (all P < 0.001) [Table 3]. | Table 3: Comparison of ß-hCG and thyroid function among pregnant women at different gestation weeks
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Correlation of β-hCG with thyroid function indicators and Visual Analogue Scale scores
Extensive evidence has shown that serum thyroid markers (FT3, FT4, TSH, TPOAb, and TgAb) are associated with GDM.[16] In this study, we observed that serum β-hCG levels were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels in pregnant women with HG (r1 = 0.575; r2 = 0.603; r3 = 0.415; r4 = 0.654; r5 = 0.765; r6 = 0.699; r7= −0.781, all P < 0.001) [Table 4]. | Table 4: Correlation of ß-hCG with thyroid function indicators and Visual Analog Scale scores
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Correlation between indicators and gestation period
As mentioned above, we have observed a significant positive correlation between β-hCG levels and FT3 and FT4 and a significant negative correlation between β-hCG and TSH. In our work, we also found that serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with gestation period, while TSH levels had a positive correlation with gestation period (r1= −0.790; r2= −0.698; r3= −0.561; r4= −0.503; r5= −0.737; r6= −0.553; r7= −0.749; r8 = 0.793, all P < 0.001) [Table 5].
Diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for hyperemesis gravidarum
The ROC curve analysis showed that the area under the curve, sensitivity, and specificity of serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb, and TSH levels for the diagnosis of HG were 0.870, 70.30%, and 91.70%; 0.808, 69.20%, and 79.80%; 0.898, 74.70%, and 95.20%; 0.872, 69.20%, and 98.80%; 0.876, 69.20%, and 97.60%; 0.877, 73.60%, and 95.20%; 0.832, 73.60%, and 79.80%, respectively [Table 6] and [Figure 1], suggesting that all of the above indicators have some diagnostic efficiency for HG. | Figure 1: ROC curve for analyzing the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. ROC: Receiver operating characteristic, HG: Hyperemesis gravidarum, β-hCG: Beta-human chorionic gonadotropin, FT3: Free triiodothyronine, FT4: Free thyroxine, TSH: Thyroid-stimulating hormone, TPOAb: Thyroid peroxidase antibody, TRAb: Thyroid hormone receptor antibody, TgAb: Thyroglobulin antibody.
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 | Table 6: Diagnostic values of thyroid hormones, thyroid-related antibodies, and ß-hCG levels for hyperemesis gravidarum
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| Discussion | | |
HG is an intense and prolonged form of nausea and vomiting during pregnancy and is able to result in vitamin deficiencies.[21] HG persists throughout pregnancy, resulting in unintended weight loss, malnutrition, dehydration, and electrolyte imbalance, needing hospital admission in multiple cases. In addition, HG negatively impacts fetal growth and might have negative consequences on offspring health.[2] This study focused on the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with HG.
As previously reported, etiological factors for HG may include elevated hCG and steroids, many pregnancies, and vitamin deficiencies.[22] It is also reported that HG is linked to elevated levels of free β-hCG, and these changes are independent of serum indicators of thyroid function.[18] Moreover, HG is linked to not only higher levels of serum β-hCG levels but also hyperthyroidism.[23] In the article, it was found that serum β-hCG levels were abnormally elevated in pregnant women with HG, which is in line with the previous findings. T3 concentration could provide an indicator of the severity of HG.[24] Besides, T4 and TSH could serve as vital factors in the etiology of HG.[25] In our research, we observed high levels of FT3 and FT4 and lower levels of TSH in pregnant women with HG. Similarly, a previous study has indicated that β-hCG and FT4 titers are higher in patients with HG, but none of the patients displayed hyperthyroidism signs.[19] Gestational transient thyrotoxicosis is involved in direct stimulation of the maternal thyroid gland by hCG and is marked by slightly raised thyroid hormone and reduced TSH levels in EP and mild or no symptoms.[26] TPOAb can positively alleviate gestational thyroid responses to hCG in pregnancy. In addition, during the first half of pregnancy, TgAb can interfere with thyroidal responses to hCG.[20] Similarly, in our study it was found that serum TPOAb, TRAb, and TgAb levels were elevated in pregnant women with HG.
Subsequently, we compared β-hCG and thyroid function among pregnant women with HG at different gestation periods, and it was also found that compared to those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, and TgAb levels were lower and TSH levels were higher in the MP and LP groups, with the increase and reduction in the LP group being more significant than those in the MP group. It has been demonstrated that there is a significant positive correlation between β-hCG levels and FT3 and FT4 and a significant negative correlation between β-hCG and TSH.[20] In our study, Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. It was found that serum β-hCG levels were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels in pregnant women with HG. Furthermore, serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. Furthermore, the ROC curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. The results indicated that thyroid hormones, thyroid-related antibodies, and β-hCG levels had some predictive values for HG.
| Conclusion | | |
In summary, this research demonstrates that β-hCG expression in the serum of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. This study lays a foundation to explore the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with HG. This article also indicates that serum β-hCG levels are closely related to the levels of serum thyroid function and the degree of HG, indicating that serum β-hCG levels not only reflect the condition of patients with HG but also provide a reference for clinical assessment of thyroid function and that the detection of its changes can provide a reference for the clinical formulation of interventions and treatment measures, which can help improve the prognosis of patients. Our study is based on limited clinical data, which is the main limitation of our research, and further exploration is necessary to further convince our findings.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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