|Year : 2020 | Volume
| Issue : 2 | Page : 76-81
Prevalence of thyroid dysfunction and thyroid autoimmunity in polycystic ovary syndrome: A multicenter study from Bangladesh
A. B. M. Kamrul-Hasan1, Fatema Tuz Zahura Aalpona2, Marufa Mustari3, Farhana Akter4, Palash Kumar Chanda1, Mohammad Motiur Rahman5, Mohammad Imtiaj Mahbub6, Shahjada Selim3
1 Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
2 Department of Gyne and Obs, Mymensingh Medical College Hospital, Mymensingh, Bangladesh
3 Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
4 Department of Endocrinology, Chittagong Medical College, Chittagong, Bangladesh
5 Department of Medicine, Rajshahi Medical College Hospital, Rajshahi, Bangladesh
6 Department of Endocrinology, Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh
|Date of Submission||30-Jan-2020|
|Date of Acceptance||27-Mar-2020|
|Date of Web Publication||17-Jul-2020|
Dr. A. B. M. Kamrul-Hasan
Department of Endocrinology, Mymensingh Medical College, Mymensingh-2200
Source of Support: None, Conflict of Interest: None
Background: Women with polycystic ovary syndrome (PCOS) have increased risks of thyroid dysfunction and thyroid autoimmunity. Data are limited regarding the prevalence of thyroid dysfunction and thyroid autoimmunity in patients with PCOS.
Objective: The objective of this study was to evaluate thyroid function and thyroid autoimmunity in patients with PCOS.
Materials and Methods: In this cross-sectional study, 500 women newly-diagnosed with PCOS attending the endocrinology outpatient departments of several tertiary hospitals of Bangladesh were evaluated. Serum thyroid-stimulating hormone (TSH), free thyroxine, and anti-thyroid peroxidase (anti-TPO) were measured in all.
Results: The prevalence of thyroid dysfunction was 17% (11% subclinical hypothyroidism, 5.2% overt hypothyroidism, 0.4% subclinical hyperthyroidism, and 0.4% overt hyperthyroidism). Patients with normal and abnormal thyroid function had similar mean age, body mass index, waist circumference, diastolic blood pressure (BP), fasting plasma glucose, plasma glucose 2 h after oral glucose tolerance test, serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total testosterone, and prolactin levels. The frequencies of menstrual irregularities, acne, a first-degree family member with thyroid dysfunction, acanthosis nigricans, biochemical hyperandrogenism, and hyperprolactinemia were also similar. The patients with thyroid dysfunction had lower modified Ferriman–Gallwey score and hirsutism frequency. More patients in the thyroid dysfunction group had a history of weight gain during the course of PCOS onset. Higher rates of subfertility and goiter were also observed in patients with thyroid dysfunction; systolic BP was higher in this group. More than one-fifth (20.6%) of the study participants were positive for the anti-TPO antibody.
Conclusions: Thyroid dysfunction and thyroid autoimmunity in Bangladeshi PCOS patients are very common.
Keywords: Polycystic ovary syndrome, thyroid dysfunction, hypothyroidism, thyroid autoimmunity, anti-thyroid peroxidase, Bangladesh
|How to cite this article:|
Kamrul-Hasan AB, Aalpona FT, Mustari M, Akter F, Chanda PK, Rahman MM, Mahbub MI, Selim S. Prevalence of thyroid dysfunction and thyroid autoimmunity in polycystic ovary syndrome: A multicenter study from Bangladesh. Thyroid Res Pract 2020;17:76-81
|How to cite this URL:|
Kamrul-Hasan AB, Aalpona FT, Mustari M, Akter F, Chanda PK, Rahman MM, Mahbub MI, Selim S. Prevalence of thyroid dysfunction and thyroid autoimmunity in polycystic ovary syndrome: A multicenter study from Bangladesh. Thyroid Res Pract [serial online] 2020 [cited 2020 Aug 10];17:76-81. Available from: http://www.thetrp.net/text.asp?2020/17/2/76/290004
| Introduction|| |
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is a heterogeneous androgen-excess disorder with different degrees of reproductive and metabolic dysfunctions. Thyroid disorders are also prevalent and are, arguably, among the most common endocrine disorders worldwide. Although they have completely different etiopathogeneses, PCOS and thyroid dysfunction have multiple common presentations, and both have profound effects on fertility and reproductive biology. More interestingly, hypothyroidism can initiate, maintain, or worsen PCOS. In the past few years, different studies from various parts of the world have tried to explore the PCOS-thyroid interface. In a Danish study, the overall prevalence of thyroid diseases was 3.6 times higher in PCOS patients versus controls. High frequencies of thyroid dysfunction among PCOS patients were also observed in recent Indian studies, which were higher than that of healthy controls.,, Recently, in a small single-center study in Bangladesh, Mustari et al. found 21% of PCOS patients to have thyroid dysfunction. There is an association between PCOS and autoimmune diseases, and different autoantibodies have been documented in PCOS, raising the suspicion that there are autoantibodies that might affect the long-term clinical management of these patients. Several clinical studies reported that the presence of thyroid autoantibodies and autoimmune thyroiditis is more prevalent in patients with PCOS compared to the healthy controls.,,,
Data are inadequate regarding the prevalence of thyroid dysfunction and thyroid autoimmunity in patients with PCOS in the context of Bangladesh. This study was conducted to address this knowledge gap.
| Materials and Methods|| |
This cross-sectional study was conducted among newly diagnosed patients with PCOS attending the endocrinology outpatient departments of several tertiary hospitals of Bangladesh from January 2017 to December 2019. The protocol of the study obtained approval from the Institutional Review Board of Mymensingh Medical College, Bangladesh; written permission was taken from the authorities of the other hospitals before the commencement of the study. In adults, the diagnosis of PCOS was made using the revised Rotterdam criteria, 2003; the diagnosis of PCOS in adolescent girls was made based on the presence of clinical and/or biochemical evidence of hyperandrogenism (after exclusion of other pathologies) in the presence of persistent menstrual irregularities., Pregnant and lactating patients and those having the pelvic inflammatory disease or any malignancy were excluded. Patients with a known history of thyroid dysfunction, those with a history of thyroid surgery or radioiodine ablation, and those taking drugs that may interfere with thyroid function were also excluded. All consecutive patients with PCOS giving consent for the study were included in the sample. A semi-structured questionnaire-based interview on a one-to-one basis was conducted to collect detailed information on clinical presentation and family history. Height (to ± 0.1 cm) was measured in all the individuals using wall-mounted stadiometers, and body weight (to ± 0.1 kg) was measured using electronic calibrated scales; body mass index (BMI) was calculated from height and weight using the formula: Height/weight2. Waist circumference (WC) was measured (to ± 0.1 cm) at the end of a gentle expiration midway between the lower rib margin and iliac crest. Blood pressure (BP) was measured two times in every study participant by the auscultatory method using standard validated aneroid sphygmomanometer after at least 5 min of rest; two separate readings were taken at an interval of minimum 3 min, and the average of the two readings was used. The presence of goiter was judged by the concerned investigator as a visible enlargement of the thyroid gland. Hirsutism was assessed by the modified Ferriman–Gallwey (F-G) score; a score ≥8 was the cut point for the diagnosis of hirsutism. Subfertility in the study participants was defined as the failure to conceive after 1 year of unprotected regular (at least twice a week) sexual intercourse with the exclusion of subfertility of the male partner evidenced by a normal semen analysis report. Oral glucose tolerance test (OGTT) with a 75-g glucose load was done in all after overnight fasting for at least 8 h; fasting plasma glucose (FPG) and plasma glucose 2 h after OGTT (PG 2H-OGTT) were measured by glucose oxidase method using fully automatic biochemistry analyzers. Lipid profile was measured in all in fasting states using fully automatic biochemistry analyzers. Transvaginal ultrasonography (USG) was preferred in the married patients, whereas transabdominal pelvic USG was done in unmarried ones. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO) antibody, total testosterone, and prolactin were measured by automated hormone analyzers using either the chemiluminescence immunoassay or radioimmunoassay depending on the availability of the test method at the particular center; the hormone levels were interpreted according to the normal reference ranges of the corresponding laboratories. For the convenience of data analysis, FT4 levels were converted to ng/dL unit, if reported in other units, using appropriate conversion factors. Thyroid function status was categorized according to the American Thyroid Association guidelines.,
Statistical analysis was done using the Statistical Package for the Social Sciences for Windows, version 23.0 software (SPSS Inc.; Chicago, IL, USA). The categorical variables were presented as number (%); measurable variables with normal distribution were presented as mean ± standard deviation, and those not following normal distribution were presented as median (interquartile range). Student's t-test, Chi-square test, and Mann–Whitney U-tests were performed as applicable for comparing the variables between different groups. P ≤0.05 was considered to be statistically significant.
| Results|| |
Five hundred women with PCOS in the age group of 12–40 years (mean age: 22.58 ± 5.41 years) were evaluated in this study. Among them, 17% had thyroid dysfunction: 11% subclinical hypothyroidism (SCH), 5.2% overt hypothyroidism, 0.4% subclinical hyperthyroidism, and 0.4% overt hyperthyroidism. More than one-fifth (20.6%) of the study participants were positive for anti-TPO antibody [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Thyroid function status of the study participants. (b) Status of anti-thyroid peroxidase among the study participants|
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The demographic, anthropometric, and clinical parameters of the study participants are shown in [Table 1]. Patients with normal thyroid function test (TFT) and thyroid dysfunction had similar mean age, age at the onset of PCOS features, BMI, WC, and diastolic BP. The frequencies of married women, menstrual irregularities, acne, a first-degree family member with thyroid dysfunction, and acanthosis nigricans were also similar. The patients with abnormal TFT had lower modified F-G score and hirsutism frequency. More patients in the thyroid dysfunction group had a history of weight gain during the course of PCOS onset. Higher rates of subfertility and goiter were observed in patients with thyroid dysfunction; systolic BP was higher in this group.
|Table 1: Demographic, anthropometric, and clinical parameters of the study participants|
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The metabolic and hormonal parameters of the study participants are given in [Table 2]. Patients with normal TFT and thyroid dysfunction had similar FPG, PG 2H-OGTT, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), testosterone, and prolactin levels. The frequencies of biochemical hyperandrogenism (elevated total testosterone) and hyperprolactinemia were also similar in the two groups. Serum TSH and anti-TPO levels were higher, and the FT4 level was significantly lower in the thyroid dysfunction group.
| Discussion|| |
In this multicenter study, we observed that 17% of the PCOS patients had thyroid dysfunction, and 20.6% were positive for the anti-TPO antibody. Higher frequencies of goiter and subfertility were found among the patients with thyroid dysfunction, and systolic BP was higher in them; these patients tended to be less hirsute and had a lower FG score in comparison to the euthyroid ones.
Thyroid disorders and PCOS are common endocrine disorders. Although these two are clinically separate entities, they share many clinical, biochemical, and radiological abnormalities, including menstrual irregularities, infertility, spontaneous abortion, obesity, lipid abnormalities, and enlarged ovaries with polycystic morphology., Although the exact interlinks connecting the pathophysiology and clinical manifestations of PCOS and thyroid disorders have not been established until now, these may be due to some common factors predisposing an individual to both disorders or due to a pathophysiological connection between the two disorders. However, it is now evident that thyroid disorders are more common in women with PCOS as compared to age-matched healthy women.,,,,,,, Both genetic and environmental factors are believed to be contributing to thyroid disorders in PCOS. Hypothyroidism is known to cause PCOS-like ovaries and overall worsening of PCOS and insulin resistance.,
In this study, 16.2% of the participants had either overt (5.2%) or subclinical (11.0%) hypothyroidism, though hyperthyroidism was seen in only 0.8% (0.4% subclinical and 0.4% overt hyperthyroid) of them. The prevalence of thyroid dysfunction in Bangladesh is yet to be determined though it is believed that 20% of our general population is suffering from any type of thyroid disorder. In one study from Bangladesh, the observed frequency of thyroid dysfunction among patients with type 2 diabetes was 21.9%. In India, the prevalence of thyroid dysfunction was 20.91% in a multicenter study. However, the study participants from Kolkata, which has almost similar geographical and population characteristics of Bangladesh, had a higher prevalence (34.91%). We observed that 17% of the PCOS patients have thyroid dysfunction, which is lower than the presumed prevalence of thyroid disorder in our general population. From the previous studies, it is also evident that the prevalence of thyroid disorders is lower in women of reproductive age than the general population as a whole. For an example, the prevalence of subclinical thyroid dysfunction in the general population has been estimated around 10%, but in reproductive years, this prevalence is considerably low at 4%–6%., In this background, our PCOS patients might have a higher prevalence of thyroid dysfunction, particularly subclinical thyroid dysfunctions, than women of reproductive age at a similar age group.
Worldwide, many researchers have evaluated the thyroid function in PCOS. In India, the observed frequency of thyroid dysfunction in PCOS was 27.5% by Sinha et al., 46.66% by Ganvir et al., 25.72% by Goyal et al., and 15% by Ramanand et al.,,, Morgante et al., in Italy, found 33.7% infertile PCOS patients to have subclinical thyroid dysfunction. In another study conducted by Arduc et al. in Ankara, Turkey, 26.7% of the PCOS patients had elevated TSH. In a study, Mustari et al. found 21% of Bangladeshi patients diagnosed as PCOS to have thyroid dysfunction, which is higher than the present study. With the above results, it is evident that there is a large heterogeneity in the prevalence of thyroid dysfunction in PCOS. The geographical location, iodization status, and the characteristics of the studied population may be responsible for such varying prevalence of thyroid disorders even in the same country. The prevalence of thyroid dysfunction was higher in PCOS compared to the healthy women of reproductive age in the studies done by Sinha et al. (27.5% vs. 11.25%), Morgante et al. (33.7% vs. 23.2%), and Arduc et al. (26.7 vs. 5%).,, Goyal et al. also observed a higher frequency of thyroid dysfunction in the PCOS group though it was not statistically significant. Furthermore, most of the researchers have found higher TSH levels in PCOS patients compared to the controls, though one study from India reported the opposite findings.,,,,
In this study, the mean age was similar in the euthyroid and thyroid dysfunction groups. Mustari et al., Benetti-Pinto et al., Trummer et al., and Enzevaei et al. had similar observations, though Yu and Wang found a higher mean age in the PCOS patients with SCH compared to euthyroid ones.,,,, Yasar et al. observed that the increased prevalence of SCH in women with PCOS might be the result of increased BMI. We observed similar BMI in PCOS women with normal and abnormal thyroid function. The findings of some other researchers were similar to ours in this regard.,, Similar to Enzevaei et al., we observed no differences in WC between the two groups. Although systolic BP was higher in the thyroid dysfunction group, the two groups had similar diastolic BP in our study participants. Both systolic and diastolic BP were similar in the PCOS patients with normal and abnormal thyroid function in the previous studies by Mustari et al., Benetti-Pinto et al., and Trummer et al.,,
In this study, the thyroid dysfunction group had a lower modified F-G score and hirsutism frequency; the total testosterone level, the frequencies of patients having acne, and elevated testosterone were similar in PCOS patients with or without thyroid dysfunction. F-G score, testosterone level, and hirsutism frequency were similar in the two groups in studies done by Mustari et al., Benetti-Pinto et al., and Trummer et al.,, Free testosterone was higher in euthyroid in comparison to SCH patients with PCOS in the study done by Enzevaei et al. Similar to Mustari et al. and Trummer et al., we observed no differences in the frequency of menstrual irregularity between the two groups., Although Benetti-Pinto et al. observed similar frequencies of subfertility in PCOS women with SCH and euthyroidism, we observed a higher frequency of subfertility in patients with thyroid dysfunction.
A higher frequency of acanthosis nigricans was observed in PCOS women with thyroid dysfunction than euthyroid ones by Mustari et al. We found both the groups to be similar in this aspect. Both the groups had similar FPG, PG 2H-OGTT, TC, TG, LDL-C, and HDL-C in our study. Other researchers also observed similar fasting and 2H-OGTT plasma glucose values in the two groups.,,, Mustari et al. and Enzevaei et al. also found comparable lipid profiles in the two groups., TC, LDL-C, and TG were significantly higher in subclinical hypothyroid PCOS patients compared to euthyroid ones in a study done by Yu and Wang, whereas Benetti-Pinto et al. observed similar TC, TG, and HDLC in euthyroid and subclinical hypothyroid PCOS patients but LDL-C level was higher in the SCH group; Trummer et al. found lower HDL-C in hypothyroid PCOS patients in comparison to euthyroid PCOS women and similar TC, TG, and LDL-C in both the groups.,,
Benetti-Pinto et al. found higher prolactin levels in PCOS women with SCH, though Mustari et al. did not find any difference in prolactin levels among PCOS patients having normal and abnormal TFT., We observed similar prolactin levels in the two groups; the frequency of hyperprolactinemia was also similar in the two groups.
The prevalence of thyroid autoimmunity in PCOS was found to be higher in comparison to age-matched healthy women in some studies done abroad.,,,,,, Researchers suggest an increased estrogen and estrogen/progesterone ratio to be directly involved in high anti-TPO levels in PCOS patients. Estrogen's immune-stimulatory activity is normally countered by anti-inflammatory actions of progesterone, levels of which are near zero in PCOS because of the anovulatory cycles. As a result, the immune system is overstimulated, resulting in autoimmunity and a high incidence of autoimmune thyroid diseases. Janssen et al., in Germany, found elevated anti-thyroid antibodies in 26.9% PCOS patients versus 8.3% controls (P< 0.001). Al-Saab and Haddad in Syria (19.6% vs. 3.3%), Novais Jde et al. in Brazil (43.1% vs. 26.2%), Arduc et al. in Turkey (26.7 and 6.6%), and Garelli et al. in Italy (27% vs. 8%) also observed higher frequencies of thyroid autoimmunity in POCS patients compared to the healthy controls.,,, PCOS patients had higher frequencies of anti-TPO positivity than controls in some Indian studies by Sinha et al. (22.5% vs. 1.25%) and Goyal et al. (25.7% vs. 17.1%); however, the intergroup difference observed by Goyal et al. was not statistically significant., Women with PCOS had higher serum levels of anti-TPO in comparison to controls in some studies., In our study, 20.6% of the PCOS patients were found to be positive for anti-TPO. As we had no healthy control group, we are unable to comment on whether this frequency of thyroid autoimmunity is higher than age-matched controls. The prevalence of autoimmune thyroid disease in Bangladesh is not known. In this aspect, it may be mentioned that, the prevalence of autoimmune thyroid disease was found very high (32.9%) in a study conducted in Bangladesh among the patients with type 2 diabetes.
Limitations and strengths of the study
The absence of a non-PCOS, healthy control group to compare with the PCOS patients was the major limitation of the study. There was also a lack of a unique assay method for TSH, FT4, and anti-TPO as different centers used different methods of hormone assay. However, the reference ranges of the corresponding laboratory were used to define thyroid status. Clinical assessment by multiple investigators imparts the risk of observer bias. The major strengths of the study are its multicenter design and large sample size from different parts of the country. Despite all these, this is the first large-scale study in Bangladesh that evaluated the thyroid function status and thyroid autoimmunity in PCOS, and the result of this study may direct future research studies in this field in the country.
| Conclusions|| |
Thyroid dysfunction and thyroid autoimmunity in Bangladeshi PCOS patients are very common. A large-scale study with the incorporation of aged-matched healthy controls in the comparison group may answer the actual scenario in this aspect.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
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[Table 1], [Table 2]