|Year : 2019 | Volume
| Issue : 2 | Page : 55-59
Prevalence of hypothyroidism and thyroid autoimmunity in polycystic ovarian syndrome patients: A North Indian study
Diksha Goyal1, Pooja Relia2, Angela Sehra3, Deepak Khandelwal4, Deep Dutta5, Dimpy Jain6, Sanjay Kalra7
1 Department of Family Medicine, Maharaja Agrasen Hospital, Delhi, India
2 Department of Medicine, Maharaja Agrasen Hospital, Delhi, India
3 Department of Obstetrics and Gynecology, Maharaja Agrasen Hospital, Delhi, India
4 Department of Endocrinology, Maharaja Agrasen Hospital, Delhi, India
5 Department of Endocrinology, Venkateshwar Hospitals, Dwarka, New Delhi, India
6 Department of Dietetics, Maharaja Agrasen Hospital, Delhi, India
7 Department of Endocrinology, Bharti Hospital and Bharti Research Institute of Diabetes and Endocrinology, Karnal, Haryana, India
|Date of Web Publication||15-Jul-2019|
Dr. Deepak Khandelwal
Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, Delhi - 110 026
Source of Support: None, Conflict of Interest: None
Background: There is limited data regarding the prevalence of hypothyroidism and thyroid autoimmunity in patients with polycystic ovarian syndrome (PCOS).
Objective: To evaluate thyroid status and frequency of hypothyroidism and thyroid autoimmunity in patients with PCOS in comparison to age-matched controls.
Materials and Methods: In a case–control study conducted at Gynecology outpatients department of our institute, 70 consecutive PCOS women diagnosed by Rotterdam criteria as well as 70 age-matched controls were evaluated. All patients underwent history, physical examination, thyroid function tests, and anti-thyroid peroxidase antibody (TPO Ab) tests. All patients who had positive TPO Ab also underwent ultrasonography of thyroid.
Results: Mean serum thyroid-stimulating hormone (TSH) in PCOS was significantly higher (5.11 ± 4.41 uU/ml vs. 3.62 ± 3.38 uU/ml; P = 0.026) than age-matched controls. Subclinical hypothyroidism (14.3% vs. 7.1%) and TPO Ab positivity (25.7% vs. 17.1%) were numerically higher in PCOS patients as compared to age-matched controls, although not statistically significant.
Conclusions: Mean serum TSH was significantly higher in PCOS patients as compared to age-matched controls. Numerically higher percentage of patients with PCOS had subclinical hypothyroidism and TPO Ab positivity; however, these were not statistically significant.
Keywords: Hypothyroidism, polycystic ovarian syndrome, subclinical hypothyroidism, thyroid, thyroid autoimmunity
|How to cite this article:|
Goyal D, Relia P, Sehra A, Khandelwal D, Dutta D, Jain D, Kalra S. Prevalence of hypothyroidism and thyroid autoimmunity in polycystic ovarian syndrome patients: A North Indian study. Thyroid Res Pract 2019;16:55-9
|How to cite this URL:|
Goyal D, Relia P, Sehra A, Khandelwal D, Dutta D, Jain D, Kalra S. Prevalence of hypothyroidism and thyroid autoimmunity in polycystic ovarian syndrome patients: A North Indian study. Thyroid Res Pract [serial online] 2019 [cited 2020 Jan 19];16:55-9. Available from: http://www.thetrp.net/text.asp?2019/16/2/55/262734
| Introduction|| |
Polycystic ovarian syndrome (PCOS), also known as Stein and Leventhal syndrome, is one of the most common female endocrine disorders with a prevalence of 5%–10% in women of reproductive age group. It is a complex disorder wherein numerous genetic variants and environmental factors combine and contribute to the pathogenesis. PCOS is of both clinical and public health importance, and its prevalence has recently been shown up to 18% in premenopausal women with current Rotterdam diagnostic criteria. The increased prevalence of obesity and metabolic syndrome in the general population is contributing to the increased burden of PCOS in our society.
Thyroid disorders are arguably the most common endocrine disorder worldwide. In two large studies from India, the prevalence of antithyroid peroxidase antibody (TPO Ab) positivity, overt hypothyroidism, and subclinical hypothyroidism has been reported to be 13.3%–21.8%, 3.5%–4.2%, and 8.02%–19.3%, respectively.,,
Although the etiopathogenesis of hypothyroidism and PCOS is completely different, these two disorders have many features in common. Thyroid disorders can be associated with menstrual disturbances and infertility, which are also common symptoms in PCOS. An increase in ovarian volume as well as cystic changes in the ovaries has been reported in primary hypothyroidism. Mildly raised prolactin has been observed in PCOS. Raised prolactin levels have been documented in children and adults with mild subclinical hypothyroidism, which may also contribute to the overlapping features of menstrual irregularity seen both in hypothyroidism and PCOS., Few studies have shown that thyroid disorders are more common in women with PCOS as compared to the normal population.,, Whether this is due to some common factors predisposing an individual to both disorders or due to a pathophysiological connection between the two disorders has not been established till now. There is limited data regarding the prevalence of hypothyroidism and thyroid autoimmunity in patients with PCOS, especially in Indian context. Hence, the aim of this study was to evaluate the occurrence of thyroid disorders in patients with PCOS as compared to age-matched controls.
| Materials and Methods|| |
A case–control study was conducted in the outpatient department (OPD) of gynecology clinic at our hospital, which is a 400-bedded teaching, superspeciality, National Accreditation Board for hospitals and healthcare providers and Joint commission International-accredited hospital serving patients from both urban and rural areas. The institutional ethics committee approved this study.
70 consecutive premenopausal women with PCOS aged 13–45 years diagnosed by Rotterdam criteria 2003, who consented for the study were included. Patients with current pregnancy, lactation, pelvic inflammatory disease and known cases of congenital adrenal hyperplasia, type 2 diabetes mellitus, and any history of malignancy in the past were excluded. Seventy apparently healthy age-matched controls were also taken from either nursing staff working in our hospital or relatives of patients attending the gynecology OPD. Healthy controls were chosen on the basis of clinical screening by single endocrinologist after detailed history and clinical examination. The study and its procedure were explained to the patients as well as controls, and informed written consent was taken.
The clinical and laboratory assessments were conducted in accordance with the regular clinical practice and institutional protocols. Details of acne, hirsutism (Ferriman–Gallwey scoring), and menstrual irregularity were ascertained. Laboratory investigations were done as a part of routine clinical practice, and the data were captured and used for analysis. All participants underwent thyroid function test as well as TPO Ab. Furthermore, the ultrasonography (USG) thyroid was done in patients who were TPO Ab positive.
Statistical testing was conducted with the statistical package for the social science system version 17.0 (Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp). Continuous variables were presented as mean ± standard deviation or median (interquartile range) for normally distributed data. Categorical variables were expressed as frequencies and percentages. The comparison of normally distributed continuous variables between the groups was performed using Student's t-test. Nominal categorical data between the groups were compared using Chi-squared test or Fisher's exact test as appropriate. Nonnormal distribution continuous variables were compared using Mann–Whitney U-test. For all statistical tests, P < 0.05 was considered as statistically significant.
| Results|| |
A total of 228 consecutive patients attending the gynecology OPD of our hospital who were presenting with menstrual irregularity and/or androgenic manifestations were screened. Diagnosis of PCOS was ascertained with Rotterdam criteria. Ninety-six patients were found to be eligible for the study, of which 26 did not consent for the study. Hence, data from 70 females with PCOS and 70 healthy age-matched controls who gave informed written consent were included in the study.
Baseline parameters of study participants are shown in [Table 1]. The maximum numbers of participants were in the age group of 21–30 years. PCOS patients had significantly higher body mass index (BMI) as compared to controls. Furthermore, proportion of individuals with overweight (BMI ≥ 25) as well as obesity (BMI ≥ 30) was significantly higher in women with PCOS as compared to controls. The most common symptoms were oligomenorrhea (44%) and infertility (28%) followed by amenorrhea (21.4%) in PCOS group; all symptomatology was significantly more common in PCOS patients as compared to controls.
|Table 1: Distribution of clinical symptoms and signs among study participants (n=70)|
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Laboratory parameters of study participants have been elaborated in [Table 2]. PCOS patients had significantly elevated postprandial blood glucose, fasting and postprandial serum insulin levels, higher serum luteinizing hormone levels as well as serum-free testosterone levels than in controls.
Of 70 cases and controls, there were 7 and 5 females, respectively, who self-reported hypothyroidism and were already on levothyroxine. Mean serum thyroid-stimulating hormone (TSH) in PCOS patients was significantly higher (5.11 ± 4.41 uU/ml vs. 3.62 ± 3.38 uU/ml) than age-matched controls (P = 0.026). The prevalence of newly detected subclinical hypothyroidism (14.28% vs. 7.1%) was higher in PCOS patients, although not statistically significant. Furthermore, TPO Ab positivity was found numerically higher (25.7% vs. 17.1%) in PCOS patients as compared to controls but not statistically significant [Table 3]. Similarly, patients with both TPO Ab positive along with heterogeneous thyroid gland on USG were not significantly different between PCOS group as compared to controls (20% vs. 15.7%; P = 0.508).
|Table 3: Laboratory and sonographic findings related to thyroid among study participants|
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| Discussion|| |
Our study showed a higher frequency of thyroid dysfunction in PCOS patients compared to controls. The mean serum TSH was found to be significantly high among PCOS patients as compared to controls. Newly detected subclinical hypothyroidism was twice more common in PCOS patients as compared to controls but not statistically significant. Furthermore, TPO Ab was prevalent in 25.7% of PCOS patients as compared to 17.1% among controls.
Primary hypothyroidism is widely prevalent worldwide., Overall, the prevalence of overt primary hypothyroidism is between 1% and 2% and almost 10 times more common in females as compared to males, while up to 10% of general population may have subclinical hypothyroidism.,, Deficiency of thyroid hormone has many profound end-organ effects, which also include those in reproductive system of human females. Long-standing hypothyroidism can interfere with gonadotropin secretion by increasing serum prolactin levels.
In recent years, a number of publications have reported increased incidence of thyroid disorders in females with PCOS. Sinha et al. compared 80 PCOS females with 80 controls and found significantly higher prevalence of goiter (27.5% vs. 7.5%) and subclinical hypothyroidism (22.5% vs. 8.75%) in PCOS patients as compared to controls. Another study in young women with PCOS found the prevalence of subclinical hypothyroidism to be 11.3%, with mean TSH level of 6.1 ± 1.2 mIU/L in their study. Another recent Indian study found high prevalence of thyroid disorders among PCOS women; 33% of overall PCOS women had any thyroid dysfunction, 11% of them had goiter, and 18% had subclinical hypothyroidism. However, one of the main limitation of this study was lack of controls.
Few studies have documented higher prevalence of thyroid autoimmunity in patients with PCOS. Janssen et al. showed females with PCOS have higher thyroid antibody levels, larger thyroid volumes, and higher prevalence of hypoechogenic thyroid glands (compatible with thyroiditis) when compared to controls. Furthermore, in their study, PCOS patients had a higher mean TSH level and a higher incidence of TSH levels above the upper limit of normal as compared to controls, almost similar findings observed in our study. Kachuei et al. found significantly higher prevalence of antithyroglobulin antibody in PCOS patients compared to normal controls in Iranian population; however, in their study, serum TSH level was not different from control population. Garelli et al. also found higher prevalence of TPO Ab positivity in patients with PCOS (27%) when compared to controls (8%).
The pathophysiological pathway connecting these two disorders has not been clearly delineated as of now. A multidirectional link with complex interplay of PCOS, adiposity, thyroid dysfunction, and autoimmunity, working to produce varying clinical pictures, seems to be the best explanation as of now. Vitamin D deficiency may also have some role. Vitamin D deficiency is more common in obesity and metabolic syndrome due to increased sequestration of this fat-soluble vitamin., Vitamin D deficiency has also been linked to thyroid autoimmunity. The most obvious connection, perhaps, is the increased BMI and insulin resistance common to both conditions. Obesity through undefined mechanisms leads to decreased deiodinase2 activity at pituitary level, resulting in relative triiodothyronine deficiency and increase in TSH levels. Furthermore, increased leptin in obesity has been proposed to act directly on the hypothalamus resulting in increased thyrotropin-releasing hormone secretion. Possible explanation for higher thyroid autoimmunity in PCOS is likely because of hyperestrogenic state of PCOS. Hyperestrogenism has been proposed as one explanation for the occurrence of increased autoimmune diseases in females when compared to males.,
Hypothyroidism per se can initiate, maintain, and worsen PCOS. An increase in ovarian volume as well as cystic changes in the ovaries has been reported in overt primary hypothyroidism. Hypothyroidism may result in lowering of sex hormone-binding globulin level and increment of testosterone level but not invariably directed toward estriol overproduction thereby resulting in polycystic ovaries., However, subclinical hypothyroidism does not influence the hormonal profile of women with PCOS. On the other hand, it may result in mild metabolic abnormalities, which may not be clinically important at least in short-term setting.,
Few limitations of our study need mention. One of the main limitation was small sample size limited to single center. Hence, results may not be generalized to larger group of such population. Furthermore, few parameters failed to achieve statistical significance because of small sample size. Furthermore, controls were only age matched but were not matched for BMI. Some of the findings seen in PCOS patients like higher TSH can be because of effect of higher BMI.
| Conclusions|| |
In our study, mean TSH was significantly higher in PCOS patients than age-matched controls. Furthermore, numerically higher percentage of patients with PCOS had subclinical hypothyroidism as well as TPO Ab positivity as compared to controls, although not statistically significant. However, further studies with larger sample size as well as interventional studies with levothyroxine treatment are required to see effect on ovarian size and follicular development in patients with PCOS.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]