Thyroid Research and Practice

EDITORIAL
Year
: 2019  |  Volume : 16  |  Issue : 2  |  Page : 53--54

Thyroid autoimmunity, hypothyroidism, and polycystic ovarian syndrome: In search of the missing link


Partha Pratim Chakraborty, Asish Kumar Basu 
 Department of Endocrinology and Metabolism, Medical College, Kolkata, West Bengal, India

Correspondence Address:
Dr. Partha Pratim Chakraborty
Department of Endocrinology and Metabolism, 4th Floor, MCH Building, 88 College Street, Kolkata - 700 073, West Bengal
India




How to cite this article:
Chakraborty PP, Basu AK. Thyroid autoimmunity, hypothyroidism, and polycystic ovarian syndrome: In search of the missing link.Thyroid Res Pract 2019;16:53-54


How to cite this URL:
Chakraborty PP, Basu AK. Thyroid autoimmunity, hypothyroidism, and polycystic ovarian syndrome: In search of the missing link. Thyroid Res Pract [serial online] 2019 [cited 2019 Aug 21 ];16:53-54
Available from: http://www.thetrp.net/text.asp?2019/16/2/53/262729


Full Text



Autoimmune hypothyroidism, subclinical or overt, and polycystic ovarian syndrome (PCOS) are undoubtedly the most common endocrine disorders encountered in women of reproductive age group. These two conditions share a number of clinical and radiological abnormalities, menstrual irregularities, infertility, spontaneous abortion, and enlarged ovaries with polycystic morphology, to name a few. A number of studies have demonstrated increased prevalence of elevated thyroid-stimulating hormone (TSH) in women with PCOS compared to age-matched general population, and the recent study by Goyal et al. adds to the list. Underlying risk factors common to both these conditions if any or possible pathophysiological link, however, are yet to be identified, and a number of postulations have been put forward.

The most plausible explanation seems to be increased body mass index (BMI) that is more prevalent in both these conditions compared to “healthy” subjects. Elevated TSH is seen in about a quarter of obese patients without thyroid autoimmunity, and a positive correlation between TSH and BMI has also been identified. Concentration of leptin, an adipokine, is directly proportional to the degree of adipose tissue mass and plays a pivotal role in elevating TSH possibly by stimulating thyrotropin-releasing hormone, up-regulating pro-opiomelanocortin/cocaine and amphetamine-regulated transcript neurons, and inhibiting neuropeptide Y/agouti-related protein and pituitary deiodinase-2. Injury to thyroid cells or sodium/iodide cotransporter due to elevated pro-inflammatory cytokines, mitochondrial dysfunction, functional thyroid hormone resistance at the level of hypothalamus and pituitary, bioinactive TSH, and TSH-receptor mutation also contribute to higher than normal TSH seen in obesity. Last but not the least, this could be an adaptive process as well. Goyal et al. reported significantly higher BMI in PCOS patients as compared to age-matched healthy controls which might have contributed to higher TSH in the PCOS subgroup.

In a study conducted by Benetti-Pinto et al. involving 168 young women (mean age 24 ± 5.8 years) with PCOS, 19 individuals (11.3%) had subclinical hypothyroidism (defined as TSH >4.5 μIU/ml). Although the mean BMI of the cohort was 33.4 ± 8.2 kg/m2, no difference was observed in between two groups (with or without subclinical hypothyroidism) with respect to BMI or waist circumference (WC).[1] In individuals with normal BMI, thyroxine produces an equal amount of triiodothyronine (T3) and reverse T3 (rT3). Obesity is characterized by increased T3 production and decreased rT3 production; hence, high normal/elevated total T3 and free T3 (FT3) often accompany elevated TSH in an obese individual. The absence of significant difference in FT3 level in between two groups of this particular study probably points toward factors other than obesity that have contributed to elevated TSH in PCOS cases.

Increased prevalence of autoimmunity, including autoimmune thyroid disease (AITD), has been observed in PCOS. Women with PCOS have higher thyroid autoantibodies, larger thyroid volumes, and hypoechoic thyroids, suggesting thyroiditis compared to controls. PCOS is a hyperestrogenic state and high estrogen has been proposed to be responsible for the occurrence of increased autoimmune diseases in females of child-bearing age when compared to their male counterparts. Goyal et al., however, failed to replicate such an association in their study. The prevalence of anti-thyroid peroxidase (anti-TPO) antibody and anti-thyroglobulin (anti-Tg) antibody in patients of AITD is 90%–100% and 80%–90%, respectively. Hence, a small fraction of individuals with underlying thyroid autoimmunity may be tested negative for thyroid autoantibodies; however, fine-needle aspiration cytology (FNAC) of the thyroid confirms AITD. Ultrasonography (USG), being an operator-dependent investigation, not testing anti-Tg antibody level in the study population, not performing thyroidal USG and FNAC in anti-TPO-negative women may have confounded the findings.

Interestingly, in a study by Ganie et al., euthyroid young women (mean age 14.7 years) with underlying AITD have significantly higher BMI, WC, and PCOS compared to age-matched controls without AITD.[2] Higher leptin seen in obese individuals has been proposed to be the underlying factor as a positive correlation of anti-TPO antibodies with BMI and weight gain has been observed.[3] Vitamin D deficiency may also play a role. Vitamin D, being fat soluble, is sequestered in the fat mass; hence, serum levels are lower in obese individuals. Vitamin D deficiency has also been linked to autoimmunity.

Certain issues are worthy of consideration before drawing a definite conclusion from this particular study that analyzed 140 subjects. Women aged 13–45 years were included, and PCOS was diagnosed by the Rotterdam Criteria 2003. Diagnosis of PCOS is not always straightforward in adolescence, as normal girls of this age may have polycystic-appearing ovaries, acne, and menstrual abnormalities. Moreover, Rotterdam criteria are based on transvaginal USG, which is avoided in unmarried women and may not be feasible in the control subjects before ruling out PCOS in that group with confidence.

Lean PCOS is a well-established entity. Hence, a larger case–control study looking at thyroid function tests, thyroid autoantibodies (anti-TPO and anti-Tg), and thyroid cytology in age-matched, BMI-matched, and Vitamin D level-matched nonobese groups may unveil the hitherto unidentified missing link between thyroid autoimmunity, hypothyroidism, and PCOS.

References

1Benetti-Pinto CL, Berini Piccolo VR, Garmes HM, Teatin Juliato CR. Subclinical hypothyroidism in young women with polycystic ovary syndrome: An analysis of clinical, hormonal, and metabolic parameters. Fertil Steril 2013;99:588-92.
2Ganie MA, Marwaha RK, Aggarwal R, Singh S. High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: A case-control study. Eur J Endocrinol 2010;162:1117-22.
3Ong KK, Kuh D, Pierce M, Franklyn JA; Medical Research Council National Survey of Health and Development Scientific and Data Collection Teams. Childhood weight gain and thyroid autoimmunity at age 60-64 years: The 1946 British birth cohort study. J Clin Endocrinol Metab 2013;98:1435-42.