In asymptomatic preconception women with history of miscarriage or subfertility, the prevalence of subclinical hypothyroidism (SCH), defined as thyrotropin (TSH) levels ≥2.50 mIU/L, may reach up to 1 in 5 women, according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Previous studies have reported associations between thyroid dysfunction — including subclinical hyperthyroidism or hypothyroidism — and the presence of thyroid peroxidase antibodies (TPOAb) and adverse pregnancy outcomes, including subfertility and miscarriage. The definition of SCH varies between guidelines, as do recommendations for screening for thyroid disease and treatment for subfertile women and women with history of miscarriage or preterm birth. The American Thyroid Association guidelines recommend using a cutoff of >2.5 mIU/L for TSH level when initiating levothyroxine treatment in pregnant women with evidence of TPOAb.
The goal of the current study was to assess the prevalence of thyroid dysfunction and autoimmunity in preconception asymptomatic women with a history of miscarriage or subfertility.
The multicenter prospective observational study included individuals aged 16 to 41 years from 49 hospitals in the United Kingdom between November 2011 and January 2016. All included individuals had a history of miscarriage or subfertility and were actively trying to conceive in the subsequent 12 months.
The researchers classified the study cohort into 5 groups, which were not mutually exclusive: overt hypothyroidism, overt hyperthyroidism, SCH with TSH level >4.50 mIU/L, SCH with TSH level ≥2.50 mIU/L, and SCH with TSH level ≥2.50 mIU/L with TPOAb positivity. They also categorized the cohort according to age and body mass index (BMI).
The study cohort comprised 19,350 women, including 19,213 with available thyroid function results and 19,237 with available TPOAb data. Of these women, overt hypothyroidism was evident in 36 (0.2%) and overt hyperthyroidism was evident in 49 (0.3%). A total of 451 women (2.4%) had SCH with TSH level >4.50 mIU/L, while 3825 (19.9%) had SCH with TSH level ≥2.50 mIU/L and normal thyroxine levels.
Statistical analysis showed an increased risk for SCH with TSH level >4.50 mIU/L for women with BMI ≥35.0 kg/m2 (adjusted odds ratio [aOR], 1.71; 95% CI, 1.13-2.57; P =.01), women of Asian ethnicity (aOR, 1.76; 95% CI, 1.31-2.37; P <.001), and women with subfertility (aOR, 1.16; 95% CI, 1.04-1.29; P =.008).
A total of 1827 women (9.5%) were TPOAb positive and the prevalence of the autoantibodies was significantly higher in those with overt hypothyroidism (69.4%) or overt hyperthyroidism (40.8%) than in those without. Women with a history of recurrent (≥3) miscarriages or subfertility were not more likely to be TPOAb positive than those with 1 or 2 previous miscarriages. A dose-response between TPOAb positivity and BMI was documented, as the prevalence of the autoantibodies was significantly higher in women with obesity (BMI ≥35.0 kg/m2) compared with those with normal weight.
The study had several limitations, including lack of a control group, potential selection bias, missing data on the prevalence of thyroid dysfunction according to the cause of subfertility, and lack of assessment of iodine status.
“We have shown the prevalence of differing thyroid abnormalities when universally screening otherwise healthy women with history of miscarriage or subfertility… Screening for SCH, using a TSH cut off of 2.5mIU/L as recommended for women with subfertility or recurrent miscarriage, will result in up to 20% of women diagnosed as having thyroid dysfunction and potentially requiring levothyroxine treatment,” concluded the researchers.
“This could constitute a significant burden to healthcare systems, and may generate unnecessary patient anxiety. In the absence of evidence of benefit with [levothyroxine] treatment and possible suggestion of harm, for mild SCH or TPOAb positivity we pose the question of whether screening should be performed at all in asymptomatic individuals,” they added.
Dhillon-Smith RK, Tobias A, Smith PP, et al. The prevalence of thyroid dysfunction and autoimmunity in women with history of miscarriage or subfertility [published online June 17, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa302