Progression to overt hypothyroidism more likely with subclinical disease during pregnancy
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Key takeaways:
- Pregnant women with subclinical hypothyroidism are more likely to develop overt hypothyroidism than those with hypothyroxinemia.
- Most women with overt hypothyroidism were not diagnosed clinically.
Women with subclinical hypothyroidism during the first half of pregnancy are more likely to develop overt hypothyroidism 5 years after delivery than women with hypothyroxinemia, according to a study published in Thyroid.
In a secondary analysis of two multicenter treatment trials assessing women diagnosed with subclinical hypothyroidism or hypothyroxinemia at 8 and 20 weeks’ gestation, those diagnosed with subclinical hypothyroidism were more than twice as likely to have overt hypothyroidism at 1 year and 5 years after delivery than women with hypothyroxinemia. Additionally, elevated thyroid peroxidase levels were tied to higher odds for overt hypothyroidism.
“Our data lend further evidence to the postpartum time period as a time when autoimmune diseases, in this case, hypothyroidism, are more likely to be present,” Michael W. Varner, MD, emeritus professor in the department of obstetrics and gynecology at the Spencer Fox Eccles School of Medicine at University of Utah, told Healio.
Varner and colleagues collected data from 307 women diagnosed with subclinical hypothyroidism during the first half of pregnancy and 229 diagnosed with hypothyroxinemia in pregnancy with follow-up data available 1 year and 5 years after delivery. All women participated in the placebo group of two randomized controlled trials assessing thyroxine therapy for subclinical hypothyroid disorders during pregnancy. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone level of 4 mU/L or higher and a normal free thyroxine level of 0.86 ng/dL to 1.9 ng/dL. Hypothyroxinemia was defined as a normal TSH concentration of 0.08 mU/L to 3.99 mU/L and free T4 of less than 0.86 ng/dL. Serum samples were collected at enrollment and 1 and 5 years after delivery. Overt hypothyroidism diagnoses were collected at 1 and 5 years. Women were considered to have overt hypothyroidism if they had a maternal history of concurrent thyroid replacement therapy or a serum sample with a TSH level of 4 mU/L or higher and free T4 of less than 0.86 ng/dL.
There were two women in the subclinical hypothyroidism group and one in the hypothyroxinemia group diagnosed with overt hypothyroidism at 1 year. Four women in the subclinical hypothyroidism group and four women with hypothyroxinemia during pregnancy were diagnosed with hypothyroidism at 5 years.
At 1 year or 5 years, 23.1% of the subclinical hypothyroidism group developed overt hypothyroidism compared with 4.8% of the hypothyroxinemia group (P < .001). Women with subclinical hypothyroidism at baseline had higher rates of overt hypothyroidism at 1 year and 5 years than those with hypothyroxinemia (OR = 2.85; 95% CI, 1.38-5.9). Specifically, at 1 year, the rate of overt hypothyroidism was 13.4% in the subclinical hypothyroidism group and 3.1% in the hypothyroxinemia group, and at 5 years, it was 15.6% in the subclinical hypothyroidism group and 2.6% in the hypothyroxinemia group (P < .001 for both), the researchers wrote.
“The majority of women with overt hypothyroidism had not been diagnosed clinically, but rather were identified as a result of participation in the research studies,” Varner said. “Unfortunately, we do not have any information on whether these women had previously reported their signs or symptoms to health care providers.”
Women with subclinical hypothyroidism and a baseline thyroid peroxidase level of more than 50 IU/mL were more likely to develop hypothyroidism at 1 year (OR = 5.3; 95% CI, 2.6-10.7) and 5 years (OR = 5.4; 95% CI, 2.8-10.6) than those with subclinical hypothyroidism and a baseline thyroid peroxidase of 50 IU/mL or less. Women with hypothyroxinemia and a baseline thyroid peroxidase level of more than 50 IU/mL had higher odds for hypothyroidism at 5 years than those with hypothyroxinemia and a thyroid peroxidase of 50 IU/mL or less at baseline (OR = 13.4; 95% CI, 2.1-84.1). When both study groups were combined, having a thyroid peroxidase level of more than 50 IU/mL at baseline increased the likelihood for hypothyroidism at 1 year or 5 years (OR = 7.16; 95% CI, 4.09-12.56).
For more information:
Michael W. Varner, MD, can be reached at michael.varner@hsc.utah.edu.
Perspective
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This secondary analysis of two trial cohorts examined the likelihood of progression to overt hypothyroidism over 1 to 5 years of postpartum follow-up in untreated women with subclinical hypothyroidism or isolated hypothyroxinemia diagnosed before week 21 of gestation. Progression to overt hypothyroidism was more common in women with subclinical hypothyroidism compared to those with hypothyroxinemia. The risk was highest (26.7% at 1 year and 30.5% at 5 years) in those with both baseline subclinical hypothyroidism and thyroid peroxidase antibody positivity. Among those with subclinical hypothyroidism, risk for progression was also increased when the baseline thyroid-stimulating hormone was greater than 10 mIU/L. It is interesting to note that 53% of women in the subclinical hypothyroid group had at least one normal subsequent TSH value in pregnancy and 62% of those with isolated hypothyroxinemia had at least one subsequent normal free thyroxine value in pregnancy despite a lack of therapy. Strengths of the study include its prospective design, inclusion of subjects representative of the U.S. population and duration of follow-up.
Overall, these data add to the body of evidence demonstrating that thyroid peroxidase antibody positivity and subclinical hypothyroidism, particularly in combination, are powerful predictors of the eventual development of overt hypothyroidism. Early pregnancy thyroid peroxidase antibody positivity is also known to predict the development of postpartum thyroiditis.
The optimal strategy for monitoring untreated women with a history of gestational thyroid hypofunction has not been established. At a minimum, women with a history of gestational hypothyroidism/hypothyroxinemia or known thyroid peroxidase antibody positivity should be counseled about symptoms of hypothyroidism that should prompt TSH testing (although the majority of women who developed overt hypothyroidism in this study were not diagnosed clinically). I think it is also important to monitor serum TSH levels prior to and during subsequent pregnancies in these patients, as untreated overt hypothyroidism in pregnancy can lead to devastating maternal and fetal outcomes.
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