The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 6 1819-1821
Copyright © 1999 by The Endocrine Society
Postpartum Thyroiditis: The Case For Selective Screening
Alex Stagnaro-Green
Division of Endocrinology and Metabolism
Department of Medicine Mount Sinai School of Medicine
New York, New York 10029
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Introduction
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POSTPARTUM thyroiditis is one of the most common diseases
of the thyroid and has important clinical sequelae. In studies in North
America postpartum thyroiditis affects between 6.0–8.8% of all
pregnant women (1, 2, 3). Postpartum thyroiditis also has clearly defined
morbidities. Women with postpartum thyroiditis may experience symptoms
in both the hyperthyroid and hypothyroid phase, and may have an
increased incidence of postpartum depression (4, 5). Long-term
follow-up reveals that approximately 25% of women with postpartum
thyroiditis develop permanent primary hypothyroidism within 5 yr of
delivery (6, 7). Furthermore, the presence of thyroid autoantibodies in
the first trimester of pregnancy is associated with an increased rate
of spontaneous abortion (8, 9, 10, 11). Given both the prevalence of the
disorder and the associated morbidities, the argument for screening for
postpartum thyroiditis seems iron clad, and one can only wonder why a
screening program for postpartum thyroiditis has not already been
instituted.
On the other hand, screening for postpartum thyroiditis is an enormous
undertaking with tremendous fiscal implications. Every pregnant women
would need to be screened for the presence of thyroid peroxidase
autoantibodies. Women who test positive would require a minimum of two
measurements of TSH in the postpartum (3 and 6 months). Furthermore,
the following three unproven assumptions underlie the argument for
screening; a) that the optimal screening strategy is known, b) that
treating women with postpartum thyroiditis would decrease the incidence
or severity of postpartum depression, and c) that treating postpartum
thyroiditis would decrease the incidence of, or the symptoms associated
with, long-term primary hypothyroidism. Given these arguments, it now
appears that screening for postpartum thyroiditis is premature and a
questionable use of limited fiscal resources.
Given the powerful but conflicting, scientific, fiscal, and emotional
arguments for screening for postpartum thyroiditis the clinician is
left in a quandary. A rational approach to resolve the screening debate
requires the following four questions be addressed:
- Is postpartum thyroiditis a common enough clinical entity to
warrant screening?
- Are there important morbidities associated with postpartum
thyroiditis?
- Can the morbidities of postpartum thyroiditis be prevented with
levothyroxine therapy?
- Is there an inexpensive, easily available, and accurate
screening test?
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Prevalence
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Worldwide, the prevalence of postpartum thyroiditis varies widely,
from 1.1% in Thailand to 16.7% in the United Kingdom (12, 13). The
disparity is explained both by true geographic differences in
prevalence rates as well as by critical study design issues such as the
length of follow-up in the postpartum period and the frequency of
screening. Studies performed in the United States and Canada that
extend beyond three months postpartum have revealed similar prevalence
rates (6% in Canada, 6.7% in Wisconsin, and 8.8% in the New York
Metropolitan area) (1, 2, 3). In women with Type I diabetes mellitus,
another autoimmune disorder, the prevalence in North America is
substantially higher at 25% (14, 15).
The highest prevalence rates of postpartum thyroiditis are found in
women with a prior history of postpartum thyroiditis. Lazarus et
al. (16) found that 69% of women who had a history of postpartum
thyroiditis developed a recurrence with a subsequent pregnancy.
Twenty-five percent of women who were antibody positive in the initial
pregnancy, but euthyroid in the postpartum period, developed postpartum
thyroiditis after the next delivery.
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Associated morbidities
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Women with postpartum thyroiditis develop both short-term and
long-term complications. Although few women require treatment in the
hyperthyroid phase, and in fact many women are not diagnosed until they
develop hypothyroidism, studies have revealed an increase in
palpitations, heat intolerance, and tremulousness during the
hyperthyroid period (3). Classical symptoms of hypothyroidism, as well
as concentration and memory deficits, are present in the hypothyroid
phase of postpartum thyroiditis (5). The final short-term complication
is an increased incidence of postpartum depression. Studies have
indicated a 38–53% incidence of nonpsychotic depression in women
affected with postpartum thyroiditis (4, 5). One study has even found
an increased incidence of postpartum depression in women who were
thyroid autoantibody positive but who did not develop postpartum
thyroiditis (17). Finally, long-term follow of women with postpartum
thyroiditis has revealed an incidence of long term primary
hypothyroidism of approximately 25% (6, 7).
The correlation between thyroid autoantibodies and an increase in
spontaneous abortions is also pertinent to the screening debate. Four
studies have revealed a 2- to 3-fold doubling in the rate of
spontaneous miscarriage in un-selected women who screened positive
for thyroid autoantibodies in the first trimester of pregnancy (8, 9, 10, 11).
In women with recurrent abortion, defined as three or more spontaneous
miscarriages without an intervening live birth, the data has been
mixed. Three of five studies have shown an increased incidence of
thyroid autoantibodies in women with recurrent abortion (18, 19, 20, 21, 22).
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Intervention/prevention
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The impact of levothyroxine therapy on the short- and long-term
complications of postpartum thyroiditis is largely unknown. Beta
blockers during the hyperthyroid phase and levothyroxine therapy in
women who are hypothyroid are effective interventions. However, whether
or not levothyroxine therapy alters the incidence or severity of the
depression associated with postpartum thyroiditis has not been
evaluated.
Studies attempting to prevent the occurrence of postpartum thyroiditis
through the administration of iodide or levothyroxine in antibody
positive women have been unsuccessful (23). Furthermore, at present
there are no known interventions which, administered during the
hyperthyroid or hypothyroid phase, would result in a decrease in the
high rate of permanent hypothyroidism.
A recent study has demonstrated a decrease in the rate of recurrent
abortion in women who were thyroid antibody positive through the
administration of intravenous immunoglobulin before conception and
throughout the first 8 months of pregnancy (24). Replication of these
results are required before their implementation outside of a research
setting.
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Screening
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A successful screening strategy for postpartum thyroiditis depends
on the availability of an accurate test. As defined in the Guide
to Clinical Preventive Services, accuracy relates to the
sensitivity, specificity, and reliability of a screening test. In
short, "The test must be able to detect the target condition earlier
than without screening and with sufficient accuracy to avoid producing
large numbers of false-positive and false-negative results..."
(25).
Thyroid peroxidase antibody is the potential screening test of choice
for postpartum thyroiditis. It is widely available, easily
reproducible, and relatively cheap. Screening for thyroid peroxidase
antibodies would need to occur early in pregnancy in order to identify
women who were going to develop postpartum thyroiditis before its
manifestation. Given the dramatic and well documented decrease (often
to undetectable levels) in thyroid antibodies during pregnancy,
screening at delivery would miss a large percentage of the cases and
consequently would have an unacceptably high false negative rate.
Five studies have prospectively followed a cohort of antibody positive
and antibody negative women during pregnancy and into the postpartum
(1, 13, 26, 27, 28). The positive predictive value of thyroid peroxidase
(defined as the percentage of women who have thyroid antibodies during
pregnancy and who subsequently develop postpartum thyroiditis) was
relatively low and ranged from 30–52%. Furthermore, 9–39% of the
women who developed postpartum thyroiditis in these studies were
antibody negative during pregnancy. The positive predictive value of
thyroid peroxidase could be increased by focusing on women with high
titers of thyroid peroxidase, but this would result in an increased
false negative rate.
The positive predictive value of thyroid peroxidase in women with Type
I diabetes mellitus was also limited, ranging from 33–67% (14, 15, 29). Similarly, 17–57% of women with Type I diabetes who developed
postpartum thyroiditis, tested negative for thyroid peroxidase
antibodies during pregnancy.
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Conclusion
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Despite the high prevalence of postpartum thyroiditis in the
general population, screening of all women cannot be justified at
present. The limited positive predictive value of thyroid peroxidase
antibodies, the presence of a substantial number of antibody negative
women who develop postpartum thyroiditis, and the unproven efficacy of
levothyroxine in preventing postpartum depression or long-term primary
hypothyroidism, makes screening all pregnant women untenable.
Furthermore, the conflicting data on the association of thyroid
antibodies and recurrent abortion (despite the clear association
between thyroid antibodies and spontaneous miscarriage in unselected
women) requires further elucidation before it could be used as a
rationale for screening.
Two specific populations however, would clearly benefit from testing
for postpartum thyroiditis. Specifically, women with a prior history of
postpartum thyroiditis (prevalence of recurrent thyroiditis—69%) and
individuals with Type I diabetes mellitus (prevalence of postpartum
thyroiditis—25%) should have TSH determinations at 3 and 6 months
postpartum. In these select groups screening with thyroid peroxidase
antibodies offers no advantages. Women who exhibit either suppressed or
elevated TSH levels would require further evaluation. Whether or not
women with a history of another autoimmune disorder (such as systemic
lupus erythematosus or Sjogren’s disease), or who have a strong family
history of autoimmune disease, should be screened is at present an
unresolved question.
Research in the future should focus on refining screening strategies
for postpartum thyroiditis and determining the efficacy of
levothyroxine in preventing or ameliorating postpartum depression and
primary hypothyroidism. In the interim, a dedicated effort to educate
obstetricians, internists, pediatricians, family practitioners, and
psychiatrists is needed so that the acute symptoms associated with the
hyperthyroid and hypothyroid phase can be recognized, diagnosed, and
appropriately treated.
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Top
Introduction
Prevalence
