Screening for Postpartum Thyroid Dysfunction in the General Population Is Beneficial
Nobuyuki Amino,
Hisato Tada and
Yoh Hidaka
Department of Laboratory Medicine, Osaka University Medical School, Osaka
565-0871, Japan
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Introduction
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POSTPARTUM thyroid dysfunction is recognized as a common disease
among postpartum women (1), with a prevalence rate of around 5%,
i.e. 1 in 20 pregnant women suffers from thyroid dysfunction
after parturition (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14). To discuss whether screening for postpartum
thyroid dysfunction is beneficial, we shall examine the following
questions:
- Are there any effective tests or protocols to screen
postpartum thyroid dysfunction?
- What is the benefit of the screening for postpartum thyroid
dysfunction?
- Does the effectiveness meet the costs?
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There are effective protocols to screen postpartum thyroid
dysfunction
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Postpartum autoimmune thyroid dysfunction is briefly
characterized as a postpartum exacerbation of subclinical autoimmune
thyroid disease, wherein some immunological abnormalities are observed
before the onset of thyroid dysfunction. Therefore, we can detect the
high-risk group for postpartum thyroid dysfunction by screening, in
early pregnancy, those with subclinical autoimmune thyroiditis. Among
several methods for detecting thyroid autoimmunities, the measurement
of anti-thyroid microsomal antibody (MCAb) or thyroid peroxidase (TPO)
antibody is the most useful marker for detecting subclinical autoimmune
thyroiditis and, therefore, for predicting the occurrence of postpartum
thyroid dysfunction. When MCAb is positive, there is always lymphocytic
infiltration into the thyroid, indicating subclinical autoimmune
thyroiditis (15) that may be exacerbated after delivery. Sixty to
seventy percent of women with positive MCAb in early pregnancy develop
postpartum thyroid dysfunction (1). Other investigators have also
reported that MCAb-positive subjects had approximately 2023 times the
relative risk (over normal subjects) for developing postpartum thyroid
dysfunction (16, 17). On the other hand, the prevalence of postpartum
thyroid dysfunction in the MCAb-negative subjects in early pregnancy is
estimated as 1/100 of that in MCAb-positive subjects (Fig. 1
).So, when we screen 1000 early pregnant women in the general population,
we can expect to find about 50 patients with postpartum thyroid
dysfunction.

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Figure 1. The prevalence of antithyroid MCAb and the occurrence of postpartum thyroid dysfunction among pregnant women in the general population.
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Although MCAb is a good marker for the occurrence of postpartum
thyroid dysfunction, it gives no information about the type of
dysfunction that will occur. Among the various types of dysfunctions,
postpartum Graves disease is clinically the most important and is
predicted by the measurement of thyroid-stimulating antibodies (TSAb)
with a sensitive bioassay (18). Our subsequent study (19) revealed that
pregnant women with positive TSAb in early pregnancy had a much higher
risk of developing postpartum Graves disease. We observed 71 pregnant
women with positive MCAb from early pregnancy through the postpartum
period. Among them, 7 showed positive TSAb, and 5 of those 7 (71%)
developed postpartum Graves disease. Thyrotoxicosis in 3 of those 5
was transient and spontaneously improved within a year. Graves
disease did not occur in the TSAb-negative subjects. Anti-TSH receptor
(TSHR) antibodies (TRAb) with conventional radio-receptor assay
(thyrotropin binding inhibitory immunoglobulin; TBII) were not
useful in predicting postpartum Graves disease.
Figure 2s
hows a protocol that we have tentatively employed to screen for
postpartum thyroid dysfunction at the outpatient maternity clinic of
the Osaka University Hospital for several years. In the protocol,
MCAb-positive mothers are examined for thyroid status, measuring serum
free thyroxine (FT4), serum free triiodothyronine (FT3), serum
thyrotropin (TSH), anti-TSHR antibody (TRAb), and antithyroglobulin
(TgAb), and are observed every 48 weeks. We believe that this
close observation protocol for MCAb-positive subjects is practical in
only a few countries, such as Japan, where the national health
insurance system is well-established. It should be modified according
to the situation and health system of each country.

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Figure 2. A protocol to screen and follow MCAb-positive mothers. MCAb, antithyroid microsomal antibody; FT4, free thyroxine; FT3, free triiodothyronine; TSH, thyrotropin; TRAb, anti-TSH receptor antibody.
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The benefits of screening postpartum thyroid dysfunction
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Although postpartum thyroid dysfunction may be transient in many
cases (20), we should pay close attention to the possibility that
mothers with thyroid dysfunction already tired from the birth and from
taking care of a newborn, may feel terribly worn out and helpless or
may become ill in bed. Postpartum depression, which in severe cases may
result in a forced double suicide of mother and baby (called
"Shinjuh" in Japanese), can be screened by MCAb measurement,
although postpartum depression may occur not in association with
thyroid dysfunction (17, 21, 22, 23) but with antithyroid MCAb (24, 25).
The main benefit of screening for postpartum thyroid dysfunction is the
opportunity to improve the quality of life of mothers who may suffer
from the above symptoms. Even when the patient does not want drug
therapy, she benefits by being informed about what is happening to her.
From our experience, patients with mild to moderate thyroid dysfunction
can live well with the support of family without medication. Further,
prevention of future episodes of postpartum thyroid dysfunction may be
possible. We have experienced one case of successful prevention. The
patient had developed severe postpartum thyroid dysfunction in each of
her previous parturitions, and she did not want to repeat the condition
after the next delivery. Moderate doses of glucocorticoid,
gradually decreased and stopped in one month, suppressed her thyroid
dysfunction to only a small fluctuation within the normal range.
Postpartum Graves disease accounts for 11.4% of postpartum thyroid
dysfunctions (occurring in 0.54% of all mothers in the general
population) (19). Conversely, 40% of Graves patients 2039 yr old,
who have had one or more deliveries, developed their disease during the
postpartum period (26). Diagnosis of postpartum Graves disease early,
while it is mild, may easily lead to remission and may reduce Graves
disease in older age. In our experience, the early start of antithyroid
therapy reduces the period of therapy by half (19). Antithyroid therapy
may be a good choice for first-line therapy (27) because postpartum
Graves hyperthyroidism is often transient and because mothers may not
want to interrupt breast-feeding to undergo radioiodine therapy.
An additional benefit to screening with anti-MCAb antibodies in early
pregnancy may be not only to find postpartum thyroid dysfunction, but
also to find mothers at high risk for spontaneous abortion. In
our prospective study, the spontaneous abortion rate in MCAb-positive
mothers was twice as high as that in MCAb-negative mothers (28).
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There has been no analysis of the cost-effectiveness of screening
for postpartum thyroid dysfunction
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The cost of MCAb measurement to screen for the occurrence of
postpartum thyroid dysfunction is low when we use semiquantitative
particle agglutination tests. However, thyroid function tests and
anti-TSHR antibody measurement for MCAb-positive subjects are not
cheap, especially when patients are observed closely and are tested
repeatedly. On the other hand, the main benefit of screening for
postpartum thyroid dysfunction is improving the mothers quality of
life, which is difficult to numerically assess. Heyslip et
al. (29) tried to estimate the costs of several screening methods
and concluded that MCAb measurement is the most cost-effective, but
their report compares only the screening methods for postpartum thyroid
dysfunction; they did not analyze the benefit of mothers quality of
life, nor did they discuss cost-effectiveness compared with the
screening for other diseases or other health services. Indeed, there
seems no analysis of the cost-effectiveness of screening for postpartum
thyroid dysfunction (23, 30). However, the observation protocol we
describe can be modified to be less expensive, and screening subjects
may be restricted to certain high-risk groups, such as the patients
with IDDM. We believe an optimized system of screening will be found
whose costs are acceptable for each society.
We experimentally applied TSAb to the second-line screening of
MCAb-positive mothers and found that TSAb gives predictive information
on potential development of postpartum Graves disease. TSAb
measurement is obviously too expensive, and the procedure is too
complicated to apply screening to the general population. However, we
expect the development of a more sensitive radioreceptor assay may
change the situation (31).
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Conclusion
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The benefit of screening for postpartum thyroid dysfunction mainly
concerns elusive, nonquantitative parametersthe quality of life of
mothersthat can be difficult to assess. However, we would hope to
find an acceptable, cost-effective system of screening for postpartum
thyroid dysfunction.
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Footnotes
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Address correspondence and requests for reprints to: Alex
Stagnaro-Green, MD, Dean for Student Affairs and Medical Education,
Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1255,
New York, New York 10029-6574.
Accepted March 8, 1999.
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