Screening for Postpartum Thyroid Dysfunction in the General Population Is Beneficial

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 (2–14). 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? 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 20–23 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. The prevalence of antithyroid MCAb and the occurrence of postpartum thyroid dysfunction among pregnant women in the general population. The prevalence of antithyroid MCAb and the occurrence of postpartum thyroid dysfunction among pregnant women in the general population. 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 2shows 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 4–8 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. 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. 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. 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, 21–23) 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 20–39 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). 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 mother’s 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). The benefit of screening for postpartum thyroid dysfunction mainly concerns elusive, nonquantitative parameters—the quality of life of mothers—that can be difficult to assess. However, we would hope to find an acceptable, cost-effective system of screening for postpartum thyroid dysfunction.