The natural history of Hashimoto's thyroiditis is highly variable. The clinical presentation can vary from the presence of thyroid antibodies persisting for many years (the slow form) to the rapid onset of thyroid destruction and permanent hypothyroidism (the fast form). Similarly, the disease may present with a goiter (classical Hashimoto's thyroiditis) or with thyroid atrophy (still often referred to as primary myxedema). This variability in the clinical phenotype has made the disease difficult to study and, to date, no genetic correlation or environmental relationships exist with these different natural histories. We do know that over 20 or more years, patients who show early thyroid failure by small increases in their serum TSH levels, when accompanied by thyroid antibodies (the slow form), progress to overt disease at a rate of 3%–5% per year (28
). This type of analysis ignores those patients presenting with the fast form of the disease. One well-recognized acute precipitator of the fast form is postpregnancy. While often termed PPT, the disease appears to be identical to a transient form of Hashimoto's thyroiditis, and can be predicted by the presence of thyroid antibodies before pregnancy and is considered secondary to an exacerbated autoimmune response following the loss of placenta-induced immune suppression (7
). Nevertheless, PPT may not always be transient and can also appear as a slow or fast evolution of permanent thyroid failure. Recent studies have showed significantly higher serum TSH levels 12 months postpartum in thyroid-antibody-positive women than in thyroid-antibody-negative women, reflecting pregnancy-related thyroid damage (30
). In fact, long-term follow-up of transient PPT patients indicates that at least 30% develop more classical Hashimoto's thyroiditis with time (31
). The present data from the control women indicate that the natural evolution of the slow form of Hashimoto's thyroiditis is a very gradual tendency to progressive thyroid function failure. Our data indicated that the pace of this impairment was ~3.5% of thyroid function loss every year, as manifested by the increase in levothyroxine requirements, but we had no way to precisely predict the total exhaustion of the thyroid gland reserve without dynamic testing studies being applied in the form of TSH stimulation.
As discussed earlier, autoimmune thyroid disease in the form of Graves' disease is known to ameliorate during pregnancy secondary to the onset of placenta-induced immunosuppression. Because of decreases in serum thyroid antibody levels during pregnancy, this logic has also been assumed to be relevant to Hashimoto's thyroiditis. Yet, the data to support this conclusion have been absent. The many causes of an increased need for thyroid hormones in pregnancy have precluded any easy analysis of a change in need secondary to improvement or worsening of the destructive thyroiditis characteristic of Hashimoto's thyroiditis. Women who already take levothyroxine before pregnancy may need to increase their daily dose by, on average, 30%–50% above their preconception amount, but not all patients have this need (21
). Several reasons have been promulgated to explain the incremental thyroid hormone requirements, including the rapid rise in levels of T4 binding globulin secondary to estrogen-induced changes in its glycosylation, the increased distribution volume of thyroid hormones in the vascular, hepatic, and fetal-placental units, the enhanced renal clearance of iodine, and the increased placental transport and metabolism of maternal levothyroxine (23
). None of this excludes autoimmunity itself as a factor contributing to the maternal levothyroxine increase. All we can conclude at this stage is that the natural pace of levothyroxine requirements in women with Hashimoto's thyroiditis was dramatically increased from the control value of 3.5% to >15% under the influence of the physiological changes induced by pregnancy. Our data, however, revealed longer term changes in the requirement for levothyroxine supplementation during the postpartum when compared with prepregnancy dosing, indicating that, at least in the postpartum period, there had been a highly significant exacerbation of Hashimoto's thyroiditis resulting in a fall in thyroid reserve. While all such studies have their limitations, including their retrospective nature, these were unlikely to have influenced this conclusion.
In keeping with these results, Caixàs et al
) showed that a high proportion of pregnant hypothyroid women change their levothyroxine requirements at some point during the follow-up after delivery. This occurred in ~60% of women with autoimmune hypothyroidism compared to ~20% of women who had received thyroid ablation, and we found that ~30% of women still had thyroid dysfunction at the 9 month visit after delivery. The suggestion that postpartum exacerbation of autoimmune thyroiditis may still occur in Hashimoto's patients (21
) seems highly plausible, but manifestations of PPT may be easily masked in those patients who are already taking replacement medication. However, the question of the status of Hashimoto's thyroiditis during pregnancy itself remains unresolved. The different patterns of levothyroxine requirements revealed by this study strongly suggest that Hashimoto's thyroiditis may deteriorate during pregnancy itself in a subset of women, but we did not have a control group of women with total thyroid ablation to allow us to draw our own comparison of levothyroxine needs in pregnancy and be able to deduce the impact of the immune changes rather than the normal physiological regulation of thyroid hormone requirements.
Nevertheless, we speculate that glands from women with enough reserve will be able to cope with the demands of pregnancy (giving pattern 1 requirements), whereas those with deficient thyroids will need a continuous increase in external hormone supplementation (pattern 2). There are no diagnostic tools for the beginning of the pregnancy that are currently able to discriminate women that will follow each pattern, although those women who are fully replaced (>1.2
μg/Kg) may be more likely to follow pattern 2, adding to the findings of Loh et al
) that the magnitude of the replacement depends not just on the etiology of the thyroid failure but also on the degree of failure even within a single cause.
Whereas the common recommendation in clinical practice is to reduce the levothyroxine supplementation dose after delivery in patients with Hashimoto's thyroiditis to the pregestational dose (22
), we and others (21
) have found no support for this routine practice. To come to such a conclusion, postpartum follow-up needs to be lengthy and is often absent in such studies. The best practice scenario remains the careful monitoring of serum TSH levels in the postpartum and the adjustment of levothyroxine replacement according to individual results.
In conclusion, we found that pregnancy induced a postpartum increase of an average 21% in levothyroxine requirements in a subset of pregnant women with Hashimoto's thyroiditis and this effect was mostly manifested in the first 3 months after delivery. These data suggested that clinically significant numbers of women with Hashimoto's thyroiditis have exacerbation of their hypothyroidism after childbirth compared to nulliparous women. In addition, a pattern of gradual increases in levothyroxine supplementation during pregnancy predicted this exacerbation most likely secondary to a further loss of thyroid reserve.