Postpartum Thyroiditis

Etiology

Postpartum thyroiditis is an autoimmune disease and associated with the presence of antibodies to thyroid peroxidase (TPO). Postpartum thyroiditis also is known as destructive thyroiditis with lymphocytic infiltration within the thyroid gland. Histological features of postpartum thyroiditis are similar to Hashimoto thyroiditis, and both are associated with HLA-D and HLA-B haplotypes. These findings indicate the importance of inherited risk factors.[4][5]

The presence of TPO antibodies is seen in other autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis. The level of TPO antibodies reflects the severity of the infiltration of lymphocytes within the thyroid gland. TPO antibodies are complement-fixing, which subsequently induce antibody-dependent cell-mediated cytotoxicity.[3]

Epidemiology

Prevalence and frequency of postpartum thyroiditis (PPT) are 8% and 1.1% to 16.7% of pregnancies, respectively. Different rates have been reported worldwide. Multiple factors are affecting the rates such as length of follow up in the postpartum period, iodine status of studied populations. In Thailand, the reported rate is 1.1%, whereas the incidence rate in Brazil is reported at 13.3%. Both of these regions have low iodine intake. Prevalence of postpartum thyroiditis in the high-risk group, including diabetes mellitus type 1 and positive family history, reported 19.1% and 20.0%, respectively. The recurrence risk of postpartum thyroiditis in a patient with the previous history of PPT is reported at 42.4%.[6][7]

Pathophysiology

The inflammatory process in postpartum thyroiditis initiates with the presence of thyroid antibodies (TPOAb and TgAb), activation of the complement cascade, increased levels of IgG1, lymphocyte abnormalities, increased activity of NK cells, and specific HLA haplotypes. The inflammatory process activates the proteolysis of the thyroglobulin within the thyroid follicles. The result is the destruction of the thyroid follicles and releasing significant amounts of thyroxine (T4) and triiodothyronine (T3) into the blood and subsequently hyperthyroid state. This hyperthyroid state is transient and lasts until all thyroglobulin storages released into circulation and no more thyroglobulin left within the follicles. During the hyperthyroid state, the synthesis of new hormones becomes shutdown because excessive T4/T3 in circulation causes downregulation of TSH secretion. Synthesis of thyroid hormones will be resumed once all inflammatory process subsides.

Histopathology

Histopathologic examination of the thyroid gland in cases with postpartum thyroiditis reveals prominent infiltration of lymphocyte, including associated germinal centers, and the collapse of thyroid follicles. Fine-needle aspiration of the thyroid gland shows thyroid follicular cells, lymphocytes, and accumulation of colloid. During the recovery phase, follicles are more normal, but some degree of fibrosis and lymphocytic infiltration could be seen.

History and Physical

Postpartum thyroiditis is a painless condition. Most of the patients with postpartum thyroiditis are symptom-free or showing mild symptoms during thyrotoxic state, including irritability, palpitation, fatigue, and heat intolerance. The hypothyroid state of postpartum thyroiditis is mostly symptomatic, including constipation, dry skin, fatigue, impaired concentration, cold intolerance, and paresthesia. A study reported that patients with postpartum thyroiditis and positive TPO antibodies were more symptomatic than patients who had negative TPO antibodies.[8]

Evaluation

The diagnosis of postpartum thyroiditis depends on clinical presentation and thyroid function tests (level of TSH and free T4). Patients with postpartum thyroiditis have similar biochemical findings that can be detected in the patients with painless thyroiditis: high or upper limit of normal serum free T4 and T3 levels and low serum TSH level in the hyperthyroid phase, which could be subclinical or overt. In patients with hyperthyroid state followed by hypothyroid state, serum T4 level could be low for days to weeks before serum TSH level rises beyond the normal range, as a result of prolonged suppressed TSH which had occurred in the hyperthyroid state. Serum levels of anti-thyroid peroxidase antibody are high in 60 to 85 percent of patients with postpartum thyroiditis and are highest in the hypothyroid state or soon thereafter. Some of the patients may have a slight increase in C-reactive protein and/or erythrocyte sedimentation rate.[9][10][11] Clinicians in charge of women after pregnancy have to be aware of the possible postpartum thyroid dysfunction, which can result in different symptoms during the postpartum period.

Treatment / Management

A prospective study that evaluated 605 asymptomatic pregnant women and women in the postpartum period showed that none of the cases with thyrotoxicosis and 40% of cases with hypothyroid state needed treatment. If treatment is necessitated, it could usually be tapered over one year. Several studies have shown that long-term treatment would be required in up to 20% of cases with postpartum thyroiditis. There have not been any prospective studies to evaluate when and how to treat postpartum thyroiditis. Management of the thyrotoxic state is guided by its transitory nature. Anti-thyroid medications (methimazole and propylthiouracil) have been ineffective in the treatment of the thyrotoxic state of postpartum thyroiditis as it is destructive thyroiditis in which there is no increase in the synthesis of thyroid hormones. Symptoms are usually mild. In a few cases with clinically significant symptoms, a low dose of propranolol may be helpful. The thyrotoxic state of postpartum thyroiditis should be differentiated from Graves disease. When thyrotoxic state of postpartum thyroiditis resolved, the serum TSH level should be measured in about four to eight weeks (or in case of development of new symptoms) in order to screen for the hypothyroid state. In cases who develop significant symptoms, and currently lactating or cases who want to get pregnant, treatment should be initiated. Treatment with levothyroxine (LT4) 4 should be considered in the hypothyroid state of postpartum thyroiditis if the patient has mild symptoms, or advice if the patient wants to get pregnant again. If treatment is delayed, thyroid function must be evaluated every four to eight weeks until the patient gets euthyroid. In addition, women must be counseled to have contraception. The duration that the patient should continue to take LT4 has not been evaluated. Based on the guidelines, the euthyroid state should be maintained in cases who are pregnant or wants to get pregnant. To assess if the hypothyroid state of postpartum thyroiditis is permanent or transient, LT4 doses can be tapered starting 12 months after delivery. The dose should be tapered gradually, and serum TSH level must be monitored every six to eight weeks.[8]

Differential Diagnosis

• Graves disease
• Hashimoto thyroiditis 
• Postpartum mood disorder 

Prognosis

As discussed above the clinical course of postpartum thyroiditis is variable. Only 30% of cases with postpartum thyroiditis will remain in hypothyroid state one year postpartum.[12]

Complications

Thyroid function in most of the cases with postpartum thyroiditis returns to a normal state within 12 to 18 months of the onset of the symptoms. However, some cases do not recover from the hypothyroid phase, and they will develop permanent hypothyroidism.