Postpartum thyroiditis (PPT) is a destructive autoimmune disease occurring in the first year after delivery in women without a history of thyroid disease prior to pregnancy. Postpartum thyroiditis could cause transient or permanent thyroid disease. Three clinical presentations have been suggested for postpartum thyroiditis are as follows: (1) transient hyperthyroidism (32% of patients), (2) transient hypothyroidism (43% of patients), and (3) transient hyperthyroidism followed by hypothyroidism and then recovery, which is the classic form of PPT (25% of patients). Postpartum thyroiditis is an autoimmune disease and associated with the presence of antibodies to thyroid peroxidase (TPO). Chances of developing postpartum thyroiditis in pregnant women who have positive TPO antibodies early in pregnancy are 30% to 52%. Postpartum thyroiditis could occur after the loss of a pregnancy at 5 to 20 weeks gestation. During pregnancy level of TPO antibodies naturally decreases due to the immunosuppressed state of pregnancy. Women who remain positive for TPO antibodies in the third trimesters of pregnancy will have an 80% chance of developing postpartum thyroiditis. Screening of high-risk women for developing postpartum thyroiditis, such as a positive test for antithyroid peroxidase antibody, history of postpartum thyroiditis, type 1 diabetes mellitus, is recommended by Endocrine Society clinical guidelines. High-risk women should be evaluated for serum TSH levels at three and six months postpartum.
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.
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.
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%.
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.
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.
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.
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. 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.
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.
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.
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.
Endocrinology should be consulted if there is any question as to the diagnosis or other issues.
Postpartum thyroiditis is not a preventable disease. Patients, especially those who are high risk for developing postpartum thyroiditis (as discussed above), should counsel with the primary care physician or obstetrician if they have symptoms and do not assume that the symptoms are related to the stress of caring for a newborn.
All clinicians should be aware of postpartum thyroiditis as it is common, and symptoms usually do not develop at the six-week postpartum visit. Screening of high-risk women for developing postpartum thyroiditis such as a positive test for antithyroid peroxidase antibody, history of postpartum thyroiditis, type 1 diabetes mellitus is recommended by Endocrine Society clinical guidelines. High-risk women should be evaluated for serum TSH levels at three and six months postpartum.  If TSH level is not normal, TFTs should be repeated in one to two weeks (check T3 level if TSH is low). Postpartum thyroiditis screening for all pregnant women is not recommended, as there is not enough evidence to support this.
|||Muller AF,Drexhage HA,Berghout A, Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocrine reviews. 2001 Oct; [PubMed PMID: 11588143]|
|||De Groot L,Abalovich M,Alexander EK,Amino N,Barbour L,Cobin RH,Eastman CJ,Lazarus JH,Luton D,Mandel SJ,Mestman J,Rovet J,Sullivan S, Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2012 Aug; [PubMed PMID: 22869843]|
|||Prummel MF,Wiersinga WM, Thyroid peroxidase autoantibodies in euthyroid subjects. Best practice [PubMed PMID: 15826919]|
|||LiVolsi VA, Postpartum thyroiditis. The pathology slowly unravels. American journal of clinical pathology. 1993 Sep; [PubMed PMID: 8379524]|
|||Kologlu M,Fung H,Darke C,Richards CJ,Hall R,McGregor AM, Postpartum thyroid dysfunction and HLA status. European journal of clinical investigation. 1990 Feb; [PubMed PMID: 2108037]|
|||Stagnaro-Green A, Postpartum thyroiditis. Best practice [PubMed PMID: 15157842]|
|||Nicholson WK,Robinson KA,Smallridge RC,Ladenson PW,Powe NR, Prevalence of postpartum thyroid dysfunction: a quantitative review. Thyroid : official journal of the American Thyroid Association. 2006 Jun; [PubMed PMID: 16839259]|
|||Alexander EK,Pearce EN,Brent GA,Brown RS,Chen H,Dosiou C,Grobman WA,Laurberg P,Lazarus JH,Mandel SJ,Peeters RP,Sullivan S, 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid : official journal of the American Thyroid Association. 2017 Mar; [PubMed PMID: 28056690]|
|||Nikolai TF,Turney SL,Roberts RC, Postpartum lymphocytic thyroiditis. Prevalence, clinical course, and long-term follow-up. Archives of internal medicine. 1987 Feb; [PubMed PMID: 3492979]|
|||Lazarus JH,Hall R,Othman S,Parkes AB,Richards CJ,McCulloch B,Harris B, The clinical spectrum of postpartum thyroid disease. QJM : monthly journal of the Association of Physicians. 1996 Jun; [PubMed PMID: 8758046]|
|||Gerstein HC, How common is postpartum thyroiditis? A methodologic overview of the literature. Archives of internal medicine. 1990 Jul; [PubMed PMID: 2196025]|
|||Stagnaro-Green A, Clinical review 152: Postpartum thyroiditis. The Journal of clinical endocrinology and metabolism. 2002 Sep; [PubMed PMID: 12213841]|