Abstract
Case History
A 30-year-old woman comes to your office complaining of irritability, depressed mood, insomnia, fatigue, and occasional palpitations for the past 3 weeks. Her first child was born 3 months ago, at 39 weeks of gestation. Pregnancy and delivery were uneventful. He is a healthy baby who is exclusively breastfed. On physical examination, her heart rate is 92 bpm and blood pressure is normal. Thyroid examination shows a small soft gland that is nontender and without nodules. Past medical history is significant for allergic rhinosinusitis and a history of positive serum thyroid peroxidase antibody (TPOAb). Thyroid function before and during pregnancy was normal.
Laboratory examination shows a thyroid-stimulating hormone (TSH) of 0.01 μU/mL (normal range 0.27–4.2), total T4 of 16 μg/dL, total T3 of 2.1 ng/mL (0.8–2.0), free T4 of 2.6 ng/dL (0.8–1.7), and free T3 of 5.2 ng/mL (0.8–2.0).
What would you recommend to this patient?
(A) Start therapy with an antithyroid drug for treatment of Graves' disease.
(B) Perform a radioiodine uptake test as soon as possible to determine the cause of the thyrotoxicosis.
(C) Measure thyroid antibodies (TPO and TRAb).
(D) Prescribe an anti-inflammatory drug as you suspect subacute thyroiditis.
(E) She has likely developed postpartum depression and an appropriate antidepressant should be started.
Postpartum thyrotoxicosis
The patient described earlier has clinical and laboratory features of thyrotoxicosis. In the general population the incidence of hyperthyroidism is 1% and the most common etiology is Graves' disease. However, this patient is 3 months postpartum, and during this period the most common etiology of thyrotoxicosis is postpartum thyroiditis (PPT), with an incidence of 4%–7% as compared with Graves' disease with an incidence of 0.2% during this period. 1 PPT is an autoimmune thyroid disease that occurs during the first postpartum year in women who were euthyroid before the pregnancy, and with Graves' disease excluded. 1,2
A study performed in Japan of 42 patients who developed thyrotoxicosis within the first year after pregnancy showed that 86% of patients who developed disease within the first 3 months after delivery had thyroiditis. All who developed thyrotoxicosis 6 months after delivery had Graves' disease. 3
Serum positivity for thyroid autoantibodies (TPOAb or antithyroglobulin antibodies [TgAb]) during the first trimester of pregnancy is considered a major risk factor for the development of PPT. Other risk factors include the presence of other autoimmune disorders such as systemic lupus erythematosus, chronic viral hepatitis, and type 1 diabetes. 4,5 Women who fully recover from PPT have a 70% chance of recurrence with a subsequent pregnancy. 6
The development of PPT results from rebound of the immune system in the postpartum period after the relative immune suppression of pregnancy. To suppress an intrauterine immune response against the fetus, the maternal immune system undergoes several adjustments. This is carried out by regulatory CD4+ CD25+ T cells that rapidly increase during pregnancy peaking in the second trimester. These cells significantly suppress cellular and humoral immunity against paternal/fetal alloantigens. This physiological state of lowered immune responsiveness in pregnancy results in amelioration of some pre-existing autoimmune disorders, including thyroid autoimmune disease. After delivery, the regulatory cell response declines, triggering a rebound of the immune system. 7
Clinical Picture of PPT
The classic form of this disease presents as a transient period of thyrotoxicosis that usually occurs during the first 2–6 postpartum months and persists for 1–2 months. This is followed by the hypothyroid phase that usually occurs during 3–12 postpartum months and lasts for 4–6 months before euthyroidism is restored. However, this classic presentation is seen only in one-fourth of the patients. About half the women initially present with isolated hypothyroidism and one quarter with transient thyrotoxicosis. It should be noted, however, that 10%–20% of patients the hypothyroid phase will result in permanent hypothyroidism. 2
PPT is a painless condition and most women are asymptomatic or only mildly symptomatic during the thyrotoxic phase, with reported symptoms that overlap with depressive symptoms, including insomnia, irritability, fatigue, mood changes, and palpitations. 8 It is, therefore, important to rule out thyroid dysfunction when postpartum depression is suspected.
Laboratory testing in the thyrotoxic phase of PPT shows a low TSH and high levels of T3 and T4, with a serum T3:T4 ratio of usually <20 ng/μg, that reflects the destructive nature of this disease caused by leakage of preformed thyroid hormone from the inflamed thyroid gland. 6 For this reason antithyroid drugs that inhibit thyroid hormone synthesis will be ineffective and should not be used as excess thyroid hormone synthesis does not occur. The thyrotoxic phase of PPT must be differentiated from Graves' disease. Antibody testing can be helpful in distinguishing between these two diseases and maybe the most helpful test in distinguishing these in the breast feeding woman as radioiodine uptake testing would be contraindicated. TPOAb are positive in the majority of women with PPT, and the TSH receptor stimulating antibodies (TRAb) are positive in 95% of Graves' disease and negative in PPT. 1,6 Normally, the definitive diagnosis of thyroiditis would be made with radioactive iodine scanning to demonstrate low update of iodine in the thyrotoxic state. However, radioactive iodine concentrates in breast milk and has a half-life of 8 days, so radioiodine uptake is contraindicated n breastfeeding women.
A small randomized double-blind placebo-controlled study evaluated the effect of
Although 80% of women will recover normal thyroid function within a year, up to 50% will develop chronic hypothyroidism in the following 3–10 years. Therefore, it is important to monitor TSH levels annually in patients with prior history or PPT.
Answer: C
The most likely scenario is that the patient is currently in the thyrotoxic phase of PPT. She is 3 months postpartum and symptoms are mild. It is important to exclude the possibility of Graves' disease by measuring TRAb. If negative, this makes the diagnosis of Graves's disease less likely. The presence of thyroid antibodies, TPOAb and/or TgAb, will also confirm the diagnosis of PPT. During the thyrotoxic phase of PPT, women with symptoms can be successfully treated with a beta blocker. Both propranolol and metoprolol are safe to use in lactating women. Treatment should be used for the shortest time needed to manage symptoms. As discussed previously, there is no role for antithyroid drugs in this condition.