Painful Thyroiditis and Subsequent Atrophic Hypothyroidism After Cord Blood Transfusion

Dear Editor:

We report the case of a 12-year-old girl who developed severe thyrotoxicosis after an unrelated cord blood transplantation for relapsed acute myelogenous leukemia. On day 43 after the transfusion, she complained of severe neck swelling and redness with pain and high fever of 39 (see Supplementary Data, available online at www.liebertonline.com/thy). Tests showed thyrotoxicosis. Her serum thyrotropin (TSH) was 0.04 μU/mL (normal 0.38–4.31), the free triiodothyronine (fT3) was 8.7 pg/mL (normal 2.1–3.8), and the free thyroxine (fT4) was 4.17 ng/dL (normal 0.82–1.63). Her white blood cell count was 9400/μL (normal 3500–9200), the C-reactive protein was 14.14 mg/dL (normal 0.0–0.3), and the erythrocyte sedimentation rate was 54 mm (normal 2–16). Apart from a slightly elevated thyroid peroxidase antibody level of 0.9 U/mL (normal range <0.3), she was negative for all thyroid autoantibodies.

Based on her clinical manifestations including pain, swelling, and high fever, in addition to laboratory data and computed tomography (CT) and ultrasound images (see Supplementary Data), subacute thyroiditis was deemed to be the most probable diagnosis, despite the lack of any preceding symptoms of viral infection. However, since she was immunocompromised due to recent treatment with FK506, we were also concerned about the possibility of acute suppurative thyroiditis or thyroiditis, as it has been reported after transplantation (1) (i.e., post-transplant thyroiditis). With these two diagnoses in mind, we prescribed antibiotics empirically and also prednisolone, 20 mg per day. The neck pain quickly alleviated after this intervention, and she became afebrile with a decrease in the serum C-reactive protein. Sixty-two days after transfusion, replacement therapy with 25 μg of levothyroxine per day was introduced, because her thyroid hormone levels became significantly low (fT3 1.3 pg/mL and fT4 0.52 ng/dL). On day 84, thyroid CT showed a very low density thyroid (see Supplementary Data), consistent with a reduced pool of iodine (2). About 3 months after transfusion, thyroid function tests showed hypothyroidism in spite of supplementation of 75 μg of levothyroxine (TSH 23.13, fT3 2.50, and fT4 0.87), and the dose was increased up to 100 μg per day. About 4 months after transfusion, ultrasound images revealed an extremely atrophic thyroid (see Supplementary Data).

We retrospectively consider that she had suffered post-transplant thyroiditis, because ultrasound images were incompatible with acute suppurative thyroiditis and as symptoms such as high fever and neck pain did not relapse in spite of the relatively fast tapering of prednisolone therapy. Unusual points are that it occurred very early after transplantation and gave her severe neck pain. It has been reported that thyroiditis after bone marrow transplantation occurs within 6 months in most cases. In the case of cord blood transplantation, however, it has been reported that it occurs during the very early periods after the transplantation (3). The authors discuss the fact that cord blood grafts contain fetal lymphocytes and, therefore, that there may be some similarities between postpartum thyroiditis and thyroiditis after cord blood transplantation. Based on the presence of antithyroglobulin antibodies and concomitant graft versus host disease after the transplantation, we suspected that immune-mediated reactions might underlie the onset of thyroiditis in our patient.

Given the onset of thyroiditis after cord blood transplantation in our patient, similar to postpartum thyroiditis, the accompanying severe pain and enlarged thyroid are unusual. According to previous reports, there have been patients with post-transplant thyroiditis who complained of neck pain (1,4), and subacute thyroiditis was diagnosed in one of them (4). We suspect that the accompanying pain depends on the acute nature and degree of the swelling. In fact, all previous cases with neck pain have been associated with thyroid enlargement. Consistently, CT images revealed thyroid swelling in our current case (see Supplement).

In conclusion, we propose that post-transplant thyroiditis is a distinct clinical entity, sometimes accompanied by pain and, therefore, possibly misdiagnosed as subacute thyroiditis.