A 28-year-old woman, gravida 2 para 0 aborta 2, comes to the office following a miscarriage. She had a previous first-trimester miscarriage 9 months ago. The patient has no other known medical problems. She has not experienced any recent change in appetite or weight, diarrhea, constipation, heat or cold intolerance, dyspnea, or hoarseness. The patient's mother has hypothyroidism treated with levothyroxine and hypertension treated with hydrochlorothiazide. The patient does not use tobacco or alcohol. Examination shows a symmetrically enlarged, nontender, firm thyroid gland. There is no cervical lymphadenopathy, and the rest of the physical examination is normal. Her TSH level is 7.2 μU/mL and free T4 is normal. Pelvic ultrasonography is normal. Which of the following autoantibodies is most likely associated with this patient's medical condition?
Causes of recurrent pregnancy loss | |
Structural |
|
Chromosomal |
|
Immunologic/ |
|
Endocrine |
|
Other |
|
This patient has subclinical hypothyroidism (normal thyroxine level with a mild elevation in TSH) and a symmetrically enlarged nontender thyroid, consistent with chronic lymphocytic (Hashimoto) thyroiditis. Antithyroid peroxidase (anti-TPO) and antithyroglobulin antibodies are present in >90% of patients with Hashimoto thyroiditis, and high titers of anti-TPO antibodies are associated with an increased risk of progression from subclinical to overt hypothyroidism. High titers of anti-TPO are also associated with increased risk of miscarriage in both euthyroid and hypothyroid women (possibly due to disruptions in thyroid metabolism, to which the body is particularly sensitive in pregnancy).
Treatment with levothyroxine is recommended in patients with subclinical hypothyroidism who have elevated anti-TPO antibodies even if they do not have symptoms. Treatment likely reduces the risk of future miscarriage. The titers of anti-TPO antibodies are often highest early in the course of Hashimoto thyroiditis but decrease with time and thyroid hormone treatment.
(Choice A) The risk of recurrent pregnancy loss is also increased in patients with antiphospholipid antibody syndrome (APS). Anticardiolipin antibodies and lupus anticoagulant are typically checked in women with recurrent pregnancy loss. However, APS is not associated with thyroid dysfunction or goiter.
(Choice B) Antimitochondrial antibodies are present in primary biliary cholangitis, which characteristically presents with fatigue and pruritus associated with elevated alkaline phosphatase levels, and may progress to cirrhosis.
(Choice D) Thyroid-stimulating immunoglobulins (TSIs) are present in patients with Graves disease. TSIs stimulate TSH receptors on the thyroid follicular cells, resulting in thyroid hormone overproduction rather than hypothyroidism.
(Choice E) Antibodies against TSH receptors can block the interaction of TSH with its receptors on thyroid follicular cells and are a less common cause of hypothyroidism. Hypothyroid individuals with TSH-blocking antibodies would have thyroid atrophy rather than enlargement. Anti-TPO antibodies are more likely associated with miscarriage.
Educational objective:
Antithyroid peroxidase (anti-TPO) antibodies are present in >90% of patients with Hashimoto thyroiditis, and high titers of anti-TPO are associated with an increased risk of progression to overt hypothyroidism. High titers of anti-TPO are also associated with increased risk of miscarriage in both euthyroid and hypothyroid women.