A 30-year-old woman comes to the office due to tiredness for the past 3 months. She has been unable to exercise due to excessive fatigue and muscle cramps. The patient has had no cold intolerance, constipation, or dry skin. She states, "My menstrual cycles have been unpredictable and very heavy." Medical history is notable for episodic migraines, for which she began taking topiramate 6 months ago. The patient initially had significant weight loss after starting topiramate, but she has regained most of the weight over the last 2 months and continues to have occasional migraines. She also has a history of chronic anxiety and an episode of nephrolithiasis a few months ago. The patient lives alone, is not sexually active, and has had no pregnancies. She does not use tobacco, alcohol, or illicit drugs. The patient's sister underwent a thyroidectomy for unknown reasons. Blood pressure is 136/80 mm Hg and pulse is 68/min. BMI is 28 kg/m². The thyroid gland is normal in size and nontender. Deep tendon reflexes are normal; the remainder of the examination is unremarkable. Serum TSH is 5.7 µU/mL. Repeat TSH a month later is 5.6 µU/mL, and free T4 is normal. Which of the following additional findings is most likely to be associated with this patient's condition?

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Explanation: Subclinical hypothyroidism is associated with an increased risk for a number of pregnancy complications, including recurrent miscarriages, severe preeclampsia, preterm birth, low birth weight, and placental abruption. In addition, anti-thyroid peroxidase (anti-TPO) antibodies are associated with increased risk for pregnancy loss, even in women who are biochemically euthyroid. Treatment of subclinical hypothyroidism associated with high titers of anti-TPO antibodies may reduce the risk of recurrent miscarriages. (Choice A) Serum calcitonin is a useful marker for medullary thyroid cancer (MTC), which can occur as an isolated disorder or as a component of multiple endocrine neoplasia (MEN) 2A and 2B. MTC usually presents as a palpable nodule, and neither isolated MTC nor MEN 2A or 2B would be associated with subclinical hypothyroidism. (Choice B) The most common cause of hypercalcemia in outpatient settings is primary hyperparathyroidism. Mild hypercalcemia can also be seen in hyperthyroidism due to increased bone turnover. Subclinical hypothyroidism is not associated with hypercalcemia. Although kidney stones are a potential complication of primary hyperparathyroidism, the recent kidney stone in this patient is most likely due to topiramate, which is an inhibitor of renal carbonic anhydrase. (Choice C) Pretibial myxedema (thyroid dermopathy) causes patchy nonpitting edema, typically in the lower legs. It is primarily seen in patients with hyperthyroidism due to Graves disease and is rare among those with other autoimmune thyroid disorders. (Choice E) Enlargement of the tongue is seen in severe, longstanding hypothyroidism. Other causes of tongue enlargement include amyloidosis, acromegaly, mucopolysaccharidosis, and MEN 2B. Educational objective: Subclinical hypothyroidism is associated with an increased risk for a number of pregnancy complications, including recurrent miscarriages, severe preeclampsia, preterm birth, low birth weight, and placental abruption. References: Thyroid autoimmunity and miscarriage: a meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/21198746)

A 30-Year-Old Woman Comes to the Office Due to Tiredness