A 31-year-old woman comes to the office due to fatigue and cold intolerance. She has also experienced abdominal bloating, and states, "I can't think clearly and I feel like I am always in a fog." The patient has a history of hypothyroidism treated with levothyroxine and has required escalating doses (currently 200 mcg/day) over the last several months as her serum TSH has remained elevated. She has been compliant in taking her levothyroxine every day 1 hour before breakfast and takes no other medications or supplements. The patient had a miscarriage at age 25, and her menstrual periods have been irregular since then. She quit smoking cigarettes 10 years ago, drinks a few beers on most weekends, and does not use recreational drugs.
Blood pressure is 136/92 mm Hg and pulse is 66/min. BMI is 30 kg/m². Examination shows diffuse firm enlargement of the thyroid gland. Cardiopulmonary and abdominal examinations are unremarkable.
Laboratory results are as follows:
Which of the following is the most appropriate diagnostic study for this patient?

Question

A 31-year-old woman comes to the office due to fatigue and cold intolerance. She has also experienced abdominal bloating, and states, "I can't think clearly and I feel like I am always in a fog." The patient has a history of hypothyroidism treated with levothyroxine and has required escalating doses (currently 200 mcg/day) over the last several months as her serum TSH has remained elevated. She has been compliant in taking her levothyroxine every day 1 hour before breakfast and takes no other medications or supplements. The patient had a miscarriage at age 25, and her menstrual periods have been irregular since then. She quit smoking cigarettes 10 years ago, drinks a few beers on most weekends, and does not use recreational drugs.
Blood pressure is 136/92 mm Hg and pulse is 66/min. BMI is 30 kg/m². Examination shows diffuse firm enlargement of the thyroid gland. Cardiopulmonary and abdominal examinations are unremarkable.
Laboratory results are as follows:

Which of the following is the most appropriate diagnostic study for this patient?

Quizplus · Accepted Answer

This patient has hypothyroid symptoms and an elevated serum TSH despite escalating doses of levothyroxine, good compliance, and proper medication technique. This scenario is common in patients taking medications (eg, bile acid sequestrants, antacids, proton pump inhibitors) that decrease absorption of levothyroxine, but this patient is not taking any such medications. In light of her microcytic anemia (possibly due to impaired absorption of iron), a malabsorption syndrome should be considered. Primary hypothyroidism is commonly associated with other autoimmune disorders (eg, adrenal insufficiency, type 1 diabetes, vitiligo). In addition, celiac disease has increased incidence in patients with autoimmune hypothyroidism and could account for this patient's malabsorption and elevated hepatic transaminases. She therefore should have an IgA anti-tissue transglutaminase antibody assay. If celiac disease is confirmed, a gluten-free diet usually restores the absorption of levothyroxine. (Choice B) Serum IgE assays are used in the evaluation of allergic bronchopulmonary aspergillosis, other serious allergic disorders, and certain immune deficiencies. IgE-mediated food allergy typically presents with acute symptoms (eg, nausea, diarrhea, abdominal pain), but food allergy as a cause of chronic malabsorption is uncommon and usually non-IgE-mediated. (Choice C) Dose adjustments in levothyroxine therapy are primarily based on serum TSH levels. Free T4 is occasionally useful in patients with very high TSH levels. Although a small amount of T3 is released by the thyroid, the majority is formed by conversion from T4 in peripheral tissues. Therefore, in patients taking levothyroxine (T4), serum T3 levels do not correlate with physiologic activity and serum T3 assays are not useful in most cases. (Choice D) Thyroid peroxidase antibodies are associated with chronic lymphocytic (Hashimoto) thyroiditis and related disorders (eg, silent thyroiditis, postpartum thyroiditis). Assay is useful in evaluation of hypothyroid goiter and can predict progression in patients with subclinical hypothyroidism. Once the diagnosis of primary hypothyroidism has been established, this test has little clinical utility. (Choice E) Thyrotropin receptor antibodies are responsible for Graves disease, which would typically present with hyperthyroidism and a suppressed TSH. Educational objective: The incidence of celiac disease is increased in patients with autoimmune hypothyroidism and can lead to undertreatment of hypothyroidism due to malabsorption of levothyroxine. Initial testing should include an IgA anti-tissue transglutaminase antibody assay. A gluten-free diet usually restores the absorption of levothyroxine. __________ References: Atypical celiac disease as cause of increased need for thyroxine: a systematic study. (http://www.ncbi.nlm.nih.gov/pubmed/22238404)

A 31-Year-Old Woman Comes to the Office Due to Fatigue