A 25-year-old man comes to the office for follow-up. The patient was diagnosed with Graves disease 12 months ago during an evaluation for diarrhea, tremor, and palpitations. He received radioiodine therapy and required initiation of levothyroxine due to iatrogenic hypothyroidism. The patient reports that most of his symptoms have improved with treatment, but he still has occasional diarrhea and fatigue. In addition, his serum TSH levels have remained elevated despite escalating dosages of levothyroxine. The patient takes no other medications and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/90 mm Hg and pulse is 64/min. The thyroid is not palpable and skin is mildly dry; otherwise, physical examination is unremarkable. Laboratory results are as follows: Stool occult blood test is negative. Which of the following is the best next step in management of this patient?

Question

A 25-year-old man comes to the office for follow-up.  The patient was diagnosed with Graves disease 12 months ago during an evaluation for diarrhea, tremor, and palpitations.  He received radioiodine therapy and required initiation of levothyroxine due to iatrogenic hypothyroidism.  The patient reports that most of his symptoms have improved with treatment, but he still has occasional diarrhea and fatigue.  In addition, his serum TSH levels have remained elevated despite escalating dosages of levothyroxine.  The patient takes no other medications and does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 130/90 mm Hg and pulse is 64/min.  The thyroid is not palpable and skin is mildly dry; otherwise, physical examination is unremarkable.  Laboratory results are as follows:  Stool occult blood test is negative.  Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

Explanation: 11ec2b69_bf23_12d5_8f63_41271cbf8d4f_MD0005_00 Following radioiodine therapy for Graves disease, many patients are left with a residual hypothyroid state and require lifelong levothyroxine replacement. This patient was started on appropriate therapy but continues to have an elevated TSH despite escalating levothyroxine doses. This suggests levothyroxine malabsorption. To ensure adequate gastrointestinal absorption, levothyroxine should be taken on an empty stomach 30-60 minutes before eating and at least 4 hours before other drugs (eg, ferrous sulfate, calcium carbonate, sucralfate) that can interfere with absorption. This patient takes no medications that would reduce absorption, but has a number of features (eg, diarrhea, microcytic anemia) that suggest an underlying malabsorptive disorder. Celiac disease has an increased prevalence in patients with autoimmune thyroid disease and is an important cause of levothyroxine malabsorption. Initial testing with serologic studies (eg, anti-transglutaminase IgA or anti-endomysial IgA antibodies) is indicated for this patient, followed by endoscopy if positive. If celiac disease is confirmed, absorption of levothyroxine can be restored with a gluten-free diet. (Choice A) T3 (the more active form of thyroid hormone) is derived primarily by deiodination of T4 in peripheral tissues in response to circulating TSH. Supplemental T3 (liothyronine) is not needed for most patients taking supplemental T4 (levothyroxine). In addition, T3 has a very short half-life, and liothyronine supplementation can lead to an uneven thyroid hormone effect through the day. (Choice C) Ectopic thyroid hormone production from ovarian teratomas (struma ovarii) is a very rare cause of hyperthyroidism. In these patients, the serum TSH is low from the suppressive effect of thyroid hormone overproduction. (Choice D) MRI of the pituitary is warranted to evaluate a TSH-secreting pituitary adenoma, which presents with thyrotoxicosis associated with inappropriately normal or elevated serum TSH. The increased serum TSH level in this patient represents a physiologic response to inadequate circulating thyroid hormone levels. (Choice E) Radioactive iodine treatment for Graves disease is successful in most patients. Retreatment is performed only if thyrotoxicosis persists for several months following initial radioiodine treatment. Educational objective: In patients on levothyroxine replacement therapy, escalating dose requirements suggest poor absorption due to interaction with other medications (eg, iron, calcium, sucralfate) or an underlying malabsorptive disorder. In patients with autoimmune thyroid disorders, celiac disease has an increased prevalence and can lead to impaired absorption of levothyroxine. References: Diagnosis and management of refractory hypothyroidism: an expert consensus report. (http://www.ncbi.nlm.nih.gov/pubmed/28695483)

A 25-Year-Old Man Comes to the Office for Follow-Up