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The Use of Bile Acid Sequestrants to Lower Serum Thyroid Hormones in Iatrogenic Hyperthyroidism
- K. M. Mohamed Shakir, MD;
- Rodney D. Michaels, MD;
- James H. Hays, MD; and
- Bonnie B. Potter, MD
- From the National Naval Medical Center and the Uniformed Services University of the Health Sciences, Bethesda, Maryland. Requests for Reprints: CAPT K. M. M. Shakir, MC, USN, Division of Endocrinology and Metabolism, National Naval Medical Center, Bethesda, MD 20889-5000. Acknowledgment: The authors thank Ms. Pat Rattal for editorial assistance.
Abstract
Hyperthyroidism occasionally must be rapidly restored to euthyroidism, especially if it is associated with an emergent condition such as myocardial infarction. Several modalities are available to render endogenous hyperthyroid patients to a euthyroid state rapidly. Few therapeutic options, however, are available to rapidly treat hyperthyroidism caused by ingestion of excess thyroid hormones, except perhaps the use of β-blockers. We observed hypothyroidism develop in two patients taking stable doses of levothyroxine after cholestyramine was added to their drug regimen. This finding led us to treat two patients with iatrogenic hyperthyroidism with cholestyramine. A euthyroid state was achieved in 72 to 96 hours whereas in three similar patients without cholestyramine treatment it had taken almost 8 days for serum thyroid hormone levels to fall into normal range. Our preliminary results suggest that bile acid sequestrants may be useful in treating exogenous thyroid-hormone-induced hyperthyroidism in emergent situations.
Patients with hyperthyroidism occasionally need rapid restoration to the euthyroid state, especially if associated with certain emergent situations such as myocardial infarction. Few treatments are available that rapidly correct hyperthyroidism resulting from excessive ingestion of thyroid hormone [1, 2]. In these situations, emergent surgery or invasive procedures may have to be postponed. We recently observed the development of mild hypothyroidism in two patients treated with L-thyroxine when cholestyramine was added to the drug regimen. This observation prompted us to treat two patients with iatrogenic hyperthyroidism with cholestyramine to achieve euthyroid status rapidly.
Case Reports
Patient 1
A 58-year-old white woman with a diagnosis of right breast carcinoma was referred to us for evaluation. The patient had been taking 0.25 mg L-thyroxine per day for primary hypothyroidism for 3 years. She had a resting pulse rate of 110 beats per minute, a fine tremor in the fingers, and hyperactive deep tendon reflexes. The thyroid gland was not palpable. The serum T4 was 223 nmol/L; serum free T4, 53 pmol/L; T3 resin uptake, 0.36 (normal, 0.25 to 0.35); T3 (by radioimmunoassay), 4.00 nmol/L; thyroid stimulating hormone (TSH), < 0.1 mU/L; and thyroglobulin, < 1.2 mg/dL (normal, 1.2 to 2.8 mg/dL) (Figure 1).
In order to allow the patient to undergo mastectomy as quickly as possible, she was started on cholestyramine (Questran; Bristol Laboratory, Evansville, Indiana), 4 g four times daily along with the withdrawal of L-thyroxine. Seventy-two hours after treatment was initiated, the thyroid functions returned to normal (see Figure 1), and a right mastectomy was done without complications on day 5.
Patient 2
A 64-year-old white man developed laryngeal carcinoma for which surgery was recommended. The patient had a history of papillary thyroid carcinoma, treated with total thyroidectomy and iodine-131 ablation 18 years ago. Six months before the clinic visit, the patient, on his own initiative, had doubled his L-thyroxine dose to 0.3 mg daily. At admission, he had resting tachycardia and fine tremors of the fingers. No abnormalities were found on neck examination. Laboratory evaluation showed a serum TSH of < 0.1 mU/L; T (4), 218 nmol/L; free T4, 69 pmol/L; T3, 3.69 nmol/L; and T3 resin uptake, 0.39 (see Figure 1). Because the hyperthyroid state had to be corrected rapidly, L-thyroxine was discontinued and the patient was started on oral cholestyramine, 4 g four times daily. Ninety-six hours after treatment was begun, laboratory test results of thyroid function were normal (see Figure 1). On day 6, the patient had surgery without complications.
To investigate whether the mere discontinuation of L-thyroxine may have brought the serum thyroid hormone levels to normal range without the use of the resin, we followed three patients who had primary hypothyroidism and were taking higher than normally prescribed daily doses of L-thyroxine (0.258 ± 0.018 mg; mean ± SE) (see Figure 1). All three patients had mild hyperthyroid symptoms, and the initial serum levels of the hormone were in hyperthyroid range. The changes in serum thyroid hormone levels were monitored for several days after discontinuation of the hormone, and serum T4 and T3 were not in the normal range until day 8.
Discussion
Overdosage with thyroid hormones, either intentional or iatrogenic, is occasionally seen in clinical practice [1]. If patients with this problem need emergent surgery or if they have potential life-threatening conditions such as myocardial infarction, few therapeutic options, except perhaps the use of β-blockers, are available. Our observation, along with those of others [3], of the effect of cholestyramine on patients maintained on thyroxine prompted us to treat exogenous hyperthyroidism with the resin. It may be argued that in hyperthyroid patients with accelerated thyroid hormone clearance [4], mere discontinuation of L-thyroxine would have brought the serum levels to the normal range without the use of the resin. However, control patients in whom thyroxine was stopped but cholestyramine was not given took much longer to return to normal serum hormone levels.
The liver is the major site of degradation of thyroid hormones. In this organ, both T4 and T3 undergo conjugation, and the conjugation products are excreted in the bile [2]. Free hormones are released in the intestine and are reabsorbed, and an enterohepatic circulation occurs [5, 6]. It has been shown that 50 mg of cholestyramine can bind at least 3000 µg of thyroxine [5] and therefore can enhance the clearance of thyroid hormones. Our preliminary observation thus shows that anion exchange resin may be useful in treating iatrogenic hyperthyroidism in emergent situations.
The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Navy Department or the Naval Service at large.
- Copyright ©2004 by the American College of Physicians
