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A 76-year-old woman is reevaluated after results of thyroid function tests performed 2 weeks ago are abnormal. The patient otherwise feels well. She has a history of hypertension, atrial fibrillation, gastroesophageal reflux disease, and depression. Current medications are metoprolol, amiodarone, warfarin, omeprazole, and sertraline.
On physical examination, blood pressure is 125/65 mm Hg, pulse rate is 83/min, and respiration rate is 15/min. The thyroid gland is smooth and of normal size. Cardiac examination reveals an irregularly irregular rhythm. Deep tendon reflexes are normal.
Laboratory studies:
| Thyroid-stimulating hormone | 6.5 µU/mL (6.5 mU/L) |
| Thyroxine (T4), free | 2.4 ng/dL (31.0 pmol/L) |
| Triiodothyronine (T3), free | 0.8 ng/L (1.2 pmol/L) |
Which of the following medications is most likely responsible for the laboratory results?
A) Amiodarone
B) Metoprolol
C) Omeprazole
D) Sertraline
The correct answer is A. Amiodarone. This item is available to MKSAP 15 subscribers as item 76 in the Endocrinology and Metabolism section.
Amiodarone has been associated with several abnormalities in thyroid function, including amiodarone-induced thyrotoxicosis (hyperthyroidism [type 1] and thyroiditis [type 2]), hypothyroidism, and inhibition of thyroxine (T4) to triiodothyronine (T3) conversion. Because of the drug’s high iodine content and fat solubility, its effects on the thyroid gland have been reported to persist from months to up to 1 year. The results of this patient’s thyroid function studies are consistent with decreased T4 to T3 conversion with a concomitant increase in the serum thyroid-stimulating hormone level, which can occur with use of amiodarone. The decision to discontinue amiodarone can be complex. Amiodarone is usually not discontinued unless it fails to control the underlying arrhythmia. In patients with hypothyroidism who must continue amiodarone, thyroid replacement therapy is indicated. In patients with previously normal thyroid gland function who discontinue amiodarone, hypothyroidism often resolves.
Amiodarone-induced thyrotoxicosis can be a management challenge. Theoretically, antithyroidal drugs are preferred in type 1 (hyperthyroidism) and prednisone therapy in type 2 (thyroiditis). In practice, however, a combination of both may be needed in patients with either type.
Whereas propranolol is known to affect T4 to T3 conversion, other β-blockers, such as metoprolol, are not. Discontinuing metoprolol in this patient is unlikely to restore normal thyroid function.
Omeprazole and other proton-pump inhibitors can affect hormone absorption in patients on thyroid hormone replacement therapy. Given that this patient is not receiving levothyroxine, the use of omeprazole does not explain her findings.
Sertraline appears to enhance thyroid hormone metabolism but does not cause the abnormal results on thyroid function tests seen in this patient.
Key Point
- Amiodarone has been associated with thyrotoxicosis, hypothyroidism, and inhibition of thyroxine (T4) to triiodothyronine (T3) conversion.
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