A publication of the American Thyroid Association

Summaries for Patients from Clinical Thyroidology by Ernest Mazzaferri, MD MACP
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Abbreviations & Definitions

L-T4 is levothyroxine, the standard drug for treatment of hypothyroidism and thyroid cancer

Gastrin is a stomach hormone that stimulates stomach acid secretion

Famotidine (Pepcid), a histamine H-2 antagonist that inhibits gastric acid secretion

Esomeprazole, (Nexium a proton-pump inhibitor) that lowers gastric acid secretion

Ezetimibe (Zetia) a lipid-lowering drug

What is the study about? Intestinal absorption of thyroid hormone may be impaired by drugs that impair gastric acid secretion.

The full article title: “Altered Intestinal Absorption of L-Thyroxine Caused by Coffee.” It is in the May 2008 Issue of Thyroid (volume 18 Issue 5, pages 493-8). The authors are S Ananthakrishnan, LE Braverman, RM Levin,, B Magnani, and EN Pearce. The abstract can be obtained from:

What is known about the problem being studied? Gastric acid suppression is inconsistently reported to interfere with levothyroxine (L-T4) absorption.

What was the aim of the study? This is a prospective study of the absorption of L-T4 in normal volunteers taking famotidine (Pepcid, a histamine H-2 antagonist) esomeprazole, (Nexium a proton-pump inhibitor) and ezetimibe (Zetia, a lipid-lowering drug that inhibits intestinal absorption of cholesterol).

Who was studied? The study subjects were 30 carefully screened healthy, euthyroid volunteers.

How was the study done? Volunteers were assigned to one of three independent study groups, famotidine, esomeprazole, and ezetimibe, with 10 in each group. The mean age was 28.1, 26.1 and 27 years, respectively, in each group. L‐T4 absorption was tested before study, and the final L‐T4 absorption test was performed approximately 1 week after the subjects were assigned to drug administration and immediately before a third and final L‐T4 absorption test.

The study was performed as follows in the three study groups: 1 week of 20 mg famotidine (Pepcid) twice daily with meals, or 1 week of 40 mg esomeprazole (Nexium) daily with breakfast, or a single 10-mg dose of ezetimibe (Zetia). A 1-week administration of the gastric acid suppressive medications was selected to achieve a gastric pH >4 (range, 12 19)

Patients were divided into three normal reference groups that were selected with increasingly more stringent criteria to identify those without evidence of thyroid disease. TSH was retested by both older and contemporary laboratory methods.

What were the results of the study? Mean peak serum thyroxine levels did not change significantly before and after famotidine, esomeprazole, or ezetimibe. Serum fasting gastrin levels were significantly higher than baseline levels as a result of taking the each of the drugs that impair gastric acid secretion.

How does this compare with other studies? The rate of thyroid hormone absorption can be estimated by the ingestion of radioactive iodine–labeled L-T4 or simply with large oral doses of L-T4, in the range of 600 μg. These observations have led to the discovery of a number of conditions that can lead to malabsorption of L-T4, ranging from intestinal disease, timing of L-T4 ingestion with meals, and the simultaneous use of drugs that inhibit L-T4 absorption such as iron and calcium. Previous studies have shown that patients with impaired gastric acid secretion require an increased dose of L-T4, suggesting that normal gastric acid secretion is necessary for effective absorption of oral L-T4.

What are the Limitations of this study? The main limitation is that this was an acute study and the two gastric acid inhibitors are likely to cause some malabsorption when L-T4 is taken over an extended period, or when patients taking these drugs have gastritis.

What are the implications of this study? This study shows that normal subjects taking famotidine and esomeprazole for a short period of time does not impair thyroid hormone absorption. However, taking these drugs for an extended time would likely cause L-T4 malabsorption.

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