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Factors That Influence Levothyroxine Dose

Levothyroxine is the form of thyroid hormone that is generally recommended for replacement or suppressive therapy. Once a patient has been taking levothyroxine regularly for four to six weeks, measurement of serum TSH can indicate whether the patient is taking the correct dose. If the patient is taking too much levothyroxine, the pituitary stops making TSH and the level falls; if the dose is too low, TSH increases.

The dose of levothyroxine that an individual requires is dependent partly upon body weight, age, and sex. Patients who weigh more require higher doses, while elderly patients require considerably less hormone. Women in general require less levothyroxine than men. Average replacement doses for women are 0.112-0.125 mg daily, but may fall to 0.075 mg during the seventh and eighth decades.

Men generally require 0.025-0.050 mg more levothyroxine than women.

Approximately three-fourths of the levothyroxine (Synthroid, Levothroid, Levoxyl, and others) that a patient ingests is absorbed and finds its way into the bloodstream. Since the introduction of sensitive TSH assays which allow us to determine the appropriateness of an individual’s levothyroxine dose more precisely than ever before, a number of factors have been found which interfere with the absorption of levothyroxine. This can either lead to variability of hormone levels, or increased dose requirements. When a patient’s dose requirements seem to fluctuate unexpectedly, one must consider factors that can interfere with absorption.

The cholesterol lowering resins cholestyramine (Questran) and colestipol, and the antacid medication carafate may bind levothyroxine in the gastrointestinal tract and prevent its absorption. Aluminum-containing antacids and iron tablets or iron-containing vitamins (common over-the-counter medications), also can interfere with levothyroxine absorption. And a recent report suggests that dietary bran might also bind and limit the absorption of levothyroxine. It is likely that this list of medications and foods will increase in the future.

For this reason, many pharmacists now recommend that levothyroxine be taken on an empty stomach.

For patients who have taken levothyroxine for years, who now use the medications listed in the prior paragraph, and who have had stable TSH levels, I do not recommend a change in the manner or time of day that they take their medication. Theoretically, if a patient has always taken levothyroxine with breakfast and had a normal TSH, taking it on an empty stomach might result in higher absorption and require a subsequent reduction in dose. However, patients who have had variable TSH levels or difficulty adjusting the dose should take levothyroxine on an empty stomach—or several hours after ingesting food or other medications. And certainly if the need arises to take any of the medications noted above, they should be taken several hours before or after taking levothyroxine.

There are several other medications and diseases that can influence the dose of levothyroxine that an individual patient requires. Patients with gastrointestinal disorders that result in malabsorption such as chronic diarrhea, inflammatory bowel disease or sprue may require very high doses of levothyroxine because of poor absorption. Patients with nephrotic syndrome may lose thyroid hormone in their urine and require higher doses of levothyroxine. And several drugs increase the metabolism of levothyroxine and patients starting these medications may require a higher dose: dilantin, carbamezine (Tegretol), phenobarbitol, and rifampin.

Finally, pregnancy is associated with significantly increased levothyroxine requirements and many hypothyroid pregnant women will require a 30% or higher increase in their dose. Estrogen therapy increases the protein that binds thyroxine in the blood. It is possible that some patients who start treatment with estrogen hormones (for example, Premarin or oral contraceptives) may require an adjustment in their levothyroxine dose. It is prudent to check a TSH a few months after starting an estrogen containing medication to be sure that the dose requirements have not changed.

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