Abstract: Background: Failure to treat persistent hypothyroidism despite the use of adequately prescribed doses of levothyroxine should be evaluated for malabsorption and nonadherence to medication. Previous literature suggested that orally administered levothyroxine showed maximum absorption at or near 2 hours. This rapid absorption suggests the use of a 2-hour levothyroxine absorption test as an alternative to long, cumbersome protocols. Limited data is available measuring free thyroxine (FT4) levels at 2 hours after oral administration of 1000 mcg of levothyroxine. Cases presentation: Six patients who continued to have hypothyroidism despite taking ostensibly high doses of levothyroxine underwent a 2-hour protocol levothyroxine absorption test. All patients were given 1000 mcg of levothyroxine, and serum levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured at 0, 60, and 120 minutes. All patients showed an increasing trend in FT4 in subsequent samples at 60 min and 120 min, compared to base line values, providing strong evidence of peak levothyroxine absorption at 2 hours. Five patients had raised baseline TSH levels, indicating nonadherence to treatment, and one had normal baseline TSH levels, indicating adherence to levothyroxine therapy on prior test scheduling, with increased FT3 and FT4 levels in subsequent samples at 60 min and 120 min. Conclusion: We conclude that the rapid levothyroxine absorption test, using a 2-hour protocol, is a more convenient method to differentiate nonadherence from malabsorption. Moreover, scheduling the patient will result in adherence to levothyroxine therapy in some patients.

Keywords: Levothyroxine absorption test, nonadherence, malabsorption, case series.