Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With "Refractory Hypothyroidism"

Hypothyroidism is a frequent disease, and oral levothyroxine is the mainstay of its treatment. However, more than 15% of levothyroxine-treated patients fail to achieve the recommended serum TSH level, and "refractory hypothyroidism" is due to either malabsorption, increased metabolism of thyroxine, or nonadherence to treatment. A levothyroxine absorption test must be used to differentiate true malabsorption from nonadherence or pseudo-malabsorption. We analyzed 166 levothyroxine absorption tests in 143 hypothyroid patients (109 women, mean age 43 ± 1 years) treated with oral levothyroxine. Despite a daily dose of 3.26 ± 0.09 g/kg/day, mean serum TSH concentration was 25.7 ± 3.7 mU/L. "Refractory hypothyroidism" was in the context of gastritis (24%), Helicobacter pylori infection (18%), drug interference with levothyroxine absorption (15.6%), nonadherence to treatment (10%), celiac disease (2.5%), or bariatric surgery (1.2%). After an overnight fast, patients orally took their daily dose of levothyroxine (220 ± 6 g), and blood samples were drawn before levothyroxine intake and every 2 hours for 24 hours. After levothyroxine intake, the mean total (basal = 7.64 ± 0.26 g/dL, peak 9.41 ± 0.28 g/dL), and free (basal = 12.58 ± 0.42 pg/mL, peak 15.77 ± 0.51 pg/mL) T4 levels increased (P < .001), total and free T4 peaks were observed at 4.2 ± 0.23 and 4.30 ± 9.27 hours, respectively. Levothyroxine absorption tests were well tolerated. In conclusion, in most patients with "refractory hypothyroidism," this clinical study revealed that the levothyroxine absorption test can be achieved via the absorption of the daily dosage of levothyroxine, and the evaluation of total or free T4 concentrations over 4- or 6-hour follow-up. The test is well tolerated without cardiovascular adverse events.