Endocrine Abstracts

Primary hypothyroidism is a frequent disease and oral levothyroxine is the mainstay of its treatment. However, more than 20% of levothyroxine-treated patients fail to achieve the recommended serum TSH level with a body weight–based dose of levothyroxine. Refractory hypothyroidism is due to either malabsorption or nonadherence. In clinical practice, a levothyroxine absorption test is part of the workup of a refractory hypothyroid patient for confirming normal levothyroxine absorption or diagnosing malabsorption. This test is not standardized and published procedures differ markedly in the test dose, formulation, test duration, frequency of blood collection, analyte (total thyroxine or free thyroxine), metric (absolute or relative peak or increment, or area under the curve) and threshold for normal absorption. We analyzed 166 levothyroxine absorption tests performed in 143 refractory hypothyroid patients (109 women, 34 men, mean age 42 ± 15 years) treated with oral levothyroxine dose > 2 mg/kg/day for postsurgical hypothyroidism (n = 101) in the context of differentiated thyroid cancer (n = 40) or autoimmune hypothyroidism (n = 29). Despite a daily dose of 3.26 ± 1.18 mg/kg/day, mean serum TSH concentration was 25.7 ± 43.3 mU/l. Refractory hypothyroidism was due to Helicobacter pylori infection (27%), autoimmune atrophic gastritis (12%), celiac disease (2.5%), drug interference with levothyroxine absorption (27%) or nonadherence to daily treatment (10%). After an overnight fast, patients take orally their daily dose of levothyroxine (220 ± 80 mg) under the supervision of medical staff. Blood samples for total and free T4 levels were drawn before levothyroxine intake and then every two hours during 24 hours. The percentage of levothyroxine absorption was calculated by the following formula: [(peak total T4-baseline total T4) mg/dl x 10 x 0.442 x BMI / levothyroxine dose (mg/day)] with normal absorption being > 60%. After levothyroxine intake, the mean total (basal = 7.66 ± 3.22 mg/dl, peak 9.44 ± 3.50 mg/dl, P < 0.001), and free (basal = 12.48 ± 5.50 pg/ml, peak 15.74 ± 6.55 pg/ml, P < 0.001) T4 levels increased. Total and free T4 peaks were observed at 4.0 ± 2.39 and 3.96 ± 2.71 hours, respectively. A normal percentage of absorption was observed at 6 and 8 hours in 70% and 71% of the patients, respectively. The percentage of levothyroxine absorption was correlated with the levothyroxine dose (in mg/day, P = 0.0016; in mg/kg/day, P = 0.0002). Rapid levothyroxine absorption tests were well tolerated, and no patient experienced adverse cardiovascular events. In conclusion, in patients with refractory hypothyroidism (increased TSH level despite levothyroxine dose > 2 mg/kg/day) this clinical study revealed that rapid levothyroxine absorption test can be achieved via the absorption of the daily dosage of levothyroxine and the evaluation of total and free T4 concentrations over 6 hours. The test is well tolerated without cardiovascular adverse events.