Liquid and softgel capsules of 1-thyroxine results lower serum thyrotropin levels more than tablet formulations in hypothyroid patients

Objective: Evidence indicates that L-T4 in liquid and softgel capsule are absorbed better than tablets in hypothyroid patients, even when patients are under medications that impair the intestinal absorption of L-T4. However, no study has evaluated all three L-T4 formulations in the same hypothyroid patients. This study aims to fill this gap. The outcome was the degree of TSH change in the liquid and softgel formulations, using tablet L-T4 as the reference, regardless of sequence of formulation and regardless of whether patients were co-ingesting with interfering medications. Methods: We recorded serum TSH levels in two groups of L-T4 replaced patients with primary hypothyroidism (23 subjects who did not co-ingest interfering medications, and 20 subjects who did). Either group of patients took one formulation of L-T4 at a time with variable sequences. In the first group, the median durations of exposure to tablet, liquid or softgel L-T4 were 14, 9 and 10 months, respectively. In the second group the corresponding durations were 13, 11 and 10 months, during which patients co-ingested interfering medications. Results: In the 23 patients, there were 78, 74 or 101 TSH determinations during liquid, softgel capsule or tablet L-T4 regimens. Serum TSH levels associated with liquid, capsule or tablet L-T4 were 1.62 +/- 0.51, 1.77 +/- 0.44 mU/L (P = 0.049 vs liquid) or 2.38 +/- 0.69 mU/L (P < 0.0001 vs liquid or capsule). Rates of TSH <= 2.50 mU/L were 97.4% (liquid), 95.9% (softgel) or 64.4% (tablet, P < 0.0001 vs liquid or capsule). Rates of TSH <= 4.12 mU/L were 100%, 100% or 98.0%. In the 20 patients, the corresponding TSH determinations were 56, 57 and 41, and corresponding TSH levels were 2.74 +/- 0.98, 2.70 +/- 0.79 or 7.53 +/- 2.82 mU/L. Rates of TSH <= 2.50 mU/L were 51.8% (liquid), 47.4% (capsule, P = 0.64) or 2.4% (tablet, P < 0.0001 vs liquid or capsule). Rates of TSH <= 4.12 mU/L were 92.8% (liquid), 94.7% (capsule, P = 0.68) or 12.2% (tablet, P < 0.0001 vs liquid or capsule). Conclusions: L-T4 ingested as liquid solution or softgel capsule is more bioavailable compared to L-T4 ingested as tablet, and it is slightly superior to capsule L-T4 only in the absence of co-ingestion of interfering medications.