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

Abstract

ObjectiveEvidence 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.MethodsWe 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.ResultsIn 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).ConclusionsL-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.

Expert opinion on liquid L-thyroxine usage in hypothyroid patients and new liquid thyroxine formulation — Tirosint SOL [Opinia ekspertów dotycząca stosowania płynnej postaci lewotyroksyny oraz nowego preparatu Tirosint SOL u chorych na niedoczynność tarczycy]

“…Four prospective studies with 200 participants evaluating replacement liquid LT4 therapy in hypothyroid patients and one population-based study with 56,354 patients treated with L-T4 mostly for hypothyroidism and non-toxic goitre were found [25][26][27][28][29]. In three out of four prospective studies including 185 subjects, switching from tablet LT4 to liquid LT4 appeared more effective; only in a single paper including 15 participants no difference in TSH between tablet and liquid LT4 formulations was noted [26].…”

“…Five prospective observational studies were found evaluating liquid LT4 efficacy in 117 patients with malabsorption due to interfering drugs (proton pump inhibitors [PPIs], calcium, ferrous sulphate, polypharmacy) and a single prospective observational study assessing liquid LT4 results in 13 patients with malabsorption caused by bariatric surgery [38][39][40][41][42][43]. In five out of six studies patients were switched from tablet levothyroxine to the equivalent dose of liquid formulation.…”

“…In five out of six studies patients were switched from tablet levothyroxine to the equivalent dose of liquid formulation. In one study the patients were randomised to tablet or liquid LT4 [42]. In all studies, higher efficacy of liquid LT4 compared to tablet formulation treatment…”

“…No control group was recruited. The median starting dose was 12.3 µg/kg (range 9.8-17.1 µg/kg) and decreased to about 5 [42] 43 Two groups of patients were analysed:…”

“…Analizę przeprowadzono wśród chorych na niedoczynność tarczycy stosujących terapię zastępczą oraz u chorych na zróżnicowanego raka tarczycy (ZRT) poddanych terapii supresyjnej. Wyłoniono cztery badania prospektywne przeprowadzone z udziałem 200 chorych na niedoczynność tarczycy oceniające wyniki terapii zastępczej płynną LT4 oraz pojedyncze badanie populacyjne, podczas którego 56 354 chorych leczono LT4 głównie z powodu niedoczynności tarczycy i wola nietoksycznego [25][26][27][28][29].…”