Abstract
Levothyroxine (L-T4) absorption can be impaired by various causes: a) L-T4 ingestion during breakfast, or with food; b) conditions of reduced gastric acidity; c) intestinal procedures and diseases such as bariatric surgery, lactose intolerance (LI), celiac disease (CD), inflammatory bowel disease; d) drugs that alter L-T4 absorption, increasing the gastric pH, or preventing the dissolution of tablets. The development of new oral formulations, i.e. the liquid preparation and the soft gel capsule, represents the most recent advance regarding L-T4 therapy. Treating hypothyroidism with L-T4 tablets can lead to an improper control of thyroid-stimulating hormone (TSH) in ~10%–15% of patients. The improperly elevated TSH is usually managed by increasing the L-T4 daily dose, and revaluating TSH upon 2-6 months. The increase of the L-T4 dosage may cause iatrogenic hyperthyroidism, especially when the underlying disorders are cured. Liquid L-T4 can be administered in patients unable to swallow capsules or tablets, and this is one of its major benefits. Liquid L-T4 can: 1- overcome food and beverages interference; 2- bypass the malabsorption associated with an increased gastric pH; 3- circumvent the issue of malabsorption in patients who underwent bariatric surgery; 4-maintain TSH values under control better than L-T4 tablets in hypothyroid patients with typical or atypical CD, or in patients with LI. Few clinical studies evaluated soft gel L-T4 with encouraging findings in patients with gastric- or coffee-related malabsorption, or hypothyroid patients without malabsorption. Additional research is necessary to investigate liquid L-T4, or soft gel capsule, in other conditions of altered L-T4 absorption.
Highlights
The synthetic hormone levothyroxine (L-T4) has a chemical structure comparable to T4, and it is prescribed as substitutive therapy of hypothyroidism-associated conditions [1]
In patients with Helicobacter pylori (HP) infection after 3 months, subjects treated with liquid L-T4 showed a greater thyroid-stimulating hormone (TSH) reduction and a greater homogeneity in the TSH values, compared to L-T4 tablet. These results suggested that L-T4 liquid formulation may produce a better clinical response compared to the tablet formulation in hypothyroid subjects with HP infection [50]
A crossover study, conducted in patients in whom tablet L-T4 absorption was impaired by pump inhibitors (PPIs), demonstrated a significant decrease in circulating TSH following the switch from the tablet preparation to the liquid one, at the same daily dose, maintaining the co-ingestion of PPI [57]
Summary
The synthetic hormone levothyroxine (L-T4) has a chemical structure comparable to T4, and it is prescribed as substitutive therapy of hypothyroidism-associated conditions [1]. The dosage of 1.5–1.7 μg/kg body weight/day is considered as the optimal daily L-T4 replacement dose, which can normalize TSH levels in most hypothyroid patients [15]. A first meta-analysis suggested that subjects receiving L-T4 tablets with suboptimal TSH values can achieve the desirable TSH after the switch to liquid L-T4 using the same dosage [32], and a second one indicated that the effectiveness of liquid L-T4 is higher (vs tablets) in patients having or not having malabsorption in replacement or suppressive treatment [33]. Another study demonstrated a greater stability in the thyroid profile of hypothyroid elderly patients treated with liquid thyroxine as opposed to those being treated with tablet formulation over 5 years of follow-up [34]. The liquid L-T4 permitted to control better the stability of TSH levels in patients who underwent thyroidectomy for cancer [38], or after bariatric surgery [39]
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