LAUSR

Hypothyroidism is a condition that is more frequent in women, particularly those older than 60 years of age. It is readily diagnosed by the measurement of blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) (1). Common causes of hypothyroidism include (2–4): A) a low iodine intake in iodine deficient areas; B) autoimmune thyroiditis (the principal cause in iodine sufficient areas); C) total thyroidectomy; D) radioiodine therapy as for therapy of hyperthyroidism; E) drugs (i.e., immune checkpoint inhibitors, and tyrosine kinase inhibitors) (5–7); F) other rare causes (8). Levothyroxine (L-T4) is a synthetic hormone with a chemical structure similar to natural endogenous T4, that is prescribed at the dose of 1.5-1.7 mg/kg body weight/day as substitutive therapy for any of the conditions associated with hypothyroidism. The treatment will lower elevated levels of TSH into the normal range for virtually all hypothyroid patients, with normalization as well of circulating free triiodothyronine (FT3) and free T4 (FT4) levels (1, 9). Nevertheless and owing to various interfering issues, ~20-50% of patients do not have an optimal response to this therapy (10, 11), and require titration with higher dosage while monitoring TSH and thyroid hormones levels (12). Pseudomalabsorption of L-T4 caused by poor patience adherence to the prescribed dosage must be excluded, and having done so, then a decreased intestinal absorption of L-T4 associated with either intrinsic gastrointestinal diseases or pharmacological interference with absorption, remains the primary explanation for refractory hypothyroidism (11). In the twelve papers that constitute this Research Topic, various innovative aspects related to therapy of hypothyroidism with L-T4 are reviewed and discussed and provide a stimulating overview of the present state of our knowledge. The review by Fallahi et al. discusses novel L-T4 formulations such as the liquid preparation (that does not need the dissolution of the tablet preparation in the acid gastric environment) and the soft gel capsule (that dissolves quickly in the stomach), both of which having been developed to potentially bypass the problem of refractoriness reported with “usual formulations” of L-T4. The use of the soft gel capsule of L-T4 has been studied in some clinical trials with promising results in subjects with gastricor coffee-associated T4 malabsorption (13), as well as in hypothyroidism without demonstrable malabsorption. Liquid L-T4 can avoid possible absorption interference related to coffee or food that has been reported with L-T4 tablets, and may overcome the problem of malabsorption observed in the