Challenges in the treatment of hypothyroidism: malabsorption and pseudo-malabsorption of levothyroxine.

Levothyroxine (LT4) is the gold standard for the treatment of hypothyroidism. After ingestion, it undergoes changes in the stomach, a process critically dependent on gastric acidity. Within the following three hours, LT4 is absorbed in the small intestine. Taking LT4 on an empty stomach enhances its absorption, although night-time administration has shown similar results. Several foods, particularly fibers, espresso coffee, and grapefruit juice, interfere with its absorption. Certain medications have similar effects (calcium and iron salts and proton pump inhibitors). In the presence of food or medication that may interfere with LT4 absorption, it is recommended to separate their intake by 3 to 4 hours. Certain gastrointestinal conditions can also affect the absorption of LT4 into the bloodstream. Helicobacter pylori infection and atrophic gastritis increase stomach pH, while celiac disease alters the absorption surface in the small intestine. Bariatric surgery can affect LT4 absorption; however, the associated loss of lean body mass can also lower LT4 requirements. As the net effect may be an increase or decrease in LT4 requirement, close monitoring is advisable. Pseudo-malabsorption is a psychiatric condition that is difficult to diagnose and requires an LT4 absorption test for confirmation. Once diagnosed, management is complex. Weekly dosing appears to be the most recommended approach to improve adherence.