• Increased TSH levels in patients on levothyroxine often result from absorption problems caused by medications like iron, calcium, and proton pump inhibitors.
• Malabsorption disorders such as celiac disease and atrophic gastritis can also impair levothyroxine absorption.
• Recommendations for managing elevated TSH include reviewing medications, performing absorption tests, and addressing underlying malabsorption syndromes.

The article addresses the clinical scenario where a patient with hypothyroidism, treated with levothyroxine, experiences an unexpected increase in thyroid-stimulating hormone (TSH) levels. It explains that while adherence to medication is a primary consideration, the more common causes stem from impaired levothyroxine absorption. This can arise due to interactions with other medications, underlying malabsorption disorders, or dietary factors. The article emphasizes the importance of a thorough investigation to identify and address the root cause of the increased TSH, ensuring optimal thyroid hormone levels and patient well-being.

• What: The article discusses the increase in TSH levels in patients treated with levothyroxine for hypothyroidism, focusing on the common causes of impaired levothyroxine absorption.
• Who: The primary audience is healthcare professionals managing patients with hypothyroidism. Key individuals mentioned include Douglas S. Paauw and Veda Gadiraju (authors), Liwanpo and Hershman, Skelin and colleagues, and Irving and colleagues.
• When: The article was published on May 01, 2025. It discusses a common clinical problem encountered in patients on long-term levothyroxine therapy.
• Where: The context is a clinical setting, likely in the United States, given the affiliation of the authors with the University of Washington.

The article provides a concise overview of the factors contributing to increased TSH levels despite levothyroxine treatment. The emphasis on medication interactions and malabsorption disorders highlights the importance of a comprehensive patient history and appropriate diagnostic testing. The recommendations for levothyroxine administration provide practical guidance for clinicians. Further research is needed to determine the effects of specific dietary components on levothyroxine absorption.

The most common cause of these absorption problems is other medications that block levothyroxine absorption.

Given that the absorption of levothyroxine is affected by diet and various medications, it is recommended that levothyroxine tablets be taken in the morning at least 30-60 minutes before eating or 3-4 hours after dinner.

Elevated TSH levels in patients on levothyroxine necessitate a thorough investigation into potential causes of impaired drug absorption. Medication interactions, malabsorption syndromes, and dietary factors are key considerations. By addressing these issues, clinicians can optimize levothyroxine effectiveness and ensure appropriate thyroid hormone replacement.